Patients with relapsed or refractory multiple myeloma (R/R-MM) are more susceptible to develop severe coronavirus disease 2019 (COVID-19) for their immunocompromised states. Despite good responses to B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cell therapy, deficiencies in humoral immunity following CAR-T cell infusions can still cause life-threatening complications in these patients. We conducted a comparative study to delineate the clinical characteristics and outcomes between recipients of BCMA-targeted CAR-T cell therapy who contracted COVID-19 vs. unaffected counterparts. Advanced age (odds ratio [OR] = 1.367, 95% confidence interval [CI] = 1.017-1.838, P = 0.038) was a risk factor for developing severe COVID-19, while complete remission (CR) achieved by CAR-T cell therapy (OR = 0.012, 95% CI = 0.000-0.674, P = 0.032) was protective. Male sex (hazard ratio [HR] = 5.274, 95% CI = 1.584-17.562, P = 0.007) and CR achieved by CAR-T cell therapy (HR = 3.107, 95% CI = 1.025-9.418, P = 0.045) were protective factors associated with COVID-19 duration. CR achieved by CAR-T cell therapy (HR = 0.064, 95% CI = 0.007-0.589, P = 0.015) was also a protective factor for OS, while progression disease at the time of COVID-19 diagnosis (HR = 14.206, 95% CI = 1.555-129.819, P = 0.019) was regarded as a risk factor. Thus, older patients with R/R-MM and those who do not achieve CR after CAR-T cell therapy should be most protected from COVID-19 infection by the Omicron variant.

Although, COVID-19 has resulted in over 7 million deaths globally, many questions still remain about the risk factors for disease severity and the effects of variants and vaccinations over the course of the pandemic. To address this gap, we conducted a retrospective analysis of electronic health records from COVID-19 patients over 2.5 years of the COVID-19 pandemic to identify associated clinical features.

We analyze a retrospective cohort of 21,312 acute-care patients over a 2.5 year period and define six clinical trajectory groups (TGs) associated with demographics, diagnoses, vitals, labs, imaging, consultations, and medications.

We show that the proportion of mild patients increased over time, particularly during Omicron waves. Additionally, while mild and fatal patients had differences in age, age did not distinguish patients with severe versus critical disease. Furthermore, we find that both male sex and Hispanic/Latino ethnicity are associated with more severe/critical TGs. More severe patients also have a higher rate of neuropsychiatric diagnoses and consultations, along with an immunological signature of high neutrophils and immature granulocytes, and low lymphocytes and monocytes. Interestingly, low albumin is one of the best lab predictors of COVID-19 severity in association with higher malnutrition in severe/critical patients, raising concern of nutritional insufficiency influencing COVID-19 outcomes. Despite this, only a small fraction of severe/critical patients had nutritional labs checked (e.g. Vitamin D, thiamine, B vitamins) or received vitamin supplementation.

Our findings expand on clinical risk factors in COVID-19, and highlight the interaction between severity, nutritional status, and neuropsychiatric complications in acute care patients to enable identification of patients at risk for severe disease.

Ensitrelvir, a novel oral 3C-like protease inhibitor targeting severe acute respiratory syndrome coronavirus 2, has been available in Japan since November 2022. This report presents patient characteristics and treatment outcomes of patients receiving ensitrelvir with comparison to remdesivir during the same period.

A single-center chart review was conducted at Rinku General Medical Center, one of four designated medical institutions for specific infectious diseases in Japan. All hospitalized patients with coronavirus disease 2019 (COVID-19) between November 2022 and August 2024 who received either ensitrelvir or remdesivir in accordance with the on-label dosage and administration were included in the review. Information on patient background, severity of COVID-19, mortality after initiation of either treatment, post-treatment virologic outcomes, and clinical outcomes were collected from electronic records. Day 28 mortality, time to discharge, and time to viral clearance were calculated with and without adjustment using the inverse probability of treatment weighting (IPTW) method.

During the study period, 156 patients received ensitrelvir and 337 received remdesivir as initial treatments, with average ages of 76.8 and 75.7 years, respectively. For baseline severity, 24.4% of ensitrelvir recipients and 50.7% of remdesivir recipients had moderate to severe COVID-19. All-cause mortality at day 28 was 1.9% for ensitrelvir and 5.9% for remdesivir and the hazard ratio was 0.32 (95% CI 0.09-1.07). All-cause mortality after IPTW adjustment was 3.8% and 5.7%, respectively, and the hazard ratio was 0.66 (95% CI 0.19-2.29). Time to discharge was shorter with ensitrelvir, and viral clearance was similar between groups.

Ensitrelvir demonstrated a low day 28 mortality, even among patients with advanced age, immunosuppressive conditions, and moderate to severe COVID-19. These findings may suggest a potential role for ensitrelvir in the treatment of hospitalized patients with COVID-19.

This study was registered in UMIN Clinical Trials Registry (study ID UMIN000056047).

Objective Thymus and activation-regulated chemokine (TARC) can predict severe disease in patients with coronavirus disease 2019 (COVID-19). However, no reports have addressed the predictive value of TARC with the widespread use of vaccines and medications for COVID-19 during the Omicron variant period of the pandemic. Methods This single-center prospective cohort study enrolled COVID-19 patients admitted to our institution between December 1, 2021, and August 15, 2022. Patients with respiratory failure due to diseases other than COVID-19 were also excluded. We measured the serum TARC levels of patients at admission. Results We enrolled 157 patients, with 89 in the severe group and 68 in the non-severe group. The severe group was more likely than the non-severe group to include older patients, those with no or one dose of vaccine, and those with interstitial lung disease. The cutoff level of TARC derived from a receiver operator characteristic curve analysis to predict severe disease was 174.0 pg/mL. The sensitivity, specificity, positive predictive value, and negative predictive value were 72.1%, 69.7%, 64.5%, and 76.5%, respectively. The area under the curve was 0.722 (95% confidence interval: 0.635-0.809). A multivariate analysis showed that 2 vaccination doses were associated with non-severe disease, and TARC ≤174 pg/mL was associated with severe disease. Conclusion TARC was a predictive factor for severe disease, but its cutoff value was higher and its predictive accuracy lower than those in previous reports. We surmised that during the Omicron variant period of the pandemic, the widespread use of vaccines and medications for COVID-19 decreased the predictive accuracy of TARC.

