|
1
|
Bohoněk M, Máca J, Sagan J, Řezáč D, Fridrich V, Burantová A, Kutáč D, Vabroušek P, Kubů J, Chrdle A, Volfová K, Blahutová Š, Rychlík I, Vonášková K, Majerčin R, Králová R, Štěpánek P, Holub M. Convalescent anti-SARS-CoV-2 plasma for the treatment of patients with COVID-19: a retrospective study RESCOVID-19. Virol J 2024; 21:239. [PMID: 39350163 PMCID: PMC11443855 DOI: 10.1186/s12985-024-02475-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 08/20/2024] [Indexed: 10/04/2024] Open
Abstract
PURPOSE Convalescent plasma (CP) collected from people who recovered from COVID-19 became a rapidly available treatment modality in numerous countries, including the Czech Republic. The aims of our study were to evaluate the effectiveness and safety of CP in the treatment of COVID-19. METHODS This retrospective observational study involved six Czech hospitals. This study enrolled patients with and without CP treatment who were hospitalized between April 2020 and April 2021. Propensity score matching and logistic regression analysis were performed to evaluate the influence of CP administration and its timing on the in-hospital survival of COVID-19 patients. RESULTS A total of 1,498 patients were enrolled in the study; 406 (27%) were administered CP, and 1,092 (73%) were not treated with CP. The propensity score-matched control group consisted of 1,218 subjects. The survival of patients treated with CP was 79%, while that of patients in the matched control group was 62% (P<0.001). Moreover, the chance of survival was significantly greater when CP was administered within three days after the onset of COVID-19 symptoms than when CP was administered after four or more days (87% vs. 76%, P <0.001). In addition, adverse effects related to CP administration were recorded in only 2% of patients and were considered mild in all patients. CONCLUSIONS Our study demonstrated that the administration of CP was safe and possibly associated with positive effects that were more pronounced if CP was administered within the first three days after the onset of COVID-19 symptoms.
Collapse
Affiliation(s)
- Miloš Bohoněk
- Department of Hematology and Blood Transfusion, Military University Hospital Prague, Prague, Czech Republic
- Faculty of Biomedical Engineering, Czech Technical University in Prague, Prague, Czech Republic
| | - Jan Máca
- Department of Anesthesiology and Intensive Care, Faculty of Medicine, University of Ostrava and University Hospital Ostrava, Ostrava, Czech Republic
- Institute of Physiology and Pathological Physiology, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Jiří Sagan
- Department of Infectious Diseases, Faculty of Medicine, University of Ostrava and University Hospital Ostrava, Ostrava, Czech Republic
- Department of Clinical Studies, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - David Řezáč
- The 7th Field Hospital of the Army of the Czech Republic, Hradec Králové, Czech Republic
| | - Viktor Fridrich
- Department of Infectious Diseases, First Faculty of Medicine, Charles University and Military University Hospital Prague, Prague, Czech Republic
| | - Anna Burantová
- Department of Infectious Diseases, First Faculty of Medicine, Charles University and Military University Hospital Prague, Prague, Czech Republic
| | - Dominik Kutáč
- Department of Hematology and Blood Transfusion, Military University Hospital Prague, Prague, Czech Republic
| | - Pavel Vabroušek
- Department of Hematology and Blood Transfusion, Military University Hospital Prague, Prague, Czech Republic
| | - Jan Kubů
- Department of Science and Research, University Hospital Bulovka Prague, Prague, Czech Republic
| | - Aleš Chrdle
- Department of Infectious Diseases, České Budejovice Hospital, České Budějovice, Czech Republic
- Faculty of Health and Social Sciences, University of South Bohemia, České Budějovice, Czech Republic
| | - Kateřina Volfová
- Department of Infectious Diseases, České Budejovice Hospital, České Budějovice, Czech Republic
| | - Šárka Blahutová
- Institute of Laboratory Hematology and Transfusion Medicine, Department of Biomedical Sciences, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic
| | - Ivan Rychlík
- Department of Internal Medicine, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, Prague, Czech Republic
| | - Kateřina Vonášková
- Department of Internal Medicine, Third Faculty of Medicine, Charles University and University Hospital Královské Vinohrady, Prague, Czech Republic
| | - Radek Majerčin
- Department of Anesthesiology and Resuscitation, Regional Hospital Jičín, Jičín, Czech Republic
| | - Radka Králová
- Department of Anesthesiology and Resuscitation, Regional Hospital Jičín, Jičín, Czech Republic
| | - Petr Štěpánek
- Department of Anesthesiology and Resuscitation, Regional Hospital Náchod, Náchod, Czech Republic
| | - Michal Holub
- Department of Infectious Diseases, First Faculty of Medicine, Charles University and Military University Hospital Prague, Prague, Czech Republic.
- Ústřední vojenská nemocnice - Vojenská fakultní nemocnice Praha, U Vojenské nemocnice 1200, Praha 6, 169 06, Czech Republic.
| |
Collapse
|
|
2
|
Hashem M, El-Kassas M. Diagnosis, treatment protocols, and outcomes of liver transplant recipients infected with COVID-19. World J Clin Cases 2023; 11:2140-2159. [PMID: 37122505 PMCID: PMC10131019 DOI: 10.12998/wjcc.v11.i10.2140] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 01/20/2023] [Accepted: 03/09/2023] [Indexed: 03/30/2023] Open
Abstract
Several cases of fatal pneumonia during November 2019 were linked initially to severe acute respiratory syndrome coronavirus 2, which the World Health Organization later designated as coronavirus disease 2019 (COVID-19). The World Health Organization declared COVID-19 as a pandemic on March 11, 2020. In the general population, COVID-19 severity can range from asymptomatic/mild symptoms to seriously ill. Its mortality rate could be as high as 49%. The Centers for Disease Control and Prevention have acknowledged that people with specific underlying medical conditions, among those who need immunosuppression after solid organ transplantation (SOT), are at an increased risk of developing severe illness from COVID-19. Liver transplantation is the second most prevalent SOT globally. Due to their immunosuppressed state, liver transplant (LT) recipients are more susceptible to serious infections. Therefore, comorbidities and prolonged immunosuppression among SOT recipients enhance the likelihood of severe COVID-19. It is crucial to comprehend the clinical picture, immunosuppressive management, prognosis, and prophylaxis of COVID-19 infection because it may pose a danger to transplant recipients. This review described the clinical and laboratory findings of COVID-19 in LT recipients and the risk factors for severe disease in this population group. In the following sections, we discussed current COVID-19 therapy choices, reviewed standard practice in modifying immunosuppressant regimens, and outlined the safety and efficacy of currently licensed drugs for inpatient and outpatient management. Additionally, we explored the clinical outcomes of COVID-19 in LT recipients and mentioned the efficacy and safety of vaccination use.
Collapse
Affiliation(s)
- Mai Hashem
- Fellow of Tropical Medicine and Gastroenterology, Assiut University Hospital, Assiut 71515, Egypt
| | - Mohamed El-Kassas
- Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo 11795, Egypt
| |
Collapse
|
|
3
|
Kandula UR, Tuji TS, Gudeta DB, Bulbula KL, Mohammad AA, Wari KD, Abbas A. Effectiveness of COVID-19 Convalescent Plasma (CCP) During the Pandemic Era: A Literature Review. J Blood Med 2023; 14:159-187. [PMID: 36855559 PMCID: PMC9968437 DOI: 10.2147/jbm.s397722] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 02/08/2023] [Indexed: 02/25/2023] Open
Abstract
Worldwide pandemic with coronavirus disease-2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As November 2, 2022, World Health Organization (WHO) received 628,035,553 reported incidents on COVID-19, with 6,572,800 mortalities and, with a total 12,850,970,971 vaccine doses have been delivered as of October 31, 2022. The infection can cause mild or self-limiting symptoms of pulmonary and severe infections or death may be caused by SARS-CoV-2 infection. Simultaneously, antivirals, corticosteroids, immunological treatments, antibiotics, and anticoagulants have been proposed as potential medicines to cure COVID-19 affected patients. Among these initial treatments, COVID-19 convalescent plasma (CCP), which was retrieved from COVID-19 recovered patients to be used as passive immune therapy, in which antibodies from cured patients were given to infected patients to prevent illness. Such treatment has yielded the best results in earlier with preventative or early stages of illness. Convalescent plasma (CP) is the first treatment available when infectious disease initially appears, although few randomized controlled trials (RCTs) were conducted to evaluate its effectiveness. The historical record suggests with potential benefit for other respiratory infections, as coronaviruses like Severe Acute Respiratory Syndrome-CoV-I (SARS-CoV-I) and Middle Eastern Respiratory Syndrome (MERS), though the analysis of such research is constrained by some non-randomized experiments (NREs). Rigorous studies on CP are made more demanding by the following with the immediacy of the epidemics, CP use may restrict the ability to utilize it for clinical testing, non-homogenous nature of product, highly decentralized manufacturing process; constraints with capacity to measure biologic function, ultimate availability of substitute therapies, as antivirals, purified immune globulins, or monoclonal antibodies. Though, it is still not clear how effectively CCP works among hospitalized COVID-19 patients. The current review tries to focus on its efficiency and usage in clinical scenarios and identifying existing benefits of implementation during pandemic or how it may assist with future pandemic preventions.
Collapse
Affiliation(s)
- Usha Rani Kandula
- Department of Nursing, College of Health Sciences, Arsi University, Asella, Ethiopia
| | - Techane Sisay Tuji
- Department of Nursing, College of Health Sciences, Arsi University, Asella, Ethiopia
| | | | - Kassech Leta Bulbula
- Department of Nursing, College of Health Sciences, Arsi University, Asella, Ethiopia
| | | | - Ketema Diriba Wari
- Department of Nursing, College of Health Sciences, Arsi University, Asella, Ethiopia
| | - Ahmad Abbas
- Department of Nursing, College of Health Sciences, Arsi University, Asella, Ethiopia
| |
Collapse
|
|
4
|
Validation of a SARS-CoV-2 Surrogate Virus Neutralization Test in Recovered and Vaccinated Healthcare Workers. Viruses 2023; 15:v15020426. [PMID: 36851641 PMCID: PMC9958856 DOI: 10.3390/v15020426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 01/03/2023] [Accepted: 01/28/2023] [Indexed: 02/05/2023] Open
Abstract
Vaccination against COVID-19 is the main public health approach to fight against the pandemic. The Spike (S) glycoprotein of SARS-CoV-2 is the principal target of the neutralizing humoral response. We evaluated the analytical and clinical performances of a surrogate virus neutralization test (sVNT) compared to conventional neutralization tests (cVNTs) and anti-S eCLIA assays in recovered and/or vaccinated healthcare workers. Our results indicate that sVNTs displayed high specificity and no cross-reactivity. Both eCLIA and sVNT immunoassays were good at identifying cVNT serum dilutions ≥1:16. The optimal thresholds when identifying cVNT titers ≥1:16, were 74.5 U/mL and 49.4 IU/mL for anti-S eCLIA and sVNT, respectively. Our data show that neutralizing antibody titers (Nab) differ from one individual to another and may diminish over time. Specific assays such as sVNTs could offer a reliable complementary tool to routine anti-S serological assays.
Collapse
|
|
5
|
Differential persistence of neutralizing antibody against SARS-CoV-2 in post immunized Bangladeshi population. Sci Rep 2022; 12:14681. [PMID: 36038600 PMCID: PMC9421641 DOI: 10.1038/s41598-022-18302-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 08/09/2022] [Indexed: 11/09/2022] Open
Abstract
Development of effective vaccines have been immensely welcomed by the world to prevent the transmission of SARS-CoV-2. However, the duration and clinical implications of antibody-mediated natural immunity in SARS-CoV-2 have not been adequately elucidated alongside some other immune system transforming factors. In a cohort study, we measured NAb titer following the 2nd immunization dosage of the CoviShield (AZD1222) vaccine. The enzyme-linked immunoassay was used to look for SARS-CoV-2—specific NAb. We measured NAb at 30 days after the 2nd dosage of immunization and > 96% titer was detected in 42.9% of subjects, but only 5.1% of subjects retained the same level after 180 days. The median NAb titer dropped significantly, from 92% at 30 days to 58% at 180 days (p < 0.001). Besides, there were significant differences observed in NAb titer after 180 days by age, sex, COVID-19 infection, tobacco use, and asthma patients. However, SARS-CoV-2 infection along with two dosages of immunization upheld NAb titer (p < 0.001) even at the end of the study period.
Collapse
|
|
6
|
Chauhan L, Pattee J, Ford J, Thomas C, Lesteberg K, Richards E, Bernas CA, Loi M, Dumont L, Annen K, Berg M, Zirbes M, Knight V, Miller A, Jenkins TC, Bennett TD, Monkowski D, Boxer RS, Beckham JD. A Multicenter, Prospective, Observational, Cohort-Controlled Study of Clinical Outcomes Following Coronavirus Disease 2019 (COVID-19) Convalescent Plasma Therapy in Hospitalized Patients With COVID-19. Clin Infect Dis 2022; 75:e466-e472. [PMID: 34549274 PMCID: PMC9612788 DOI: 10.1093/cid/ciab834] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high inpatient mortality and morbidity throughout the world. COVID-19 convalescent plasma (CCP) has been utilized as a potential therapy for patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. This study evaluated the outcomes of hospitalized patients with COVID-19 treated with CCP in a prospective, observational, multicenter trial. METHODS From April through August 2020, hospitalized patients with COVID-19 at 16 participating hospitals in Colorado were enrolled and treated with CCP and compared with hospitalized patients with COVID-19 who were not treated with convalescent plasma. Plasma antibody levels were determined following the trial, given that antibody tests were not approved at the initiation of the trial. CCP-treated and untreated hospitalized patients with COVID-19 were matched using propensity scores followed by analysis for length of hospitalization and inpatient mortality. RESULTS A total of 542 hospitalized patients with COVID-19 were enrolled at 16 hospitals across the region. A total of 468 hospitalized patients with COVID-19 were entered into propensity score matching with 188 patients matched for analysis in the CCP-treatment and control arms. Fine-Gray models revealed increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared with controls. In subgroup analysis of CCP-treated patients within 7 days of admission, there was no difference in length of hospitalization and inpatient mortality. CONCLUSIONS These data show that treatment of hospitalized patients with COVID-19 treated with CCP did not significantly improve patient hospitalization length of stay or inpatient mortality.
Collapse
Affiliation(s)
- Lakshmi Chauhan
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Jack Pattee
- Center for Innovative Design and Analysis, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Joshay Ford
- University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Chris Thomas
- University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Kelsey Lesteberg
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Eric Richards
- University of Colorado Hospital System, Denver, Colorado, USA
| | - Carl A Bernas
- University of Colorado Hospital System, Denver, Colorado, USA
| | - Michele Loi
- Children’s Hospital Colorado, Aurora, Colorado, USA
| | - Larry Dumont
- University of Colorado School of Medicine, Aurora, Colorado, USA
- Vitalant Research Institute, Denver, Colorado, USA
| | - Kyle Annen
- Children’s Hospital Colorado, Aurora, Colorado, USA
| | - Mary Berg
- University of Colorado Hospital System, Denver, Colorado, USA
| | - Mercedes Zirbes
- Colorado Clinical and Translational Sciences Institute, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | | | - Amanda Miller
- Colorado Clinical and Translational Sciences Institute, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | | | - Tellen D Bennett
- Children’s Hospital Colorado, Aurora, Colorado, USA
- Colorado Clinical and Translational Sciences Institute, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- Department of Pediatrics, Section of Informatics and Data Science, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | | | - Rebecca S Boxer
- Institute for Health Research, Kaiser Permanente of Colorado, Aurora, Colorado, USA
| | - J David Beckham
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- University of Colorado School of Medicine, Aurora, Colorado, USA
- Colorado Clinical and Translational Sciences Institute, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| |
Collapse
|
|
7
|
Beraud M, Goodhue Meyer E, Lozano M, Bah A, Vassallo R, Brown BL. Lessons learned from the use of convalescent plasma for the treatment of COVID-19 and specific considerations for immunocompromised patients. Transfus Apher Sci 2022; 61:103355. [PMID: 35063360 PMCID: PMC8757642 DOI: 10.1016/j.transci.2022.103355] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/10/2022] [Indexed: 12/11/2022]
Abstract
Coronavirus disease 2019 (COVID-19) convalescent plasma (CovCP) infusions have been widely used for the treatment of hospitalized patients with COVID-19. The aims of this narrative review were to analyze the safety and efficacy of CovCP infusions in the overall population and in immunocompromised patients with COVID-19 and to identify the lessons learned concerning the use of convalescent plasma (CP) to fill treatment gaps for emerging viruses. Systematic searches (PubMed, Scopus, and COVID-19 Research) were conducted to identify peer-reviewed articles and pre-prints published between March 1, 2020 and May 1, 2021 on the use of CovCP for the treatment of patients with COVID-19. From 261 retrieved articles, 37 articles reporting robust controlled studies in the overall population of patients with COVID-19 and 9 articles in immunocompromised patients with COVID-19 were selected. While CovCP infusions are well tolerated in both populations, they do not seem to improve clinical outcomes in critically-ill patients with COVID-19 and no conclusion could be drawn concerning their potential benefits in immunocompromised patients with COVID-19. To be better prepared for future epidemics/pandemics and to evaluate potential benefits of CP treatment, only CP units with high neutralizing antibodies (NAbs) titers should be infused in patients with low NAb titers, patient eligibility criteria should be based on the disease pathophysiology, and measured clinical outcomes and methods should be comparable across studies. Even if CovCP infusions did not improve clinical outcomes in patients with COVID-19, NAb-containing CP infusions remain a safe, widely available and potentially beneficial treatment option for future epidemics/pandemics.
