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Zhai Y, Li H, Xia P, Jiang Y, Tong H, Zhou D, Jiang C, Liu Y, Wang J. Intravenous immunoglobulin‑based adjuvant therapy for severe fever with thrombocytopenia syndrome: A single‑center retrospective cohort study. J Med Virol 2024; 96:e70017. [PMID: 39494463 PMCID: PMC11600480 DOI: 10.1002/jmv.70017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/21/2024] [Accepted: 10/08/2024] [Indexed: 11/05/2024]
Abstract
Intravenous immunoglobulin (IVIG) is frequently administered to patients with severe fever with thrombocytopenia syndrome (SFTS), particularly those with severe manifestations, although its efficacy remains controversial. The study retrospectively analyzed the effects of IVIG administration on SFTS patients in both mild and severe groups. The primary outcome measure was 28-day mortality. Inverse probability of treatment weighting (IPTW) with propensity score was used to account for baseline confounders. A total of SFTS patients with complete data enrolled from January 1, 2015, to August 1, 2023. Death at 28 days occurred for 68 (17.5%) patients. By unadjusted analysis, no difference was observed for 28-day mortality between the IVIG and non-IVIG groups in both the mild and severe groups. Similar results were found by propensity score matching and by IPTW analysis. Although IVIG is frequently used as adjuvant therapy for severe SFTS patients, no significant association was observed between IVIG treatment and reduced mortality in this patient population.
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Affiliation(s)
- Yu Zhai
- Department of Emergency MedicineNanjing Drum Tower Hospital Clinical College of Xuzhou Medical UniversityNanjingChina
- Department of Emergency MedicineNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
| | - Haopeng Li
- Department of Emergency MedicineNanjing Drum Tower Hospital Clinical College of Xuzhou Medical UniversityNanjingChina
| | - Peng Xia
- Department of Pharmacy, Nanjing Drum Tower Hospital, School of PharmacyNanjing Medical UniversityNanjingChina
| | - Yunfei Jiang
- Department of Emergency MedicineNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
| | - Hanwen Tong
- Department of Emergency MedicineNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
| | - Dongming Zhou
- Department of HematologyNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
| | - Chenxiao Jiang
- Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical SchoolNanjing UniversityNanjingChina
| | - Yun Liu
- Department of Emergency MedicineNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
| | - Jun Wang
- Department of Emergency MedicineNanjing Drum Tower Hospital Clinical College of Xuzhou Medical UniversityNanjingChina
- Department of Emergency MedicineNanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing UniversityNanjingChina
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Pandey P, Ranjan S, Setya D, Kumari S, Mandal S. The Effect of COVID Convalescent Plasma on Hospital Stay: A Retrospective Observational Study from a Tertiary Care Hospital in North India. RECENT ADVANCES IN ANTI-INFECTIVE DRUG DISCOVERY 2024; 19:95-103. [PMID: 37032501 DOI: 10.2174/2772434418666230407133720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 12/27/2022] [Accepted: 01/18/2023] [Indexed: 04/11/2023]
Abstract
INTRODUCTION COVID convalescent plasma (CCP) has been used as standard of care in patients all over the world. CCP is plasma collected from recently infected and currently recovered COVID-19 patients, which contains antiviral antibodies that can be used to treat patients with COVID-19. Several studies have shown a shorter hospital stay and lower mortality in patients treated with convalescent plasma in comparison with those not treated with it. OBJECTIVES This study aims to determine the effect of COVID convalescent plasma (CCP) on the length of hospital stay in symptomatic patients and to determine outcome of the disease in patients who were administered CCP. METHODS This was a retrospective observational study done at a tertiary health care centre from July 2020 to May 2021, including patients who received CCP during the course of their stay in the hospital. RESULTS Among 257 participants, the patients with multiple comorbidities who were administered CCP had the longest average length of stay in the hospital which was 15 days, out of which, 92 (35.8%) patients were discharged while 9 (3.5%) patients died. Also, the maximum number of deaths was observed in those patients who had no associated comorbidity, being 11 (4.3%). It was observed that earlier administration of CCP in patients (< 5 days from symptom onset) was associated with a higher number of discharges as compared to deaths. CONCLUSION Our study indicates that CCP may be efficient in treating COVID-19 patients if given in early course of the disease.
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Affiliation(s)
- Prashant Pandey
- Transfusion Medicine & Blood Centre, Jaypee Hospital, Noida, Delhi NCR, India
| | - Shweta Ranjan
- Transfusion Medicine & Blood Centre, Jaypee Hospital, Noida, Delhi NCR, India
| | - Divya Setya
- Transfusion Medicine & Blood Centre, Jaypee Hospital, Noida, Delhi NCR, India
| | - Supriya Kumari
- Transfusion Medicine & Blood Centre, Jaypee Hospital, Noida, Delhi NCR, India
| | - Saikat Mandal
- Transfusion Medicine & Blood Centre, Jaypee Hospital, Noida, Delhi NCR, India
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Madhurantakam S, Karnam JB, Muthukumar S, Prasad S. COVID severity test (CoST sensor)-An electrochemical immunosensing approach to stratify disease severity. Bioeng Transl Med 2023; 8:e10566. [PMID: 37693054 PMCID: PMC10486328 DOI: 10.1002/btm2.10566] [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: 11/22/2022] [Revised: 06/07/2023] [Accepted: 06/10/2023] [Indexed: 09/12/2023] Open
Abstract
With the evolution of the COVID-19 pandemic, there is now a need for point-of-care devices for the quantification of disease biomarkers toward disease severity assessment. Disease progression has been determined as a multifactor phenomenon and can be treated based on the host immune response within each individual. CoST is an electrochemical immunosensor point-of-care device that can determine disease severity through multiplex measurement and quantification of spike protein, nucleocapsid protein, D-dimer, and IL-2R from 100 μL of plasma samples within a few minutes. The limit of detection was found to be 3 ng/mL and 21 ng/mL for S and N proteins whereas for D-dimer and IL-2R it was 0.0006 ng/mL and 0.242 ng/mL, respectively. Cross-reactivity of all the biomarkers was studied and it was found to be <20%. Inter and intra-assay variability of the CoST sensor was less than <15% confirming its ability to detect the target biomarker in body fluids. In addition, this platform has also been tested to quantify all four biomarkers in 40 patient samples and to predict the severity index. A significant difference was observed between healthy and COVID-19 samples with a p-value of 0.0002 for D-dimer and <0.0001 for other proteins confirming the ability of the COST sensor to be used as a point of care device to assess disease severity at clinical sites. This device platform can be modified to impact a wide range of disease indications where prognostic monitoring of the host response can be critical in modulating therapy.
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Affiliation(s)
- Sasya Madhurantakam
- Department of BioengineeringThe University of Texas at DallasRichardsonTexasUSA
| | | | | | - Shalini Prasad
- Department of BioengineeringThe University of Texas at DallasRichardsonTexasUSA
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Verma G, Dhawan M, Saied AA, Kaur G, Kumar R, Emran TB. Immunomodulatory approaches in managing lung inflammation in COVID-19: A double-edge sword. Immun Inflamm Dis 2023; 11:e1020. [PMID: 37773723 PMCID: PMC10521379 DOI: 10.1002/iid3.1020] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 06/19/2023] [Accepted: 09/09/2023] [Indexed: 10/01/2023] Open
Abstract
INTRODUCTION The novel coronavirus infectious disease 2019 (COVID-19) which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a gigantic problem. The lung is the major target organ of SARS-CoV-2 and some of its variants like Delta and Omicron variant adapted in such a way that these variants can significantly damage this vital organ of the body. These variants raised a few eyebrows as the outbreaks have been seen in the vaccinated population. Patients develop severe respiratory illnesses which eventually prove fatal unless treated early. MAIN BODY Studies have shown that SARS-CoV-2 causes the release of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α which are mediators of lung inflammation, lung damage, fever, and fibrosis. Additionally, various chemokines have been found to play an important role in the disease progression. A plethora of pro-inflammatory cytokines "cytokine storm" has been observed in severe cases of SARS-CoV-2 infection leading to acute respiratory distress syndrome (ARDS) and pneumonia that may prove fatal. To counteract cytokine storm-inducing lung inflammation, several promising immunomodulatory approaches are being investigated in numerous clinical trials. However, the benefits of using these strategies should outweigh the risks involved as the use of certain immunosuppressive approaches might lead the host susceptible to secondary bacterial infections. CONCLUSION The present review discusses promising immunomodulatory approaches to manage lung inflammation in COVID-19 cases which may serve as potential therapeutic options in the future and may prove lifesaving.
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Affiliation(s)
- Geetika Verma
- Department of Experimental Medicine and BiotechnologyPost Graduate Institute of Medical Education and Research (PGIMER)ChandigarhIndia
| | - Manish Dhawan
- Department of MicrobiologyPunjab Agricultural UniversityLudhianaIndia
- Trafford CollegeAltrinchamUK
| | | | - Geetika Kaur
- Department of Opthalmology, Visual and Anatomical SciencesWayne State University School of MedicineDetroitMichiganUSA
| | - Reetesh Kumar
- Department of Agricultural Sciences, Institute of Applied Sciences and HumanitiesGLA UniversityMathuraIndia
| | - Talha Bin Emran
- Department of Pharmacy, Faculty of Allied Health SciencesDaffodil International UniversityDhakaBangladesh
- Department of Pathology and Laboratory Medicine, Warren Alpert Medical School & Legorreta Cancer CenterBrown UniversityProvidenceRhode IslandUnited States
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Sun J. A mathematic equation derived from host-pathogen interactions elucidates the significance of integrating modern medicine with traditional Chinese medicine to treat infectious diseases. JOURNAL OF INTEGRATIVE MEDICINE 2023:S2095-4964(23)00046-8. [PMID: 37349214 DOI: 10.1016/j.joim.2023.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 05/12/2023] [Indexed: 06/24/2023]
Abstract
The prognosis of infectious diseases is determined by host-pathogen interactions. Control of pathogens has been the central dogma of treating infectious diseases in modern medicine, but the pathogen-directed medicine is facing significant challenges, including a lack of effective antimicrobials for newly emerging pathogens, pathogen drug resistance, and drug side effects. Here, a mathematic equation (termed equation of host-pathogen interactions, HPI-Equation) is developed to dissect the key variables of host-pathogen interactions. It shows that control of pathogens does not necessarily lead to host recovery. Instead, a combination of promoting a host's power of self-healing and balancing immune responses provides the best benefit for host. Moreover, the HPI-Equation elucidates the scientific basis of traditional Chinese medicine (TCM), a host-based medicine that treats infectious diseases by promoting self-healing power and balancing immune responses. The importance of self-healing power elucidated in the HPI-Equation is confirmed by recent studies that the tolerance mechanism, which is discovered in plants and animals and conceptually similar to self-healing power, improves host survival without directly attacking pathogens. In summary, the HPI-Equation describes host-pathogen interactions with mathematical logic and precision; it translates the ancient wisdoms of TCM into apprehensible modern sciences and opens a new venue for integrating TCM and modern medicine for a future medicine.
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Affiliation(s)
- Jianjun Sun
- Department of Biological Sciences, Border Biomedical Research Center, University of Texas at El Paso, TX 79968, USA.
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Ludhiadch A, Yadav UP, Munshi A. Currently available COVID-19 management options. OMICS APPROACHES AND TECHNOLOGIES IN COVID-19 2023:111-124. [DOI: 10.1016/b978-0-323-91794-0.00001-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Promoting self‐healing power and balancing immune response: a holistic, effective strategy of traditional Chinese medicine in treating COVID‐19. PHARMACOLOGICAL RESEARCH. MODERN CHINESE MEDICINE 2022; 5:100199. [PMCID: PMC9674391 DOI: 10.1016/j.prmcm.2022.100199] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/15/2022] [Accepted: 11/18/2022] [Indexed: 06/24/2023]
Abstract
The COVID-19 pandemic is a serious challenge to human medicines. Modern medicine (MM) has been excellent in identifying the virus, sequencing its mutants, and monitoring the pandemic progress. However, due to lack of effective antivirals in the first two years of the pandemic, MM treated COVID-19 mainly by conventional supportive care with limited efficacy. In China, traditional Chinese medicine (TCM) has been actively participating the control of COVID-19, and the combination of TCM and conventional supportive care has shown better efficacies than the conventional care alone. Purpose: Clinical studies have shown that TCM treats COVID-19 through a holistic action, such as repairing organ injuries, anti-inflammation, immunoregulation and antiviral activities, etc. However, it is not clear how TCM is able to achieve these effects, and the scientific interpretation of TCM theories is lacking. This review aims to elucidate the scientific basis underlying TCM theories in the context of host-pathogen interaction and provide a working model for TCM in treating infectious diseases. Procedure: This review focuses on the essential components of host-pathogen interaction and performs an in-depth analysis of current literatures, including TCM theories and clinical studies as well as the most recent findings of tolerance (self-healing) mechanism in biomedical sciences. Conclusion: TCM treats COVID-19 through a holistic regulation of host responses, particularly by promoting patients’ self-healing power and balancing immune responses. Compared to the pathogen-centered MM, the host-centered TCM doesn't require specific antivirals and has less side-effects and drug resistance. This review provides a scientific insight into the mechanism of TCM and sheds a light on the prospective integration of TCM and MM for future challenges.
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Sharun K, Tiwari R, Yatoo MI, Natesan S, Megawati D, Singh KP, Michalak I, Dhama K. A comprehensive review on pharmacologic agents, immunotherapies and supportive therapeutics for COVID-19. NARRA J 2022; 2:e92. [PMID: 38449903 PMCID: PMC10914132 DOI: 10.52225/narra.v2i3.92] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 12/06/2022] [Indexed: 03/08/2024]
Abstract
The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.