Participants: The study population included UIC-affiliated gala attendees. Outbreak-associated cases tested positive for COVID-19 between April 2 and April 11, 2022. Attendees who did not test positive or develop symptoms within ten days of the event were classified as contacts.

Methods: We ascertained cases through phone-based contact tracing and a survey and evaluated symptom severity using a novel classification system.

Results: Among 307 UIC students registered to attend the gala, the minimum attack rate was 14.0%. Approximately 56% of cases were mildly symptomatic, and 38.9% reported severe symptoms.

Conclusions: Our findings align with prior research documenting heightened transmissibility of Omicron-variant-related strains and highlight the need for nuanced symptom assessment methodologies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines are effective at protecting from severe disease, but the protective antibodies wane rapidly even though SARS-CoV-2-specific plasma cells can be found in the bone marrow (BM). Here, to explore this paradox, we enrolled 19 healthy adults at 2.5-33 months after receipt of a SARS-CoV-2 mRNA vaccine and measured influenza-, tetanus- or SARS-CoV-2-specific antibody-secreting cells (ASCs) in long-lived plasma cell (LLPC) and non-LLPC subsets within the BM. Only influenza- and tetanus-specific ASCs were readily detected in the LLPCs, whereas SARS-CoV-2 specificities were mostly absent. The ratios of non-LLPC:LLPC for influenza, tetanus and SARS-CoV-2 were 0.61, 0.44 and 29.07, respectively. In five patients with known PCR-proven history of recent infection and vaccination, SARS-CoV-2-specific ASCs were mostly absent from the LLPCs. We show similar results with measurement for secreted antibodies from BM ASC culture supernatant. While serum IgG titers specific for influenza and tetanus correlated with IgG LLPCs, serum IgG levels for SARS-CoV-2, which waned within 3-6 months after vaccination, were associated with IgG non-LLPCs. In all, our studies suggest that rapid waning of SARS-CoV-2-specific serum antibodies could be accounted for by the absence of BM LLPCs after these mRNA vaccines.

The emergence of SARS-CoV-2 variants of concern (VOCs) during the COVID-19 pandemic necessitates investigation into their clinical differentiation and outcomes. This study aimed to examine these differences among VOCs, considering multiple related factors. An observational cohort study was conducted on patients diagnosed with SARS-CoV-2 infection via nasopharyngeal/oropharyngeal swab who visited the emergency department of a public Greek hospital between October 2020 and July 2022 during different VOC circulation in the region. Data on clinical manifestations, outcomes, and medical history (comorbidities, prior SARS-CoV-2 infection, vaccination status against COVID-19) were collected through a questionnaire and medical records for those hospitalized. A total of 913 patients were included in this study (813 adults ≥18 years old, 100 children <18 years old). Significant differences were observed across VOCs for both adults and children. A lower proportion of children developed symptoms during the non-Omicron variants, 73.5%, compared to Omicron variants, 86.4%. Fever, dyspnea, and taste and smell disorders were observed more frequently among non-Omicron adult cases, in contrast to upper respiratory symptoms, which were more common symptoms among Omicron infections. The non-Omicron variants were associated with higher rates of hospitalization at 30.6%, pneumonia at 23.0%, and death at 6.1% compared to Omicron variants at 8.0%, 5.0%, and 1.8%, respectively. Vaccination against COVID-19 was shown to be a protective factor for severe outcomes. Our findings suggest distinct clinical presentations and outcomes associated with different VOCs. Despite the fact that current VOCs circulating are less severe, the COVID-19 vaccine continues to play a protective role for severe cases.

The continued emergence of SARS-CoV-2 variants and the threat of future Sarbecovirus zoonoses have spurred the design of vaccines that can induce broad immunity against multiple coronaviruses. Here, we use computational methods to infer ancestral phylogenetic reconstructions of receptor binding domain (RBD) sequences across multiple Sarbecovirus clades and incorporate them into a multivalent adenoviral-vectored vaccine. Mice immunized with this pan-Sarbecovirus vaccine are protected in the upper and lower respiratory tracts against infection by historical and contemporary SARS-CoV-2 variants, SARS-CoV, and pre-emergent SHC014 and Pangolin/GD coronavirus strains. Using genetic and immunological approaches, we demonstrate that vaccine-induced protection unexpectedly is conferred principally by CD4+ and CD8+ T cell-mediated anamnestic responses. Importantly, prior mRNA vaccination or SARS-CoV-2 respiratory infection does not alter the efficacy of the mucosally delivered pan-Sarbecovirus vaccine. These data highlight the promise of a phylogenetic approach for antigen and vaccine design against existing and pre-emergent Sarbecoviruses with pandemic potential.

Haemodialysis (HD) patients are predisposed to physical ailments, and their occurrence of coronavirus disease 2019 (COVID-19) could potentially lead to a more unfavourable prognosis. However, the impact of SARS-CoV-2 (Omicron variant) infection on the prognosis of HD patients remains unclear. This study aimed to explore the impact of Omicron variant infection on the prognosis of HD patients.

Eligible participants were patients undergoing maintenance HD treatment during a large-scale outbreak of COVID-19 (Omicron variant) in Shanghai, China, from April 7 to May 30, 2022. According to SARS-CoV-2 infection status of participants, the HD patients were divided into two groups: a COVID-19 group and a non-COVID-19 group. The primary outcome assessed was in-hospital mortality, and secondary outcomes encompassed the incidence of severe cases, admission to intensive care, length of hospital stay, and blood indices. Statistical analysis was conducted by comparative analysis and multiple logistic regression.