Collapse
Affiliation(s)
- Mickael Beraud
- Terumo Blood and Cell Technologies Europe NV, Ikaroslaan 41, 1930, Zaventem, Belgium.
| | - Erin Goodhue Meyer
- Terumo Blood and Cell Technologies, 10811 W Collins Ave, Lakewood, CO, 80215, United States.
| | - Miquel Lozano
- Department of Hemotherapy and Hemostasis, ICMHO, University Clinic Hospital, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Catalonia, Spain.
| | - Aicha Bah
- Terumo Blood and Cell Technologies Europe NV, Ikaroslaan 41, 1930, Zaventem, Belgium.
| | - Ralph Vassallo
- Vitalant, 6210 E Oak St, Scottsdale, AZ, 85257, United States.
| | - Bethany L Brown
- American Red Cross, Biomedical Services, Holland Laboratory for the Biomedical Sciences, 15601 Crabbs Branch Way, Rockville, MD, 20855, United States.
| |
Collapse
|
|
8
|
Amri N, Bégin R, Tessier N, Vachon L, Villeneuve L, Bégin P, Bazin R, Loubaki L, Martel C. Use of Early Donated COVID-19 Convalescent Plasma Is Optimal to Preserve the Integrity of Lymphatic Endothelial Cells. Pharmaceuticals (Basel) 2022; 15:ph15030365. [PMID: 35337162 PMCID: PMC8948637 DOI: 10.3390/ph15030365] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/11/2022] [Accepted: 03/16/2022] [Indexed: 01/27/2023] Open
Abstract
Convalescent plasma therapy (CPT) has gained significant attention since the onset of the coronavirus disease 2019 (COVID-19) pandemic. However, clinical trials designed to study the efficacy of CPT based on antibody concentrations were inconclusive. Lymphatic transport is at the interplay between the immune response and the resolution of inflammation from peripheral tissues, including the artery wall. As vascular complications are a key pathogenic mechanism in COVID-19, leading to inflammation and multiple organ failure, we believe that sustaining lymphatic vessel function should be considered to define optimal CPT. We herein sought to determine what specific COVID-19 convalescent plasma (CCP) characteristics should be considered to limit inflammation-driven lymphatic endothelial cells (LEC) dysfunction. CCP donated 16 to 100 days after the last day of symptoms was characterized and incubated on inflammation-elicited adult human dermal LEC (aHDLEC). Plasma analysis revealed that late donation correlates with higher concentration of circulating pro-inflammatory cytokines. Conversely, extracellular vesicles (EVs) derived from LEC are more abundant in early donated plasma (r = −0.413, p = 0.004). Thus, secretion of LEC-EVs by an impaired endothelium could be an alarm signal that instigate the self-defense of peripheral lymphatic vessels against an excessive inflammation. Indeed, in vitro experiments suggest that CCP obtained rapidly following the onset of symptoms does not damage the aHDLEC junctions as much as late-donated plasma. We identified a particular signature of CCP that would counteract the effects of an excessive inflammation on the lymphatic endothelium. Accordingly, an easy and efficient selection of convalescent plasma based on time of donation would be essential to promote the preservation of the lymphatic and immune system of infected patients.
Collapse
Affiliation(s)
- Nada Amri
- Faculty of Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Edouard Montpetit Blvd, Montreal, QC H3T 1J4, Canada; (N.A.); (R.B.); (N.T.); (L.V.)
- Montreal Heart Institute, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada;
| | - Rémi Bégin
- Faculty of Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Edouard Montpetit Blvd, Montreal, QC H3T 1J4, Canada; (N.A.); (R.B.); (N.T.); (L.V.)
- Montreal Heart Institute, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada;
| | - Nolwenn Tessier
- Faculty of Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Edouard Montpetit Blvd, Montreal, QC H3T 1J4, Canada; (N.A.); (R.B.); (N.T.); (L.V.)
- Montreal Heart Institute, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada;
| | - Laurent Vachon
- Faculty of Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Edouard Montpetit Blvd, Montreal, QC H3T 1J4, Canada; (N.A.); (R.B.); (N.T.); (L.V.)
- Montreal Heart Institute, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada;
| | - Louis Villeneuve
- Montreal Heart Institute, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada;
| | - Philippe Bégin
- Department of Pediatrics, CHU Sainte-Justine, 3175 Chem. de la Côte-Sainte-Catherine, Montreal, QC H3T 1C5, Canada;
- Department of Medicine, Centre Hospitalier de l’Université de Montréal, 900 Rue Saint-Denis, Montreal, QC H2X 0A9, Canada
| | - Renée Bazin
- Medical Affairs and Innovation, Héma-Québec, 1070 Avenue des Sciences-de-la-Vie, Québec, QC G1V 5C3, Canada; (R.B.); (L.L.)
| | - Lionel Loubaki
- Medical Affairs and Innovation, Héma-Québec, 1070 Avenue des Sciences-de-la-Vie, Québec, QC G1V 5C3, Canada; (R.B.); (L.L.)
| | - Catherine Martel
- Faculty of Medicine, Université de Montréal, Pavillon Roger-Gaudry, 2900 Edouard Montpetit Blvd, Montreal, QC H3T 1J4, Canada; (N.A.); (R.B.); (N.T.); (L.V.)
- Montreal Heart Institute, 5000 Belanger Street, Montreal, QC H1T 1C8, Canada;
- Correspondence: ; Tel.: +1-(514)-376-3330 (ext. 2977)
| |
Collapse
|
|
9
|
Sturek JM, Thomas TA, Gorham JD, Sheppard CA, Raymond AH, Petros De Guex K, Harrington WB, Barros AJ, Madden GR, Alkabab YM, Lu DY, Liu Q, Poulter MD, Mathers AJ, Thakur A, Schalk DL, Kubicka EM, Lum LG, Heysell SK. Convalescent Plasma for Preventing Critical Illness in COVID-19: a Phase 2 Trial and Immune Profile. Microbiol Spectr 2022; 10:e0256021. [PMID: 35196802 PMCID: PMC8865433 DOI: 10.1128/spectrum.02560-21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 01/24/2022] [Indexed: 12/15/2022] Open
Abstract
The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring frequent adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28-day mortality or alter levels of specific antibody responses before and after CIP infusion. In a single-arm phase II study, patients >18 years-old with respiratory symptoms with confirmed COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 h of admission. Levels of SARS-CoV-2 detected by PCR in the respiratory tract and circulating anti-SARS-CoV-2 antibody titers were sequentially measured before and after CIP transfusion. Twenty-nine patients were transfused high titer CIP and 48 contemporaneous comparable controls were identified. All classes of antibodies to the three SARS-CoV-2 target proteins were significantly increased at days 7 and 14 post-transfusion compared with baseline (P < 0.01). Anti-nucleocapsid IgA levels were reduced at day 28, suggesting that the initial rise may have been due to the contribution of CIP. The groups were well-balanced, without statistically significant differences in demographics or co-morbidities or use of remdesivir or dexamethasone. In participants transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1.554), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298). IMPORTANCE Transfusion of high-titer CIP to non-critically ill patients early after admission with COVID-19 respiratory disease was associated with significantly increased anti-SARS-CoV-2 specific antibodies (compared to baseline) and a non-significant reduction in ICU transfer and death (compared to controls). This prospective phase II trial provides a suggestion that the antiviral effects of CIP from early in the COVID-19 pandemic may delay progression to critical illness and death in specific patient populations. This study informs the optimal timing and potential population of use for CIP in COVID-19, particularly in settings without access to other interventions, or in planning for future coronavirus pandemics.
Collapse
Affiliation(s)
- Jeffrey M. Sturek
- Division of Pulmonary & Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Tania A. Thomas
- Division of Infectious Diseases & International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - James D. Gorham
- Division of Laboratory Medicine, Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Chelsea A. Sheppard
- Division of Laboratory Medicine, Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Allison H. Raymond
- Division of Cardiology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Kristen Petros De Guex
- Division of Infectious Diseases & International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - William B. Harrington
- Division of Infectious Diseases & International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Andrew J. Barros
- Division of Pulmonary & Critical Care Medicine, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Gregory R. Madden
- Division of Infectious Diseases & International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Yosra M. Alkabab
- Division of Infectious Diseases & International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - David Y. Lu
- College of Arts and Sciences, Cornell University, Ithaca, New York, USA
| | - Qin Liu
- The Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Melinda D. Poulter
- Division of Laboratory Medicine, Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Amy J. Mathers
- Division of Infectious Diseases & International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
- Division of Laboratory Medicine, Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Archana Thakur
- Division of Hematology and Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Dana L. Schalk
- Division of Hematology and Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Ewa M. Kubicka
- Division of Hematology and Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Lawrence G. Lum
- Division of Hematology and Oncology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Scott K. Heysell
- Division of Infectious Diseases & International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| |
Collapse
|
|
10
|
Dhand A, Razonable RR. COVID-19 and Solid Organ Transplantation: Role of Anti-SARS-CoV-2 Monoclonal Antibodies. CURRENT TRANSPLANTATION REPORTS 2022; 9:26-34. [PMID: 35070639 PMCID: PMC8760599 DOI: 10.1007/s40472-022-00357-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/08/2021] [Indexed: 01/06/2023]
Abstract
Purpose of Review Solid organ transplant recipients (SOTRs) are ideal candidates for early treatment or prevention of coronavirus disease 2019 (COVID-19) using anti-SARS-CoV-2 monoclonal antibodies because of multiple underlying medical conditions, chronic immune-suppression, sub-optimal immunogenic response to vaccination, and evolving epidemiological risks. In this article, we review pertinent challenges regarding the management of COVID-19 in SOTRs, describe the role of active and passive immunity in the treatment and prevention of COVID-19, and review real-world data regarding the use of anti-SARS-CoV-2 monoclonal antibodies in SOTRs. Recent Findings The use of an anti-SARS-CoV-2 monoclonal antibody in high-risk solid organ transplant recipients is associated with a reduction in the risk of hospitalization, need for intensive care, and death related to COVID-19. Overall, the early experiences from a diverse population of solid organ transplant recipients who were treated with anti-spike monoclonal antibodies are encouraging with no reported acute graft injury, severe adverse events, or deaths related to COVID-19. Summary Anti-SARS-CoV-2 antibodies are currently authorized for treatment of mild-moderate COVID-19 and post-exposure prophylaxis, including in SOTRs. Potential future uses include pre-exposure prophylaxis in certain high-risk persons and synergistic use along with emerging oral treatment options. Successful timely administration of anti-SARS-CoV-2 monoclonal antibodies requires a multidisciplinary team approach, effective communication between patients and providers, awareness of circulating viral variants, acknowledgement of various biases affecting treatment, and close monitoring for efficacy and tolerability.
Collapse
Affiliation(s)
- Abhay Dhand
- Transplant Infectious Diseases, Department of Medicine and Surgery, ACP-Transplant Center, Westchester Medical Center/New York Medical College, 100 Woods Road, Valhalla, NY 10595 USA
| | - Raymund R. Razonable
- Division of Infectious Diseases, Department of Medicine and the William J von Leibig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN USA
| |
Collapse
|
|
11
|
Sinha K, Som Chaudhury S, Sharma P, Ruidas B. COVID-19 rhapsody: Rage towards advanced diagnostics and therapeutic strategy. J Pharm Anal 2021; 11:529-540. [PMID: 34178413 PMCID: PMC8214321 DOI: 10.1016/j.jpha.2021.06.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 05/29/2021] [Accepted: 06/17/2021] [Indexed: 02/06/2023] Open
Abstract
The deadly global outbreak of coronavirus disease-2019 (COVID-19) has forged an unrivaled threat to human civilization. Contemplating its profuse impact, initial risk management and therapies are needed, as well as rapid detection strategies alongside treatments with existing drugs or traditional treatments to provide better clinical support for critical patients. Conventional detection techniques have been considered but do not sufficiently meet the current challenges of effective COVID-19 diagnosis. Therefore, several modern techniques including point-of-care diagnosis with a biosensor, clustered regularly interspaced short palindromic repeats (CRISPR)-associated proteins that function as nuclease (Cas) technology, next-generation sequencing, serological, digital, and imaging approaches have delivered improved and noteworthy success compared to that using traditional strategies. Conventional drug treatment, plasma therapy, and vaccine development are also ongoing. However, alternative medicines including Ayurveda, herbal drugs, homeopathy, and Unani have also been enlisted as prominent treatment strategies for developing herd immunity and physical defenses against COVID-19. All considered, this review can help develop rapid and simplified diagnostic strategies, as well as advanced evidence-based modern therapeutic approaches that will aid in combating the global pandemic.
Collapse
Affiliation(s)
- Koel Sinha
- Centre for Healthcare Science and Technology, Indian Institute of Engineering Science Technology, Shibpur, Howrah, 711103, India
| | - Sutapa Som Chaudhury
- Centre for Healthcare Science and Technology, Indian Institute of Engineering Science Technology, Shibpur, Howrah, 711103, India
| | - Pramita Sharma
- Centre for Healthcare Science and Technology, Indian Institute of Engineering Science Technology, Shibpur, Howrah, 711103, India
- Department of Zoology, Hooghly Mohsin College Affiliated to University of Burdwan, Hooghly, 712101, India
| | - Bhuban Ruidas
- Centre for Healthcare Science and Technology, Indian Institute of Engineering Science Technology, Shibpur, Howrah, 711103, India
| |
Collapse
|
|
12
|
Amrutiya V, Patel R, Baghal M, Patel B, Waykole T, Patel H, Govil S, Lo A. Transfusion-related acute lung injury in a COVID-19-positive convalescent plasma recipient: a case report. J Int Med Res 2021; 49:3000605211032814. [PMID: 34412545 PMCID: PMC8381434 DOI: 10.1177/03000605211032814] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
We present a case of transfusion-related acute lung injury as a complication of convalescent plasma transfusion in a patient who presented with COVID-19-related severe acute respiratory syndrome. Despite treatment with tocilizumab, remdesivir, and intravenous steroids, worsening dyspnea prompted adjunctive treatment with convalescent plasma. Two hours after completion of the plasma transfusion, the patient developed hypoxia-induced cardiac arrest secondary to transfusion-related acute lung injury. This case sheds light on life-threatening transfusion reactions and emphasizes the need to investigate post-transfusion monitoring protocols as well as the possible role of surveillance equipment.
