A prospective study of asymptomatic SARS-CoV-2 infection among individuals involved in academic research under limited operations during the COVID-19 pandemic

BackgroundEarly in the pandemic, transmission risk from asymptomatic infection was unclear making it imperative to monitor infection in workplace settings. Further, data on SARS-CoV-2 seroprevalence within university populations has been limited. MethodsWe performed a longitudinal study of University research employees on campus July-December 2020. We conducted questionnaires on COVID-19 risk factors, RT-PCR testing, and SARS-CoV-2 serology using an in-house spike RBD assay, laboratory-based Spike NTD assay, and standard nucleocapsid platform assay. We estimated prevalence and cumulative incidence of seroconversion with 95% confidence intervals using the inverse of the Kaplan-Meier estimator. Results910 individuals were included in this analysis. At baseline, 6.2% (95% CI 4.29-8.19) were seropositive using the spike RBD assay; four (0.4%) were seropositive using the nucleocapsid assay, and 44 (4.8%) using the Spike NTD assay. Cumulative incidence was 3.61% (95% CI: 2.04-5.16). Six asymptomatic individuals had positive RT-PCR results. ConclusionsPrevalence and incidence of SARS-CoV-2 infections was low; however differences in target antigens of serological tests provided different estimates. Future research on appropriate methods of serological testing in unvaccinated and vaccinated populations is needed. Frequent RT-PCR testing of asymptomatic individuals is required to detect acute infections, and repeated serosurveys are beneficial for monitoring subclinical infection.

SARS-CoV-2 mRNA Vaccine Induces Robust Specific and Cross-reactive IgG and Unequal Strain-specific Neutralizing Antibodies in Naïve and Previously Infected Recipients

With the advance of SARS-CoV-2 vaccines, the outlook for overcoming the global COVID-19 pandemic has improved. However, understanding of immunity and protection offered by the SARS-CoV-2 vaccines against circulating variants of concern (VOC) is rapidly evolving. We investigated the mRNA vaccine-induced antibody responses against the referent WIV04 (Wuhan) strain, circulating variants, and human endemic coronaviruses in 168 naive and previously infected people at three-time points. Samples were collected prior to vaccination, after the first and after the second doses of one of the two available mRNA-based vaccines. After full vaccination, both naive and previously infected participants developed comparable robust SARS-CoV-2 specific spike IgG levels, modest IgM and IgA binding antibodies, and varying degrees of HCoV cross-reactive antibodies. However, the strength and frequency of neutralizing antibodies produced in naive people were significantly lower than in the previously infected group. We also found that 1/3rd of previously infected people had undetectable neutralizing antibodies after the first vaccine dose; 40% of this group developed neutralizing antibodies after the second dose. In all subjects neutralizing antibodies produced against the B.1.351 and P.1 variants were weaker than those produced against the reference and B.1.1.7 strains. Our findings provide support for future booster vaccinations modified to be active against the circulating variants.

The RBD Of The Spike Protein Of SARS-Group Coronaviruses Is A Highly Specific Target Of SARS-CoV-2 Antibodies But Not Other Pathogenic Human and Animal Coronavirus Antibodies

A new Severe Acute Respiratory Syndrome Coronavirus variant (SARS-CoV-2) that first emerged in late 2019 is responsible for a pandemic of severe respiratory illness. People infected with this highly contagious virus present with clinically inapparent, mild or severe disease. Currently, the presence of the virus in individual patients and at the population level is being monitored by testing symptomatic cases by PCR for the presence of viral RNA. There is an urgent need for SARS-CoV-2 serologic tests to identify all infected individuals, irrespective of clinical symptoms, to conduct surveillance and implement strategies to contain spread. As the receptor binding domain (RBD) of the viral spike (S) protein is poorly conserved between SARS-CoVs and other pathogenic human coronaviruses, the RBD represents a promising antigen for detecting CoV specific antibodies in people. Here we use a large panel of human sera (70 SARS-CoV-2 patients and 71 control subjects) and hyperimmune sera from animals exposed to zoonotic CoVs to evaluate the performance of the RBD as an antigen for accurate detection of SARS-CoV-2-specific antibodies. By day 9 after the onset of symptoms, the recombinant SARS-CoV-2 RBD antigen was highly sensitive (98%) and specific (100%) to antibodies induced by SARS-CoVs. We observed a robust correlation between levels of RBD binding antibodies and SARS-CoV-2 neutralizing antibodies in patients. Our results, which reveal the early kinetics of SARS-CoV-2 antibody responses, strongly support the use of RBD-based antibody assays for population-level surveillance and as a correlate of neutralizing antibody levels in people who have recovered from SARS-CoV-2 infections.