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Affiliation(s)
- Khan Sharun
- Division of Surgery, ICAR-Indian Veterinary Research Institute, Izatnagar, India
| | - Ruchi Tiwari
- Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, UP Pandit Deen Dayal Upadhayay Pashu Chikitsa Vigyan Vishwavidyalay Evum Go-Anusandhan Sansthan (DUVASU), Mathura, India
| | - Mohd I. Yatoo
- Division of Veterinary Clinical Complex, Faculty of Veterinary Sciences and Animal Husbandry, Shuhama, Alusteng Srinagar, Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Jammu and Kashmir, India
| | - Senthilkumar Natesan
- Department of Infectious Diseases, Indian Institute of Public Health Gandhinagar, Opp to Airforce station HQ, Gandhinagar, India
| | - Dewi Megawati
- Department of Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Warmadewa University, Denpasar, Indonesia
- Department of Medical Microbiology and Immunology, University of California, Davis, California, USA
| | - Karam P. Singh
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, India
| | - Izabela Michalak
- Faculty of Chemistry, Department of Advanced Material Technologies, Wrocław University of Science and Technology, Wrocław, Poland
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, India
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Rajendran R, Chathambath A, Al-Sehemi AG, Pannipara M, Unnikrishnan MK, Aleya L, Raghavan RP, Mathew B. Critical role of nitric oxide in impeding COVID-19 transmission and prevention: a promising possibility. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:38657-38672. [PMID: 35258738 PMCID: PMC8902850 DOI: 10.1007/s11356-022-19148-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Accepted: 02/06/2022] [Indexed: 05/06/2023]
Abstract
COVID-19 is a serious respiratory infection caused by a beta-coronavirus that is closely linked to SARS. Hypoxemia is a symptom of infection, which is accompanied by acute respiratory distress syndrome (ARDS). Augmenting supplementary oxygen may not always improve oxygen saturation; reversing hypoxemia in COVID-19 necessitates sophisticated means to promote oxygen transfer from alveoli to blood. Inhaled nitric oxide (iNO) has been shown to inhibit the multiplication of the respiratory coronavirus, a property that distinguishes it from other vasodilators. These findings imply that NO may have a crucial role in the therapy of COVID-19, indicating research into optimal methods to restore pulmonary physiology. According to clinical and experimental data, NO is a selective vasodilator proven to restore oxygenation by helping to normalize shunts and ventilation/perfusion mismatches. This study examines the role of NO in COVID-19 in terms of its specific physiological and biochemical properties, as well as the possibility of using inhaled NO as a standard therapy. We have also discussed how NO could be used to prevent and cure COVID-19, in addition to the limitations of NO.
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Affiliation(s)
- Rajalakshmi Rajendran
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - Anjana Chathambath
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India
| | - Abdullah G Al-Sehemi
- Research Center for Advanced Materials Science, King Khalid University, Abha, 61413, Saudi Arabia
- Department of Chemistry, King Khalid University, Abha, 61413, Saudi Arabia
| | - Mehboobali Pannipara
- Research Center for Advanced Materials Science, King Khalid University, Abha, 61413, Saudi Arabia
- Department of Chemistry, King Khalid University, Abha, 61413, Saudi Arabia
| | | | - Lotfi Aleya
- Laboratoire Chrono-Environment, Universite de Bourgogne Franche-Comte, CNRS6249, Besancon, France
| | - Roshni Pushpa Raghavan
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, Kochi, 682041, Kerala, India.
| | - Bijo Mathew
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, AIMS Health Sciences Campus, Amrita Vishwa Vidyapeetham, Kochi, 682 041, India
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Bagri A, Assis RR, Tsai C, Simmons G, Mei ZW, Von Goetz M, Gatmaitan M, Stone M, Di Germanio C, Martinelli R, Darst O, Rioveros J, Robinson PV, Ward D, Ziman A, Seftel D, Khan S, Busch MP, Felgner PL, Corash LM. Antibody profiles in
COVID
‐19 convalescent plasma prepared with Amotosalen/
UVA
pathogen reduction treatment. Transfusion 2022; 62:570-583. [PMID: 35128658 PMCID: PMC9115453 DOI: 10.1111/trf.16819] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Revised: 11/03/2021] [Accepted: 11/15/2021] [Indexed: 01/08/2023]
Abstract
Background COVID‐19 convalescent plasma (CCP), from donors recovered from severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection, is one of the limited therapeutic options currently available for the treatment of critically ill patients with COVID‐19. There is growing evidence that CCP may reduce viral loads and disease severity; and reduce mortality. However, concerns about the risk of transfusion‐transmitted infections (TTI) and other complications associated with transfusion of plasma, remain. Amotosalen/UVA pathogen reduction treatment (A/UVA‐PRT) of plasma offers a mitigation of TTI risk, and when combined with pooling has the potential to increase the diversity of the polyclonal SARS‐CoV‐2 neutralizing antibodies. Study design and methods This study assessed the impact of A/UVA‐PRT on SARS‐CoV‐2 antibodies in 42 CCP using multiple complimentary assays including antigen binding, neutralizing, and epitope microarrays. Other mediators of CCP efficacy were also assessed. Results A/UVA‐PRT did not negatively impact antibodies to SARS‐CoV‐2 and other viral epitopes, had no impact on neutralizing activity or other potential mediators of CCP efficacy. Finally, immune cross‐reactivity with other coronavirus antigens was observed raising the potential for neutralizing activity against other emergent coronaviruses. Conclusion The findings of this study support the selection of effective CCP combined with the use of A/UVA‐PRT in the production of CCP for patients with COVID‐19.
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Affiliation(s)
- Anil Bagri
- Cerus Corporation Concord California United States
| | - Rafael R. Assis
- Department of Physiology and Biophysics School of Medicine, University of California Irvine Irvine California United States
| | - Cheng‐ting Tsai
- ENable Biosciences Inc South San Francisco California United States
| | - Graham Simmons
- Vitalant Research Institute San Francisco California United States
| | - Zhen W. Mei
- Wing‐Kwai and Alice Lee‐Tsing Chung Transfusion Service, Department of Pathology and Laboratory Medicine David Geffen School of Medicine at University of California Los Angeles California USA
| | | | | | - Mars Stone
- Vitalant Research Institute San Francisco California United States
| | | | | | - Orsolya Darst
- Vitalant Research Institute San Francisco California United States
| | - Jowin Rioveros
- Wing‐Kwai and Alice Lee‐Tsing Chung Transfusion Service, Department of Pathology and Laboratory Medicine David Geffen School of Medicine at University of California Los Angeles California USA
| | | | - Dawn Ward
- Wing‐Kwai and Alice Lee‐Tsing Chung Transfusion Service, Department of Pathology and Laboratory Medicine David Geffen School of Medicine at University of California Los Angeles California USA
| | - Alyssa Ziman
- Wing‐Kwai and Alice Lee‐Tsing Chung Transfusion Service, Department of Pathology and Laboratory Medicine David Geffen School of Medicine at University of California Los Angeles California USA
| | - David Seftel
- ENable Biosciences Inc South San Francisco California United States
| | - Saahir Khan
- Division of Infectious Diseases, Department of Medicine University of California Irvine Health Orange California United States
| | - Michael P. Busch
- Vitalant Research Institute San Francisco California United States
| | - Philip L. Felgner
- Department of Physiology and Biophysics School of Medicine, University of California Irvine Irvine California United States
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Effect of Convalescent Plasma Therapy on Clinical Improvement of COVID-19 Patients: A Randomized Clinical Trial. TANAFFOS 2022; 21:24-30. [PMID: 36258918 PMCID: PMC9571240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Accepted: 05/29/2021] [Indexed: 11/11/2022]
Abstract
Background Due to the critical condition of COVID-19, it is necessary to evaluate the efficacy of administrating convalescent plasma to COVID-19 patients. Therefore, we decided to design a clinical trial to investigate the effect of convalescent plasma of patients recovered from COVID-19 on the treatment outcome of COVID-19-infected patients. Materials and Methods In this parallel randomized controlled clinical trial, patients in the intervention group received standard treatment plus convalescent plasma of patients recovered from COVID-19. We allocated 60 patients to each treatment group through balanced block randomization. Then, COVID-19 outcomes, vital signs, and biochemical parameters were compared between the two treatment groups by the independent t test and ANCOVA. Results The mean age (SD) of the patients in the intervention and standard treatment groups was 52.84 (15.77) and 55.15 (14.34) years, respectively. Although patients in the intervention group reported more hospitalization days (11.45±5.86 vs. 10.42±6.79), death rates (26.67% vs. 18.13%), ICU admission (45 vs. 41.67%), and ARDS (11.67% vs. 3.33%), these differences were not statistically significant (P>0.05). Moreover, the two groups were homogenous in vital signs and biochemical parameters before and after treatment (P>0.05). Conclusion The present study indicated that convalescent plasma therapy has no significant effect on the survival, hospitalization, and ICU admission of COVID-19 patients.
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12
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Stephensen CB, Lietz G. Vitamin A in resistance to and recovery from infection: relevance to SARS-CoV2. Br J Nutr 2021; 126:1663-1672. [PMID: 33468263 PMCID: PMC7884725 DOI: 10.1017/s0007114521000246] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Revised: 12/30/2020] [Accepted: 01/13/2021] [Indexed: 12/16/2022]
Abstract
SARS-CoV2 infects respiratory epithelial cells via its cellular receptor angiotensin-converting enzyme 2, causing a viral pneumonia with pronounced inflammation resulting in significant damage to the lungs and other organ systems, including the kidneys, though symptoms and disease severity are quite variable depending on the intensity of exposure and presence of underlying conditions that may affect the immune response. The resulting disease, coronavirus disease 2019 (COVID-19), can cause multi-organ system dysfunction in patients requiring hospitalisation and intensive care treatment. Serious infections like COVID-19 often negatively affect nutritional status, and the resulting nutritional deficiencies may increase disease severity and impair recovery. One example is the viral infection measles, where associated vitamin A (VA) deficiency increases disease severity and appropriately timed supplementation during recovery reduces mortality and hastens recovery. VA may play a similar role in COVID-19. First, VA is important in maintaining innate and adaptive immunity to promote clearance of a primary infection as well as minimise risks from secondary infections. Second, VA plays a unique role in the respiratory tract, minimising damaging inflammation, supporting repair of respiratory epithelium and preventing fibrosis. Third, VA deficiency may develop during COVID-19 due to specific effects on lung and liver stores caused by inflammation and impaired kidney function, suggesting that supplements may be needed to restore adequate status. Fourth, VA supplementation may counteract adverse effects of SARS-CoV2 on the angiotensin system as well as minimises adverse effects of some COVID-19 therapies. Evaluating interactions of SARS-CoV2 infection with VA metabolism may thus provide improved COVID-19 therapy.
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Affiliation(s)
- C. B. Stephensen
- Immunity and Disease Prevention Research Unit, USDA Western Human Nutrition Research Center, and Nutrition Department, University of California, Davis, CA, USA
| | - G. Lietz
- Human Nutrition Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon TyneNE2 4HH, UK
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Zou H, Yang Y, Dai H, Xiong Y, Wang JQ, Lin L, Chen ZS. Recent Updates in Experimental Research and Clinical Evaluation on Drugs for COVID-19 Treatment. Front Pharmacol 2021; 12:732403. [PMID: 34880750 PMCID: PMC8646041 DOI: 10.3389/fphar.2021.732403] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 10/13/2021] [Indexed: 12/17/2022] Open
Abstract
Since the outbreak of corona virus disease 2019 (COVID-19) in Wuhan (China) in December 2019, the epidemic has rapidly spread to many countries around the world, posing a huge threat to global public health. In response to the pandemic, a number of clinical studies have been initiated to evaluate the effect of various treatments against COVID-19, combining medical strategies and clinical trial data from around the globe. Herein, we summarize the clinical evaluation about the drugs mentioned in this review for COVID-19 treatment. This review discusses the recent data regarding the efficacy of various treatments in COVID-19 patients, to control and prevent the outbreak.
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Affiliation(s)
| | - Yuqi Yang
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, United States
| | - Huiqiang Dai
- Cell Research Center, Shenzhen Bolun Institute of Biotechnology, Shenzhen, China
| | - Yunchuang Xiong
- Cell Research Center, Shenzhen Bolun Institute of Biotechnology, Shenzhen, China
| | - Jing-Quan Wang
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, United States
| | - Lusheng Lin
- Cell Research Center, Shenzhen Bolun Institute of Biotechnology, Shenzhen, China
| | - Zhe-Sheng Chen
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, United States
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14
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Basheer M, Saad E, Shlezinger D, Assy N. Convalescent Plasma Reduces Mortality and Decreases Hospitalization Stay in Patients with Moderate COVID-19 Pneumonia. Metabolites 2021; 11:metabo11110761. [PMID: 34822419 PMCID: PMC8622396 DOI: 10.3390/metabo11110761] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 11/01/2021] [Accepted: 11/03/2021] [Indexed: 12/15/2022] Open
Abstract
Humans infected with SARS-CoV-2 may develop COVID-19, which manifests across a wide spectrum of clinical severity ranging from mild upper respiratory tract illnesses to diffuse viral pneumonia, causing acute respiratory failure. Many therapies have been tested for their efficacy in treating COVID-19. Controversy surrounds convalescent plasma transfusions as an effective treatment for COVID-19. This study discusses the efficacy of this treatment on COVID-19 patients. Electronic medical record data were collected from patients diagnosed with COVID-19, from November 2020 to August 2021, in the Galilee Medical Center's COVID-19 departments. Epidemiological, clinical, laboratory and imaging variables were analyzed. Multivariate stepwise regression and discriminant analyses were used to identify and validate the correlation between convalescent treatment and either death or time to negative PCR and hospitalization length. The study population included 270 patients, 100 of them treated with convalescent plasma. The results show that convalescent plasma therapy significantly prevented mortality in moderate patients, reduced hospitalization length and time to negative PCR. Additionally, high BMI, elderly age, high CRP and 4C-scores correlated with the severity and mortality of COVID-19 patients. Convalescent plasma also significantly reduced inflammatory markers, especially in moderate COVID-19 patients. In non-critical hospitalized patients, convalescent plasma therapy reduces morbidity and mortality in moderate COVID-19 patients and hospitalization length. Identifying patients who could benefit from this treatment could reduce the risk of death and shorten their hospitalization stay.