Collapse
Affiliation(s)
- Viralkumar Amrutiya
- Internal Medicine Department, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Rutwik Patel
- Internal Medicine Department, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Moaaz Baghal
- Internal Medicine Department, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Bhoomi Patel
- Internal Medicine Department, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Trupti Waykole
- Internal Medicine Department, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Harshana Patel
- Internal Medicine Department, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Swati Govil
- Internal Medicine Department, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Abraham Lo
- Internal Medicine Department, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| |
Collapse
|
|
13
|
Conan PL, Ficko C, Chueca M, Rolland C, Javaudin O, Bigaillon C, Durand GA, Leparc-Goffart I, Verret C, Aletti M, Dutasta F, Savini H, Bosson JL, Martinaud C. COVID-19 Repeated Convalescent Plasma Collection: Analysis of 149 Donations from 88 French Military Health Workers. Transfus Med Hemother 2021; 395:1-6. [PMID: 34580580 PMCID: PMC8450834 DOI: 10.1159/000515843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Accepted: 02/16/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Passive therapy with convalescent plasma (CP) could be an effective and safe treatment option in COVID-19 patients. Neutralizing antibodies present in CP generated in response to SARS-CoV-2 infection and directed against the receptor-binding domain of the spike protein are considered to play a major role in the viral clearance. CP infusion may also contribute to the modulation of the immune response through its immunomodulatory effect. We describe for the first time the effectiveness of a CP collection protocol from repeated donations in young patients. MATERIALS AND METHODS We enrolled health service workers who experienced mild to moderate COVID-19 and from whom several donations have been collected. No minimal severity threshold and no biological cure criteria were required. Donors could return to a second plasma donation 14 days after the first donation. A minimal neutralizing antibody titer of 1:40 was considered for clinical use. RESULTS Eighty-eight donors were included (median age 35 [28-48] years, 41 women), and 149 plasma products were collected. COVID-19 were mainly WHO stage 2 infections (96%). Among the 88 first donations, 76% had neutralizing antibody titers higher than or equal to 1:40. Eighty-eight percent of donors who came for a second donation had a neutralizing antibody titer of 1:40. Median durations were 15 (15-19) and 38 (33-46) days from the first to the second donation and from recovery to the second donation, respectively. Sixty-nine percent of donors who came for a third donation had a neutralizing antibody titer of 1:40. Median durations were 16 (13-37) and 54 (49-61) days from the second to the third donation and from recovery to the third donation, respectively. No significant difference was observed between the IgG ratio and the age of the donors or the time between recovery and donation. The average IgG ratio did not significantly vary between donations. When focused on repeated blood donors, no significant differences were observed either. CONCLUSION The recruitment of young patients with a mild to moderate CO-VID-19 course is an efficient possibility to collect CP with a satisfactory level of neutralizing antibodies. Repeated donations are a well-tolerated and effective way of CP collection.
Collapse
Affiliation(s)
- Pierre-Louis Conan
- Service de maladies infectieuses et tropicales − Hôpital d'Instruction des Armées Bégin, Saint-Mandé, France
| | - Cécile Ficko
- Service de maladies infectieuses et tropicales − Hôpital d'Instruction des Armées Bégin, Saint-Mandé, France
| | - Marine Chueca
- Centre de transfusion des Armées - Hôpital d'Instruction des Armées Percy, Clamart, France
| | - Carole Rolland
- Laboratoire TIMC-IMAG, UMR, CNRS 5525, Université Grenoble Alpes, Grenoble, France
| | - Olivier Javaudin
- Centre de transfusion des Armées - Hôpital d'Instruction des Armées Percy, Clamart, France
| | - Christine Bigaillon
- Service de Biologie - Hôpital d'Instruction des Armées Bégin, Saint-Mandé, France
| | - Guillaume-André Durand
- French Armed Forces Biomedical Research Institute, National Reference Laboratory for Arboviruses, Marseille, France
| | - Isabelle Leparc-Goffart
- French Armed Forces Biomedical Research Institute, National Reference Laboratory for Arboviruses, Marseille, France
| | - Catherine Verret
- Direction de la Formation de la Recherche et de l'Innovation, Direction Centrale du Service de Santé des Armées, Paris, France
| | - Marc Aletti
- Service de médecine interne − Hôpital d'Instruction des Armées Percy, Clamart, France
| | - Fabien Dutasta
- Service de médecine interne et maladies infectieuses et tropicales − Hôpital d'Instruction des Armées Saint-Anne, Toulon, France
| | - Hélène Savini
- Service de maladies infectieuses et tropicales − Hôpital d'Instruction des Armées Laveran, Marseille, France
| | - Jean-Luc Bosson
- Laboratoire TIMC-IMAG, UMR, CNRS 5525, Université Grenoble Alpes, Grenoble, France
| | - Christophe Martinaud
- Centre de transfusion des Armées - Hôpital d'Instruction des Armées Percy, Clamart, France
| |
Collapse
|
|
14
|
Wang K, Long QX, Deng HJ, Hu J, Gao QZ, Zhang GJ, He CL, Huang LY, Hu JL, Chen J, Tang N, Huang AL. Longitudinal Dynamics of the Neutralizing Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. Clin Infect Dis 2021; 73:e531-e539. [PMID: 32745196 PMCID: PMC7454328 DOI: 10.1093/cid/ciaa1143] [Citation(s) in RCA: 143] [Impact Index Per Article: 35.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 07/31/2020] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is a global pandemic with no licensed vaccine or specific antiviral agents for therapy. Little is known about the longitudinal dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing antibodies (NAbs) in patients with COVID-19. METHODS Blood samples (n = 173) were collected from 30 patients with COVID-19 over a 3-month period after symptom onset and analyzed for SARS-CoV-2-specific NAbs using the lentiviral pseudotype assay, coincident with the levels of IgG and proinflammatory cytokines. RESULTS SARS-CoV-2-specific NAb titers were low for the first 7-10 days after symptom onset and increased after 2-3 weeks. The median peak time for NAbs was 33 days (interquartile range [IQR], 24-59 days) after symptom onset. NAb titers in 93.3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34.8% (IQR, 19.6-42.4%). NAb titers increased over time in parallel with the rise in immunoglobulin G (IgG) antibody levels, correlating well at week 3 (r = 0.41, P < .05). The NAb titers also demonstrated a significant positive correlation with levels of plasma proinflammatory cytokines, including stem cell factor (SCF), TNF-related apoptosis-inducing ligand (TRAIL), and macrophage colony-stimulating factor (M-CSF). CONCLUSIONS These data provide useful information regarding dynamic changes in NAbs in patients with COVID-19 during the acute and convalescent phases.
Collapse
Affiliation(s)
- Kai Wang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Quan-Xin Long
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Hai-Jun Deng
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Jie Hu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Qing-Zhu Gao
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Gui-Ji Zhang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Chang-Long He
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Lu-Yi Huang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Jie-Li Hu
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Juan Chen
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Ni Tang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Ai-Long Huang
- Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| |
Collapse
|
|
15
|
Noor R, Tasnim N, Saha C. COVID-19 Pandemic and the Convalescent Plasma Therapy: Possible Benefits and Risks. CURRENT CLINICAL MICROBIOLOGY REPORTS 2021; 8:194-198. [PMID: 34249604 PMCID: PMC8254626 DOI: 10.1007/s40588-021-00174-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/07/2021] [Indexed: 12/28/2022]
Abstract
Purpose of Review COVID-19 pandemic has been the major threat to the global public health for a year (last of 2019-till date); and unfortunately, there is still as no specific antiviral agent which can be effectively used against this disease curation. Present review focused on the application of the convalescent plasma (CP) therapy as a quick remediation of the disease severity. Recent Findings While several drugs have been repurposed based on a number of completed clinical trials together with a huge ongoing effort to develop appropriate vaccine against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the therapeutic approach of the CP therapy appears to be one of the effective methods to rescue the severely affected COVID-19 patients. Such a therapy based on passive immunity evolved from the SARS-CoV-2-infected patients who have fully recovered from COVID-19; and hence these individuals are quite likely to possess high titers of the SARS-CoV-2-neutralizing immunoglobulins (antibodies). However, there are some risks such therapy, and its effectivity also appeared doubtful in some cases. Thus, the current review discussed the issues raised by the administration of such plasma into the SARS-CoV-2-infected individuals. Summary Application of CP therapy has been conducted since long time; and for the mitigation of COVID-19 severity, such pharmaceutical strategy is also being employed in spite of several risks which actually can be monitored as well as optimized in order to combat the SARS-CoV-2 infection.
Collapse
Affiliation(s)
- Rashed Noor
- Department of Life Sciences (DLS), School of Environment and Life Sciences (SELS), Independent University, Bangladesh (IUB), Plot 16, Block B, Aftabuddin Ahmed Road, Bashundhara, Dhaka, 1229 Bangladesh
| | - Nishat Tasnim
- Department of Life Sciences (DLS), School of Environment and Life Sciences (SELS), Independent University, Bangladesh (IUB), Plot 16, Block B, Aftabuddin Ahmed Road, Bashundhara, Dhaka, 1229 Bangladesh
| | - Chandrika Saha
- Department of Life Sciences (DLS), School of Environment and Life Sciences (SELS), Independent University, Bangladesh (IUB), Plot 16, Block B, Aftabuddin Ahmed Road, Bashundhara, Dhaka, 1229 Bangladesh
| |
Collapse
|
|
16
|
Dhanasekaran S, Vajravelu LK, Venkatesalu V. Risk-benefit analysis on the clinical significance of convalescent plasma therapy in the management of COVID-19. Postgrad Med J 2021; 97:467-468. [PMID: 32817576 PMCID: PMC10016903 DOI: 10.1136/postgradmedj-2020-138056] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/29/2020] [Indexed: 12/28/2022]
Affiliation(s)
- Sivaraman Dhanasekaran
- Department of Pharmacology and Toxicology, Centre for Laboratory Animal Technology and Research, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
- School of Pharmacy, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
| | - Leela Kagithakara Vajravelu
- Department of Microbiology, SRM Medical College Hospital and Research Centre, Kancheepuram, Tamil Nadu, India
| | - Venugopal Venkatesalu
- Department of Internal Medicine, Sundaram Health Centre, Sholinghur, Tamil Nadu, India
| |
Collapse
|
|
17
|
Abstract
The coronavirus disease 2019 (COVID‐19) pandemic has triggered a global health emergency and brought disaster to humans. Tremendous efforts have been made to control the pandemic, among which neutralizing antibodies (NAbs) are of specific interest to researchers. Neutralizing antibodies are generated within weeks after infection or immunization and can protect cells from virus intrusion and confer protective immunity to cells. Thus, production of NAbs is considered as a main goal for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccines and NAbs may be used for patient treatment in the form of monoclonal antibodies. Neutralization assays are capable of quantitatively detecting NAbs against SARS‐CoV‐2, allowing to explore the relationship between the level of NAbs and the severity of the disease, and may predict the possibility of re‐infection in COVID‐19 patients. They can also be used to test the effects of monoclonal antibodies, convalescent plasma and vaccines. At present, wild‐type virus neutralization assay remains the gold standard for measuring Nabs, while pseudovirus neutralization assays, Surrogate virus neutralization test (sVNT) and high‐throughput versions of neutralization assays are popular alternatives with their own advantages and disadvantages. In this review article, we summarize the characteristics and recent progress of SARS‐CoV‐2 neutralization assays. Special attention is given to the current limitations of various neutralization assays so as to promote new possible strategies with NAbs by which rapid SARS‐CoV‐2 serological diagnosis and antiviral screening in the future will be achieved.
Collapse
Affiliation(s)
- Yuying Lu
- Department of Epidemiology School of Public Health Sun Yat‐Sen University Guangzhou China
| | - Jin Wang
- Department of Epidemiology School of Public Health Sun Yat‐Sen University Guangzhou China
| | - Qianlin Li
- Department of Epidemiology School of Public Health Sun Yat‐Sen University Guangzhou China
| | - Huan Hu
- Department of Epidemiology School of Public Health Sun Yat‐Sen University Guangzhou China
| | - Jiahai Lu
- Department of Epidemiology School of Public Health Sun Yat‐Sen University Guangzhou China
| | - Zeliang Chen
- Department of Epidemiology School of Public Health Sun Yat‐Sen University Guangzhou China
| |
Collapse
|
|
18
|
Rejeki MS, Sarnadi N, Wihastuti R, Fazharyasti V, Samin WY, Yudhaputri FA, Johar E, Nurainy N, Bachtiar NS, Muljono DH. Convalescent plasma therapy in patients with moderate-to-severe COVID-19: A study from Indonesia for clinical research in low- and middle-income countries. EClinicalMedicine 2021; 36:100931. [PMID: 34104878 PMCID: PMC8175127 DOI: 10.1016/j.eclinm.2021.100931] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 04/29/2021] [Accepted: 05/12/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND We explored the outcome of convalescent plasma (CP) treatment in patients with moderate and severe coronavirus disease 2019 (COVID-19) and investigated variables for the design of further trials in Indonesia. METHODS Hospitalised patients with moderate (n = 5) and severe (n = 5) COVID-19 were recruited and transfused with CP from donors who recovered from mild (n = 5), moderate (n = 5), or severe (n = 1) COVID-19. Neutralising antibodies (NAbs) to the virus were measured at the end of the study using a surrogate virus neutralisation test as an alternative to the plaque reduction assay. Clinical improvement was assessed based on the modified World Health Organization Research and Development Blueprint six-point scale, Brixia Chest-X-Ray scoring, and laboratory parameters. The study was registered at ClinicalTrials.gov (NCT04407208). FINDINGS CP transfusion in three doses of 3 mL/kg of recipient body weight at 2-day intervals was well tolerated. Good clinical improvement was achieved in all patients with moderate disease and in two patients with severe disease. Most patients at baseline had detectable NAbs with median inhibition rates comparable to those of the donors (90·91% vs. 86·31%; p = 0·379). This could be due to the unavailability of pre-donation NAb testing and postponed CP administration that required communal consent. INTERPRETATION This study highlights the safety of CP therapy. Although improvements were observed, we could not conclude that the outcomes were solely due to CP treatment. Further randomised controlled trials that cover different disease stages with pre-donation NAb measurements using locally applicable strategies are warranted. FUNDING The study was supported by PT Bio Farma, Indonesia.
Collapse
Affiliation(s)
- Marliana S. Rejeki
- Gatot Soebroto Central Army Hospital (RSPAD), Jl. Abdul Rahman Saleh No. 24, Jakarta 10410, Indonesia
| | - Nana Sarnadi
- Gatot Soebroto Central Army Hospital (RSPAD), Jl. Abdul Rahman Saleh No. 24, Jakarta 10410, Indonesia
| | - Retno Wihastuti
- Gatot Soebroto Central Army Hospital (RSPAD), Jl. Abdul Rahman Saleh No. 24, Jakarta 10410, Indonesia
| | - Vininta Fazharyasti
- Gatot Soebroto Central Army Hospital (RSPAD), Jl. Abdul Rahman Saleh No. 24, Jakarta 10410, Indonesia
| | - Wisvici Y. Samin
- Gatot Soebroto Central Army Hospital (RSPAD), Jl. Abdul Rahman Saleh No. 24, Jakarta 10410, Indonesia
| | | | - Edison Johar
- Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia
| | - Neni Nurainy
- PT Bio Farma, Jl. Pasteur No. 28, Bandung 40161, Indonesia
| | | | - David H. Muljono
- Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, Jakarta 10430, Indonesia
- Faculty of Medicine, Universitas Hasanuddin, Jl. Perintis Kemerdekaan Km10, Makassar 90245, Indonesia
- Faculty of Medicine and Health, University of Sydney, New South Wales, Australia
| |
Collapse
|
|
19
|
Taylor PC, Adams AC, Hufford MM, de la Torre I, Winthrop K, Gottlieb RL. Neutralizing monoclonal antibodies for treatment of COVID-19. Nat Rev Immunol 2021; 21:382-393. [PMID: 33875867 PMCID: PMC8054133 DOI: 10.1038/s41577-021-00542-x] [Citation(s) in RCA: 512] [Impact Index Per Article: 128.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/17/2021] [Indexed: 12/15/2022]
Abstract
Several neutralizing monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and are now under evaluation in clinical trials. With the US Food and Drug Administration recently granting emergency use authorizations for neutralizing mAbs in non-hospitalized patients with mild-to-moderate COVID-19, there is an urgent need to discuss the broader potential of these novel therapies and to develop strategies to deploy them effectively in clinical practice, given limited initial availability. Here, we review the precedent for passive immunization and lessons learned from using antibody therapies for viral infections such as respiratory syncytial virus, Ebola virus and SARS-CoV infections. We then focus on the deployment of convalescent plasma and neutralizing mAbs for treatment of SARS-CoV-2. We review specific clinical questions, including the rationale for stratification of patients, potential biomarkers, known risk factors and temporal considerations for optimal clinical use. To answer these questions, there is a need to understand factors such as the kinetics of viral load and its correlation with clinical outcomes, endogenous antibody responses, pharmacokinetic properties of neutralizing mAbs and the potential benefit of combining antibodies to defend against emerging viral variants.