This study recruited 588 HD patients, including 199 cases in the COVID-19 group and 389 in the non-COVID-19 group. In the COVID-19 group, the mortality rate was 8.45% (17/199), whereas in the non-COVID-19 group, the rate was 3.34% (13/389) (p < 0.05). Compared with the non-COVID-19 group, the COVID-19 group had a risk ratio (RR) with 95% confidence interval (CI) of 2.56 (1.27-5.15) for mortality, and the absolute risk difference (ARD) with 95% CI of 5.20% (1.34%-9.06%). Multiple logistic regression confirmed Omicron variant as a risk factor for mortality among HD patients. Additionally, the COVID-19 group had a higher proportion of severe cases, intensive care admission, hypocalcaemia and hyperphosphatemia and longer hospitalization duration, compared to the non-COVID-19 group (p < 0.05).

Omicron variant infection was associated with increased mortality risk in HD patients, and Omicron infection worsen the prognosis of HD patients. Enhancing immune protection against SARS-CoV-2 is crucial for HD patients during the ongoing COVID-19 pandemic.

Elderly patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we retrospectively described the clinical features and outcomes of the first time infection of Omicron SARS-CoV-2 in 364 elderly patients with lymphoma enrolled in Jiangsu Cooperative Lymphoma Group (JCLG) between November 2022 and April 2023 in China. Median age was 69 years (range 60-92). 54.4% (198/364) of patients were confirmed as severe and critical COVID-19 infection. In univariable analysis, Age > 70 years (OR 1.88, p = 0.003), with multiple comorbidities (OR 1.41, p = 0.005), aggressive lymphoma (OR 2.33, p < 0.001), active disease (progressive or relapsed/refractory, OR 2.02, p < 0.001), and active anti-lymphoma therapy (OR 1.90, p < 0.001) were associated with severe COVID-19. Multiple (three or more) lines of previous anti-lymphoma therapy (OR 3.84, p = 0.021) remained an adverse factor for severe COVID-19 in multivariable analysis. Moreover, CD20 antibody (Rituximab or Obinutuzumab)-based treatments within the last 6 months was associated with severe COVID-19 in the entire cohort (OR 3.42, p < 0.001). Continuous BTK inhibitors might be protective effect on the outcome of COVID-19 infection (OR 0.44, p = 0.043) in the indolent lymphoma cohort. Overall, 7.7% (28/364) of the patients ceased, multiple lines of previous anti-lymphoma therapy (OR 3.46, p = 0.016) remained an adverse factor for mortality.

We aimed to investigate risk factors for COVID-19 pneumonia in patients with hematological malignancies (HM) after Omicron infection.

Data from a registered multi-center, prospective, observational study (ChiCTR2300071830) during the latest Omicron BA.5.2 wave in Chongqing, China was used for analysis.

A total of 475 HM patients enrolled in this study. COVID-19 pneumonia was observed in 15.8% (75/475) of patients, with a median age of 58 years (interquartile range [IQR], 48-69 years) and males accounting for 61.3%. Risk factors associated with COVID-19 pneumonia included: 1) Active disease status of HM at infection, with an odds ratio (OR) of 3.42 (95% confidence interval [CI]: 1.59-7.37, P=0.002) compared to complete remission (CR); 2) Incomplete COVID-19 vaccination, 1-2 doses of the vaccine (OR=2.55, 95% CI: 1.28-5.10, P=0.008) or no vaccination (OR=4.81, 95% CI: 2.45-9.43, P<0.001), as opposed to 3 doses (booster); 3) chemotherapy prior to infection, <6 months (OR=2.58, 95% CI: 1.12-5.96, P=0.027) or ≥ 6 months (OR=2.93, 95% CI: 1.31-6.53, P=0.009) compared to no chemotherapy history; 4) NK-cell reduction (< 150/μL) (OR=2.19, 95% CI: 1.27-3.79, P=0.005) versus a normal range of NK cells. During the 6-week follow-up period, 12 patients (2.5%) died, accounting for 16% of COVID-19 pneumonia patients.

Our study investigated risk factors for COVID-19 pneumonia in HM patients after Omicron BA.5.2 infection. Highlights that HM patients with these risk factors may be susceptible to lung involvement after Omicron BA.5.2 infection and need to be taken seriously in clinical practice.

https://www.chictr.org.cn/bin/project/edit?pid=195998, identifier ChiCTR2300071830.