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Affiliation(s)
- Maamoun Basheer
- Internal Medicine Department, Galilee Medical Center, Nahariya 2210001, Israel; (M.B.); (E.S.); (D.S.)
| | - Elias Saad
- Internal Medicine Department, Galilee Medical Center, Nahariya 2210001, Israel; (M.B.); (E.S.); (D.S.)
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safad 2210001, Israel
| | - Dorin Shlezinger
- Internal Medicine Department, Galilee Medical Center, Nahariya 2210001, Israel; (M.B.); (E.S.); (D.S.)
| | - Nimer Assy
- Internal Medicine Department, Galilee Medical Center, Nahariya 2210001, Israel; (M.B.); (E.S.); (D.S.)
- The Azrieli Faculty of Medicine, Bar-Ilan University, Safad 2210001, Israel
- Correspondence:
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15
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Stoian A, Bajko Z, Maier S, Cioflinc RA, Grigorescu BL, Moțățăianu A, Bărcuțean L, Balașa R, Stoian M. High-dose intravenous immunoglobulins as a therapeutic option in critical illness polyneuropathy accompanying SARS-CoV-2 infection: A case-based review of the literature (Review). Exp Ther Med 2021; 22:1182. [PMID: 34475972 PMCID: PMC8406741 DOI: 10.3892/etm.2021.10616] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 07/27/2021] [Indexed: 01/08/2023] Open
Abstract
The still ongoing COVID-19 pandemic has exposed the medical community to a number of major challenges. A significant number of patients require admission to intensive care unit (ICU) services due to severe respiratory, thrombotic and septic complications and require long-term hospitalization. Neuromuscular weakness is a common complication in critically ill patients who are treated in ICUs and are mechanically ventilated. This complication is frequently caused by critical illness myopathy (CIM) or critical illness polyneuropathy (CIP) and leads to difficulty in weaning from the ventilator. It is thought to represent an important neurologic manifestation of the systemic inflammatory response syndrome (SIRS). COVID-19 infection is known to trigger strong immune dysregulation, with an intense cytokine storm, as a result, the frequency of CIP is expected to be higher in this setting. The mainstay in the diagnosis of this entity beside the high level of clinical awareness is the electrophysiological examination that provides evidence of axonal motor and sensory polyneuropathy. The present article presents the case of a 54-year-old woman with severe COVID 19 infection who developed neuromuscular weakness, which turned out to be secondary to CIP and was treated successfully with a high dose of human intravenous immunoglobulins. Related to this case, we reviewed the relevant literature data regarding the epidemiology, pathophysiology and clinical features of this important complication and discussed also the treatment options and prognosis.
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Affiliation(s)
- Adina Stoian
- Department of Pathophysiology, ‘George Emil Palade’ University of Medicine, Pharmacy, Sciences and Technology, 540136 Targu Mures, Romania
| | - Zoltan Bajko
- Department of Neurology, ‘George Emil Palade’ University of Medicine, Pharmacy, Sciences and Technology, 540136 Targu Mures, Romania
| | - Smaranda Maier
- Department of Neurology, ‘George Emil Palade’ University of Medicine, Pharmacy, Sciences and Technology, 540136 Targu Mures, Romania
| | | | - Bianca Liana Grigorescu
- Department of Pathophysiology, ‘George Emil Palade’ University of Medicine, Pharmacy, Sciences and Technology, 540136 Targu Mures, Romania
| | - Anca Moțățăianu
- Department of Neurology, ‘George Emil Palade’ University of Medicine, Pharmacy, Sciences and Technology, 540136 Targu Mures, Romania
| | - Laura Bărcuțean
- Department of Neurology, ‘George Emil Palade’ University of Medicine, Pharmacy, Sciences and Technology, 540136 Targu Mures, Romania
| | - Rodica Balașa
- Department of Neurology, ‘George Emil Palade’ University of Medicine, Pharmacy, Sciences and Technology, 540136 Targu Mures, Romania
| | - Mircea Stoian
- Department of Anesthesiology and Intensive Therapy, ‘George Emil Palade’ University of Medicine, Pharmacy, Sciences and Technology, 540136 Targu Mures, Romania
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16
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Wang X, Lei J, Li Z, Yan L. Potential Effects of Coronaviruses on the Liver: An Update. Front Med (Lausanne) 2021; 8:651658. [PMID: 34646834 PMCID: PMC8502894 DOI: 10.3389/fmed.2021.651658] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 07/22/2021] [Indexed: 02/06/2023] Open
Abstract
The coronaviruses that cause notable diseases, namely, severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19), exhibit remarkable similarities in genomic components and pathogenetic mechanisms. Although coronaviruses have widely been studied as respiratory tract pathogens, their effects on the hepatobiliary system have seldom been reported. Overall, the manifestations of liver injury caused by coronaviruses typically involve decreased albumin and elevated aminotransferase and bilirubin levels. Several pathophysiological hypotheses have been proposed, including direct damage, immune-mediated injury, ischemia and hypoxia, thrombosis and drug hepatotoxicity. The interaction between pre-existing liver disease and coronavirus infection has been illustrated, whereby coronaviruses influence the occurrence, severity, prognosis and treatment of liver diseases. Drugs and vaccines used for treating and preventing coronavirus infection also have hepatotoxicity. Currently, the establishment of optimized therapy for coronavirus infection and liver disease comorbidity is of significance, warranting further safety tests, animal trials and clinical trials.
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Affiliation(s)
- Xinyi Wang
- Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, China
- Liver Surgery Center, West China Hospital of Sichuan University, Chengdu, China
| | - Jianyong Lei
- Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, China
- Liver Surgery Center, West China Hospital of Sichuan University, Chengdu, China
| | - Zhihui Li
- Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, China
- Liver Surgery Center, West China Hospital of Sichuan University, Chengdu, China
| | - Lunan Yan
- Liver Surgery Center, West China Hospital of Sichuan University, Chengdu, China
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17
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Chen L, Han X, Li Y, Zhang C, Xing X. The severity and risk factors for mortality in immunocompromised adult patients hospitalized with influenza-related pneumonia. Ann Clin Microbiol Antimicrob 2021; 20:55. [PMID: 34429126 PMCID: PMC8383249 DOI: 10.1186/s12941-021-00462-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 08/16/2021] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE To explore disease severity and risk factors for 30-day mortality of adult immunocompromised (IC) patients hospitalized with influenza-related pneumonia (Flu-p). METHOD A total of 122 IC and 1191 immunocompetent patients hospitalized with Flu-p from January 2012 to December 2018 were recruited retrospectively from five teaching hospitals in China. RESULTS After controlling for confounders, multivariate logistic regression analysis showed that immunosuppression was associated with increased risks for invasive ventilation [odds ratio: (OR) 2.475, 95% confidence interval (CI): 1.511-4.053, p < 0.001], admittance to the intensive care unit (OR: 3.247, 95% CI 2.064-5.106, p < 0.001), and 30-day mortality (OR: 3.206, 95% CI 1.926-5.335, p < 0.001) in patients with Flu-p. Another multivariate logistic regression model revealed that baseline lymphocyte counts (OR: 0.993, 95% CI 0.990-0.996, p < 0.001), coinfection (OR: 5.450, 95% CI 1.638-18.167, p = 0.006), early neuraminidase inhibitor therapy (OR 0.401, 95% CI 0.127-0.878, p = 0.001), and systemic corticosteroid use at admission (OR: 6.414, 95% CI 1.348-30.512, p = 0.020) were independently related to 30-day mortality in IC patients with Flu-p. Based on analysis of the receiver operating characteristic curve (ROC), the optimal cutoff for lymphocyte counts was 0.6 × 109/L [area under the ROC (AUROC) = 0.824, 95% CI 0.744-0.887], sensitivity: 97.8%, specificity: 73.7%]. CONCLUSIONS IC conditions are associated with more severe outcomes in patients with Flu-p. The predictors for mortality that we identified may be valuable for the management of Flu-p among IC patients.
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Affiliation(s)
- Liang Chen
- Department of Infectious Diseases, Nanjing Lishui People's Hospital, Lishui District, No. 86 Chongwen Road, Nanjing, China.
- Department of Infectious Diseases, Beijing Jishuitan Hospital, 4Th Medical College of Peking University, Beijing, China.
| | - Xiudi Han
- Department of Pulmonary and Critical Care Medicine, Qingdao Municipal Hospital, Qingdao City, Shandong Province, China
| | - YanLi Li
- Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Chunxiao Zhang
- Department of Pulmonary and Critical Care Medicine, Beijing Huimin Hospital, Beijing, China
| | - Xiqian Xing
- Department of Pulmonary and Critical Care Medicine, The 2Nd People's Hospital of Yunnan Province, Kunming City, Yunnan Province, China
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18
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Zhao B, Yang TF, Zheng R. Theory and reality of antivirals against SARS-CoV-2. World J Clin Cases 2021; 9:6663-6673. [PMID: 34447813 PMCID: PMC8362513 DOI: 10.12998/wjcc.v9.i23.6663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/16/2021] [Accepted: 07/02/2021] [Indexed: 02/06/2023] Open
Abstract
At present, over 180 million people have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide and there have been more than 3.8 million deaths due to the virus. However, specific effective antiviral treatment for this infectious disease is absent. At the beginning of the epidemic, relevant cellular and animal experiments of antiviral treatment for SARS-CoV-2 were conducted based on the prior studies of SARS-CoV and Middle East respiratory syndrome coronavirus. Some antivirals were preliminarily validated to be potentially effective in the clinical settings. But as the epidemic continued and more studies were carried out, the efficacy of these antiviral drugs became controversial. This paper reviews the pharmacology and application of interferon, lopinavir/ritonavir, ribavirin, chloroquine, arbidol, favipiravir, remdesivir, and thymosin α1 in coronavirus disease 2019. The actual effect of these drugs remains controversial. Meanwhile, the efficacy and safety of these drugs for patients with coronavirus disease 2019 still need to be explored.
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Affiliation(s)
- Bo Zhao
- Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Teng-Fei Yang
- Department of Health Management and Family Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
| | - Rui Zheng
- Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
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19
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Long CM, Marzi A. Biodefence research two decades on: worth the investment? THE LANCET. INFECTIOUS DISEASES 2021; 21:e222-e233. [PMID: 34331891 DOI: 10.1016/s1473-3099(21)00382-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/13/2021] [Accepted: 06/14/2021] [Indexed: 12/15/2022]
Abstract
For the past 20 years, the notion of bioterror has been a source of considerable fear and panic worldwide. In response to the terror attacks of 2001 in the USA, extensive research funding was awarded to investigate bioterror-related pathogens. The global scientific legacy of this funding has extended into the present day, highlighted by the ongoing COVID-19 pandemic. Unsurprisingly, the surge in biodefence-related research and preparedness has been met with considerable apprehension and opposition. Here, we briefly outline the history of modern bioterror threats and biodefence research, describe the scientific legacy of biodefence research by highlighting advances pertaining to specific bacterial and viral pathogens, and summarise the future of biodefence research and its relevance today. We sought to address the sizeable question: have the past 20 years of investment into biodefence research and preparedness been worth it? The legacy of modern biodefence funding includes advancements in biosecurity, biosurveillence, diagnostics, medical countermeasures, and vaccines. In summary, we feel that these advances justify the substantial biodefence funding trend of the past two decades and set a precedent for future funding.
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Affiliation(s)
- Carrie M Long
- Laboratory of Bacteriology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA
| | - Andrea Marzi
- Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
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20
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Park A, Harris LK. Gene Expression Meta-Analysis Reveals Interferon-Induced Genes Associated With SARS Infection in Lungs. Front Immunol 2021; 12:694355. [PMID: 34367154 PMCID: PMC8342995 DOI: 10.3389/fimmu.2021.694355] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 07/05/2021] [Indexed: 01/01/2023] Open
Abstract
Background Severe Acute Respiratory Syndrome (SARS) corona virus (CoV) infections are a serious public health threat because of their pandemic-causing potential. This work is the first to analyze mRNA expression data from SARS infections through meta-analysis of gene signatures, possibly identifying therapeutic targets associated with major SARS infections. Methods This work defines 37 gene signatures representing SARS-CoV, Middle East Respiratory Syndrome (MERS)-CoV, and SARS-CoV2 infections in human lung cultures and/or mouse lung cultures or samples and compares them through Gene Set Enrichment Analysis (GSEA). To do this, positive and negative infectious clone SARS (icSARS) gene panels are defined from GSEA-identified leading-edge genes between two icSARS-CoV derived signatures, both from human cultures. GSEA then is used to assess enrichment and identify leading-edge icSARS panel genes between icSARS gene panels and 27 other SARS-CoV gene signatures. The meta-analysis is expanded to include five MERS-CoV and three SARS-CoV2 gene signatures. Genes associated with SARS infection are predicted by examining the intersecting membership of GSEA-identified leading-edges across gene signatures. Results Significant enrichment (GSEA p<0.001) is observed between two icSARS-CoV derived signatures, and those leading-edge genes defined the positive (233 genes) and negative (114 genes) icSARS panels. Non-random significant enrichment (null distribution p<0.001) is observed between icSARS panels and all verification icSARSvsmock signatures derived from human cultures, from which 51 over- and 22 under-expressed genes are shared across leading-edges with 10 over-expressed genes already associated with icSARS infection. For the icSARSvsmock mouse signature, significant, non-random significant enrichment held for only the positive icSARS panel, from which nine genes are shared with icSARS infection in human cultures. Considering other SARS strains, significant, non-random enrichment (p<0.05) is observed across signatures derived from other SARS strains for the positive icSARS panel. Five positive icSARS panel genes, CXCL10, OAS3, OASL, IFIT3, and XAF1, are found across mice and human signatures regardless of SARS strains. Conclusion The GSEA-based meta-analysis approach used here identifies genes with and without reported associations with SARS-CoV infections, highlighting this approach’s predictability and usefulness in identifying genes that have potential as therapeutic targets to preclude or overcome SARS infections.