Collapse
MESH Headings
- Antibodies, Monoclonal/therapeutic use
- Antibodies, Monoclonal, Humanized/therapeutic use
- Antibodies, Neutralizing/therapeutic use
- Antibodies, Viral/therapeutic use
- Antibody-Dependent Enhancement
- COVID-19/immunology
- COVID-19/therapy
- COVID-19/virology
- Drug Development
- Drug Resistance, Viral/genetics
- Drug Resistance, Viral/immunology
- Humans
- Immunization, Passive/adverse effects
- Immunization, Passive/methods
- Models, Immunological
- Pandemics
- SARS-CoV-2/drug effects
- SARS-CoV-2/genetics
- SARS-CoV-2/immunology
- COVID-19 Serotherapy
Collapse
Affiliation(s)
- Peter C Taylor
- Botnar Research Centre, University of Oxford, Oxford, UK.
| | | | | | | | | | - Robert L Gottlieb
- Baylor University Medical Center, Dallas, TX, USA
- Baylor Scott & White Research Institute, Dallas, TX, USA
| |
Collapse
|
|
20
|
Kornguth SE, Hawley RJ. Autoimmune Processes Involved in Organ System Failure Following Infection with SARS-CoV-2. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1318:355-368. [PMID: 33973189 DOI: 10.1007/978-3-030-63761-3_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
During the COVID-19 pandemic associated with high incidence, transmissibility, and mortality, this chapter focuses on three phases of the disease: initial exposure, initiation of the immune response to the agent, and finally, an inflammatory/autoimmune-like presentation with pulmonary, neurological, and renal failure and disseminated intravascular coagulation which occurs in a small proportion of the patients. The elegant demonstration of the site of interaction between the spike (S) protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of COVID-19, and the ACE (angiotensin-converting enzyme) 2 receptor of cells distributed throughout the body has enabled research efforts to develop pharmacological and immune countermeasures to the viral phase of the disease. This chapter rapidly reviews the molecular and structural organization of SARS-CoV-2 and its interaction with ACE2. It is followed by a discussion over the role of the major histocompatibility complex (MHC) in recognition of the virus. The importance of rapid compartmentation of the viral genome into the target cells as opposed to the binding constant of the virus for the ACE receptor is discussed. Host factors affecting the immune response to the virus are examined, and the subsequent inflammatory dysregulation enabling the cytokine storm leading to system organ failure is described. Finally, the similarities of the clinical effects of the murine hepatitis virus-JHM (a coronavirus) on multi-organ systems (liver, brain, clotting cascade) as described by Perlman and colleagues permit insights regarding the role of the interaction between the host and the virus in developing the clinical presentation of the inflammatory/autoimmune disorders that occur in multiple sclerosis, neuromyelitis optica, and more interestingly, during the third phase of COVID-19.
Collapse
Affiliation(s)
- Steven E Kornguth
- Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, USA.
- Biological Safety and Security, Frederick, MD, USA.
| | - Robert J Hawley
- Biological Safety and Security, Frederick, MD, USA
- Department of Kinesiology and Health Education, University of Texas at Austin, Austin, TX, USA
| |
Collapse
|
|
21
|
Sheervalilou R, Shirvaliloo M, Sargazi S, Bahari S, Saravani R, Shahraki J, Shirvalilou S, Shahraki O, Nazarlou Z, Shams Z, Ghaznavi H. Convalescent Blood: Current Perspective on the Efficacy of a Legacy Approach in COVID-19 Treatment. Blood Purif 2021; 51:1-14. [PMID: 33789273 PMCID: PMC8089443 DOI: 10.1159/000513164] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 11/17/2020] [Indexed: 12/15/2022]
Abstract
Since early 2020, COVID-19 has wreaked havoc in many societies around the world. As of the present, the SARS-CoV-2-borne disease is propagating in almost all countries, affecting hundreds of thousands of people in an unprecedented way. As the name suggests, the novel coronavirus, widely known as SARS-CoV-2, is a new emerging human pathogen. A novel disease of relatively unknown origin, COVID-19 does not seem to be amenable to the currently available medicines since there is no specific cure for the disease. In the absence of any vaccine or effective antiviral medication, we have no tools at our disposal, but the method of quarantine, be it domestic or institutional, to hinder any further progression of this outbreak. However, there is a record of physicians in the past who practiced convalescent blood transfusion. To their awe, the method seemed to be useful. It is anticipated that these contemporary methods will outdo any other vaccination process in the time being, as blood transfusion is instead a cost-effective and time-friendly technique. Following a successful trial, this new approach of contemporary nature to a viral disease may serve as an emergency intervention to intercept infectious outbreaks and prevent an impending epidemic/pandemic. In this review, we document the most recent evidence regarding the efficiency of convalescent plasma and serum therapy on SARS, MERS, and particularly COVID-19, while discussing potential advantages and possible risks of such practice.
Collapse
Affiliation(s)
- Roghayeh Sheervalilou
- Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
- Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Milad Shirvaliloo
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saman Sargazi
- Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Soraiya Bahari
- Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ramin Saravani
- Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Jafar Shahraki
- Department of Toxicology and Pharmacology, School of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
| | - Sakine Shirvalilou
- Finetech in Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Omolbanin Shahraki
- Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
- Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Ziba Nazarlou
- Material Engineering Department, College of Science Koç University, Istanbul, Turkey
| | - Zinat Shams
- Department of Biological Science, Kharazmi University, Tehran, Iran
| | - Habib Ghaznavi
- Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| |
Collapse
|
|
22
|
Gaborit B, Vanhove B, Vibet MA, Le Thuaut A, Lacombe K, Dubee V, Ader F, Ferre V, Vicaut E, Orain J, Le Bras M, Omnes A, Berly L, Jobert A, Morineau-Le Houssine P, Botturi K, Josien R, Flet L, Degauque N, Brouard S, Duvaux O, Poinas A, Raffi F. Evaluation of the safety and efficacy of XAV-19 in patients with COVID-19-induced moderate pneumonia: study protocol for a randomized, double-blinded, placebo-controlled phase 2 (2a and 2b) trial. Trials 2021; 22:199. [PMID: 33750432 PMCID: PMC7942514 DOI: 10.1186/s13063-021-05132-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 02/13/2021] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunting an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions. By providing immediate immunity and inhibiting entry into cells, neutralizing antibody treatment is of interest for patient with COVID-19-induced moderate pneumonia. Convalescent plasma to treat infected patients is therefore a relevant therapeutic option currently under assessment (CORIMUNO-PLASM NCT04324047). However, the difficulties of collecting plasma on the long term are not adapted to a broad use across all populations. New polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) developed by Xenothera and administered intravenous. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, blocking infection of ACE-2-positive human cells with SARS-CoV-2. METHODS Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates. A first human study with another fully representative GH-pAb from Xenothera is ongoing in recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans. The objectives of this 2-step phase 2 randomized double-blinded, placebo-controlled study are to define the safety and the optimal XAV-19 dose to administrate to patients with SARS-CoV-2 induced moderate pneumonia, and to assess the clinical benefits of a selected dose of XAV-19 in this population. DISCUSSION This study will determine the clinical benefits of XAV-19 when administered to patients with SARS-CoV-2-induced moderate pneumonia. As a prerequisite, a first step of the study will define the safety and the dose of XAV-19 to be used. Such treatment might become a new therapeutic option to provide an effective treatment for COVID-19 patients (possibly in combination with anti-viral and immunotherapies). Further studies could later evaluate such passive immunotherapy as a potential post-exposure prophylaxis. TRIAL REGISTRATION ClinicalTrials.gov NCT04453384 , registered on 1 July 2020, and EUDRACT 2020-002574-27, registered 6 June 2020.
Collapse
Affiliation(s)
- Benjamin Gaborit
- CHU Nantes, Department of Infectious Disease, Clinical Investigation, Nantes, France
- CHU Nantes and Inserm, Clinical Investigation Centre CIC1413, Nantes, France
| | | | | | | | - Karine Lacombe
- Institut Pierre Louis d’Epidémiologie et de Santé Publique, Sorbonne Université, INSERM, AP-HP, Hôpital Saint-Antoine, Service des Maladies Infectieuses et Tropicales, Paris, France
| | - Vincent Dubee
- CHU Angers, Service de Maladies Infectieuses et Tropicales, Angers, France
| | - Florence Ader
- Centre International de Recherche en Infectiologie (CIRI), Inserm 1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, F-69007 Lyon, France
- Département des Maladies infectieuses et tropicales, Hospices Civils de Lyon, F-69004 Lyon, France
| | - Virginie Ferre
- CHU Nantes and Inserm, Clinical Investigation Centre CIC1413, Nantes, France
- CHU Nantes, Virology Laboratory, Nantes, France
| | - Eric Vicaut
- APHP, Department of Biostatistics, Université Paris-Diderot, Sorbonne-Paris Cité, Fernand Widal Hospital, Paris, France
| | - Jéremie Orain
- CHU Nantes, Department of Infectious Disease, Clinical Investigation, Nantes, France
- CHU Nantes and Inserm, Clinical Investigation Centre CIC1413, Nantes, France
| | - Morgane Le Bras
- CHU Nantes, Department of Infectious Disease, Clinical Investigation, Nantes, France
- CHU Nantes and Inserm, Clinical Investigation Centre CIC1413, Nantes, France
| | - Anne Omnes
- CHU Nantes, Sponsor Department, Nantes, France
| | | | | | - Pascale Morineau-Le Houssine
- CHU Nantes, Department of Infectious Disease, Clinical Investigation, Nantes, France
- CHU Nantes and Inserm, Clinical Investigation Centre CIC1413, Nantes, France
| | - Karine Botturi
- CHU Nantes, Partnership and Innovation Department, Nantes, France
| | - Régis Josien
- Nantes Université, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France
- CHU Nantes, Laboratoire d’Immunologie, Nantes, France
| | | | - Nicolas Degauque
- Nantes Université, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France
- CHU Nantes, Nantes Université, Institut de Transplantation Urologie Néphrologie (ITUN), Nantes, France
| | - Sophie Brouard
- Nantes Université, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000 Nantes, France
- CHU Nantes, Nantes Université, Institut de Transplantation Urologie Néphrologie (ITUN), Nantes, France
| | | | - Alexandra Poinas
- CHU Nantes and Inserm, Clinical Investigation Centre CIC1413, Nantes, France
| | - François Raffi
- CHU Nantes, Department of Infectious Disease, Clinical Investigation, Nantes, France
- CHU Nantes and Inserm, Clinical Investigation Centre CIC1413, Nantes, France
| |
Collapse
|
|
23
|
Rahmani F, Ziaeemehr A, Alijannejad S, Ferns GA, Khazaei M, Shahidsales S, Avan A. A mini review on the pathogenesis, diagnosis and treatment options for COVID-19. Infect Disord Drug Targets 2021; 22:e170322191922. [PMID: 33645489 DOI: 10.2174/1871526521666210301142223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 11/19/2020] [Accepted: 01/11/2021] [Indexed: 12/15/2022]
Abstract
Coronavirus disease 2019 (COVID-19) is a serious viral disease caused by SARS-CoV-2, associated with a high morbidity and mortality, and represents the greatest public health crisis worldwide. Despite recent efforts for developing novel antiviral agents, no specific drugs are approved for management and treatment of COVID-19. The immune responses to viral infection followed by cytokine storm and acute respiratory distress syndrome are serious issues that may cause death in patients with severe COVID-19. Therefore, developing a novel therapeutic strategy for management of COVID-19 is urgently needed to control the virus spread and improving patient survival rate and clinical outcomes. In this mini review, we summarize the symptoms, pathogenesis and therapeutic approaches that are currently being used to managing the spread of SARS-CoV-2.
Collapse
Affiliation(s)
- Farzad Rahmani
- Iranshahr University of Medical Sciences, Iranshahr. Iran
| | - Aghigh Ziaeemehr
- Cancer Research Center, Mashhad University of Medical Sciences, Mashhad. Iran
| | - Sajede Alijannejad
- Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad. Iran
| | - Gordon A Ferns
- Brighton & Sussex Medical School, Division of Medical Education, Falmer, Brighton, Sussex BN1 9PH. United Kingdom
| | - Majid Khazaei
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad. Iran
| | - Soodabeh Shahidsales
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad. Iran
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad. Iran
| |
Collapse
|
|
24
|
Shoaib MH, Ahmed FR, Sikandar M, Yousuf RI, Saleem MT. A Journey From SARS-CoV-2 to COVID-19 and Beyond: A Comprehensive Insight of Epidemiology, Diagnosis, Pathogenesis, and Overview of the Progress into Its Therapeutic Management. Front Pharmacol 2021; 12:576448. [PMID: 33732150 PMCID: PMC7957225 DOI: 10.3389/fphar.2021.576448] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 01/11/2021] [Indexed: 01/10/2023] Open
Abstract
The 2019 novel coronavirus (2019-nCoV), commonly known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), was first revealed in late 2019 in Wuhan city, Hubei province, China. It was subsequently spread globally and thereby declared as a pandemic by WHO in March 2020. The disease causes severe acute respiratory illness and is highly contagious due to the fast-onward transmission. As of the mid of November 2020, the disease has affected 220 countries with more than 16 million active cases and 1.3 million deaths worldwide. Males, pregnant women, the elderly, immunosuppressed patients, and those with underlying medical conditions are more vulnerable to the disease than the general healthy population. Unfortunately, no definite treatment is available. Although remdesivir as an antiviral had been approved for use in those above 12 years of age and 40 kg weight group, it has been observed to be ineffective in large-scale SOLIDARITY trials by WHO. Moreover, dexamethasone has been found to increase the recovery rate of ventilated patients; oxygen and inhaled nitric oxide as a vasodilator have been given emergency expanded access. In addition, more than 57 clinical trials are being conducted for the development of the vaccines on various platforms. Two vaccines were found to be significantly promising in phase III results. It is concluded that till the approval of a specific treatment or development of a vaccine against this deadly disease, the preventive measures should be followed strictly to reduce the spread of the disease.
Collapse
Affiliation(s)
- Muhammad Harris Shoaib
- Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, Pakistan
| | | | | | | | | |
Collapse
|
|
25
|
Sayinalp B, Çinar OE, Haznedaroğlu İC. Perspectives for immune plasma treatment of COVID-19. Turk J Med Sci 2021; 51:1-9. [PMID: 32718128 PMCID: PMC7991854 DOI: 10.3906/sag-2005-410] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Accepted: 07/27/2020] [Indexed: 02/04/2023] Open
Abstract
Background/aim The SARS-CoV-2 infection was declared as a pandemic by the World Health Organization (WHO) on March 11, 2020, and the death toll from COVID-19, which is the disease caused by SARS-CoV-2, has already surpassed that of many previous epidemics. A wide variety of treatment options are being considered for COVID-19, but there is still no definitive treatment or vaccine. This study aims to explain the background of convalescent plasma (CP) treatment and its relations with COVID-19 immunity, to define ideal treatment procedures, and to reveal present and future perspectives in the light of the rapidly growing data.
Immunological basis of COVID-19-associated immune response and convalescent plasma as a treatment option:
Since it has been shown that the impaired immune response of the host is one of the most important factors that increase the severity of the infection, treatment strategies to suppress aberrant immune activation are currently being considered. CP, which is derived from recently recovered patients and contains neutralizing antibodies and many other immune- modulatory substances, seems to be the most convenient strategy to restore normal immune function considering the fast spreading nature of the ongoing pandemic. Conclusion Even though mechanisms of action of plasma therapy are not fully delineated, it was shown that it could lead to a reduction in mortality since other alternatives such as monoclonal antibodies or SARS-CoV-2 hyperimmunoglobulin require much more time and effort to be developed.