Research regarding HIV, substance use disorders (SUD), and SARS-CoV-2 infections after COVID-19 vaccination is limited. In the Veterans Aging Cohort Study (VACS)-HIV cohort, we followed vaccinated persons with HIV (PWH) and without HIV (PWoH) from 12/2020 to 3/2022 and linked SARS-CoV-2 test results for laboratory-confirmed breakthrough infection through 9/2022. We examined associations of substance use (alcohol use disorder [AUD], other SUD, smoking status) and HIV status and severity with breakthrough infections, using Cox proportional hazards regression hazard ratios (HR). To test for potential interactions between substance use and HIV, we fit survival models with a multiplicative interaction term. Among 24,253 PWH and 53,661 PWoH, 8.0% of PWH and 7.1% of PWoH experienced COVID-19 breakthrough. AUD (HR 1.42, 95% CI 1.32, 1.52) and other SUD (HR 1.49, 95% CI 1.39, 1.59) were associated with increased risk of breakthrough, and this was similar by HIV status (p-interaction > 0.09). Smoking was not associated with breakthrough. Compared to PWoH, PWH at all HIV severity levels had increased risk of breakthrough ranging from 9% for PWH with CD4 count ≥ 500 cells/µl (HR 1.09, 95% CI 1.02, 1.17) to 59% for PWH with CD4 count < 200 (HR 1.59, 95% CI 1.31, 1.92). Patients with AUD (HR 1.42, 95% CI 1.33, 1.52) and other SUD (HR 1.48, 95% CI 1.38, 1.59) had increased COVID-19 breakthrough risk, regardless of HIV status. HIV was associated with breakthrough; risk was greatest among PWH with lower CD4 count. In addition to inhibiting HIV treatment adherence and increasing HIV progression, AUD and other SUD may increase COVID-19 breakthrough risk.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), rapidly spread across the globe in 2019. With the emergence of the Omicron variant, COVID-19 shifted into an endemic phase. Given the anticipated rise in cases during the fall and winter seasons, the strategy of implementing seasonal booster vaccines for COVID-19 is becoming increasingly valuable to protect public health. This practice already exists for seasonal influenza vaccines to combat annual influenza seasons. Our goal was to investigate an easily modifiable vaccine platform for seasonal use against SARS-CoV-2. In this study, we evaluated the genetically modified influenza virus ΔNA(RBD) as an intranasal vaccine candidate for COVID-19. This modified virus was engineered to replace the coding sequence for the neuraminidase (NA) protein with a membrane-anchored form of the receptor binding domain (RBD) protein of SARS-CoV-2. We designed experiments to assess the protection of ΔNA(RBD) in K18-hACE2 mice using lethal (Delta) and non-lethal (Omicron) challenge models. Controls of COVID-19 mRNA vaccine and our lab's previously described intranasal virus like particle vaccine were used as comparisons. Immunization with ΔNA(RBD) expressing ancestral RBD elicited high anti-RBD IgG levels in the serum of mice, high anti-RBD IgA in lung tissue, and improved survival after Delta variant challenge. Modifying ΔNA(RBD) to express Omicron variant RBD shifted variant-specific antibody responses and limited viral burden in the lungs of mice after Omicron variant challenge. Overall, this data suggests that ΔNA(RBD) could be an effective intranasal vaccine platform that generates mucosal and systemic immunity towards SARS-CoV-2.

Health care workers (HCWs) have been at increased risk of infection during the SARS-CoV-2 pandemic and as essential workers have been prioritised for vaccination. Due to increased exposure HCW are considered a predictor of what might happen in the general population, particularly working age adults. This study aims to summarise effect of vaccination in this 'at risk' cohort.

Ovid MEDLINE and Embase were searched, and 358 individual articles were identified. Of these 49 met the inclusion criteria for review and 14 were included in a meta-analysis.

Participants included were predominantly female and working age. Median time to infection was 51 days. Reported vaccine effectiveness against infection, symptomatic infection, and infection requiring hospitalisation were between 5 and 100 %, 34 and 100 %, and 65 and 100 % (respectively). No vaccinated HCW deaths were recorded in any study. Pooled estimates of protection against infection, symptomatic infection, and hospitalisation were, respectively, 84.7 % (95 % CI 72.6-91.5 %, p < 0.0001), 86.0 % (95 % CI 67.2 %-94.0 %; p < 0.0001), and 96.1 % (95 % CI 90.4 %-98.4 %). Waning protection against infection was reported by four studies, although protection against hospitalisation for severe infection persists for at least 6 months post vaccination.

Vaccination against SARS-CoV2 in HCWs is protective against infection, symptomatic infection, and hospitalisation. Waning protection is reported but this awaits more mature studies to understand durability more clearly. This study is limited by varying non-pharmacological responses to COVID-19 between included studies, a predominantly female and working age population, and limited information on asymptomatic transmission or long COVID protection.

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group evaluates the safety and other key features of new platform technology vaccines, including nucleic acid (RNA and DNA) vaccines. This manuscript uses the BRAVATO template to report the key considerations for a benefit-risk assessment of the coronavirus disease 2019 (COVID-19) mRNA-based vaccine BNT162b2 (Comirnaty®, or Pfizer-BioNTech COVID-19 vaccine) including the subsequent Original/Omicron BA.1, Original/Omicron BA.4-5 and Omicron XBB.1.5 variant-adapted vaccines developed by BioNTech and Pfizer to protect against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initial Emergency Use Authorizations or conditional Marketing Authorizations for the original BNT162b2 vaccine were granted based upon a favorable benefit-risk assessment taking into account clinical safety, immunogenicity, and efficacy data, which was subsequently reconfirmed for younger age groups, and by real world evidence data. In addition, the favorable benefit-risk assessment was maintained for the bivalent vaccines, developed against newly arising SARS-CoV-2 variants, with accumulating clinical trial data.

Throughout the COVID-19 pandemic, healthcare providers (HCPs)-including nurses-have played important roles in the vaccination effort. It is expected that COVID-19 vaccine hesitancy among HCPs has numerous consequences; however, the scope of these consequences and their impacts on providers, patients, and the broader healthcare system remained unclear.

To identify existing and emerging evidence to understand the state of knowledge of the consequences of COVID-19 vaccine hesitancy among HCPs.

A scoping review was completed based upon the JBI scoping review methodology. The databases searched included OVID Medline, EBSCOhost CINAHL, ProQuest Nursing and Allied Health Source, ProQuest APA PsycInfo, and ProQuest Dissertations and Theses. The final literature search was completed on June 2, 2022. Studies were screened and retrieved based on predefined inclusion and exclusion criteria using Covidence reference management software. Data extraction followed criteria recommended in the JBI scoping review framework with additional relevant variables identified by the authors.

A total of 33 sources were included in the review. Consequences of HCP COVID-19 vaccine hesitancy were grouped under three themes and seven subthemes. Consequences affecting HCPs included health-related, psychosocial, and employment-related consequences. Consequences affecting patients pertained to COVID-19 vaccination communication and COVID-19 vaccination practices of HCPs. Consequences to the healthcare system involved consequences to coworkers and employment/attendance/staffing-related consequences.

Healthcare provider COVID-19 vaccine hesitancy was found to have numerous consequences. By understanding the scope and extent of these consequences, healthcare leaders, researchers, and HCPs can work together to protect providers, patients, and healthcare systems.