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Affiliation(s)
- Amber Park
- Harris Interdisciplinary Research, Davenport University, Grand Rapids, MI, United States
| | - Laura K Harris
- Harris Interdisciplinary Research, Davenport University, Grand Rapids, MI, United States.,Institute for Cyber-Enabled Research, Michigan State University, East Lansing, MI, United States
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21
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Martínez-Flores D, Zepeda-Cervantes J, Cruz-Reséndiz A, Aguirre-Sampieri S, Sampieri A, Vaca L. SARS-CoV-2 Vaccines Based on the Spike Glycoprotein and Implications of New Viral Variants. Front Immunol 2021; 12:701501. [PMID: 34322129 PMCID: PMC8311925 DOI: 10.3389/fimmu.2021.701501] [Citation(s) in RCA: 142] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 06/28/2021] [Indexed: 12/12/2022] Open
Abstract
Coronavirus 19 Disease (COVID-19) originating in the province of Wuhan, China in 2019, is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), whose infection in humans causes mild or severe clinical manifestations that mainly affect the respiratory system. So far, the COVID-19 has caused more than 2 million deaths worldwide. SARS-CoV-2 contains the Spike (S) glycoprotein on its surface, which is the main target for current vaccine development because antibodies directed against this protein can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. However, the emergence of new SARS-CoV-2 variants could affect the effectiveness of vaccines. Here, we review the different types of vaccines designed and developed against SARS-CoV-2, placing emphasis on whether they are based on the complete S glycoprotein, its antigenic domains such as the receptor-binding domain (RBD) or short epitopes within the S glycoprotein. We also review and discuss the possible effectiveness of these vaccines against emerging SARS-CoV-2 variants.
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Affiliation(s)
- Daniel Martínez-Flores
- Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Jesús Zepeda-Cervantes
- Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
- Departamento de Microbiología e Inmunología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Adolfo Cruz-Reséndiz
- Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Sergio Aguirre-Sampieri
- Laboratorio de Fisicoquímica e Ingeniería de Proteínas, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Alicia Sampieri
- Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Luis Vaca
- Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
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22
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Kumari P, Singh P, Kaur J, Bhatti R. Design, Synthesis, and Activity Evaluation of Stereoconfigured Tartarate Derivatives as Potential Anti-inflammatory Agents In Vitro and In Vivo. J Med Chem 2021; 64:9550-9566. [PMID: 34137625 DOI: 10.1021/acs.jmedchem.1c00880] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Preclinical and clinical data reveal that inflammation is strongly correlated with the pathogenesis of a number of diseases including those of cancer, Alzheimer, and diabetes. The inflammatory cascade involves a multitude of cytokines ending ultimately with the activation of COX-2/LOX for the production of prostaglandins and leukotrienes. While the available inhibitors for these enzymes suffer from nonoptimal selectivity, in particular for COX-2, we present here the results of purposely designed tartarate derivatives that exhibit favorable selectivity and significant effectiveness against COX-2 and LOX. Integrated approaches of molecular simulation, organic synthesis, and biochemical/physical experiments identified 15 inhibiting COX-2 and LOX with respective IC50 4 and 7 nM. At a dose of 5 mg kg-1 to Swiss albino mice, 15 reversed algesia by 65% and inflammation by 33% in 2-3 h. We find good agreement between experiments and simulations and use the simulations to rationalize our observations.
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23
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Bayat M, Asemani Y, Mohammadi MR, Sanaei M, Namvarpour M, Eftekhari R. An overview of some potential immunotherapeutic options against COVID-19. Int Immunopharmacol 2021; 95:107516. [PMID: 33765610 PMCID: PMC7908848 DOI: 10.1016/j.intimp.2021.107516] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 02/15/2021] [Accepted: 02/15/2021] [Indexed: 02/07/2023]
Abstract
After the advent of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in the late 2019, the resulting severe and pernicious syndrome (COVID-19) immediately was deployed all around the world. To date, despite relentless efforts to control the disease by drug repurposing, there is no approved specific therapy for COVID-19. Given the role of innate and acquired immune components in the control and elimination of viral infections and inflammatory mutilations during SARS-CoV2 pathogenesis, immunotherapeutic strategies appear to be beneficent. Passive immunotherapies such as convalescent plasma, which has received much attention especially in severe cases, as well as suppressing inflammatory cytokines, interferon administration, inhibition of kinases and complement cascade, virus neutralization with key engineered products, cell-based therapies, immunomodulators and anti-inflammatory drugs are among the key immunotherapeutic approaches to deal with COVID-19, which is discussed in this review. Also, details of leading COVID-19 vaccine candidates as the most potent immunotherapy have been provided. However, despite salient improvements, there is still a lack of completely assured vaccines for universal application. Therefore, adopting proper immunotherapies according to the cytokine pattern and involved immune responses, alongside engineered biologics specially ACE2-Fc to curb SARS-CoV2 infection until achieving a tailored vaccine is probably the best strategy to better manage this pandemic. Therefore, gaining knowledge about the mechanism of action, potential targets, as well as the effectiveness of immune-based approaches to confront COVID-19 in the form of a well-ordered review study is highly momentous.
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Affiliation(s)
- Maryam Bayat
- Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Yahya Asemani
- Department of Immunology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mohammad Reza Mohammadi
- Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mahsa Sanaei
- Department of Environmental, Polymer and Organic Chemistry, School of Chemistry, Damghan University, Damghan, Iran
| | - Mozhdeh Namvarpour
- Department of Immunology, Shahid Sadoughi University of Medical Science and services, Yazd, Iran
| | - Reyhaneh Eftekhari
- Department of Microbiology, Faculty of Biology, Semnan University, Semnan, Iran
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24
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Bauso LV, Imbesi C, Irene G, Calì G, Bitto A. New Approaches and Repurposed Antiviral Drugs for the Treatment of the SARS-CoV-2 Infection. Pharmaceuticals (Basel) 2021; 14:503. [PMID: 34070359 PMCID: PMC8228036 DOI: 10.3390/ph14060503] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 05/02/2021] [Accepted: 05/08/2021] [Indexed: 12/15/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19). The outbreak of this coronavirus was first identified in Wuhan (Hubei, China) in December 2019, and it was declared as pandemic by the World Health Organization (WHO) in March 2020. Today, several vaccines against SARS-CoV-2 have been approved, and some neutralizing monoclonal antibodies are being tested as therapeutic approaches for COVID-19 but, one of the key questions is whether both vaccines and monoclonal antibodies could be effective against infections by new SARS-CoV-2 variants. Nevertheless, there are currently more than 1000 ongoing clinical trials focusing on the use and effectiveness of antiviral drugs as a possible therapeutic treatment. Among the classes of antiviral drugs are included 3CL protein inhibitors, RNA synthesis inhibitors and other small molecule drugs which target the ability of SARS-COV-2 to interact with host cells. Considering the need to find specific treatment to prevent the emergent outbreak, the aim of this review is to explain how some repurposed antiviral drugs, indicated for the treatment of other viral infections, could be potential candidates for the treatment of COVID-19.
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Affiliation(s)
- Luana Vittoria Bauso
- Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (L.V.B.); (C.I.); (G.I.); (G.C.)
| | - Chiara Imbesi
- Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (L.V.B.); (C.I.); (G.I.); (G.C.)
- Laboratori Campisi, Corso Vittorio Emanuele 231, 96012 Avola, Italy
| | - Gasparo Irene
- Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (L.V.B.); (C.I.); (G.I.); (G.C.)
| | - Gabriella Calì
- Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (L.V.B.); (C.I.); (G.I.); (G.C.)
| | - Alessandra Bitto
- Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (L.V.B.); (C.I.); (G.I.); (G.C.)
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25
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Hou X, Tian L, Zhou L, Jia X, Kong L, Xue Y, Hao H, Meng X, Zhang F, Dong X. Intravenous immunoglobulin-based adjuvant therapy for severe COVID-19: a single-center retrospective cohort study. Virol J 2021; 18:101. [PMID: 34020680 PMCID: PMC8139546 DOI: 10.1186/s12985-021-01575-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/11/2021] [Indexed: 12/15/2022] Open
Abstract
Objective Coronavirus disease 2019 (COVID-19) is a major challenge facing the world. Certain guidelines issued by National Health Commission of the People's Repubilic of China recommend intravenous immunoglobulin (IVIG) for adjuvant treatment of COVID-19. However, there is a lack of clinical evidence to support the use of IVIG. Methods This single-center retrospective cohort study included all adult patients with laboratory-confirmed severe COVID-19 in the Respiratory and Critical Care Unit of Dabie Mountain Regional Medical Center, China. Patient information, including demographic data, laboratory indicators, the use of glucocorticoids and IVIG, hospital mortality, the application of mechanical ventilation, and the length of hospital stay was collected. The primary outcome was the composite end point, including death and the use of mechanical ventilation. The secondary outcome was the length of hospital stay. Results Of the 285 patients with confirmed COVID-19, 113 severely ill patients were included in this study. Compared to the non-IVIG group, more patients in the IVIG group reached the composite end point [12 (25.5%) vs 5 (7.6%), P = 0.008] and had longer hospital stay periods [23.0 (19.0–31.0) vs 16.0 (13.8–22.0), P < 0.001]. After adjusting for confounding factors, differences in primary outcomes between the two groups were not statistically significant (P = 0.167), however, patients in the IVIG group had longer hospital stay periods (P = 0.041). Conclusion Adjuvant therapy with IVIG did not improve in-hospital mortality rates or the need for mechanical ventilation in severe COVID-19 patients. Our study does not support the use of immunoglobulin in patients with severe COVID-19 patients.
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Affiliation(s)
- Xiao Hou
- Pelvic Floor Disease Center, Shandong Provincial Maternal and Child Health Care Hospital, Jinan, Shandong, People's Republic of China
| | - Li Tian
- Department of Lung Disease, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China
| | - Lei Zhou
- Department of Pulmonary Critical Care Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, People's Republic of China
| | - Xinhua Jia
- Department of Lung Disease, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China
| | - Li Kong
- Department of Critical Care Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China
| | - Yitao Xue
- Department of Cardiovascular Diseases, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China
| | - Hao Hao
- Department of Critical Care Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China.
| | - Xianqing Meng
- Department of Critical Care Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China
| | - Feihu Zhang
- Department of Critical Care Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China
| | - Xiaobin Dong
- Department of Critical Care Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People's Republic of China
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Saeed H, Osama H, Madney YM, Harb HS, Abdelrahman MA, Ehrhardt C, Abdelrahim MEA. COVID-19; current situation and recommended interventions. Int J Clin Pract 2021; 75:e13886. [PMID: 33278855 PMCID: PMC7883281 DOI: 10.1111/ijcp.13886] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 11/01/2020] [Accepted: 11/30/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The new coronavirus (SARS-COV-2) that emerged at the end of 2019 was stated in China and infected millions of people around the world, with the highest spread rate amongst humans compared with other coronaviruses. This paper aimed to review and analyse the published studies about COVID-19 diagnosis, prevention, and treatment. METHOD The reviewed studies were clinical trials, in-vivo, in-vitro, guidelines, reports from the world health organization (WHO), and the centre for disease control and prevention (CDC) in addition to systemic reviews. All data extracted and analysed to stand on the latest updates and recommendations for fighting this severe attack of COVID-19. RESULTS Most important antiviral therapy of COVID-19 clinical trials is still running without clear results, but a few trials have indicated the role of numerous drugs in the treatment of COVID-19. Specific recommendations for aerosol therapy should be followed for the management of COVID-19. CONCLUSION Nature of COVID-19 is still not very clear, however, management of the condition is similar to the previous attacks of coronaviruses.
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Affiliation(s)
- Haitham Saeed
- Clinical Pharmacy DepartmentFaculty of PharmacyBeni‐Suef UniversityBeni‐SuefEgypt
| | - Hasnaa Osama
- Clinical Pharmacy DepartmentFaculty of PharmacyBeni‐Suef UniversityBeni‐SuefEgypt
| | - Yasmin M. Madney
- Clinical Pharmacy DepartmentFaculty of PharmacyBeni‐Suef UniversityBeni‐SuefEgypt
| | - Hadeer S. Harb
- Clinical Pharmacy DepartmentFaculty of PharmacyBeni‐Suef UniversityBeni‐SuefEgypt
| | - Mona A. Abdelrahman
- Clinical Pharmacy DepartmentFaculty of PharmacyBeni‐Suef UniversityBeni‐SuefEgypt
| | - Carsten Ehrhardt
- School of Pharmacy and Pharmaceutical SciencesTrinity College DublinDublin 2Ireland
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A Phase II Study on the Use of Convalescent Plasma for the Treatment of Severe COVID-19- A Propensity Score-Matched Control Analysis. Microorganisms 2021; 9:microorganisms9040806. [PMID: 33920489 PMCID: PMC8069820 DOI: 10.3390/microorganisms9040806] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 04/01/2021] [Accepted: 04/09/2021] [Indexed: 12/15/2022] Open
Abstract
COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 or higher. To evaluate the efficacy of CP, a matched propensity score analysis was used comparing the intervention (n = 59) to a control group (n = 59). Sixty patients received CP within a median time of 7 days from symptom onset. During a median follow-up of 28.5 days, 56/60 patients fully recovered and 1 patient remained in the ICU. The death rate in the CP group was 3.4% vs. 13.6% in the control group. By multivariate analysis, CP recipients demonstrated a significantly reduced risk of death [HR: 0.04 (95% CI: 0.004–0.36), p: 0.005], significantly better overall survival by Kaplan–Meir analysis (p < 0.001), and increased probability of extubation [OR: 30.3 (95% CI: 2.64–348.9), p: 0.006]. Higher levels of antibodies in the CP were independently associated with significantly reduced risk of death. CP infusion was safe with only one grade 3 adverse event (AE), which easily resolved. CP used early may be a safe and effective treatment for patients with severe COVID-19 (trial number NCT04408209).