Collapse
Affiliation(s)
- Başak Sayinalp
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Olgu Erkin Çinar
- Department of Hematology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | | |
Collapse
|
|
26
|
Sturek JM, Thomas TA, Gorham JD, Sheppard CA, Raymond AE, Guex KPD, Harrington WB, Barros AJ, Madden GR, Alkabab YM, Lu D, Liu Q, Poulter MD, Mathers AJ, Thakur A, Kubicka EM, Lum LG, Heysell SK. Convalescent plasma for preventing critical illness in COVID-19: A phase 2 trial and immune profile. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2021. [PMID: 33619508 DOI: 10.1101/2021.02.16.21251849] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Rationale The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring rapid adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. Objectives We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28 day mortality. Methods In a single-arm phase II study, patients >18 years-old with respiratory symptoms documented with COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 hours of admission. Detection of respiratory tract SARS-CoV-2 by polymerase chain reaction and circulating anti-SARS-CoV-2 antibody titers were measured before and at time points after CIP transfusion. Measurements and Main Results Twenty-nine patients were transfused CIP and forty-eight contemporaneous controls were identified with comparable baseline characteristics. Levels of anti-SARS-CoV-2 IgG, IgM, and IgA anti-spike, anti-receptor-binding domain, and anti-nucleocapsid significantly increased from baseline to post-transfusion for all proteins tested. In patients transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1.554), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298). Conclusions Transfusion of high-titer CIP to patients early after admission with COVID-19 respiratory disease was associated with reduced ICU transfer and 28-day mortality but was not statistically significant. Follow up randomized trials may inform the use of CIP for COVID-19 or future coronavirus pandemics.
Collapse
|
|
27
|
Al‐Riyami AZ, Schäfer R, van den Berg K, Bloch EM, Estcourt LJ, Goel R, Hindawi S, Josephson CD, Land K, McQuilten ZK, Spitalnik SL, Wood EM, Devine DV, So‐Osman C. Clinical use of Convalescent Plasma in the COVID-19 pandemic: a transfusion-focussed gap analysis with recommendations for future research priorities. Vox Sang 2021; 116:88-98. [PMID: 32542847 PMCID: PMC7891452 DOI: 10.1111/vox.12973] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/11/2020] [Accepted: 06/11/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND OBJECTIVES Use of convalescent plasma for coronavirus disease 2019 (COVID-19) treatment has gained interest worldwide. However, there is lack of evidence on its dosing, safety and effectiveness. Until data from clinical studies are available to provide solid evidence for worldwide applicable guidelines, there is a need to provide guidance to the transfusion community and researchers on this emergent therapeutic option. This paper aims to identify existing key gaps in current knowledge in the clinical application of COVID-19 convalescent plasma (CCP). MATERIALS AND METHODS The International Society of Blood Transfusion (ISBT) initiated a multidisciplinary working group with worldwide representation from all six continents with the aim of reviewing existing practices on CCP use from donor, product and patient perspectives. A subgroup of clinical transfusion professionals was formed to draft a document for CCP clinical application to identify the gaps in knowledge in existing literature. RESULTS Gaps in knowledge were identified in the following main domains: study design, patient eligibility, CCP dose, frequency and timing of CCP administration, parameters to assess response to CCP treatment and long-term outcome, adverse events and CCP application in less-resourced countries as well as in paediatrics and neonates. CONCLUSION This paper outlines a framework of gaps in the knowledge of clinical deployment of CPP that were identified as being most relevant. Studies to address the identified gaps are required to provide better evidence on the effectiveness and safety of CCP use.
Collapse
Affiliation(s)
- Arwa Z. Al‐Riyami
- Department of HaematologySultan Qaboos University HospitalMuscatSultanate of Oman
| | - Richard Schäfer
- Institute for Transfusion Medicine and ImmunohaematologyGerman Red Cross Blood Donor Service Baden‐Württemberg‐Hessen gGmbHGoethe University HospitalFrankfurt am MainGermany
| | - Karin van den Berg
- Medical DivisionTranslational Research DepartmentSouth African National Blood ServicePort ElizabethSouth Africa
- Division Clinical HaematologyDepartment of MedicineUniversity of Cape TownCape TownSouth Africa
| | - Evan M. Bloch
- Department of PathologyJohns Hopkins University School of MedicineBaltimoreMDUSA
| | - Lise J. Estcourt
- Radcliffe Department of MedicineUniversity of Oxford and NHS Blood and TransplantOxfordUK
| | - Ruchika Goel
- Division of Transfusion MedicineDepartment of PathologyJohns Hopkins HospitalBaltimoreMDUSA
- Division of Hematology/OncologySimmons Cancer Institute at SIU School of Medicine and Mississippi Valley Regional Blood CenterSpringfieldILUSA
| | - Salwa Hindawi
- Haematology DepartmentFaculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia
| | - Cassandra D. Josephson
- Department of Pathology and Laboratory MedicineCenter for Transfusion and Cellular TherapiesEmory University School of MedicineAtlantaGEUSA
- Department of PediatricsAflac Cancer Center and Blood DisordersChildren's Healthcare of AtlantaEmory University School of MedicineAtlantaGEUSA
| | - Kevin Land
- Corporate Medical AffairsVitalantPhoenixAZUSA
- Department of PathologyUT Health Science San AntonioSan AntonioTXUSA
| | - Zoe K. McQuilten
- Transfusion Research UnitSchool of Public Health and Preventive MedicineMonash UniversityMelbourneVICAustralia
- Department of Clinical HaematologyMonash HealthMelbourneVICAustralia
| | | | - Erica M. Wood
- Transfusion Research UnitSchool of Public Health and Preventive MedicineMonash UniversityMelbourneVICAustralia
- Department of Clinical HaematologyMonash HealthMelbourneVICAustralia
| | - Dana V. Devine
- Canadian Blood ServicesVancouverBCCanada
- Department of Pathology & Laboratory MedicineUniversity of British ColumbiaVancouverBCCanada
| | - Cynthia So‐Osman
- Department Unit Transfusion MedicineSanquin Blood Supply FoundationAmsterdamThe Netherlands
- Department HaematologyErasmus Medical CenterRotterdamThe Netherlands
| |
Collapse
|
|
28
|
Zhang XY, Guo J, Wan X, Zhou JG, Jin WP, Lu J, Wang WH, Yang AN, Liu DX, Shi ZL, Yuan ZM, Li XG, Meng SL, Duan K, Wang ZJ, Yang XM, Shen S. Biochemical and antigenic characterization of the structural proteins and their post-translational modifications in purified SARS-CoV-2 virions of an inactivated vaccine candidate. Emerg Microbes Infect 2020; 9:2653-2662. [PMID: 33232205 PMCID: PMC7738289 DOI: 10.1080/22221751.2020.1855945] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
In the face of COVID-19 pandemic caused by the newly emerged SARS-CoV-2, an inactivated, Vero cell-based, whole virion vaccine candidate has been developed and entered into phase III clinical trials within six months. Biochemical and immunogenic characterization of structural proteins and their post-translational modifications in virions, the end-products of the vaccine candidate, would be essential for the quality control and process development of vaccine products and for studying the immunogenicity and pathogenesis of SARS-CoV-2. By using a panel of rabbit antisera against virions and five structural proteins together with a convalescent serum, the spike (S) glycoprotein was shown to be N-linked glycosylated, PNGase F-sensitive, endoglycosidase H-resistant and cleaved by Furin-like proteases into S1 and S2 subunits. The full-length S and S1/S2 subunits could form homodimers/trimers. The membrane (M) protein was partially N-linked glycosylated; the accessory protein 3a existed in three different forms, indicative of cleavage and dimerization. Furthermore, analysis of the antigenicity of these proteins and their post-translationally modified forms demonstrated that S protein induced the strongest antibody response in both convalescent and immunized animal sera. Interestingly, immunization with the inactivated vaccine did not elicit antibody response against the S2 subunit, whereas strong antibody response against both S1 and S2 subunits was detected in the convalescent serum. Moreover, vaccination stimulated stronger antibody response against S multimers than did the natural infection. This study revealed that the native S glycoprotein stimulated neutralizing antibodies, while bacterially-expressed S fragments did not. The study on S modifications would facilitate design of S-based anti-SARS-CoV-2 vaccines.
Collapse
Affiliation(s)
- Xiao-Yu Zhang
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| | - Jing Guo
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| | - Xin Wan
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| | - Jin-Ge Zhou
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| | - Wei-Ping Jin
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| | - Jia Lu
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| | - Wen-Hui Wang
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| | - An-Na Yang
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| | - Ding Xiang Liu
- South China Agricultural University, Guangdong Province Key Laboratory Microbial Signals & Disease Co, & Integrative Microbiology Research Center, Guangzhou, People's Republic of China
| | - Zheng-Li Shi
- Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People's Republic of China
| | - Zhi-Ming Yuan
- Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People's Republic of China
| | - Xin-Guo Li
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| | - Sheng-Li Meng
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| | - Kai Duan
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| | - Ze-Jun Wang
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| | - Xiao-Ming Yang
- China National Biotech Group Company Ltd, Beijing, People's Republic of China
| | - Shuo Shen
- Wuhan Institute of Biological Products, Co. Ltd, Wuhan, People's Republic of China
| |
Collapse
|
|
29
|
Hossain MS, Hami I, Sawrav MSS, Rabbi MF, Saha O, Bahadur NM, Rahaman MM. Drug Repurposing for Prevention and Treatment of COVID-19: A Clinical Landscape. Discoveries (Craiova) 2020; 8:e121. [PMID: 33403227 PMCID: PMC7758544 DOI: 10.15190/d.2020.18] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 11/17/2020] [Accepted: 11/18/2020] [Indexed: 12/12/2022] Open
Abstract
SARS-CoV-2, the novel coronavirus strain responsible for the current pandemic of COVID-19, has rendered the entire humanity suffering. Several months have passed since the pandemic has struck. However, the world is still looking for an effective treatment plan to battle the viral infection. The first vaccine just received emergency approval in December 2020 for use in USA and UK. These are excellent news, however, the worldwide distribution of such vaccine, the possibility of virus mutation and the lack of data regarding the long-term effects of such vaccines are a significant concern. In addition, although remdesivir was recently approved by the FDA to be used as a clinical drug against COVID-19, it hasn't stood out yet as a proven form of therapeutics. Such inability to produce a novel therapy has caused enough inconveniences for the affected people worldwide. Repurposing the already available drugs to fight against the virus seems to be a reasonable option amidst such uncertainty. Given the vast collection of potential treatment candidates to be explored against COVID-19, there is a decent chance that a success in this regard will serve the intermediary purpose of clinically treating the infection until a COVID-19 vaccine is widely distributed worldwide and will be able to treat COVID-19 patients that do not adequately respond to vaccines. Such treatments may prove very useful in future coronavirus outbreaks too. Proper research into these repurposing treatments may yield a certain insight into the field of novel treatment production as well. This review study accumulates a relevant set of information about drugs and vaccines against COVID-19, in terms of their repurposing properties and the specific phases of clinical trials they are undergoing across the world. A potential timeline is also suggested to estimate when an effective result can be expected from the ongoing clinical trials for a better anticipation of the drug landscape. This study will hopefully help accelerate investment of resources into development and discovery of drugs and vaccines against the infection.
Collapse
Affiliation(s)
- Md. Shahadat Hossain
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali-3814, Bangladesh
| | - Ithmam Hami
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali-3814, Bangladesh
| | - Md. Sad Salabi Sawrav
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali-3814, Bangladesh
| | - Md. Fazley Rabbi
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali-3814, Bangladesh
| | - Otun Saha
- Department of Microbiology, University of Dhaka, Dhaka-1000, Bangladesh
| | - Newaz Mohammed Bahadur
- Department of Applied Chemistry and Chemical Engineering, Noakhali Science and Technology University, Noakhali-3814, Bangladesh
| | | |
Collapse
|
|
30
|
Simula ER, Manca MA, Jasemi S, Uzzau S, Rubino S, Manchia P, Bitti A, Palermo M, Sechi LA. HCoV-NL63 and SARS-CoV-2 Share Recognized Epitopes by the Humoral Response in Sera of People Collected Pre- and during CoV-2 Pandemic. Microorganisms 2020; 8:microorganisms8121993. [PMID: 33327507 PMCID: PMC7764996 DOI: 10.3390/microorganisms8121993] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 12/10/2020] [Accepted: 12/11/2020] [Indexed: 12/11/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause serious illness in older adults and people with chronic underlying medical conditions; however, children and young people are often asymptomatic or with mild symptoms. We evaluated the presence of specific antibodies (Abs) response against Human coronavirus NL63 (HCoV-NL63) S protein epitopes (NL63-RBM1, NL63-RBM2_1, NL63-RBM2_2, NL63-RBM3, NL63-SPIKE541-554, and NL63-DISC-like) and SARS-CoV-2 epitopes (COV2-SPIKE421-434 and COV2-SPIKE742-759) in plasma samples of pre-pandemic, mid-pandemic, and COVID-19 cohorts by indirect ELISA. Moreover, a competitive assay was performed to check for cross reactivity response between COV2-SPIKE421-434 and NL63-RBM3 among patients with a definitive diagnosis of SARS-CoV-2. Immune reaction against all SARS-CoV-2 and HCoV-NL63 epitopes showed a significantly higher response in pre-pandemic patients compared to mid-pandemic patients. The results indicate that probably antibodies against HCoV-NL63 may be able to cross react with SARS-CoV-2 epitopes and the higher incidence in pre-pandemic was probably due to the timing of collection when a high incidence of HCoV-NL63 is reported. In addition, the competitive assay showed cross-reactivity between antibodies directed against COV2-SPIKE421-434 and NL63-RBM3 peptides. Pre-existing HCoV-NL63 antibody response cross reacting with SARS-CoV-2 has been detected in both pre- and mid-pandemic individual, suggesting that previous exposure to HCoV-NL63 epitopes may produce antibodies which could confer a protective immunity against SARS-CoV-2 and probably reduce the severity of the disease.
Collapse
Affiliation(s)
- Elena Rita Simula
- Department of Biomedical Sciences, Division of Microbiology and Virology, University of Sassari, 07100 Sassari, Italy; (E.R.S.); (M.A.M.); (S.J.); (S.U.); (S.R.)
| | - Maria Antonietta Manca
- Department of Biomedical Sciences, Division of Microbiology and Virology, University of Sassari, 07100 Sassari, Italy; (E.R.S.); (M.A.M.); (S.J.); (S.U.); (S.R.)
| | - Seyedsomaye Jasemi
- Department of Biomedical Sciences, Division of Microbiology and Virology, University of Sassari, 07100 Sassari, Italy; (E.R.S.); (M.A.M.); (S.J.); (S.U.); (S.R.)
| | - Sergio Uzzau
- Department of Biomedical Sciences, Division of Microbiology and Virology, University of Sassari, 07100 Sassari, Italy; (E.R.S.); (M.A.M.); (S.J.); (S.U.); (S.R.)
| | - Salvatore Rubino
- Department of Biomedical Sciences, Division of Microbiology and Virology, University of Sassari, 07100 Sassari, Italy; (E.R.S.); (M.A.M.); (S.J.); (S.U.); (S.R.)
| | - Pierangela Manchia
- Patologia Clinica, ATS Sardegna, ASSL, 07100 Sassari, Italy; (P.M.); (A.B.)
| | - Angela Bitti
- Patologia Clinica, ATS Sardegna, ASSL, 07100 Sassari, Italy; (P.M.); (A.B.)
| | - Mario Palermo
- Servizio di Endocrinologia, Azienda Ospedaliera Universitaria (AOU), 07100 Sassari, Italy;
| | - Leonardo A. Sechi
- Department of Biomedical Sciences, Division of Microbiology and Virology, University of Sassari, 07100 Sassari, Italy; (E.R.S.); (M.A.M.); (S.J.); (S.U.); (S.R.)