The COVID-19 pandemic, caused by SARS-CoV-2, disproportionately affected certain segments of society, particularly the elderly population (which suffered the brunt of the burden of the pandemic in terms of severity of the disease, hospitalization, and death). This study presents a generalized multigroup model, with m heterogeneous sub-populations, to assess the population-level impact of age heterogeneity and vaccination on the transmission dynamics and control of the SARS-CoV-2 pandemic in the United States. Rigorous analysis of the model for the homogeneous case (i.e., the model with m = 1) reveal that its disease-free equilibrium is globally-asymptotically stable for two special cases (with perfect vaccine efficacy or negligible disease-induced mortality) whenever the associated reproduction number is less than one. The model has a unique and globally-asymptotically stable endemic equilibrium, for special a case, when the associated reproduction threshold exceeds one. The homogeneous model was fitted using the observed cumulative mortality data for the United States during three distinct waves (Waves A (October 17, 2020 to April 5, 2021), B (July 9, 2021 to November 7, 2021) and C (January 1, 2022 to May 7, 2022)) chosen to align with time periods when the Alpha, Delta and Omicron were, respectively, the predominant variants in the United States. The calibrated model was used to derive a theoretical expression for achieving vaccine-derived herd immunity (needed to eliminate the disease in the United States). It was shown that, using the one-group homogeneous model, vaccine-derived herd immunity is not attainable during Wave C of the pandemic in the United States, regardless of the coverage level of the fully-vaccinated individuals. Global sensitivity analysis was carried out to determine the parameters of the model that have the most influence on the disease dynamics and burden. These analyses reveal that control and mitigation strategies that may be very effective during one wave may not be so very effective during the other wave or waves. However, strategies that target asymptomatic and pre-symptomatic infectious individuals are shown to be consistently effective across all waves. To study the impact of the disproportionate effect of COVID-19 on the elderly population, we considered the heterogeneous model for the case where the total population is subdivided into the sub-populations of individuals under 65 years of age and those that are 65 and older. The resulting two-group heterogeneous model, which was also fitted using the cumulative mortality data for wave C, was also rigorously analysed. Unlike for the case of the one-group model, it was shown, for the two-group model, that vaccine-derived herd immunity can indeed be achieved during Wave C of the pandemic if at least 61% of the populace is fully vaccinated. Thus, this study shows that adding age heterogeneity into a SARS-CoV-2 vaccination model with homogeneous mixing significantly reduces the level of vaccination coverage needed to achieve vaccine-derived herd immunity (specifically, for the heterogeneous model, herd-immunity can be attained during Wave C if a moderate proportion of susceptible individuals are fully vaccinated). The consequence of this result is that vaccination models for SARS-CoV-2 that do not explicitly account for age heterogeneity may be overestimating the level of vaccine-derived herd immunity threshold needed to eliminate the SARS-CoV-2 pandemic.

The prognosis of immunocompromised individuals with COVID-19 remains a significant concern. Information regarding the clinical and virological characteristics of immunocompromised patients infected with SARS-CoV-2 during the Omicron variant period is limited.

Medical records of patients admitted to our hospital with COVID-19 during the Omicron (BA.1-5) epidemic were retrospectively reviewed. Clinical, virological (nasopharyngeal swabs and blood), and serological data were compared between immunocompromised patients receiving immunosuppressive medications (calcineurin inhibitors, mycophenolate mofetil, or steroids) and control patients not receiving immunosuppressive medications.

Twenty-eight immunocompromised patients (25 transplant recipients) and 26 control patients were included. Fourteen of the immunocompromised patients (50%) received monoclonal antibodies. The immunocompromised group included 15 mild/moderate (53.6%), 10 severe (35.7%), and three critical (10.7%) disease severities. The mortality rate due to COVID-19 during hospitalization was 3.6% (1/28) in the immunocompromised group, with no difference between the two groups. Three cases of re-exacerbation after discharge occurred in the immunocompromised group and none in the control group. Linear regression based on nasopharyngeal real-time-PCR cycle threshold (Ct) values according to the time since symptom onset showed markedly slower viral clearance in the immunocompromised group than in the control group (Pslope = 0.078). In the immunocompromised group, patients who received monoclonal antibodies showed faster viral clearance than those who did not receive monoclonal antibodies. The convalescent anti-spike IgG titers were comparable to those in the control group in patients who received monoclonal antibodies and significantly lower than those in the control patients in patients who did not receive monoclonal antibodies (P < 0.001). The prevalence of viremia at onset was significantly higher in the immunocompromised group than in the control group (35.7%, [10/28] vs. 11.5%, [3/26]; P = 0.003). All three patients with critical disease severity in the immunocompromised group exhibited viremia, one of whom died. All three patients with viremia in the control group were critical, of whom two died.

Immunocompromised individuals receiving immunosuppressive medications are more likely to show delayed post-infection SARS-CoV-2 viral clearance and the development of viremia, potentially resulting in worsening severity and outcomes, especially in viremic patients, even during the Omicron epidemic.

To effectively diagnose and treat subjective cognitive symptoms in post-acute sequalae of COVID-19 (PASC), it is important to understand objective cognitive impairment across the range of acute COVID-19 severity. Despite the importance of this area of research, to our knowledge, there are no current meta-analyses of objective cognitive functioning following non-severe initial SARS-CoV-2 infection. The aim of this meta-analysis is to describe objective cognitive impairment in individuals with non-severe (mild or moderate) SARS-CoV-2 cases in the post-acute stage of infection. This meta-analysis was pre-registered with Prospero (CRD42021293124) and utilized the PRISMA checklist for reporting guidelines, with screening conducted by at least two independent reviewers for all aspects of the screening and data extraction process. Fifty-nine articles (total participants = 22,060) with three types of study designs met our full criteria. Individuals with non-severe (mild/moderate) initial SARS-CoV-2 infection demonstrated worse objective cognitive performance compared to healthy comparison participants. However, those with mild (nonhospitalized) initial SARS-CoV-2 infections had better objective cognitive performance than those with moderate (hospitalized but not requiring ICU care) or severe (hospitalized with ICU care) initial SARS-CoV-2 infections. For studies that used normative data comparisons instead of healthy comparison participants, there was a small and nearly significant effect when compared to normative data. There were high levels of heterogeneity (88.6 to 97.3%), likely reflecting small sample sizes and variations in primary study methodology. Individuals who have recovered from non-severe cases of SARS-CoV-2 infections may be at risk for cognitive decline or impairment and may benefit from cognitive health interventions.