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28
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Doagooyan M, Alavizadeh SH, Akhtari J, Sahebkar A, Kiade SGH, Kochesfahani PH, Gheybi F. Investigation of structural, treatment and clinical characteristics of COVID-19 along with the challenges caused by its prevalence. Infect Disord Drug Targets 2021; 22:e220321192415. [PMID: 33749564 DOI: 10.2174/1871526521666210322160038] [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: 08/04/2020] [Revised: 12/11/2020] [Accepted: 12/31/2020] [Indexed: 12/15/2022]
Abstract
In the late 2019, a report from China was published stating a disease with unknown cause. After that,the outbreak of the COVID-19 caused a pandemic in the world. On March 11, 2020, the outbreak of this virus was reported in 100 countries. The virus is currently spreading rapidly around the world.In the past, coronaviruses caused life-threatening diseases such as SARS and MERSsome areas.Although there is still a debate about the origin of this new coronavirus, it is most likely linked with some animals including bats, civet and pangolin. In this review, we try to simply describe the features of the new coronavirusas well as the recent diagnostic and therapeutic findings.
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Affiliation(s)
- Maham Doagooyan
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran
| | - Seyedeh Hoda Alavizadeh
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad. Iran
| | - Javad Akhtari
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari. Iran
| | | | | | | | - Fatemeh Gheybi
- Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran
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Basiri A, Pazhouhnia Z, Beheshtizadeh N, Hoseinpour M, Saghazadeh A, Rezaei N. Regenerative Medicine in COVID-19 Treatment: Real Opportunities and Range of Promises. Stem Cell Rev Rep 2021; 17:163-175. [PMID: 32564256 PMCID: PMC7305935 DOI: 10.1007/s12015-020-09994-5] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Novel coronavirus disease (COVID-19) has attracted much attention around the world due to its rapid transmission among humans and relatively high mortality rate. Studies are increasing to find the best therapeutic approach for the disease and its management. Regenerative medicine offers various cell-tissue therapeutics and related products, such as stem cell therapy, natural killer (NK) cell therapy, Chimeric antigen receptor (CAR) T cell therapy, exosomes, and tissue products. Interestingly, mesenchymal stem cells (MSCs) can reduce inflammatory symptoms and protect against cytokine storm, which critically contributes to the COVID-19 progression. Notably, having the potentials to exert cytotoxic effects on infected cells and induce interferon production probably make NK cells a candidate for COVID-19 cell therapy. Besides, exosomes are one of the crucial products of cells that can exert therapeutic effects through the induction of immune responses and neutralizing antibody titers. The paper aims to briefly consider current options for COVID-19 therapy to show that there is no specific cure for COVID-19, and then assess the real opportunities and range of promises regenerative medicine can provide for specific treatment of COVID-19. Graphical Abstract Therapeutic Potential of Regenerative Medicine against COVID19.
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Affiliation(s)
- Arefeh Basiri
- Department of Biomaterials and Tissue Engineering, School of Advanced Technology in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
- Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Zahra Pazhouhnia
- Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Nima Beheshtizadeh
- Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahdieh Hoseinpour
- Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Amene Saghazadeh
- Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
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30
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Fang W, Jiang J, Su L, Shu T, Liu H, Lai S, Ghiladi RA, Wang J. The role of NO in COVID-19 and potential therapeutic strategies. Free Radic Biol Med 2021; 163:153-162. [PMID: 33347987 PMCID: PMC7754882 DOI: 10.1016/j.freeradbiomed.2020.12.008] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 12/02/2020] [Accepted: 12/10/2020] [Indexed: 01/08/2023]
Abstract
Nitric oxide (NO) is a free radical playing an important pathophysiological role in cardiovascular and immune systems. Recent studies reported that NO levels were significantly lower in patients with COVID-19, which was suggested to be closely related to vascular dysfunction and immune inflammation among them. In this review, we examine the potential role of NO during SARS-CoV-2 infection from the perspective of the unique physical, chemical and biological properties and potential mechanisms of NO in COVID-19, as well as possible therapeutic strategies using inhaled NO. We also discuss the limits of NO treatment, and the future application of this approach in prevention and therapy of COVID-19.
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Affiliation(s)
- Wanyi Fang
- National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Wuhan, Hubei, China; Department of Biomedicine and Biopharmacology, Hubei University of Technology, Wuhan, Hubei, China
| | - Jingrui Jiang
- National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Wuhan, Hubei, China; Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Lei Su
- School of Biomedical Engineering, Shenzhen University, Shenzhen, Guangdong, China
| | - Tong Shu
- School of Biomedical Engineering, Shenzhen University, Shenzhen, Guangdong, China
| | - Huan Liu
- National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Wuhan, Hubei, China; Department of Biomedicine and Biopharmacology, Hubei University of Technology, Wuhan, Hubei, China
| | - Shenghan Lai
- Johns Hopkins University School of Medicine, Maryland, USA
| | - Reza A Ghiladi
- Department of Chemistry, North Carolina State University, North Carolina, USA
| | - Jun Wang
- National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Wuhan, Hubei, China; Department of Biomedicine and Biopharmacology, Hubei University of Technology, Wuhan, Hubei, China.
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31
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Algahtani FD, Hassan SUN, Alsaif B, Zrieq R. Assessment of the Quality of Life during COVID-19 Pandemic: A Cross-Sectional Survey from the Kingdom of Saudi Arabia. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:847. [PMID: 33498152 PMCID: PMC7863741 DOI: 10.3390/ijerph18030847] [Citation(s) in RCA: 93] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 01/08/2021] [Accepted: 01/11/2021] [Indexed: 12/14/2022]
Abstract
The COVID-19 outbreak emerged as an ongoing crisis at the beginning of the year 2020. Its horrific manifestation at the community level significantly affects various dimensions of the quality of life (QoL) of all individuals. The study aimed to examine some of the predictors of the QoL during the first wave of the COVID-19 pandemic in Saudi Arabia. A cross-sectional online survey questionnaire was used to gather data on the participants' sociodemographic backgrounds, physical health status, psychological reactions, and QoL. We adapted 12 items from the World Health Organization Quality of Life Instruments (WHOQOL-BREF) to assess the QoL. The Depression, Anxiety and Stress Scale-21 (DASS-21) was used to assess depression, anxiety, and stress. The median and inter-quartile range were used to describe the QoL scores. A multinomial regression analysis was computed between QoL score quartiles and associated factors, and the statistical significance was set at p < 0.05. The results of the multinomial regression analysis demonstrated that males (OR = 1.96; 95% CI = 1.31-2.94); participants aged 26 to 35 years (OR = 5.1; 95% CI = 1.33-19.37); non-Saudi participants (OR = 1.69; 95% CI = 1.06-2.57); individuals with chronic diseases (OR = 2.15; 95% CI = 1.33-3.48); those who lost their job (OR = 2.18; 95% CI = 1.04-4.57); and those with depression (OR = 5.70; 95% CI = 3.59-9.05), anxiety (OR = 5.47; 95% CI = 3.38-8.84), and stress (OR = 6.55; 95% CI = 4.01-10.70) were more likely to be in the first quartile of the QoL scores. While the full model predicting the total QoL score was statistically significant (R2 = 0.962, F (750, 753) = 16,705.4, p < 0.001), the three QoL dimensions explained 0.643, 0.283, and 0.036 of the variability in environmental, social, and religious/spiritual dimensions, respectively. The COVID-19 pandemic has significantly influenced various aspects of individuals' QoL, as well as their physical and psychological health. Community-based interventions are needed to mitigate the pandemic's negative effects and enhance the health and QoL of the general population.
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Affiliation(s)
- Fahad D. Algahtani
- Department of Public Health, College of Public Health and Health Informatics, University of Ha’il, Ha’il 81451, Saudi Arabia; (F.D.A.); (B.A.); (R.Z.)
- Molecular Diagnostic & Personalized Therapeutic Unit, University of Ha’il, Ha’il 81451, Saudi Arabia
| | - Sehar-un-Nisa Hassan
- Department of Public Health, College of Public Health and Health Informatics, University of Ha’il, Ha’il 81451, Saudi Arabia; (F.D.A.); (B.A.); (R.Z.)
| | - Bandar Alsaif
- Department of Public Health, College of Public Health and Health Informatics, University of Ha’il, Ha’il 81451, Saudi Arabia; (F.D.A.); (B.A.); (R.Z.)
| | - Rafat Zrieq
- Department of Public Health, College of Public Health and Health Informatics, University of Ha’il, Ha’il 81451, Saudi Arabia; (F.D.A.); (B.A.); (R.Z.)
- Molecular Diagnostic & Personalized Therapeutic Unit, University of Ha’il, Ha’il 81451, Saudi Arabia
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32
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Perricone C, Triggianese P, Bursi R, Cafaro G, Bartoloni E, Chimenti MS, Gerli R, Perricone R. Intravenous Immunoglobulins at the Crossroad of Autoimmunity and Viral Infections. Microorganisms 2021; 9:121. [PMID: 33430200 PMCID: PMC7825648 DOI: 10.3390/microorganisms9010121] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 12/24/2020] [Accepted: 01/05/2021] [Indexed: 02/06/2023] Open
Abstract
Intravenous immunoglobulins (IVIG) are blood preparations pooled from the plasma of donors that have been first employed as replacement therapy in immunodeficiency. IVIG interact at multiple levels with the different components of the immune system and exert their activity against infections. Passive immunotherapy includes convalescent plasma from subjects who have recovered from infection, hyperimmune globulin formulations with a high titer of neutralizing antibodies, and monoclonal antibodies (mAbs). IVIG are used for the prevention and treatment of several infections, especially in immunocompromised patients, or in case of a poorly responsive immune system. The evolution of IVIG from a source of passive immunity to a powerful immunomodulatory/anti-inflammatory agent results in extensive applications in autoimmune diseases. IVIG composition depends on the antibodies of the donor population and the alterations of protein structure due to the processing of plasma. The anti-viral and anti-inflammatory activity of IVIG has led us to think that they may represent a useful therapeutic tool even in COVID-19. The human origin of IVIG carries specific criticalities including risks of blood products, supply, and elevated costs. IVIG can be useful in critically ill patients, as well as early empirical treatment. To date, the need for further well-designed studies stating protocols and the efficacy/tolerability profile of IVIG and convalescent plasma in selected situations are awaited.
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Affiliation(s)
- Carlo Perricone
- Rheumatology, Department of Medicine, University of Perugia, 06129 Perugia, Italy; (C.P.); (R.B.); (G.C.); (E.B.); (R.G.)
| | - Paola Triggianese
- Rheumatology, Allergology and Clinical Immunology, Department of “Medicina dei Sistemi”, University of Rome, 00133 Rome, Italy; (M.S.C.); (R.P.)
| | - Roberto Bursi
- Rheumatology, Department of Medicine, University of Perugia, 06129 Perugia, Italy; (C.P.); (R.B.); (G.C.); (E.B.); (R.G.)
| | - Giacomo Cafaro
- Rheumatology, Department of Medicine, University of Perugia, 06129 Perugia, Italy; (C.P.); (R.B.); (G.C.); (E.B.); (R.G.)
| | - Elena Bartoloni
- Rheumatology, Department of Medicine, University of Perugia, 06129 Perugia, Italy; (C.P.); (R.B.); (G.C.); (E.B.); (R.G.)
| | - Maria Sole Chimenti
- Rheumatology, Allergology and Clinical Immunology, Department of “Medicina dei Sistemi”, University of Rome, 00133 Rome, Italy; (M.S.C.); (R.P.)
| | - Roberto Gerli
- Rheumatology, Department of Medicine, University of Perugia, 06129 Perugia, Italy; (C.P.); (R.B.); (G.C.); (E.B.); (R.G.)
| | - Roberto Perricone
- Rheumatology, Allergology and Clinical Immunology, Department of “Medicina dei Sistemi”, University of Rome, 00133 Rome, Italy; (M.S.C.); (R.P.)
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33
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The role of serum specific- SARS-CoV-2 antibody in COVID-19 patients. Int Immunopharmacol 2020; 91:107325. [PMID: 33401205 PMCID: PMC7759121 DOI: 10.1016/j.intimp.2020.107325] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 12/04/2020] [Accepted: 12/16/2020] [Indexed: 12/11/2022]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), has rapidly spread, resulting in considerable casualties and serious economic loss worldwide. Disease severity and related symptoms markedly vary among individuals. A large number of patients present atypical symptoms, which represent a big challenge for early diagnosis and prompt infection source isolation. Currently, COVID-19 diagnosis predominantly depends on nucleic acid tests (NAT) for SARS-CoV-2 in respiratory specimens, but this method presents a high rate of false negative results. Therefore, serum antibody measurement has been rapidly developed as a supplementary method with the aim of improving diagnostic accuracy. Further, serum antibody levels might help to identify the infection stage, asymptomatic carriers, and patients with diverging severities and to monitor convalescent plasma therapy. In the current review, we aim to present comprehensive evidence to clarify the utility of SARS-CoV-2 antibodies in COVID-19 patients as a reference for use in the clinic.