- Correspondence: ; Tel.: +39-079-228-462; Fax: +39-079-212-345
| |
Collapse
|
|
31
|
Chan W, He B, Wang X, He ML. Pandemic COVID-19: Current status and challenges of antiviral therapies. Genes Dis 2020; 7:502-519. [PMID: 32837984 PMCID: PMC7340039 DOI: 10.1016/j.gendis.2020.07.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 06/23/2020] [Accepted: 07/02/2020] [Indexed: 01/18/2023] Open
Abstract
The pandemic COVID-19, caused by a new coronavirus SARS-CoV-2 infection, has infected over 12 million individuals and caused more than 55,200 death worldwide. Currently, there is no specific drug to treating this disease. Here we summarized the mechanisms of antiviral therapies and the clinic findings from different countries. Antiviral chemotherapies have been conducted by in multiple cohorts in different counties. Although FDA has fast approved remdesivir for treating COVID-19, it only speeds up recovery from COVID-19 with mildly reduced mortality. The chloroquine was suggested a potential drug against SARS-CoV-2 infection due to its in vitro antiviral effects, it is imperative high-quality data from worldwide clinical trials are necessitated for an approved therapy. In terms of hydroxychloroquine (HCQ) therapy, although WHO has stopped all the clinic trials due to its strong side-effects in COVID patients, large scale clinical trials with a long-term outcome follow-up may warrant HCQ and azithromycin combination in combating the virus. Convalescent plasma (CP) therapy suggested its safety use in SARS-CoV-2 infection; but both CP immunotherapy and NK cellular therapy must be manufactured and utilized according to scrupulous ethical and controlled conditions to guarantee a possible role of these products of human origin. Further research should be conducted to define the exact mechanism of SARS-CoV-2 pathogenesis, suitable animal models or ex vivo human lung tissues aid in studying replication, transmission and spread of the novel viruses, thereby facilitating highly effective therapies.
Collapse
Affiliation(s)
- Winglam Chan
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
| | - Betsy He
- Rensselaer Polytechnic Institute, Troy, NY, USA
| | - Xiong Wang
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
| | - Ming-Liang He
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
- CityU Shenzhen Research Institute, Nanshan, Shenzhen, China
| |
Collapse
|
|
32
|
Wendel S, Kutner JM, Machado R, Fontão‐Wendel R, Bub C, Fachini R, Yokoyama A, Candelaria G, Sakashita A, Achkar R, Hamerschlak N, Scuracchio P, Amaral M, Dal Ben M, Araujo D, Soares C, Camargo A, Kallás E, Durigon E, Reis LF, Rizzo LV. Screening for SARS-CoV-2 antibodies in convalescent plasma in Brazil: Preliminary lessons from a voluntary convalescent donor program. Transfusion 2020; 60:2938-2951. [PMID: 32935877 PMCID: PMC7756544 DOI: 10.1111/trf.16065] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 08/02/2020] [Accepted: 08/02/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) collection began in two Brazilian hospitals for treatment of severe/critical patients. METHODS AND MATERIALS Mild/moderate COVID-19 convalescents were selected as CCP donors after reverse transcription polymerase chain reaction (RT-PCR) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and absence of symptoms for ≥14 days plus (a) age (18-60 years), body weight greater than 55 kg; (b) immunohematological studies; (c) no infectious markers of hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus-1/2, Chagas and syphilis infection; (d) no HLA antibodies (multiparous); (e) second RT-PCR (nasopharyngeal swab and/or blood) negativity; (f) virus neutralization test (cytopathic effect-based virus neutralization test neutralizing antibody) and anti-nucleocapsid protein SARS-CoV-2 IgM, IgG, and IgA enzyme-linked immunosorbent assays. RESULTS Among 271 donors (41 females, 230 males), 250 presented with neutralizing antibodies. Final RT-PCR was negative on swab (77.0%) or blood (88.4%; P = .46). Final definition of RT-PCR was only defined at more than 28 days after full recovery in 59 of 174 (33.9%) RT-PCR -ve, and 25/69 RT-PCR +ve (36.2%; 13 between 35 and 48 days). Neutralizing antibody titers of 160 or greater were found in 63.6%. Correlation between IgG signal/cutoff of 5.0 or greater and neutralizing antibody of 160 or greater was 82.4%. Combination of final RT-PCR -ve with neutralizing antibody ≥160 was 41.3% (112/271). Serial plasma collection showed decline in neutralizing antibody titers and IgA levels (P < .05), probably denoting a "golden period" for CCP collection (≤28 days after joining the program); IgA might have an important role as neutralizing antibody. Donor's weight, days between disease onset and serial plasma collection, and IgG and IgM levels are important predictors for neutralizing antibody titer. CONCLUSIONS RT-PCR +ve cases are still detected in 36.2% within 28 to 48 days after recovery. High anti-nucleocapsid protein IgG levels may be used as a surrogate marker to neutralizing antibody.
Collapse
Affiliation(s)
| | | | - Rafael Machado
- Department of MicrobiologyInstitute of Biomedical Sciences, University of Sao PauloSão PauloBrazil
| | | | - Carolina Bub
- Hospital Israelita Albert Einstein Blood BankSão PauloBrazil
| | | | - Ana Yokoyama
- Hospital Israelita Albert Einstein Blood BankSão PauloBrazil
| | | | - Araci Sakashita
- Hospital Israelita Albert Einstein Blood BankSão PauloBrazil
| | - Ruth Achkar
- Hospital Sírio‐Libanês Blood BankSão PauloBrazil
| | | | | | | | | | - Danielle Araujo
- Department of MicrobiologyInstitute of Biomedical Sciences, University of Sao PauloSão PauloBrazil
| | - Camila Soares
- Department of MicrobiologyInstitute of Biomedical Sciences, University of Sao PauloSão PauloBrazil
| | | | - Esper Kallás
- Infectious Disease DepartmentUniversity of São Paulo Medical SchoolSão PauloBrazil
| | - Edison Durigon
- Department of MicrobiologyInstitute of Biomedical Sciences, University of Sao PauloSão PauloBrazil
| | | | - Luiz Vicente Rizzo
- Albert Einstein Jewish Institute for Education and ResearchSão PauloBrazil
| |
Collapse
|
|
33
|
Cimolai N. Applying Immune Instincts and Maternal Intelligence from Comparative Microbiology to COVID-19. ACTA ACUST UNITED AC 2020; 2:2670-2683. [PMID: 33195997 PMCID: PMC7652409 DOI: 10.1007/s42399-020-00634-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2020] [Indexed: 01/02/2023]
Abstract
New data specific to COVID-19 are emerging quickly on key issues of immunity and prevention, but past research in coronavirology and for other human pathogens (e.g., Mycoplasma pneumoniae) has been available and of great relevance. Considerable study of endemic human coronaviruses has shown that neutralizing antibody correlates with protection, but effective clinical protection is variable for subsequent virus exposure. Animal coronavirus research has emphasized the importance of local mucosal protection (especially IgA) and systemic responses. Animal model and human post-infection studies for SARS-CoV and MERS-CoV are largely corroborative. Whether for passive therapeutic strategies or vaccination, these findings provide a template for COVID-19. Many approaches to vaccination have emerged, and there may be more than one vaccine that will be applied, but individualized obstacles and concerns for administration, efficacy, and safety are inevitable. Regardless of safeguards or promises that may be understood from laboratory or vertebrate experiments, observations from large-scale human trials will ultimately prove to shape the medical future. Focus on common mucosal immunity can be underrated, and equally or more, focus on lactogenic immunity may be underestimated. In understanding both passive immunity and protection, the body is already primed to educate us with decisions of what constitutes protection and harm. This review provides key insights that drive hypotheses into how the instinct of immunity and the intelligence of the maternal component of the common mucosal immune system has already guided us and may continue to do so effectively into a bright and safe future.
Collapse
Affiliation(s)
- Nevio Cimolai
- Faculty of Medicine, The University of British Columbia, Vancouver, BC Canada
- Children’s and Women’s Health Centre of British Columbia, 4480 Oak Street, Vancouver, BC V6H3V4 Canada
| |
Collapse
|
|
34
|
Bellanti JA. The role of the allergist/immunologist in the COVID-19 pandemic: A Janus-faced presentation. Allergy Asthma Proc 2020; 41:397-412. [PMID: 32797762 DOI: 10.2500/aap.2020.41.200072] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Background: Following its initial description in December 2019 in Wuhan, China, coronavirus-2 (COVID-19) has rapidly progressed into a worldwide pandemic, affecting millions of lives. Although every specialty of medicine has been affected, the field of allergy/immunology holds a special place in the battle against this modern-day plague. Because of the specialized training in allergy and clinical immunology, and the familiarity with comorbid contributing conditions, the allergist/immunologist is uniquely poised to play a major role both in the delivery of specialized therapeutic procedures and practices that can improve the health of patients with COVID-19 as well as in the use of forthcoming vaccines for the prevention of its spread. Objective: The purpose of this report is to examine the current body of evidence supporting the two phases of infection and inflammation that influence the pathogenesis of COVID-19 and to provide a classification of COVID-19 disease presentations and potential therapeutic targets with which the allergist/immunologist has particular expertise. Methods: This article was based on a literature review of articles published in PubMed related to COVID-19 and the immune response, and the author's own research and clinical experiences in the field of immunology. Results: Currently, the management of COVID-19 disease is being directed by a preventive strategy based on social distancing, quarantine, and facemasks to reduce the spread of the virus. Numerous clinical trials are being initiated to identify effective treatments for COVID-19 and are directed toward treatment of the two phases of infection and inflammation that influence the pathogenesis of COVID-19. An important resource for the allergist/immunologist is the COVID-19 Treatment Guidelines Panel (COVID-19 TGP), a National Institutes of Health sponsored panel of U.S. physicians, statisticians, and other experts, which has developed a set of continuously updated treatment guidelines intended for clinicians caring for patients during the rapidly evolving COVID-19 pandemic. Conclusion: COVID-19 is unique among other infectious diseases because, in many cases, the host immune inflammatory response can cause greater harm to the individual who is infected than the pathogen itself. In this report, the pathogenesis of COVID-19 and the influence it has on COVID-19 presentations is reviewed, together with recommended potential therapeutic targets and treatment recommendations.
Collapse
Affiliation(s)
- Joseph A. Bellanti
- From the Department of Pediatrics and Microbiology-Immunology; and International Center for Interdisciplinary Studies of Immunology, Georgetown University Medical Center, Washington, D.C
| |
Collapse
|
|
35
|
Vanhove B, Duvaux O, Rousse J, Royer PJ, Evanno G, Ciron C, Lheriteau E, Vacher L, Gervois N, Oger R, Jacques Y, Conchon S, Salama A, Duchi R, Lagutina I, Perota A, Delahaut P, Ledure M, Paulus M, So RT, Mok CKP, Bruzzone R, Bouillet M, Brouard S, Cozzi E, Galli C, Blanchard D, Bach JM, Soulillou JP. High neutralizing potency of swine glyco-humanized polyclonal antibodies against SARS-CoV-2. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2020. [PMID: 34013271 DOI: 10.1101/2020.07.25.217158] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Perfusion of convalescent plasma (CP) has demonstrated a potential to improve the pneumonia induced by SARS-CoV-2, but procurement and standardization of CP are barriers to its wide usage. Many monoclonal antibodies (mAbs) have been developed but appear insufficient to neutralize SARS-CoV-2 unless two or three of them are being combined. Therefore, heterologous polyclonal antibodies of animal origin, that have been used for decades to fight against infectious agents might represent a highly efficient alternative to the use of CP or mAbs in COVID-19 by targeting multiple antigen epitopes. However, conventional heterologous polyclonal antibodies trigger human natural xenogeneic antibody responses particularly directed against animal-type carbohydrate epitopes, mainly the N-glycolyl form of the neuraminic acid (Neu5Gc) and the Gal α1,3-galactose (αGal), ultimately forming immune complexes and potentially leading to serum sickness or allergy. To circumvent these drawbacks, we engineered animals lacking the genes coding for the cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) and α1,3-galactosyl-transferase (GGTA1) enzymes to produce glyco-humanized polyclonal antibodies (GH-pAb) lacking Neu5Gc and α-Gal epitopes. We found that pig IgG Fc domains fail to interact with human Fc receptors and thereby should confer the safety advantage to avoiding macrophage dependent exacerbated inflammatory responses, a drawback possibly associated with antibody responses against SARS-CoV-2 or to avoiding a possible antibody-dependent enhancement (ADE). Therefore, we immunized CMAH/GGTA1 double knockout (DKO) pigs with the SARS-CoV-2 spike receptor-binding domain (RBD) to elicit neutralizing antibodies. Animals rapidly developed a hyperimmune response with anti-SARS-CoV-2 end-titers binding dilutions over one to a million and end-titers neutralizing dilutions of 1:10,000. The IgG fraction purified and formulated following clinical Good Manufacturing Practices, named XAV-19, neutralized Spike/angiotensin converting enzyme-2 (ACE-2) interaction at a concentration < 1μg/mL and inhibited infection of human cells by SARS-CoV-2 in cytopathic assays. These data and the accumulating safety advantages of using glyco-humanized swine antibodies in humans warranted clinical assessment of XAV-19 to fight against COVID-19.
Collapse
|
|
36
|
Augustine R, Das S, Hasan A, S A, Abdul Salam S, Augustine P, Dalvi YB, Varghese R, Primavera R, Yassine HM, Thakor AS, Kevadiya BD. Rapid Antibody-Based COVID-19 Mass Surveillance: Relevance, Challenges, and Prospects in a Pandemic and Post-Pandemic World. J Clin Med 2020; 9:E3372. [PMID: 33096742 PMCID: PMC7589650 DOI: 10.3390/jcm9103372] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 10/09/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023] Open
Abstract
The aggressive outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as COVID-19 (coronavirus disease-2019) pandemic demands rapid and simplified testing tools for its effective management. Increased mass testing and surveillance are crucial for controlling the disease spread, obtaining better pandemic statistics, and developing realistic epidemiological models. Despite the advantages of nucleic acid- and antigen-based tests such as accuracy, specificity, and non-invasive approaches of sample collection, they can only detect active infections. Antibodies (immunoglobulins) are produced by the host immune system within a few days after infection and persist in the blood for at least several weeks after infection resolution. Antibody-based tests have provided a substitute and effective method of ultra-rapid detection for multiple contagious disease outbreaks in the past, including viral diseases such as SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). Thus, although not highly suitable for early diagnosis, antibody-based methods can be utilized to detect past infections hidden in the population, including asymptomatic ones. In an active community spread scenario of a disease that can provide a bigger window for mass detections and a practical approach for continuous surveillance. These factors encouraged researchers to investigate means of improving antibody-based rapid tests and employ them as reliable, reproducible, sensitive, specific, and economic tools for COVID-19 mass testing and surveillance. The development and integration of such immunoglobulin-based tests can transform the pandemic diagnosis by moving the same out of the clinics and laboratories into community testing sites and homes. This review discusses the principle, technology, and strategies being used in antibody-based testing at present. It also underlines the immense prospect of immunoglobulin-based testing and the efficacy of repeated planned deployment in pandemic management and post-pandemic sustainable screenings globally.