Immune imprinting is a phenomenon in which prior antigenic experiences influence responses to subsequent infection or vaccination1,2. The effects of immune imprinting on serum antibody responses after boosting with variant-matched SARS-CoV-2 vaccines remain uncertain. Here we characterized the serum antibody responses after mRNA vaccine boosting of mice and human clinical trial participants. In mice, a single dose of a preclinical version of mRNA-1273 vaccine encoding Wuhan-1 spike protein minimally imprinted serum responses elicited by Omicron boosters, enabling generation of type-specific antibodies. However, imprinting was observed in mice receiving an Omicron booster after two priming doses of mRNA-1273, an effect that was mitigated by a second booster dose of Omicron vaccine. In both SARS-CoV-2-infected and uninfected humans who received two Omicron-matched boosters after two or more doses of the prototype mRNA-1273 vaccine, spike-binding and neutralizing serum antibodies cross-reacted with Omicron variants as well as more distantly related sarbecoviruses. Because serum neutralizing responses against Omicron strains and other sarbecoviruses were abrogated after pre-clearing with Wuhan-1 spike protein, antibodies induced by XBB.1.5 boosting in humans focus on conserved epitopes targeted by the antecedent mRNA-1273 primary series. Thus, the antibody response to Omicron-based boosters in humans is imprinted by immunizations with historical mRNA-1273 vaccines, but this outcome may be beneficial as it drives expansion of cross-neutralizing antibodies that inhibit infection of emerging SARS-CoV-2 variants and distantly related sarbecoviruses.

Since December 2022, the Omicron variant has led to a widespread pandemic in China. The study was to explore the safety and effectiveness of Paxlovid for the treatment of coronavirus disease 2019 (COVID-19).

We included patients at risk of developing severe COVID-19, all of whom exhibited mild to moderate symptoms and were admitted to three hospital centers. Patients were divided into two groups: one received Paxlovid alongside standard care, while the other was given only standard care. We compared clinical characteristics, hospital stay duration, and clinical outcomes between two groups. Multi-factor analysis determined the independent risk factors influencing the duration of hospitalization and disease progression.

In the study, those treated with Paxlovid shorter hospital stays than those in the control group (p < 0.001). Multivariate analysis indicated that the absence of Paxlovid treatment was a distinct risk factor for hospitalizations lasting over 7 days (OR: 4.983, 95% CI: 3.828-6.486, p < 0.001) and 14 days (OR: 2.940, 95% CI: 2.402-3.597, p < 0.001).

Amid the Omicron outbreak, Paxlovid has proven to be a safe and effective treatment for reducing hospitalization durations for patients with mild to moderate COVID-19.

We aimed to identify the severity and duration of COVID-19 infection on complications after allo-HSCT. Enrolled 179 hospitalized patients with COVID-19 were categorized into long-term infection (> 18 days, n = 90) or short-term infection group (≤ 18 days, n = 89) according to the median duration of COVID-19. The severity of COVID-19 was categorized as asymptomatic infection, mild, moderate, severe, and critical illness according to guidelines of National Institutes of Health. Particularly, severe illness and critical illness were classified as serious infection. Asymptomatic infection, mild illness and moderate illness were classified as non-serious infection. The 150-day probabilities of poor graft function (PGF), cytomegalovirus (CMV) pneumonia and non-relapse mortality (NRM) were significantly higher in long-term infection group. The 150-day probabilities of CMV pneumonia and NRM after COVID-19 were higher in serious infection group. The 150-day probabilities of overall survival (OS) was significantly lower in long-term and serious infection group. In multivariable analysis, the severity of COVID-19 was associated with NRM and OS, and the duration of COVID-19 was associated with PGF. In summary, our data reported that the severity and duration of COVID-19 were associated with several complications and contribute to poor outcomes after allo-HSCT.

Community-based mask wearing has been shown to reduce the transmission of SARS-CoV-2. However, few studies have conducted an economic evaluation of mask mandates, specifically in public transportation settings. This study evaluated the cost-effectiveness of implementing mask mandates for subway passengers in the United States by evaluating its potential to reduce COVID-19 transmission during subway travel.

We assessed the health impacts and costs of subway mask mandates compared to mask recommendations based on the number of infections that would occur during subway travel in the U.S. Using a combined box and Wells-Riley infection model, we estimated monthly infections, hospitalizations, and deaths averted under a mask mandate scenario as compared to a mask recommendation scenario. The analysis included costs of implementing mask mandates and COVID-19 treatment from a limited societal perspective. The cost-effectiveness (net cost per averted death) of mandates was estimated for three different periods based on dominant SARS-CoV-2 variants: Alpha, Beta, and Gamma (November 2020 to February 2021); Delta (July to October 2021); and early Omicron (January to March 2022).

Compared with mask recommendations only, mask mandates were cost-effective across all periods, with costs per averted death less than a threshold of $11.4 million (ranging from cost-saving to $3 million per averted death). Additionally, mask mandates were more cost-effective during the early Omicron period than the other two periods and were cost saving in January 2022. Our findings showed that mandates remained cost-effective when accounting for uncertainties in input parameters (e.g., even if mandates only resulted in small increases in mask usage by subway ridership).

The findings highlight the economic value of mask mandates on subways, particularly during high virus transmissibility periods, during the COVID-19 pandemic. This study may inform stakeholders on mask mandate decisions during future outbreaks of novel viral respiratory diseases.

