Challenges of vaccination and herd immunity in COVID-19 and management strategies.

Coronavirus disease 2019 (COVID-19), the highly contagious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide with millions of cases and more than 5 million deaths to date. SARS-CoV-2 has caused serious damage all over the world with many countries experiencing the third or the fourth wave of the viral disease outbreaks, mainly due to the emergence of mutant variants. Those who unvaccinated remain most vulnerable to COVID-19 and its variants. COVID-19 vaccination, along with prevention strategies, is a critical measure to defense against the disease. COVID-19 vaccination can reduce the spread of virus and help protect susceptible population. Although herd immunity might not be realized solely by vaccination, COVID-19 vaccines have been proved to be effective in reducing the risk of severe disease, hospitalization, and even death. It is recommended that people get vaccinated as soon as they are eligible. This review summarizes the recent SARS-CoV-2 variants that brought challenges for vaccination and herd immunity and discusses promising management strategies.

A non-ACE2 competing human single-domain antibody confers broad neutralization against SARS-CoV-2 and circulating variants.

The current COVID-19 pandemic has heavily burdened the global public health system and may keep simmering for years. The frequent emergence of immune escape variants have spurred the search for prophylactic vaccines and therapeutic antibodies that confer broad protection against SARS-CoV-2 variants. Here we show that the bivalency of an affinity maturated fully human single-domain antibody (n3113.1-Fc) exhibits exquisite neutralizing potency against SARS-CoV-2 pseudovirus, and confers effective prophylactic and therapeutic protection against authentic SARS-CoV-2 in the host cell receptor angiotensin-converting enzyme 2 (ACE2) humanized mice. The crystal structure of n3113 in complex with the receptor-binding domain (RBD) of SARS-CoV-2, combined with the cryo-EM structures of n3113 and spike ecto-domain, reveals that n3113 binds to the side surface of up-state RBD with no competition with ACE2. The binding of n3113 to this novel epitope stabilizes spike in up-state conformations but inhibits SARS-CoV-2 S mediated membrane fusion, expanding our recognition of neutralization by antibodies against SARS-CoV-2. Binding assay and pseudovirus neutralization assay show no evasion of recently prevalent SARS-CoV-2 lineages, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) for n3113.1-Fc with Y58L mutation, demonstrating the potential of n3113.1-Fc (Y58L) as a promising candidate for clinical development to treat COVID-19.

Determination of human COVID-19 total antibodies in serum using a time-resolved fluorescence immunoassay.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading rapidly around the world. Antibody detection plays an important role in the diagnosis of COVID-19. Here, we established a new time-resolved fluorescence immunoassay (TRFIA) to determine COVID-19 total antibodies. A double-antigen sandwich TRFIA was optimized and established: recombinant nucleocapsid phosphoprotein (N protein) and spike protein (S protein) of COVID-19 immobilized on 96-well plates captured human COVID-19 antibodies and then banded together with the N/S proteins labeled with europium(III) (Eu3+ ) chelates, and finally, time-resolved fluorometry was used to measure the fluorescence values. We successfully established a TRFIA method for the detection of human COVID-19 total antibodies, and the cutoff value was 2.02. There was no cross-reactivity with the negative reference of the National Reference Panel for IgM and IgG antibodies to COVID-19. The CV of the precision assay was 3.19%, and the assay could be stored stably for 15 days at 37°C. Compared with that of the colloidal gold method and chemiluminescence method, the sensitivity of the TRFIA method was higher, and the false positive/negative rate was lower. This established TRFIA has high sensitivity, accuracy, and specificity, which indicates that this method provides a new detection method for the high-throughput routine diagnosis of COVID-19.

Corticosteroid therapy for coronavirus disease 2019-related acute respiratory distress syndrome: a cohort study with propensity score analysis.

BACKGROUND: The impact of corticosteroid therapy on outcomes of patients with coronavirus disease 2019 (COVID-19) is highly controversial. We aimed to compare the risk of death between COVID-19-related ARDS patients with corticosteroid treatment and those without. METHODS: In this single-center retrospective observational study, patients with ARDS caused by COVID-19 between January 20, 2020, and February 24, 2020, were enrolled. The primary outcome was 60-day in-hospital death. The exposure was prescribed systemic corticosteroids or not. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for 60-day in-hospital mortality. RESULTS: A total of 382 patients [60.7 ± 14.1 years old (mean ± SD), 61.3% males] were analyzed. The median of sequential organ failure assessment (SOFA) score was 2.0 (IQR 2.0-3.0). Of these cases, 94 (24.6%) patients had invasive mechanical ventilation. The number of patients received systemic corticosteroids was 226 (59.2%), and 156 (40.8%) received standard treatment. The maximum dose of corticosteroids was 80.0 (IQR 40.0-80.0) mg equivalent methylprednisolone per day, and duration of corticosteroid treatment was 7.0 (4.0-12.0) days in total. In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days after adjusting for age, sex, SOFA score at hospital admission, propensity score of corticosteroid treatment, comorbidities, antiviral treatment, and respiratory supports (HR 0.42; 95% CI 0.21, 0.85; p = 0.0160). Corticosteroids were not associated with delayed viral RNA clearance in our cohort. CONCLUSION: In this clinical practice setting, low-dose corticosteroid treatment was associated with reduced risk of in-hospital death within 60 days in COVID-19 patients who developed ARDS.

Corticosteroid, oseltamivir and delayed admission are independent risk factors for prolonged viral shedding in patients with Coronavirus Disease 2019.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) has spread worldwide, and it has reached to more than 14.5 million cases. Although Hubei province is the epicenter of China, little is known about epidemiological and clinical features of COVID-19 in other areas in Hubei province around Wuhan. In addition, the virological data, particularly the factors associated with viral shedding of COVID-19 has not been well described. OBJECTIVE: To describe the epidemiological and clinical features of patients with COVID-19 in Tianmen city, and identify risk factors associated with prolonged viral shedding of COVID-19. METHODS: Inpatients with COVID-19 admitted before February 9, 2020 were included. Characteristics were compared between patients with early and late viral RNA shedding. Multivariate cox regression model was used to investigate variables associated with prolonged viral shedding. RESULTS: One hundred and eighty-three patients were included. About 8.2% patients were categorized as critical degree of severity. All patients received antiviral therapy, with arbidol and interferon being the commonest. About 38.3% and 16.9% patients were treated with corticosteroid and immunoglobulin, respectively. Time from onset to admission (HR = 0.829, P < 0.001), and administration of corticosteroid (HR = 0.496, P = 0.002), arbidol (HR = 2.605, P = 0.008) and oseltamivir (HR = 0.416, P < 0.001) were independently associated with duration of viral shedding. CONCLUSION: Symptoms of patients from Tianmen are relatively mild. Treatment should be started as early as possible, but corticosteroid and oseltamivir should be initiated with caution. In addition, clinical trials on arbidol should be conducted to demonstrate its effectiveness.