Collapse
Affiliation(s)
- Robin Augustine
- Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha PO Box 2713, Qatar;
- Biomedical Research Center (BRC), Qatar University, Doha PO Box 2713, Qatar;
| | - Suvarthi Das
- Department of Medicine, Stanford University Medical Center, Palo Alto, CA 94304, USA;
| | - Anwarul Hasan
- Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha PO Box 2713, Qatar;
- Biomedical Research Center (BRC), Qatar University, Doha PO Box 2713, Qatar;
| | - Abhilash S
- Department of Microbiology, Majlis Arts and Science College, Puramannur, Malappuram, Kerala 676552, India;
| | - Shaheen Abdul Salam
- Department of Biosciences, MES College Marampally, Aluva, Ernakulam, Kerala 683107, India;
| | - Priya Augustine
- Department of Zoology, Providence Women’s College, Kozhikode, Kerala 673009, India;
| | - Yogesh Bharat Dalvi
- Pushpagiri Research Centre, Pushpagiri Institute of Medical Science & Research, Tiruvalla, Kerala 689101, India; (Y.B.D.); (R.V.)
| | - Ruby Varghese
- Pushpagiri Research Centre, Pushpagiri Institute of Medical Science & Research, Tiruvalla, Kerala 689101, India; (Y.B.D.); (R.V.)
| | - Rosita Primavera
- Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; (R.P.); (A.S.T.); (B.D.K.)
| | | | - Avnesh S. Thakor
- Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; (R.P.); (A.S.T.); (B.D.K.)
| | - Bhavesh D. Kevadiya
- Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, School of Medicine, Stanford University, Palo Alto, CA 94304, USA; (R.P.); (A.S.T.); (B.D.K.)
| |
Collapse
|
|
37
|
Walker SN, Chokkalingam N, Reuschel EL, Purwar M, Xu Z, Gary EN, Kim KY, Helble M, Schultheis K, Walters J, Ramos S, Muthumani K, Smith TRF, Broderick KE, Tebas P, Patel A, Weiner DB, Kulp DW. SARS-CoV-2 Assays To Detect Functional Antibody Responses That Block ACE2 Recognition in Vaccinated Animals and Infected Patients. J Clin Microbiol 2020; 58:e01533-20. [PMID: 32855181 PMCID: PMC7587116 DOI: 10.1128/jcm.01533-20] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 08/21/2020] [Indexed: 12/14/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of COVID-19, resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >20 million people worldwide, with >5 million cases in the United States (11 August 2020). The development of diagnostic and research tools to determine infection and vaccine efficacy is critically needed. We have developed multiple serologic assays using newly designed SARS-CoV-2 reagents for detecting the presence of receptor-binding antibodies in sera. The first assay is surface plasmon resonance (SPR) based and can quantitate both antibody binding to the SARS-CoV-2 spike protein and blocking to the Angiotensin-converting enzyme 2 (ACE2) receptor in a single experiment. The second assay is enzyme-linked immunosorbent assay (ELISA) based and can measure competition and blocking of the ACE2 receptor to the SARS-CoV-2 spike protein with antispike antibodies. The assay is highly versatile, and we demonstrate the broad utility of the assay by measuring antibody functionality of sera from small animals and nonhuman primates immunized with an experimental SARS-CoV-2 vaccine. In addition, we employ the assay to measure receptor blocking of sera from SARS-CoV-2-infected patients. The assay is shown to correlate with pseudovirus neutralization titers. This type of rapid, surrogate neutralization diagnostic can be employed widely to help study SARS-CoV-2 infection and assess the efficacy of vaccines.
Collapse
Affiliation(s)
- Susanne N Walker
- Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Neethu Chokkalingam
- Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Emma L Reuschel
- Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Mansi Purwar
- Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Ziyang Xu
- Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Ebony N Gary
- Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Kevin Y Kim
- Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Michaela Helble
- Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, Pennsylvania, USA
| | | | - Jewell Walters
- Inovio Pharmaceuticals, Plymouth Meeting, Pennsylvania, USA
| | | | - Kar Muthumani
- Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, Pennsylvania, USA
| | | | | | - Pablo Tebas
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Ami Patel
- Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, Pennsylvania, USA
| | - David B Weiner
- Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, Pennsylvania, USA
| | - Daniel W Kulp
- Vaccine and Immunotherapy Center, Wistar Institute, Philadelphia, Pennsylvania, USA
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| |
Collapse
|
|
38
|
COVID-19 convalescent plasma clears SARS-CoV-2 refractory to remdesivir in an infant with congenital heart disease. Blood Adv 2020; 4:4278-4281. [PMID: 32915971 PMCID: PMC7509858 DOI: 10.1182/bloodadvances.2020002507] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 07/06/2020] [Indexed: 12/24/2022] Open
Abstract
COVID-19 convalescent plasma (CP) may be a safe and effective treatment option in SARS-CoV-2 infection refractory to remdesivir. Infants may benefit from CP despite developing immune systems and donor variability emphasizes the need for characterization prior to use.
Collapse
|
|
39
|
Canham MA, Campbell JDM, Mountford JC. The use of mesenchymal stromal cells in the treatment of coronavirus disease 2019. J Transl Med 2020; 18:359. [PMID: 32958009 PMCID: PMC7503434 DOI: 10.1186/s12967-020-02532-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 09/15/2020] [Indexed: 02/06/2023] Open
Abstract
More than seven months into the coronavirus disease -19 (COVID-19) pandemic, infection from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 21.2 million cases and resulted in over 760,000 deaths worldwide so far. As a result, COVID-19 has changed all our lives as we battle to curtail the spread of the infection in the absence of specific therapies against coronaviruses and in anticipation of a proven safe and efficacious vaccine. Common with previous outbreaks of coronavirus infections, SARS and Middle East respiratory syndrome, COVID-19 can lead to acute respiratory distress syndrome (ARDS) that arises due to an imbalanced immune response. While several repurposed antiviral and host-response drugs are under examination as potential treatments, other novel therapeutics are also being explored to alleviate the effects on critically ill patients. The use of mesenchymal stromal cells (MSCs) for COVID-19 has become an attractive avenue down which almost 70 different clinical trial teams have ventured. Successfully trialled for the treatment of other conditions such as multiple sclerosis, osteoarthritis and graft versus host disease, MSCs possess both regenerative and immunomodulatory properties, the latter of which can be harnessed to reduce the severity and longevity of ARDS in patients under intensive care due to SARS-CoV-2 infection.
Collapse
Affiliation(s)
- Maurice A Canham
- Tissues, Cells & Advanced Therapeutics, Scottish National Blood Transfusion Service, The Jack Copland Centre, 52 Research Avenue North, Edinburgh, EH14 4BE, UK.
| | - John D M Campbell
- Tissues, Cells & Advanced Therapeutics, Scottish National Blood Transfusion Service, The Jack Copland Centre, 52 Research Avenue North, Edinburgh, EH14 4BE, UK
| | - Joanne C Mountford
- Tissues, Cells & Advanced Therapeutics, Scottish National Blood Transfusion Service, The Jack Copland Centre, 52 Research Avenue North, Edinburgh, EH14 4BE, UK
| |
Collapse
|
|
40
|
Joyner MJ, Wright RS, Fairweather D, Senefeld JW, Bruno KA, Klassen SA, Carter RE, Klompas AM, Wiggins CC, Shepherd JR, Rea RF, Whelan ER, Clayburn AJ, Spiegel MR, Johnson PW, Lesser ER, Baker SE, Larson KF, Ripoll JG, Andersen KJ, Hodge DO, Kunze KL, Buras MR, Vogt MN, Herasevich V, Dennis JJ, Regimbal RJ, Bauer PR, Blair JE, Van Buskirk CM, Winters JL, Stubbs JR, Paneth NS, Verdun NC, Marks P, Casadevall A. Early safety indicators of COVID-19 convalescent plasma in 5000 patients. J Clin Invest 2020; 130:4791-4797. [PMID: 32525844 DOI: 10.1172/jci140200] [Citation(s) in RCA: 324] [Impact Index Per Article: 64.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Accepted: 06/03/2020] [Indexed: 01/08/2023] Open
Abstract
BACKGROUNDConvalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19.METHODSThus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma.RESULTSThe incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was <1%. Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (n = 7), transfusion-related acute lung injury (n = 11), and severe allergic transfusion reactions (n = 3). However, only 2 of 36 SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The 7-day mortality rate was 14.9%.CONCLUSIONGiven the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.TRIAL REGISTRATIONClinicalTrials.gov NCT04338360.FUNDINGMayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc.
Collapse
Affiliation(s)
| | - R Scott Wright
- Department of Cardiovascular Medicine, and.,Human Research Protection Program, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | | | | | - Rickey E Carter
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, USA
| | | | | | | | | | | | | | - Matthew R Spiegel
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, USA
| | - Patrick W Johnson
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, USA
| | - Elizabeth R Lesser
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, USA
| | - Sarah E Baker
- Department of Anesthesiology and Perioperative Medicine
| | | | - Juan G Ripoll
- Department of Anesthesiology and Perioperative Medicine
| | | | - David O Hodge
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, USA
| | - Katie L Kunze
- Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona, USA
| | - Matthew R Buras
- Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona, USA
| | | | | | | | | | - Philippe R Bauer
- Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Janis E Blair
- Department of Internal Medicine, Division of Infectious Diseases, Mayo Clinic, Phoenix, Arizona, USA
| | - Camille M Van Buskirk
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jeffrey L Winters
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - James R Stubbs
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Nigel S Paneth
- Department of Epidemiology and Biostatistics and.,Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, Michigan, USA
| | - Nicole C Verdun
- Center for Biologics Evaluation and Research, US FDA, Silver Spring, Maryland, USA
| | - Peter Marks
- Center for Biologics Evaluation and Research, US FDA, Silver Spring, Maryland, USA
| | - Arturo Casadevall
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| |
Collapse
|
|
41
|
Nittari G, Pallotta G, Amenta F, Tayebati SK. Current pharmacological treatments for SARS-COV-2: A narrative review. Eur J Pharmacol 2020; 882:173328. [PMID: 32603692 PMCID: PMC7320862 DOI: 10.1016/j.ejphar.2020.173328] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 06/26/2020] [Accepted: 06/26/2020] [Indexed: 12/27/2022]
Abstract
The novel coronavirus, later identified as SARS-CoV-2, originating from Wuhan in China in November 2019, quickly spread around the world becoming a pandemic. Despite the knowledge of previous coronaviruses, such as those responsible for the SARS and MERS-CoV epidemic, there is no drug or prophylaxis treatment to this day. The rapid succession of scientific findings on SARS-CoV-2 provides a significant number of potential drug targets. Nevertheless, at the same time, the high quantity of clinical data, generated by a large number of rapidly infected people, require accurate tests regarding effective medical treatments. Several in vitro and in vivo studies were rapidly initiated after the outbreak of the pandemic COVID-19. Initial clinical studies revealed the promising potential of remdesivir that demonstrated a powerful and specific in vitro antiviral activity for COVID-19. Promising effects appear to be attributable to hydroxychloroquine. Remdesivir and hydroxychloroquine are being tested in ongoing randomized trials. In contrast, oseltamivir was not effective and corticosteroids are not currently recommended. However, few data from ongoing clinical trials are identifying low molecular weight heparins, innate immune system stimulating agents, and inflammatory modulating agents as potential effective agents. The authors assume that the current pandemic will determine the need for a systematic approach based on big data analysis for identifying effective drugs to defeat SARS-Cov-2. This work is aimed to be a general reference point and to provide an overview as comprehensive as possible regarding the main clinical trials in progress at the moment.
Collapse
Affiliation(s)
- Giulio Nittari
- School of Pharmacy and Health Products, Telemedicine and Telepharmacy Center, University of Camerino, Via Madonna Delle Carceri 9, Camerino, MC, 62032, Italy
| | - Graziano Pallotta
- School of Pharmacy and Health Products, Telemedicine and Telepharmacy Center, University of Camerino, Via Madonna Delle Carceri 9, Camerino, MC, 62032, Italy.
| | - Francesco Amenta
- School of Pharmacy and Health Products, Telemedicine and Telepharmacy Center, University of Camerino, Via Madonna Delle Carceri 9, Camerino, MC, 62032, Italy; Research Department of International Radio Medical Center (CIRM), Via Dell'Architettura 41, Rome, 00144, Italy
| | - Seyed Khosrow Tayebati
- School of Pharmacy and Health Products, Telemedicine and Telepharmacy Center, University of Camerino, Via Madonna Delle Carceri 9, Camerino, MC, 62032, Italy
| |
Collapse
|
|
42
|
Piyush R, Rajarshi K, Khan R, Ray S. Convalescent plasma therapy: a promising coronavirus disease 2019 treatment strategy. Open Biol 2020; 10:200174. [PMID: 32898468 PMCID: PMC7536086 DOI: 10.1098/rsob.200174] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Accepted: 08/18/2020] [Indexed: 12/13/2022] Open
Abstract
The world is passing through a very difficult phase due to the coronavirus disease 2019 (COVID-19) pandemic, which has disrupted almost all spheres of life. Globally, according to the latest World Health Organization report (10 August 2020), COVID-19 has affected nearly 20 million lives, causing 728 013 deaths. Due to the lack of specific therapeutic drugs and vaccines, the outbreak of disease has spawned a corpus of contagious infection all over the world, day by day, without control. As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a very rapid infection rate, it is essential to develop a novel ameliorative and curative strategy as quickly as possible. Convalescent plasma (CP) therapy is a type of adaptive immunity that has already been found to be effective in confronting several infectious diseases from the last two decades. For example, CP therapy was used in the treatment of viral-induced diseases like SARS-CoV epidemics, Middle East respiratory syndrome coronavirus (MERS-CoV) pandemics, Ebola epidemics and H1N1 pandemic. In this review, we have mainly focused on the therapeutic role of CP therapy and its neutralizing effect to fight against the COVID-19 outbreak.
Collapse
Affiliation(s)
- Ravikant Piyush
- School of Biotechnology, Madurai Kamaraj University, Madurai, Tamil Nadu 625021, India
| | - Keshav Rajarshi
- School of Community Science and Technology (SOCSAT), Indian Institute of Engineering Science and Technology (IIEST), Shibpur, Howrah, West Bengal 711103, India
| | - Rajni Khan
- Motihari College of Engineering, Bariyarpur, Motihari, NH 28A, Furshatpur, Motihari, Bihar 845401, India
| | - Shashikant Ray
- Department of Biotechnology, Mahatma Gandhi Central University, Motihari 845401, India
| |
Collapse
|
|
43
|
Joyner MJ, Bruno KA, Klassen SA, Kunze KL, Johnson PW, Lesser ER, Wiggins CC, Senefeld JW, Klompas AM, Hodge DO, Shepherd JRA, Rea RF, Whelan ER, Clayburn AJ, Spiegel MR, Baker SE, Larson KF, Ripoll JG, Andersen KJ, Buras MR, Vogt MNP, Herasevich V, Dennis JJ, Regimbal RJ, Bauer PR, Blair JE, van Buskirk CM, Winters JL, Stubbs JR, van Helmond N, Butterfield BP, Sexton MA, Diaz Soto JC, Paneth NS, Verdun NC, Marks P, Casadevall A, Fairweather D, Carter RE, Wright RS. Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients. Mayo Clin Proc 2020; 95:1888-1897. [PMID: 32861333 PMCID: PMC7368917 DOI: 10.1016/j.mayocp.2020.06.028] [Citation(s) in RCA: 315] [Impact Index Per Article: 63.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 06/17/2020] [Accepted: 06/17/2020] [Indexed: 01/08/2023]
Abstract
OBJECTIVE To provide an update on key safety metrics after transfusion of convalescent plasma in hospitalized coronavirus 2019 (COVID-19) patients, having previously demonstrated safety in 5000 hospitalized patients. PATIENTS AND METHODS From April 3 to June 2, 2020, the US Food and Drug Administration Expanded Access Program for COVID-19 convalescent plasma transfused a convenience sample of 20,000 hospitalized patients with COVID-19 convalescent plasma. RESULTS The incidence of all serious adverse events was low; these included transfusion reactions (n=78; <1%), thromboembolic or thrombotic events (n=113; <1%), and cardiac events (n=677, ~3%). Notably, the vast majority of the thromboembolic or thrombotic events (n=75) and cardiac events (n=597) were judged to be unrelated to the plasma transfusion per se. The 7-day mortality rate was 13.0% (12.5%, 13.4%), and was higher among more critically ill patients relative to less ill counterparts, including patients admitted to the intensive care unit versus those not admitted (15.6 vs 9.3%), mechanically ventilated versus not ventilated (18.3% vs 9.9%), and with septic shock or multiple organ dysfunction/failure versus those without dysfunction/failure (21.7% vs 11.5%). CONCLUSION These updated data provide robust evidence that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19, and support the notion that earlier administration of plasma within the clinical course of COVID-19 is more likely to reduce mortality.