COVID-19 has a broad clinical spectrum, ranging from asymptomatic-mild form to severe phenotype. The severity of COVID-19 is a complex trait influenced by various genetic and environmental factors. Ethnic differences have been observed in relation to COVID-19 severity during the pandemic. It is currently unknown whether genetic variations may contribute to the increased risk of severity observed in Latin-American individuals The aim of this study is to investigate the potential correlation between gene variants at CCL2, OAS1, and DPP9 genes and the severity of COVID-19 in a population from Quito, Ecuador. This observational case-control study was conducted at the Carrera de Biologia from the Universidad Central del Ecuador and the Hospital Quito Sur of the Instituto Ecuatoriano de Seguridad Social (Quito-SUR-IESS), Quito, Ecuador. Genotyping for gene variants at rs1024611 (A>G), rs10774671 (A>G), and rs10406145 (G>C) of CCL2, OAS1, and DPP9 genes was performed on 100 COVID-19 patients (43 with severe form and 57 asymptomatic-mild) using RFLP-PCR. The genotype distribution of all SNVs throughout the entire sample of 100 individuals showed Hardy Weinberg equilibrium (P=0.53, 0.35, and 0.4 for CCL2, OAS1, and DPP9, respectively). The HWE test did not find any statistically significant difference in genotype distribution between the study and control groups for any of the three SNVs. The multivariable logistic regression analysis showed that individuals with the GG of the CCL2 rs1024611 gene variant had an increased association with the severe COVID-19 phenotype in a recessive model (P = 0.0003, OR = 6.43, 95% CI 2.19-18.89) and for the OAS1 rs10774671 gene variant, the log-additive model showed a significant association with the severe phenotype of COVID-19 (P=0.0084, OR=3.85, 95% CI 1.33-11.12). Analysis of haplotype frequencies revealed that the coexistence of GAG at CCL2, OAS1, and DPP9 variants, respectively, in the same individual increased the presence of the severe COVID-19 phenotype (OR=2.273, 95% CI: 1.271-4.068, P=0.005305). The findings of the current study suggests that the ethnic background affects the allele and genotype frequencies of genes associated with the severity of COVID-19. The experience with COVID-19 has provided an opportunity to identify an ethnicity-based approach to recognize genetically high-risk individuals in different populations for emerging diseases.

We aimed to describe the clinical characteristics, particularly the occurrence and risk factors of severe/critical illness, in allogeneic hematopoietic stem cell (allo-HSCT) recipients infected with coronavirus disease 2019 (COVID-19) caused by Omicron variant in an observational prospective study (n = 311). The median time from allo-HSCT to COVID-19 diagnosis was 8.5 months (range 0.8-106.1) months. Four patients (1.3%) were reported to be asymptomatic during Omicron variant infection, and 135 (43.4%) patients showed lower respiratory tract disease. Thirty-four (10.9%) patients were categorized into serious infection (severe illness n = 25; critical illness n = 9) and the median duration from COVID-19 diagnosis to serious infections was 6 days (range, 0-29) days. Thirteen (4.2%) and 6 (1.9%) patients required intensive care unit care and invasive mechanical ventilation, respectively. Receiving more than 1 type of immunosuppressive therapies at COVID-19 diagnosis was associated with severity and persistence of infection. Six patients (1.9%) died after diagnosis of COVID-19 infection. The 4-week probability of overall survival after COVID-19 diagnosis was 98.7%, which was 100% and 88.2% for non-serious and serious infection group (P < 0.001), respectively. Thus, we observed a relatively low serious infection and mortality rate in allo-HSCT recipients infected with COVID-19 caused by Omicron variant.

The emergence of new SARS-CoV-2 variants continues to cause challenging problems for the effective control of COVID-19. In this study, we tested the hypothesis of whether a strategy of multivalent and sequential heterologous spike protein vaccinations would induce a broader range and higher levels of neutralizing antibodies against SARS-CoV-2 variants and more effective protection than homologous spike protein vaccination in a mouse model. We determined spike-specific IgG, receptor-binding inhibition titers, and protective efficacy in the groups of mice that were vaccinated with multivalent recombinant spike proteins (Wuhan, Delta, Omicron), sequentially with heterologous spike protein variants, or with homologous spike proteins. Trivalent (Wuhan + Delta + Omicron) and sequential heterologous spike protein vaccinations were more effective in inducing serum inhibition activities of receptor binding to spike variants and virus neutralizing antibody titers than homologous spike protein vaccination. The higher efficacy of protection was observed in mice with trivalent and sequential heterologous spike protein vaccination after a challenge with a mouse-adapted SARS-CoV-2 MA10 strain compared to homologous spike protein vaccination. This study provides evidence that a strategy of multivalent and sequential heterologous variant spike vaccination might provide more effective protection against emerging SARS-CoV-2 variants than homologous spike vaccination and significantly alleviate severe inflammation due to COVID-19.

Aim: To investigate whether it is safe for patients with Omicron variant infection to undergo surgery during perioperative period. Methods: A total of 3,661 surgical patients were enrolled: 3,081 who were not infected with the Omicron variant and 580 who were infected with the Omicron variant. We conducted propensity score matching (PSM) with a ratio of 1:4 and a caliper value of 0.1 to match the infected and uninfected groups based on 13 variables. After PSM, we further divided the Infected group (560 cases) by the number of days between the preoperative Omicron variant infection and surgery: 0-7, 8-14, 15-30, and >30 days. Multivariate logistic regression analysis was subsequently conducted on the categorical variables and continuous variables with a P value below 0.05, thereby comparing the infected group (0-7, 8-14, 15-30, >30 days) and the uninfected group for perioperative complications. Results: Multivariate logistic regression analysis revealed that, compared to the uninfected group, among the four subgroups of the infected patients (0-7, 8-14, 15-30, >30 days), only renal insufficiency in the 8-14 days subgroup (OR: 0.09, 95%CI 0.01-0.74, P = 0.025) and anemia in the > 30 days subgroup (OR 0.6, 95%CI 0.4-0.9, P < 0.017) showed significant difference. However, there was no statistically significant difference in the incidence rate of blood transfusion, postoperative intensive care unit transfer, lung infection/pneumonia, pleural effusion, atelectasis, respiratory failure, sepsis, postoperative deep vein thrombosis, hypoalbuminemia, urinary tract infections, and medical expenses. Conclusion: Omicron infection does not significantly increase the risk of perioperative major complications. The Omicron infection may not be a sufficient risk factor to postpone elective surgery.