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34
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Choudhry N, Zhao X, Xu D, Zanin M, Chen W, Yang Z, Chen J. Chinese Therapeutic Strategy for Fighting COVID-19 and Potential Small-Molecule Inhibitors against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). J Med Chem 2020; 63:13205-13227. [PMID: 32845145 PMCID: PMC7489051 DOI: 10.1021/acs.jmedchem.0c00626] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 02/06/2023]
Abstract
The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 20 million people infected worldwide with an average mortality rate of 3.6%. This virus poses major challenges to public health, as it not only is highly contagious but also can be transmitted by asymptomatic infected individuals. COVID-19 is clinically difficult to manage due to a lack of specific antiviral drugs or vaccines. In this article, Chinese therapy strategies for treating COVID-19 patients, including current applications of traditional Chinese medicine (TCM), are comprehensively reviewed. Furthermore, 72 small molecules from natural products and TCM with reported antiviral activity against human coronaviruses (CoVs) are identified from published literature, and their potential applications in combating SARS-CoV-2 are discussed. Among these, the clinical efficacies of some accessible drugs such as remdesivir (RDV) and favipiravir (FPV) for COVID-19 are emphatically summarized. We hope this review provides a foundation for managing the worsening pandemic and developing antivirals against SARS-CoV-2.
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Affiliation(s)
- Namrta Choudhry
- Guangdong Provincial Key Laboratory of
Veterinary Pharmaceutics Development and Safety Evaluation, Guangdong
Laboratory for Lingnan Modern Agriculture, College of Veterinary
Medicine, South China Agricultural
University, Guangzhou 510642,
China
| | - Xin Zhao
- Guangdong Institute of
Analysis (China National Analytical Center,
Guangzhou), Guangzhou 510070,
China
| | - Dan Xu
- Guangdong Provincial Key Laboratory of
Veterinary Pharmaceutics Development and Safety Evaluation, Guangdong
Laboratory for Lingnan Modern Agriculture, College of Veterinary
Medicine, South China Agricultural
University, Guangzhou 510642,
China
| | - Mark Zanin
- State Key Laboratory of Respiratory
Disease, National Clinical Research Center for Respiratory Disease,
Guangzhou Institute of Respiratory Health, First
Affiliated Hospital of Guangzhou Medical
University, Guangzhou 510120,
China
- School of Public Health,
The University of Hong Kong, 7
Sassoon Road, Pokfulam, Hong Kong, SAR, China
| | - Weisan Chen
- Department of Biochemistry and
Genetics, La Trobe Institute for Molecular Science, La
Trobe University, Melbourne, Victoria 3086,
Australia
| | - Zifeng Yang
- State Key Laboratory of Respiratory
Disease, National Clinical Research Center for Respiratory Disease,
Guangzhou Institute of Respiratory Health, First
Affiliated Hospital of Guangzhou Medical
University, Guangzhou 510120,
China
| | - Jianxin Chen
- Guangdong Provincial Key Laboratory of
Veterinary Pharmaceutics Development and Safety Evaluation, Guangdong
Laboratory for Lingnan Modern Agriculture, College of Veterinary
Medicine, South China Agricultural
University, Guangzhou 510642,
China
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35
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Al-Romaima A, Liao Y, Feng J, Qin X, Qin G. Advances in the treatment of novel coronavirus disease (COVID-19) with Western medicine and traditional Chinese medicine: a narrative review. J Thorac Dis 2020; 12:6054-6069. [PMID: 33209439 PMCID: PMC7656369 DOI: 10.21037/jtd-20-1810] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
In December 2019, the coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was discovered. Since its emergence, COVID-19 has been outbreaking rapidly worldwide, where the virus has so far caused the death of hundreds of thousands and infected more than a million, what has been called a pandemic by the World Health Organization (WHO). According to the WHO-Coronavirus disease 2019 Situation Report-142, by June 10, 2020, there are 7,145,539 confirmed cases and 408,025 deaths. There is an urgent need to develop a suitable specific medicine against this novel coronavirus; therefore, scientists and researchers around the world are making great efforts endeavoring to discover an efficient specific medication for COVID-19 treatment. Given the similarity of the novel coronavirus with previous epidemic viruses, namely, the acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), previously tested drugs could potentially work against the novel coronavirus. In this narrative review, we aim to summarize and discuss the effectiveness of current Western medicine and traditional Chinese medicine options for COVID-19 treatment based on the overview of the scientific literature. Some Western medicines including remdesivir, chloroquine, hydroxychloroquine, favipiravir, lopinavir/ritonavir, and arbidol, as well as some traditional Chinese medicine (TCM) such as Qingfei Paidu decoction, Yupingfeng, Lianhua Qingwen, and TCM injections have revealed a relative activity against SARS-CoV-2 in vitro, in observational studies, and in clinical trials. However, further extensive studies and clinical trials including double-blind and randomized clinical trials, with a higher number of patients, are necessary to confirm the activity of these medicines. There are several ongoing trials conducted on the drugs of COVID-19, and the results are urgently needed to make a suitable treatment recommendation.
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Affiliation(s)
| | - Yinan Liao
- School of Pharmaceutical Science, Guangxi Medical University, Nanning, China
| | - Jie Feng
- School of Pharmaceutical Science, Guangxi Medical University, Nanning, China
| | - Xihui Qin
- School of Pharmaceutical Science, Guangxi Medical University, Nanning, China
| | - Guiming Qin
- School of Pharmaceutical Science, Guangxi Medical University, Nanning, China
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Mann R, Perisetti A, Gajendran M, Gandhi Z, Umapathy C, Goyal H. Clinical Characteristics, Diagnosis, and Treatment of Major Coronavirus Outbreaks. Front Med (Lausanne) 2020; 7:581521. [PMID: 33282890 PMCID: PMC7691433 DOI: 10.3389/fmed.2020.581521] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 10/12/2020] [Indexed: 12/15/2022] Open
Abstract
Human coronavirus infections have been known to cause mild respiratory illness. It changed in the last two decades as three global outbreaks by coronaviruses led to significant mortality and morbidity. SARS CoV-1 led to the first epidemic of the twenty first century due to coronavirus. SARS COV-1 infection had a broad array of symptoms with respiratory and gastrointestinal as most frequent. The last known case was reported in 2004. Middle East respiratory syndrome coronavirus (MERS-CoV) led to the second outbreak in 2012, and case fatality was much higher than SARS. MERS-CoV has a wide array of clinical presentations from mild, moderate to severe, and some patients end up with acute respiratory distress syndrome (ARDS). The third and recent outbreak by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started in December 2019, which lead to a global pandemic. Patients with SARS-CoV2 infection can be asymptomatic or have a range of symptoms with fever, cough, and shortness of breath being most common. Reverse transcriptase-Polymerase chain reaction (RT-PCR) is a diagnostic test of choice for SARS CoV-1, MERS-CoV, and SARS CoV-2 infections. This review aims to discuss epidemiological, clinical features, diagnosis, and management of human coronaviruses with a focus on SARS CoV-1, MERS-CoV, and SARS CoV-2.
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Affiliation(s)
- Rupinder Mann
- Department of Internal Medicine, Saint Agnes Medical Center, Fresno, CA, United States
| | - Abhilash Perisetti
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Mahesh Gajendran
- Department of Internal Medicine, Paul L Foster School of Medicine, Texas Tech University, El Paso, TX, United States
| | - Zainab Gandhi
- Department of Medicine, Geisinger Community Medicine Center, Scranton, PA, United States
| | - Chandraprakash Umapathy
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
| | - Hemant Goyal
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Wright Center of Graduate Medical Education, Scranton, PA, United States
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Thijssen M, Devos T, Ejtahed HS, Amini-Bavil-Olyaee S, Pourfathollah AA, Pourkarim MR. Convalescent Plasma against COVID-19: A Broad-Spectrum Therapeutic Approach for Emerging Infectious Diseases. Microorganisms 2020; 8:E1733. [PMID: 33167389 PMCID: PMC7694357 DOI: 10.3390/microorganisms8111733] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 10/30/2020] [Accepted: 10/30/2020] [Indexed: 12/12/2022] Open
Abstract
In the lack of an effective vaccine and antiviral treatment, convalescent plasma (CP) has been a promising therapeutic approach in past pandemics. Accumulating evidence in the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic corroborates the safety of CP therapy and preliminary data underline the potential efficacy. Recently, the Food and Drug Administration (FDA) permitted CP therapy for coronavirus disease 2019 (COVID-19) patients under the emergency use authorization, albeit additional clinical studies are still needed. The imminent threat of a second or even multiple waves of COVID-19 has compelled health authorities to delineate and calibrate a feasible preparedness algorithm for deploying CP as an immediate therapeutic intervention. The success of preparedness programs depends on the interdisciplinary actions of multiple actors in politics, science, and healthcare. In this review, we evaluate the current status of CP therapy for COVID-19 patients and address the challenges that confront the implementation of CP. Finally, we propose a pandemic preparedness framework for future waves of the COVID-19 pandemic and unknown pathogen outbreaks.
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Affiliation(s)
- Marijn Thijssen
- Laboratory for Clinical and Epidemiological Virology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium;
| | - Timothy Devos
- Department of Haematology, University Hospitals Leuven, 3000 Leuven, Belgium;
| | - Hanieh-Sadat Ejtahed
- Obesity and Eating Habits Research Centre, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran 1411413137, Iran;
- Endocrinology and Metabolism Research Centre, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran 1411413137, Iran
| | - Samad Amini-Bavil-Olyaee
- Biosafety Development Group, Cellular Sciences Department, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA;
| | - Ali Akbar Pourfathollah
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-111, Tehran 14117-13116, Iran;
| | - Mahmoud Reza Pourkarim
- Laboratory for Clinical and Epidemiological Virology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, 3000 Leuven, Belgium;
- Health Policy Research Centre, Institute of Health, Shiraz University of Medical Sciences, P.O. Box 71348-45794, Shiraz 71348-54794, Iran
- Blood Transfusion Research Centre, High Institute for Research and Education in Transfusion Medicine, Tehran 14665-1157, Iran
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Singh A, Kumar M, Dubey AK. Effect of pre-existing diseases on COVID-19 infection and role of new sensors and biomaterials for its detection and treatment. MEDICAL DEVICES & SENSORS 2020; 4:e10140. [PMID: 33173852 PMCID: PMC7645882 DOI: 10.1002/mds3.10140] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The entire world is suffering from a new type of viral disease, occurred by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The present article briefly discussed the genome sequencing and interaction of host cells with SARS-CoV-2. The influence of pre-existing diseases such as diabetes, heart disease and age of the patients on COVID-19 infection is reviewed. The possible treatments of SARS-CoV-2 including antiviral drugs, Chinese traditional treatment and plasma therapy are elaborately discussed. The proper vaccine for COVID-19 is not available till date. However, the trials of pre-existing antiviral vaccines such as, chloroquine/hydroxychloroquine, remdesivir, ritonavir and lopinavir and their consequences are briefly presented. Further, the importance of new materials and devices for the detection and treatment of COVID-19 has also been reviewed. The polymerase chain reaction (PCR)-based, and non-PCR based devices are used for the detection of COVID-19 infection. The non-PCR based devices provide rapid results as compared to PCR based devices.
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Affiliation(s)
- Angaraj Singh
- Department of Ceramic EngineeringIndian Institute of Technology (BHU)Varanasi221005India
| | - Manoj Kumar
- Nano 2 Micro System Design Lab, Department of Chemical Engineering and Technology Indian Institute of Technology (BHU)Varanasi221005India
- School of Biomedical EngineeringIndian Institute of Technology (BHU)Varanasi221005India
| | - Ashutosh Kumar Dubey
- Department of Ceramic EngineeringIndian Institute of Technology (BHU)Varanasi221005India
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Rao X, Wu C, Wang S, Tong S, Wang G, Wu G, Zhou R. The importance of overweight in COVID-19: A retrospective analysis in a single center of Wuhan, China. Medicine (Baltimore) 2020; 99:e22766. [PMID: 33120785 PMCID: PMC7581045 DOI: 10.1097/md.0000000000022766] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 08/15/2020] [Accepted: 09/14/2020] [Indexed: 01/01/2023] Open
Abstract
The aim of this study was to evaluate the association between overweight and severity, drug response, and clinical outcomes of novel coronavirus disease 2019 (COVID-19).In this retrospective cohort study, we reviewed medical records of 240 COVID-19 patients admitted to Union Hospital in Wuhan, China, between December 24, 2019, and March 25, 2020. Physical, clinical, laboratory, radiological characteristics, treatment, and outcome data were abstracted. Patients who were obese [body mass index (BMI) ≥28 kg/m], underweight (BMI < 18.5 kg/m), under 18 years old, pregnant, or still in hospital were excluded. Disease severity was classified as moderate or severe pneumonia based on the World Health Organization interim guidance. Overweight was defined as BMI ≥24 kg/m and <28 kg/m. Patients were followed for discharge or death through April 10, 2020. We used logistic regression models to identify risk factors for severe disease, Cox proportional hazard models to explore associations between medications and patient outcomes (discharge or in-hospital death), and Kaplan-Meier survival curves and Cox regression models to evaluate risk factors for in-hospital death.One-half of patients (120, 50.0%) had severe pneumonia, while nearly one-half (114, 47.5%) were overweight. Among patients over 45 years old, overweight patients had significantly lower rates of fatigue, higher rates of headache, and higher median C-reactive protein levels. Patients under 45 years old had higher rates of cough and myalgia and higher proportions of increased alanine aminotransferase and lactic dehydrogenase, as well as more pulmonary lobes involved in the pneumonia revealed by chest computed tomography scans. Overweight patients were at higher risk of developing severe pneumonia. Although weight was not a risk factor for in-hospital death, overweight patients showed different responses to medications compared with normal weight patients. Intravenous interferon-α, intravenous glucocorticoids, and antifungal drugs were associated with reduced mortality in overweight patients. Intravenous immunoglobulin, oseltamivir, and ribavirin were associated with reduced mortality in normal weight patients.Overweight is a worldwide health problem. We found overweight to be related to the COVID-19 severity but not to in-hospital death. Clinicians should be aware that overweight COVID-19 patients require increased attention for different clinical features and treatment response.