Collapse
Affiliation(s)
- Michael J Joyner
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN. https://twitter.com/DrMJoyner
| | - Katelyn A Bruno
- Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL
| | - Stephen A Klassen
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Katie L Kunze
- Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ
| | - Patrick W Johnson
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL
| | | | - Chad C Wiggins
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Jonathon W Senefeld
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Allan M Klompas
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - David O Hodge
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL
| | - John R A Shepherd
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Robert F Rea
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN
| | - Emily R Whelan
- Department of Cardiovascular Medicine, Mayo Clinic, Jacksonville, FL
| | - Andrew J Clayburn
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Matthew R Spiegel
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL
| | - Sarah E Baker
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Kathryn F Larson
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Juan G Ripoll
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Kylie J Andersen
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Matthew R Buras
- Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ
| | - Matthew N P Vogt
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Vitaly Herasevich
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Joshua J Dennis
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Riley J Regimbal
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Philippe R Bauer
- Department of Internal Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, MN
| | - Janis E Blair
- Department of Internal Medicine, Division of Infectious Diseases, Mayo Clinic, Phoenix, AZ
| | | | - Jeffrey L Winters
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - James R Stubbs
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Noud van Helmond
- Department of Anesthesiology, Cooper Medical School of Rowan University, Cooper University Health Care, Camden, NJ
| | - Brian P Butterfield
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Matthew A Sexton
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Juan C Diaz Soto
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN
| | - Nigel S Paneth
- Departments of Epidemiology and Biostatistics and Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing
| | - Nicole C Verdun
- Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
| | - Peter Marks
- Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD
| | - Arturo Casadevall
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | | | - Rickey E Carter
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL
| | - R Scott Wright
- Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN; Department of Human Research Protection Program, Mayo Clinic, Rochester, MN
| |
Collapse
|
|
44
|
Abdullah, Faisal S, Aman K, Rahman AU. Innate immune-mediated antiviral response to SARS-CoV-2 and convalescent sera a potential prophylactic and therapeutic agent to tackle COVID-19. Antib Ther 2020; 3:212-220. [PMID: 33912794 PMCID: PMC7454257 DOI: 10.1093/abt/tbaa019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 06/11/2020] [Accepted: 08/09/2020] [Indexed: 12/17/2022] Open
Abstract
The whole world is confronting the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unfortunately, there is no vaccine to prevent novel coronavirus infection. Besides several experimental drugs, the strong immune responses and convalescent sera are the current two potential options to tackle coronavirus disease 2019 (COVID-19) infection. Innate immune-mediated antiviral responses are initiated by the recognition of viral invasion through pathogen-associated molecular patterns (PAMPs). In coronavirus, the PAMPs are recognized by Toll-like receptors 3 and 7, endosomal ribonucleic acid receptors, RNA in cytosol, and by pattern recognition receptor (RIG-1) in the alveolar cells and site of invasion. Nuclear factor-κB and interferon regulatory transcription factor (IRF3) are activated in response to the above recognition episode and translocate to nucleus. These transcription factors in the nucleus initiate the expression of interferon type 1 and pro-inflammatory cytokine storm, which leads to first line of defense at the site of viral entrance. The effectiveness of innate immune system is greatly relies on type 1 interferons and its cascade, because of their role in the inhibition of viral replication and initiation of adaptive immune responses. The successful interferon type 1 response put down the viral replication and transmission at prompt point. Passive immunization is the administering of antibodies into infected patients, which is taken from recovered individuals. The convalescent sera of the recovered COVID-19 patients are containing antiviral neutralizing antibodies and are used therapeutically for infected individuals by SARS-CoV-2 and for the purpose of prophylaxis in exposed individuals. The convalescent sera is found effective when administered early at the onset of symptoms.
Collapse
Affiliation(s)
- Abdullah
- Department of Microbiology, Abdul Wali Khan University, Mardan, 23000, KPK, Pakistan
| | - Shah Faisal
- Department of Biotechnology, Bacha Khan University, Charsadda, 24420, KPK, Pakistan
| | - Komal Aman
- Department of Life Sciences, Abasyn University, Peshawar, 25000, KPK, Pakistan
| | - Anees Ur Rahman
- Department of Life Sciences, Abasyn University, Peshawar, 25000, KPK, Pakistan
| |
Collapse
|
|
45
|
Callender LA, Curran M, Bates SM, Mairesse M, Weigandt J, Betts CJ. The Impact of Pre-existing Comorbidities and Therapeutic Interventions on COVID-19. Front Immunol 2020; 11:1991. [PMID: 32903476 PMCID: PMC7437504 DOI: 10.3389/fimmu.2020.01991] [Citation(s) in RCA: 121] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 07/23/2020] [Indexed: 01/08/2023] Open
Abstract
Evidence from the global outbreak of SARS-CoV-2 has clearly demonstrated that individuals with pre-existing comorbidities are at a much greater risk of dying from COVID-19. This is of great concern for individuals living with these conditions, and a major challenge for global healthcare systems and biomedical research. Not all comorbidities confer the same risk, however, many affect the function of the immune system, which in turn directly impacts the response to COVID-19. Furthermore, the myriad of drugs prescribed for these comorbidities can also influence the progression of COVID-19 and limit additional treatment options available for COVID-19. Here, we review immune dysfunction in response to SARS-CoV-2 infection and the impact of pre-existing comorbidities on the development of COVID-19. We explore how underlying disease etiologies and common therapies used to treat these conditions exacerbate COVID-19 progression. Moreover, we discuss the long-term challenges associated with the use of both novel and repurposed therapies for the treatment of COVID-19 in patients with pre-existing comorbidities.
Collapse
Affiliation(s)
- Lauren A. Callender
- Immunotoxicology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, United Kingdom
- Department of Surgery, University of Cambridge, NIHR Cambridge Biomedical, Cambridge, United Kingdom
| | - Michelle Curran
- Immunotoxicology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, United Kingdom
- Department of Surgery, University of Cambridge, NIHR Cambridge Biomedical, Cambridge, United Kingdom
| | - Stephanie M. Bates
- Immunotoxicology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, United Kingdom
- Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom
| | - Maelle Mairesse
- Immunotoxicology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, United Kingdom
| | - Julia Weigandt
- Immunotoxicology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, United Kingdom
| | - Catherine J. Betts
- Immunotoxicology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, United Kingdom
| |
Collapse
|
|
46
|
Shamim S, Khan M, Kharaba ZJ, Ijaz M, Murtaza G. Potential strategies for combating COVID-19. Arch Virol 2020; 165:2419-2438. [PMID: 32778950 PMCID: PMC7416802 DOI: 10.1007/s00705-020-04768-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 06/18/2020] [Indexed: 12/19/2022]
Abstract
Coronavirus disease 2019, also known as COVID-19, is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2. The infection has now catapulted into a full-blown pandemic across the world, which has affected more than 2 million people and has led to approximately 150,000 fatalities all over the world (WHO). In this review, we elaborate all currently available data that shed light on possible methods for treatment of COVID-19, such as antiviral drugs, corticosteroids, convalescent plasma, and potentially effective vaccines. Additionally, ongoing and discontinued clinical trials that have been carried out for validating probable treatments for COVID-19 are discussed. The review also elaborates the prospective approach and the possible advantages of using convalescent plasma and stem cells for the improvement of clinical symptoms and meeting the demand for an instantaneous cure.
Collapse
Affiliation(s)
- Saba Shamim
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
| | - Maryam Khan
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
| | - Zelal Jaber Kharaba
- Department of Clinical Sciences, College of Pharmacy, Al-Ain University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Munazza Ijaz
- Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan
| | - Ghulam Murtaza
- Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Islamabad, 54000, Pakistan.
| |
Collapse
|
|
47
|
Zhand S, Saghaeian Jazi M, Mohammadi S, Tarighati Rasekhi R, Rostamian G, Kalani MR, Rostamian A, George J, Douglas MW. COVID-19: The Immune Responses and Clinical Therapy Candidates. Int J Mol Sci 2020; 21:5559. [PMID: 32756480 PMCID: PMC7432271 DOI: 10.3390/ijms21155559] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 07/29/2020] [Accepted: 07/31/2020] [Indexed: 02/06/2023] Open
Abstract
The pandemic of coronavirus disease 2019 (COVID-19), with rising numbers of patients worldwide, presents an urgent need for effective treatments. To date, there are no therapies or vaccines that are proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several potential candidates or repurposed drugs are under investigation, including drugs that inhibit SARS-CoV-2 replication and block infection. The most promising therapy to date is remdesivir, which is US Food and Drug Administration (FDA) approved for emergency use in adults and children hospitalized with severe suspected or laboratory-confirmed COVID-19. Herein we summarize the general features of SARS-CoV-2's molecular and immune pathogenesis and discuss available pharmacological strategies, based on our present understanding of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) infections. Finally, we outline clinical trials currently in progress to investigate the efficacy of potential therapies for COVID-19.
Collapse
Affiliation(s)
- Sareh Zhand
- School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW 2007, Australia;
- Department of Microbiology, Faculty of Biological Sciences and technology, Shahid Beheshti University, Tehran 1983969411, Iran
| | - Marie Saghaeian Jazi
- Metabolic Disorders Research Center, Golestan University of Medcial Sciences, Gorgan 4934174515, Iran;
- Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan 4934174515, Iran;
| | - Saeed Mohammadi
- Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan 4934174515, Iran;
- Infectious Diseases Research Center, Golestan University of Medical Sciences, Gorgan 4934174515, Iran
| | - Roozbeh Tarighati Rasekhi
- Department of Radiology and Imaging Sciences, School of Medicine, Emory University, Atlanta, GA 30322, USA;
| | | | - Mohammad Reza Kalani
- Medical Cellular and Molecular Research Centre, Golestan University of Medical Sciences, Gorgan 4934174515, Iran;
| | - Aida Rostamian
- Department of Clinical Sciences, Faculty of Veterinary Science, Islamic Azad University of Karaj, Alborz 3149968111, Iran;
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia
| | - Mark W Douglas
- Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia
- Centre for Infectious Diseases and Microbiology, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney at Westmead Hospital, Sydney, NSW 2145, Australia
| |
Collapse
|
|
48
|
Das G, Ghosh S, Garg S, Ghosh S, Jana A, Samat R, Mukherjee N, Roy R, Ghosh S. An overview of key potential therapeutic strategies for combat in the COVID-19 battle. RSC Adv 2020; 10:28243-28266. [PMID: 35685027 PMCID: PMC9127683 DOI: 10.1039/d0ra05434h] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Accepted: 07/09/2020] [Indexed: 12/27/2022] Open
Abstract
The sudden ravaging outbreak of a novel coronavirus, or SARS-CoV-2, in terms of virulence, severity, and casualties has already overtaken previous versions of coronaviruses, like SARS CoV and MERS CoV. Originating from its epicenter in Wuhan, China, this mutated version of the influenza virus with its associated pandemic effects has engulfed the whole world with awful speed. In the midst of this bewildering situation, medical and scientific communities are on their toes to produce the potential vaccine-mediated eradication of this virus. Though the chances are really high, to date no such panacea has been reported. The time requirements for the onerous procedures of human trials for the successful clinical translation of any vaccine or potential therapeutics are also a major concern. In order to build some resistance against this massive pandemic, the repurposing of some earlier antiviral drugs has been done, along with the refurbishment of some immune-responsive alternative avenues, like monoclonal antibody mediated neutralization, interferon treatment, and plasma therapy. New drugs developed from the RBD domain of the virus spike protein and drugs targeting viral proteases are also undergoing further research and have shown potential from preliminary results. The sole purpose of this review article is to provide a brief collective overview of the recent status of therapeutics advances and approaches, and their current state of implementation for the management of COVID-19.
Collapse
Affiliation(s)
- Gaurav Das
- Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology 4, Raja S. C. Mullick Road, Jadavpur Kolkata 700 032 WB India +91-33-2473-5197 ext. 0284 +91-33-2499-5872
- Academy of Scientific and Innovative Research (AcSIR) Ghaziabad 201002 India
| | - Surojit Ghosh
- Department of Bioscience & Bioengineering, Indian Institute of Technology Jodhpur NH 65, Surpura Bypass Road Karwar Rajasthan 342037 India +91-291-280-1212
| | - Shubham Garg
- Department of Bioscience & Bioengineering, Indian Institute of Technology Jodhpur NH 65, Surpura Bypass Road Karwar Rajasthan 342037 India +91-291-280-1212
| | - Satyajit Ghosh
- Department of Bioscience & Bioengineering, Indian Institute of Technology Jodhpur NH 65, Surpura Bypass Road Karwar Rajasthan 342037 India +91-291-280-1212
| | - Aniket Jana
- Department of Bioscience & Bioengineering, Indian Institute of Technology Jodhpur NH 65, Surpura Bypass Road Karwar Rajasthan 342037 India +91-291-280-1212
| | - Ramkamal Samat
- Department of Bioscience & Bioengineering, Indian Institute of Technology Jodhpur NH 65, Surpura Bypass Road Karwar Rajasthan 342037 India +91-291-280-1212
| | - Nabanita Mukherjee
- Department of Bioscience & Bioengineering, Indian Institute of Technology Jodhpur NH 65, Surpura Bypass Road Karwar Rajasthan 342037 India +91-291-280-1212
| | - Rajsekhar Roy
- Department of Bioscience & Bioengineering, Indian Institute of Technology Jodhpur NH 65, Surpura Bypass Road Karwar Rajasthan 342037 India +91-291-280-1212
| | - Surajit Ghosh
- Department of Bioscience & Bioengineering, Indian Institute of Technology Jodhpur NH 65, Surpura Bypass Road Karwar Rajasthan 342037 India +91-291-280-1212
- Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology 4, Raja S. C. Mullick Road, Jadavpur Kolkata 700 032 WB India +91-33-2473-5197 ext. 0284 +91-33-2499-5872
- Academy of Scientific and Innovative Research (AcSIR) Ghaziabad 201002 India
| |
Collapse
|
|
49
|
Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol 2020; 39:2085-2094. [PMID: 32474885 PMCID: PMC7260446 DOI: 10.1007/s10067-020-05190-5] [Citation(s) in RCA: 545] [Impact Index Per Article: 109.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 05/01/2020] [Accepted: 05/19/2020] [Indexed: 12/11/2022]
Abstract
COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-α agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.
Collapse
Affiliation(s)
- Mehmet Soy
- Internal Medicine and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Division of Rheumatology, Bahcelievler MedicalPark Hospital, Altinbas University (Previously Kemerburgaz University, Istanbul, Turkey
| | - Gökhan Keser
- Internal Medicine and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Division of Rheumatology, Ege University, Izmir, Turkey
| | - Pamir Atagündüz
- Internal Medicine and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Division of Rheumatology, Marmara University, Istanbul, Turkey
| | - Fehmi Tabak
- Internal Medicine and Infectious Disease, Department of Infectious Diseases, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Işık Atagündüz
- Internal Medicine and Hematology, Department of Internal Medicine, Faculty of Medicine, Division of Hematology, Marmara University, Istanbul, Turkey
| | - Servet Kayhan
- Bahcelievler MedicalPark Hospital; Department of Chest Disease, Faculty of Medicine, Altinbas University (Previously Kemerburgaz University), Istanbul, Turkey
| |
Collapse
|
|
50
|
Lindholm PF, Ramsey G, Kwaan HC. Passive Immunity for Coronavirus Disease 2019: A Commentary on Therapeutic Aspects Including Convalescent Plasma. Semin Thromb Hemost 2020; 46:796-803. [PMID: 32526774 PMCID: PMC7645821 DOI: 10.1055/s-0040-1712157] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In the ongoing pandemic of coronavirus disease 2019 (COVID-19), the novel virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is infecting a naïve population. The innate immunity of the infected patient is unable to mount an effective defense, resulting in a severe illness with substantial morbidity and mortality. As most treatment modalities including antivirals and anti-inflammatory agents are mostly ineffective, an immunological approach is needed. The mechanism of innate immunity to this viral illness is not fully understood. Passive immunity becomes an important avenue for the management of these patients. In this article, the immune responses of COVID-19 patients are reviewed. As SARS-CoV-2 has many characteristics in common with two other viruses, SARS-CoV that cause severe acute respiratory syndrome (SARS) and MERS-CoV (Middle East respiratory syndrome coronavirus) that causes Middle East respiratory syndrome (MERS), the experiences learned from the use of passive immunity in treatment can be applied to COVID-19. The immune response includes the appearance of immunoglobulin M followed by immunoglobulin G and neutralizing antibodies. Convalescent plasma obtained from patients recovered from the illness with high titers of neutralizing antibodies was successful in treating many COVID-19 patients. The factors that determine responses as compared with those seen in SARS and MERS are also reviewed. As there are no approved vaccines against all three viruses, it remains a challenge in the ongoing development for an effective vaccine for COVID-19.
Collapse
Affiliation(s)
- Paul F Lindholm
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Glenn Ramsey
- Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Hau C Kwaan
- Division of Hematology-Oncology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| |
Collapse
|