Despite the success of global vaccination programs in slowing the spread of COVID-19, these efforts have been hindered by the emergence of new SARS-CoV-2 strains capable of evading prior immunity. The mutation and evolution of SARS-CoV-2 have created a demand for persistent efforts in vaccine development. SARS-CoV-2 Spike protein has been the primary target for COVID-19 vaccine development, but it is also the hotspot of mutations directly involved in host susceptibility and virus immune evasion. Our ability to predict emerging mutants and select conserved epitopes is critical for the development of a broadly neutralizing therapy or a universal vaccine. In this article, we review the general paradigm of immune responses to COVID-19 vaccines, highlighting the immunological epitopes of Spike protein that are likely associated with eliciting protective immunity resulting from vaccination in humans. Specifically, we analyze the structural and evolutionary characteristics of the SARS-CoV-2 Spike protein related to immune activation and function via the TLRs, B cells, and T cells. We aim to provide a comprehensive analysis of immune epitopes of Spike protein, thereby contributing to the development of new strategies for broad neutralization or universal vaccination.

Adjuvants may enhance the efficacy of vaccines. however, the efficacy of adjuvant-associated COVID-19 vaccines (ACVs) remains unclear since the emergence of the COVID-19 pandemic. This study aimed to address this gap by conducting a systematic review and meta-analysis of the efficacy of ACVs against Severe Acute Respiratory Syndrome Coronavirus 2 CoV (SARS-CoV-2) variants of concern (VOC).

A systematic search was conducted of randomized controlled trials (RCTs) evaluating the vaccine efficacy (VE) of ACVs against VOC (alpha, beta, gamma, delta, or Omicron), up to May 27, 2023. The DerSimonian-Laird random-effects model was used to assess VE with 95% confidence intervals (CI) through meta-analysis. Cochrane Risk of Bias tools were used to assess the risk of bias in RCTs.

Eight RCTs with 113,202 participants were included in the analysis, which incorporated 4 ACVs [Matrix-M (NVX-CoV2373), Alum (BBV152), CpG-1018/Alum (SCB-2019), and AS03 (CoVLP]). The pooled efficacy of full vaccination with ACVs against VOC was 88.0% (95% CI: 83.0-91.5). Full vaccination was effective against Alpha, Beta, Delta, and Gamma variants, with VE values of 93.66% (95% CI: 86.5-100.74), 64.70% (95% CI: 41.87-87.54), 75.95% (95% CI: 67.9-83.99), and 91.26% (95% CI: 84.35-98.17), respectively. Currently, there is a lack of RCT evidence regarding the efficacy of ACVs against the Omicron variant.

In this meta-analysis, it should be that full vaccination with ACVs has high efficacy against Alpha or Gamma variants and moderate efficacy against Beta and Delta variants. Notably, with the exception of the aluminum-adjuvanted vaccine, the other ACVs had moderate to high efficacy against the SARS-CoV-2 variant. This raises concerns about the effectiveness of ACVs booster vaccinations against Omicron.

Large sample of pregnant women vaccinated with COVID-19 vaccine has not been carried out in China. The objective of this study was to evaluate the safety and effectiveness of COVID-19 inactivated vaccine in pregnant women infected with the SARS-CoV-2 Omicron variant.

A total of 1,024 pregnant women and 120 newborns were enrolled in this study. 707 pregnant women received one to three doses of the inactivated COVID-19 vaccine, and 317 unvaccinated patients served as the control group. A comparison was made between their clinical and laboratory data at different stages of pregnancy.

The incidence rate of patients infected with Omicron variant in the first, the second, and the third trimesters of pregnancy was 27.5%, 27.0%, and 45.5% in patients during, respectively. The corresponding length of hospital stay was 8.7 ± 3.3 days, 9.5 ± 3.3 days, and 11 ± 4.3 days, respectively. The hospitalization time of pregnant women who received 3 doses of vaccine was (8.8 ± 3.3) days, which was significantly shorter than that of non-vaccinated women (11.0 ± 3.9) days. (P<0.0001). The positive rate of SARS-CoV-2 IgG in patients in the early stage of pregnancy was 28.8%, while that in patients in the late stage of pregnancy was 10.3%. However, three-doses of vaccination significantly increased the SARS-CoV-2 IgG positive rate to 49.5%. The hospitalization time of SARS-CoV-2 IgG-positive patients was shorter than that of negative patients (9.9 ± 3.5 days), which was 7.4 ± 2.0 days. 12.2% of vaccinated women experienced mild adverse reactions, manifested as fatigue (10.6%) and loss of appetite (1.6%). The vaccination of mother did not affect her choice of future delivery mode and the Apgar score of their newborn. All newborns tested negative for SARS-CoV-2 nucleic acid, as well as for IgG and IgM antibodies.

Women in the third trimester of pregnancy are highly susceptible to infection with the Omicron strain. The vaccination of pregnant women with COVID-19 vaccine can accelerate the process of eliminating SARS-CoV-2 virus, and is considered safe for newborns. The recommended vaccination includes three doses.

In the past several years, the coronavirus pandemic has introduced multiple medical disciplines to various new forms of disease previously unknown and has shown us a unique presentation of already existing diseases. We continue to understand the long-term effects of the pandemic on the population's health and continue to find new unique features previously unknown. This paper presents the unique feature of lung uptake abnormalities discovered on nuclear stress testing for cardiac perfusion defects, a consistent finding in multiple individuals with recent COVID-19 or ongoing infection.