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Affiliation(s)
| | | | | | | | - Geng Wang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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40
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Shao Z, Feng Y, Zhong L, Xie Q, Lei M, Liu Z, Wang C, Ji J, Liu H, Gu Z, Hu Z, Su L, Wu M, Liu Z. Clinical efficacy of intravenous immunoglobulin therapy in critical ill patients with COVID-19: a multicenter retrospective cohort study. Clin Transl Immunology 2020; 9:e1192. [PMID: 33082954 PMCID: PMC7557105 DOI: 10.1002/cti2.1192] [Citation(s) in RCA: 89] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 09/09/2020] [Accepted: 09/13/2020] [Indexed: 01/30/2023] Open
Abstract
Objective Coronavirus disease 2019 (COVID‐19) outbreak is a major challenge all over the world, without acknowledged treatment. Intravenous immunoglobulin (IVIG) has been recommended to treat critical coronavirus disease 2019 (COVID‐19) patients in a few reviews, but the clinical study evidence on its efficacy in COVID‐19 patients was lacking. Methods 325 patients with laboratory‐confirmed critical COVID‐19 were enrolled from 4 government‐designated COVID‐19 treatment centres in southern China from December 2019 to March 2020. The primary outcomes were 28‐ and 60‐day mortality, and the secondary outcomes were the total length of in‐hospital and the total duration of the disease. Subgroup analysis was carried out according to clinical classification of COVID‐19, IVIG dosage and timing. Results In the enrolled 325 patients, 174 cases used IVIG and 151 cases did not. The 28‐day mortality was improved with IVIG after adjusting confounding in overall cohort (P = 0.0014), and the in‐hospital and the total duration of disease were longer in the IVIG group (P < 0.001). Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28‐day mortality, decrease the inflammatory response and improve some organ functions (all P < 0.05); the application of IVIG in the early stage (admission ≤ 7 days) with a high dose (> 15 g per day) exhibited significant reduction in 60‐day mortality in the critical‐type patients. Conclusion Early administration of IVIG with high dose improves the prognosis of critical‐type patients with COVID‐19. This study provides important information on clinical application of IVIG in the treatment of SARS‐CoV‐2 infection, including patient selection and administration dosage and timing.
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Affiliation(s)
- Ziyun Shao
- Department of Nephrology General Hospital of Central Theater Command of PLA Wuhan 430070 China
| | - Yongwen Feng
- Department of Critical Care Medicine and Hospital Infection Prevention and Control The Second People's Hospital of Shenzhen & First Affiliated Hospital of Shenzhen University Health Science Center Shenzhen 518035 China.,Department of Critical Care Medicine The Third People's Hospital of Shenzhen Shenzhen 518035 China
| | - Li Zhong
- Department of Critical Care Medicine The First Affiliated Hospital Guizhou University of Chinese Medicine Guiyang 550001 China
| | - Qifeng Xie
- Department of Critical Care Medicine General Hospital of Southern Theater Command of PLA Guangzhou 510010 China
| | - Ming Lei
- Department of Nephrology Guangzhou Eighth people's hospital Guangzhou Medical University Guangzhou 510060 China
| | - Zheying Liu
- Department of Critical Care Medicine General Hospital of Southern Theater Command of PLA Guangzhou 510010 China
| | - Conglin Wang
- Department of Critical Care Medicine General Hospital of Southern Theater Command of PLA Guangzhou 510010 China
| | - Jingjing Ji
- Department of Critical Care Medicine General Hospital of Southern Theater Command of PLA Guangzhou 510010 China
| | - Huiheng Liu
- Department of Emergency Zhongshan Hospital of Xiamen University Xiamen 361000 China
| | - Zhengtao Gu
- Department of Treatment Center for Traumatic Injuries The Third Affiliated Hospital Academy of Orthopedics Guangdong Province Southern Medical University Guangzhou Guangdong 515630 China
| | - Zhongwei Hu
- Department of Nephrology Guangzhou Eighth people's hospital Guangzhou Medical University Guangzhou 510060 China
| | - Lei Su
- Department of Critical Care Medicine General Hospital of Southern Theater Command of PLA Guangzhou 510010 China
| | - Ming Wu
- Department of Critical Care Medicine and Hospital Infection Prevention and Control The Second People's Hospital of Shenzhen & First Affiliated Hospital of Shenzhen University Health Science Center Shenzhen 518035 China.,Department of Critical Care Medicine General Hospital of Southern Theater Command of PLA Guangzhou 510010 China
| | - Zhifeng Liu
- Department of Critical Care Medicine General Hospital of Southern Theater Command of PLA Guangzhou 510010 China.,Key Laboratory of Hot Zone Trauma Care and Tissue Repair of PLA General Hospital of Southern Theater Command of PLA Guangzhou 510010 China
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Kumar R, Srivastava JK, Singh R, Siddiqui MH, Mansouri RA, Abdulhakim JA, Bin-Jumah MN, Alkahtani S, Abdel-Daim MM, Uddin MS. Available Compounds With Therapeutic Potential Against COVID-19: Antimicrobial Therapies, Supportive Care, and Probable Vaccines. Front Pharmacol 2020; 11:582025. [PMID: 33123014 PMCID: PMC7573470 DOI: 10.3389/fphar.2020.582025] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 09/15/2020] [Indexed: 12/15/2022] Open
Abstract
The recent outbreak of the COVID-2019 (coronavirus disease 2019) due to the infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has realized the requirement of alternative therapeutics to mitigate and alleviate this lethal infection. These alternative therapies are effective when they are started at the initial stage of the infection. Some drugs that were used in previous other related infections SARS-CoV-2003 and Middle East respiratory syndrome coronavirus (MERS-CoV)-2012 could be potentially active against currently emerging SARS-CoV-2. This fact imparts some rationale of current interventions, in the absence of any specific therapeutics for SARS-CoV-2. It is imperative to focus on the available antimicrobial and adjunct therapies during the current emergency state and overcome the challenges associated with the absence of robust controlled studies. There is no established set of drugs to manage SARS-CoV-2 infected patients. However, closely following patients’ conditions and responding with the dosage guidelines of available drugs may significantly impact our ability to slow down the infection. Of note, it depends upon the condition of the patients and associated comorbid; therefore, the health workers need to choose the drug combinations judiciously until COVID-19 specific drug or vaccine is developed with the collective scientific rigor. In this article, we reviewed the available antimicrobial drug, supportive therapies, and probable high importance vaccines for the COVID-19 treatment.
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Affiliation(s)
- Rajnish Kumar
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow, India
| | | | - Rachana Singh
- Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow, India
| | | | - Rasha A Mansouri
- Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Jawaher A Abdulhakim
- Department of Medical Laboratory, Faculty of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia
| | - May N Bin-Jumah
- Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Saad Alkahtani
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Mohamed M Abdel-Daim
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.,Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt
| | - Md Sahab Uddin
- Department of Pharmacy, Southeast University, Dhaka, Bangladesh.,Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
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Mansourabadi AH, Sadeghalvad M, Mohammadi-Motlagh HR, Rezaei N. The immune system as a target for therapy of SARS-CoV-2: A systematic review of the current immunotherapies for COVID-19. Life Sci 2020; 258:118185. [PMID: 32750438 PMCID: PMC7395832 DOI: 10.1016/j.lfs.2020.118185] [Citation(s) in RCA: 63] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 07/21/2020] [Accepted: 07/28/2020] [Indexed: 12/21/2022]
Abstract
AIMS The immune response is essential for the control and resolution of viral infections. Following the outbreak of novel coronavirus disease (COVID-19), several immunotherapies were applied to modulate the immune responses of the affected patients. In this review, we aimed to describe the role of the immune system in response to COVID-19. We also provide a systematic review to collate and describe all published reports of the using immunotherapies, including convalescent plasma therapy, monoclonal antibodies, cytokine therapy, mesenchymal stem cell therapy, and intravenous immunoglobulin and their important outcomes in COVID-19 patients. MATERIAL AND METHODS A thorough search strategy was applied to identify published research trials in PubMed, Scopus, Medline, and EMBASE from Dec 1, 2019, to May 4, 2020, for studies reporting clinical outcomes of COVID-19 patients treated with immunotherapies along with other standard cares. KEY FINDINGS From an initial screen of 80 identified studies, 24 studies provided clinical outcome data on the use of immunotherapies for the treatment of COVID-19 patients, including convalescent plasma therapy (33 patients), monoclonal antibodies (55 patients), interferon (31 patients), mesenchymal stem cell therapy (8 patient), and immunoglobulin (63 patients). Except for nine severe patients who died after treatment, most patients were recovered from COVID-19 with improved clinical symptoms and laboratory assessment. SIGNIFICANCE Based on the available evidence, it seems that treatment with immunotherapy along with other standard cares could be an effective and safe approach to modulate the immune system and improvement of clinical outcomes.
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Affiliation(s)
- Amir Hossein Mansourabadi
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mona Sadeghalvad
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Hamid-Reza Mohammadi-Motlagh
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Nima Rezaei
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
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Abhinand CS, Nair AS, Krishnamurthy A, Oommen OV, Sudhakaran PR. Potential protease inhibitors and their combinations to block SARS-CoV-2. J Biomol Struct Dyn 2020; 40:903-917. [PMID: 32924827 PMCID: PMC7544937 DOI: 10.1080/07391102.2020.1819881] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
COVID-19, which has emerged recently as a pandemic viral infection caused by SARS-coronavirus 2 has spread rapidly around the world, creating a public health emergency. The current situation demands an effective therapeutic strategy to control the disease using drugs that are approved, or by inventing new ones. The present study examines the possible repurposing of existing anti-viral protease inhibitor drugs. For this, the structural features of the viral spike protein, the substrate for host cell protease and main protease of the available SARS CoV-2 isolates were established by comparing with related viruses for which antiviral drugs are effective. The results showed 97% sequence similarity among SARS and SARS-CoV-2 main protease and has same cleavage site positions and ACE2 receptor binding region as in the SARS–CoV spike protein. Though both are N-glycosylated, unlike SARS-CoV, human SARS-CoV-2 S-protein was O-glycosylated as well. Molecular docking studies were done to explore the role of FDA approved protease inhibitors to control SARS-CoV-2 replication. The results indicated that, Ritonavir has the highest potency to block SARS-CoV-2 main protease and human TMPRSS2, a host cell factor that aids viral infection. Other drugs such as Indinavir and Atazanavir also showed favourable binding with Cathepsin B/L that helped viral fusion with the host cell membrane. Further molecular dynamics simulation and MM-PBSA binding free energy calculations confirmed the stability of protein-drug complexes. These results suggest that protease inhibitors particularly Ritonavir, either alone or in combination with other drugs such as Atazanavir, have the potential to treat COVID 19. Communicated by Ramaswamy H. Sarma
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Affiliation(s)
- Chandran S Abhinand
- Department of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, Kerala, India
| | - Achuthsankar S Nair
- Department of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, Kerala, India
| | | | - Oommen V Oommen
- Department of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, Kerala, India
| | - Perumana R Sudhakaran
- Department of Computational Biology and Bioinformatics, University of Kerala, Thiruvananthapuram, Kerala, India
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Kumar M, Taki K, Gahlot R, Sharma A, Dhangar K. A chronicle of SARS-CoV-2: Part-I - Epidemiology, diagnosis, prognosis, transmission and treatment. THE SCIENCE OF THE TOTAL ENVIRONMENT 2020; 734:139278. [PMID: 32434058 PMCID: PMC7227583 DOI: 10.1016/j.scitotenv.2020.139278] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 05/02/2020] [Accepted: 05/06/2020] [Indexed: 04/13/2023]
Abstract
In order to benefit the public, community workers and scientific community, we hereby present a chronicle of SARS-CoV-2 that leads to the unseen precedent of social distancing and lockdown owing to coronavirus disease (COVID-19). Information on this life-threatening pandemic of COVID-19 is sparse and discrete; and the urgency is such that the dissemination of information is increasing with numerous daily publications on the topic. Therefore, we developed a comprehensive review on various aspects of SARS-CoV-2 and COVID-19. We scientifically compiled published research, news, and reports from various sources to comprehend and summarize the information and findings on Coronaviruses. The review explicitly covers the aspects like genome and pedigree of SARS-CoV-2; epidemiology, prognosis, pathogenesis, symptoms and diagnosis of COVID-19 in order to catalog the right information on transmission route, and influence of environmental factors on virus transmissions, for the robust understanding of right strategical steps for proper COVID-19 management. We have explicitly highlighted several useful information and facts like: i) No established relationship between progression of SARS-CoV-2 with temperature, humidity and/or both, ii) The underlying mechanism of SARS-CoV-2 is not fully understood, iii) Respiratory droplet size determines drop and airborne-based transmission, iv) Prognosis of COVID-19 can be done by its effects on various body organs, v) Infection can be stopped by restricting the binding of S protein and AE2, vi) Hydroxychloroquine is believed to be better than chloroquine for COVID-19, vii) Ivermectin with Vero-hSLAM cells is able to reduce infection by ~5000 time within 2 days, and viii) Nafamostat mesylate can inhibit SARS-CoV-2 S protein-initiated membrane fusion. We have also suggested future research perspectives, challenges and scope.
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Affiliation(s)
- Manish Kumar
- Discipline of Earth Sciences, Indian Institute of Technology Gandhinagar, Gujarat 382355, India.
| | - Kaling Taki
- Discipline of Civil Engineering, Indian Institute of Technology Gandhinagar, Gujarat 382355, India
| | - Rohit Gahlot
- Discipline of Materials Science and Engineering, Indian Institute of Technology Gandhinagar, Gujarat 382355, India
| | - Ayushi Sharma
- Department of Pharmacology, Vallabhbhai Patel Chest Institute (VPCI), Delhi University, Delhi 110007, India
| | - Kiran Dhangar
- Discipline of Earth Sciences, Indian Institute of Technology Gandhinagar, Gujarat 382355, India
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Kumar M, Taki K, Gahlot R, Sharma A, Dhangar K. A chronicle of SARS-CoV-2: Part-I - Epidemiology, diagnosis, prognosis, transmission and treatment. THE SCIENCE OF THE TOTAL ENVIRONMENT 2020; 734:139278. [PMID: 32434058 DOI: 10.1016/j.scitotenv.2020.139278139278] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 05/02/2020] [Accepted: 05/06/2020] [Indexed: 05/21/2023]
Abstract
In order to benefit the public, community workers and scientific community, we hereby present a chronicle of SARS-CoV-2 that leads to the unseen precedent of social distancing and lockdown owing to coronavirus disease (COVID-19). Information on this life-threatening pandemic of COVID-19 is sparse and discrete; and the urgency is such that the dissemination of information is increasing with numerous daily publications on the topic. Therefore, we developed a comprehensive review on various aspects of SARS-CoV-2 and COVID-19. We scientifically compiled published research, news, and reports from various sources to comprehend and summarize the information and findings on Coronaviruses. The review explicitly covers the aspects like genome and pedigree of SARS-CoV-2; epidemiology, prognosis, pathogenesis, symptoms and diagnosis of COVID-19 in order to catalog the right information on transmission route, and influence of environmental factors on virus transmissions, for the robust understanding of right strategical steps for proper COVID-19 management. We have explicitly highlighted several useful information and facts like: i) No established relationship between progression of SARS-CoV-2 with temperature, humidity and/or both, ii) The underlying mechanism of SARS-CoV-2 is not fully understood, iii) Respiratory droplet size determines drop and airborne-based transmission, iv) Prognosis of COVID-19 can be done by its effects on various body organs, v) Infection can be stopped by restricting the binding of S protein and AE2, vi) Hydroxychloroquine is believed to be better than chloroquine for COVID-19, vii) Ivermectin with Vero-hSLAM cells is able to reduce infection by ~5000 time within 2 days, and viii) Nafamostat mesylate can inhibit SARS-CoV-2 S protein-initiated membrane fusion. We have also suggested future research perspectives, challenges and scope.
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Affiliation(s)
- Manish Kumar
- Discipline of Earth Sciences, Indian Institute of Technology Gandhinagar, Gujarat 382355, India.
| | - Kaling Taki
- Discipline of Civil Engineering, Indian Institute of Technology Gandhinagar, Gujarat 382355, India
| | - Rohit Gahlot
- Discipline of Materials Science and Engineering, Indian Institute of Technology Gandhinagar, Gujarat 382355, India
| | - Ayushi Sharma
- Department of Pharmacology, Vallabhbhai Patel Chest Institute (VPCI), Delhi University, Delhi 110007, India
| | - Kiran Dhangar
- Discipline of Earth Sciences, Indian Institute of Technology Gandhinagar, Gujarat 382355, India
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46
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Tripathi S, Tripathi MM. The COVID-19: Current understanding. Vet World 2020; 13:1998-2005. [PMID: 33132617 PMCID: PMC7566253 DOI: 10.14202/vetworld.2020.1998-2005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 09/07/2020] [Indexed: 12/15/2022] Open
Abstract
In December 2019, China reported several cases of a new coronavirus disease (COVID-19). The COVID-19 outbreak, which was initially limited to Wuhan, China, has rapidly spread worldwide. Infection of the disease occurs through exposure to the virus through inhalation of respiratory droplets or if a person touches a mucosal surface after touching an object with the virus on it. The common symptoms of COVID-19 are fever, dry cough, dyspnea (difficult or labored breathing), fatigue, chest pain, and myalgia (muscle pain), etc. Real-time polymerase chain reaction is used to detect the virus in sputum, throat, nasal swabs, and secretion of lower respiratory samples. Early diagnosis, isolation, and supportive care are necessary for the treatment of the patients. The present review aims to provide recent information on COVID-19 related to its epidemiology, clinical symptoms, and management. This article also summarizes the current understanding of severe acute respiratory syndrome coronavirus-2 and its history of origin.
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Affiliation(s)
- Shweta Tripathi
- Department of Home Science, Government PMRS College, Pendra road, Gaurela, Pendra, Marwahi, Chhattisgarh, India
| | - Mayukh Mani Tripathi
- Department of Medical and Health, Community Health Center, Chopan, Sonbhadra, Uttar Pradesh, India
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47
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Ishay Y, Kessler A, Schwarts A, Ilan Y. Antibody response to SARS-Co-V-2, diagnostic and therapeutic implications. Hepatol Commun 2020; 4:1731-1743. [PMID: 32904861 PMCID: PMC7461510 DOI: 10.1002/hep4.1600] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 07/30/2020] [Accepted: 08/17/2020] [Indexed: 12/16/2022] Open
Abstract
The immune response against SARS-CoV-2 is comprised of both cellular and humoral arms. While current diagnostic methods are mainly based on PCR, they suffer from insensitivity. Therefore, antibody-based serological tests are being developed to achieve higher sensitivity and specificity. Current efforts in treating SARS-CoV-2 infection include blocking of viral entry into the host cells, prohibiting viral replication and survival in the host cells, or reducing the exaggerated host immune response. Administration of convalescent plasma containing anti-viral antibodies was proposed to improve the outcome in severe cases. In this paper, we review some of the aspects associated with the development of antibodies against SARS-CoV-2 and their potential use for improved diagnosis and therapy.
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Affiliation(s)
- Yuval Ishay
- Department of Medicine Hebrew University-Hadassah Medical Center Jerusalem Israel
| | - Asa Kessler
- Department of Medicine Hebrew University-Hadassah Medical Center Jerusalem Israel
| | - Asaf Schwarts
- Department of Medicine Hebrew University-Hadassah Medical Center Jerusalem Israel
| | - Yaron Ilan
- Department of Medicine Hebrew University-Hadassah Medical Center Jerusalem Israel
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48
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Yang X, Liu Y, Liu Y, Yang Q, Wu X, Huang X, Liu H, Cai W, Ma G. Medication therapy strategies for the coronavirus disease 2019 (COVID-19): recent progress and challenges. Expert Rev Clin Pharmacol 2020; 13:957-975. [PMID: 32746653 DOI: 10.1080/17512433.2020.1805315] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
INTRODUCTION The coronavirus disease 2019 (COVID-19) pandemic has spread globally since it outbroke in December 2019. The urgent pandemic presents an unprecedented challenge to develop and identify effective medication therapy strategies to combat the COVID-19. AREAS COVERED Here, we summarized and evaluated the current treatment drugs and regimens, and put forward the treatment recommendations, including using the potential repurposed or experimental drugs against COVID-19, e.g. chloroquine (CQ), hydroxychloroquine (HCQ), lopinavir/ritonavir (LPV/r), remdesivir (RDV), and favipiravir (FPV). We also analyzed the specific drugs and vaccines against SARS-CoV-2 ongoing development and formulated the comprehensive treatment regimens based on condition of patients, diseases and drugs as well as concomitant medications. EXPERT OPINION No drugs and vaccines have been proven to be particularly effective against SARS-CoV-2 up to now. The recommended comprehensive medication therapy strategies have already displayed favorable effect in the fight against COVID-19. Research should be focused on the development of anti-SARS-CoV-2 drugs and vaccines based on high-quality clinical trial evidence, treatment guidelines and expert consensus.
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Affiliation(s)
- Xiaolei Yang
- School of Pharmacy, Fudan University , Shanghai, P.R. China.,Minhang Hospital, Fudan University , Shanghai, P.R. China
| | - Ye Liu
- School of Pharmacy, Fudan University , Shanghai, P.R. China.,Minhang Hospital, Fudan University , Shanghai, P.R. China
| | - Yuping Liu
- School of Pharmacy, Fudan University , Shanghai, P.R. China
| | - Qing Yang
- School of Pharmacy, Fudan University , Shanghai, P.R. China
| | - Xubo Wu
- Minhang Hospital, Fudan University , Shanghai, P.R. China
| | - Xuan Huang
- School of Pharmacy, Fudan University , Shanghai, P.R. China
| | - Huijia Liu
- School of Pharmacy, Fudan University , Shanghai, P.R. China
| | - Weimin Cai
- School of Pharmacy, Fudan University , Shanghai, P.R. China
| | - Guo Ma
- School of Pharmacy, Fudan University , Shanghai, P.R. China
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49
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Körper S, Jahrsdörfer B, Appl T, Klüter H, Seifried E, Schrezenmeier H. Rekonvaleszentenplasma zur Behandlung von schwerem COVID-19: Rationale und Design einer randomisierten, offenen klinischen Studie von Rekonvaleszentenplasma verglichen mit bestmöglicher supportiver Behandlung (CAPSID-Studie). TRANSFUSIONSMEDIZIN 2020. [PMCID: PMC7645839 DOI: 10.1055/a-1090-0408] [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] [Indexed: 11/21/2022]
Abstract
Rekonvaleszentenplasma wurde bei Patienten mit akuten, viralen respiratorischen Erkrankungen mit schwerem Verlauf eingesetzt (SARS- oder MERS-Coronavirus, Influenza H1N1, H5N1). Diese Studien erbrachten Hinweise auf eine Reduktion der Viruslast, einer Verkürzung des Krankenhausaufenthalts und eine Reduktion der Mortalität durch Rekonvaleszentenplasma. Die Wirkung konnte jedoch nicht abschließend belegt werden, da es sich nicht um randomisierte Studien handelte. Nach einer SARS-CoV-2-Infektion kommt es bei den meisten Patienten zu einer raschen Bildung von neutralisierenden Antikörpern. Wegen der pandemischen Entwicklung gibt es eine wachsende Zahl Genesener mit neutralisierenden Antikörpern, die als potenzielle Spender in Betracht kommen. Wir konzipierten eine prospektive, randomisierte Studie, um die Wirksamkeit und Sicherheit von Rekonvaleszentenplasma zur Therapie von schwerem COVID-19 und dessen Wirkmechanismus zu untersuchen (CAPSID-Studie). In diesem Beitrag werden
die Rationale und das Design der Studie vorgestellt.
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Affiliation(s)
- Sixten Körper
- Institut für Klinische Transfusionsmedizin und Immungenetik, Ulm
| | | | - Thomas Appl
- Institut für Klinische Transfusionsmedizin und Immungenetik, Ulm
| | - Harald Klüter
- Institut für Transfusionsmedizin und Immunologie, Mannheim
| | - Erhard Seifried
- Institut für Transfusionsmedizin und Immunhämatologie, Frankfurt am Main
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50
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Perotti C, Del Fante C, Baldanti F, Franchini M, Percivalle E, Vecchio Nepita E, Seminari E, De Silvestri A, Bruno R, Klersy C. Plasma from donors recovered from the new Coronavirus 2019 as therapy for critical patients with COVID-19 (COVID-19 plasma study): a multicentre study protocol. Intern Emerg Med 2020; 15:819-824. [PMID: 32468508 PMCID: PMC8849045 DOI: 10.1007/s11739-020-02384-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 05/18/2020] [Indexed: 01/09/2023]
Abstract
Since the end of 2019, a new coronavirus strain has been reported in the Chinese province of Wuhan, indicated as 2019-nCoV or SARS-CoV-2. In February 2020, the first case of transmission on Italian soil was reported. On March 09, 2020, at the time of protocol design, the Italian Ministry of Health reported 10,149 people who had contracted the virus; of these, 8514 were positive, of which 5038 were hospitalized with symptoms (59.2%) and 877 in intensive care (10.3%), while the remaining 2599 were in home isolation; 631 were deceased (6.2%) and 1004 healed (9.9%). To date there are no studies in the literature that demonstrate its feasibility and efficacy in the context of the worldwide SARS-CoV-2 epidemic. Based upon the little existing evidence, we planned to assess the efficacy of the infusion of hyperimmune plasma in COVID-19 patients in a one-arm proof-of-concept clinical trial. The primary objective of our study is to evaluate the efficacy of the administration of plasma taken from convalescent donors of COVID-19 to critically ill patients with COVID-19 in terms of their survival. Death from any cause will be considered. The main limit of this study is its one-arm proof-of-concept design with only 43 patients enrolled. However, in the absence of previous evidence, larger and/or randomized trials did not appear to be ethically acceptable. Moreover, the results from this study, if encouraging, will allow us to plan further informed large clinical trials. Trial registration: NCT04321421 March 23, 2020.
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Affiliation(s)
- Cesare Perotti
- Immunohematology and Transfusion Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Claudia Del Fante
- Immunohematology and Transfusion Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
| | - Fausto Baldanti
- Molecular Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
- Department of Clinical-SurgicalDiagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Massimo Franchini
- Immunohematology and Transfusion Service, Carlo Poma Hospital, Mantova, Italy
| | - Elena Percivalle
- Molecular Virology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Elena Seminari
- Department of Clinical-SurgicalDiagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
| | - Annalisa De Silvestri
- Clinical Epidemiology and Biometry Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Raffele Bruno
- Department of Clinical-SurgicalDiagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
- Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Catherine Klersy
- Clinical Epidemiology and Biometry Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
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