Shedding of infectious SARS-CoV-2 by hospitalized COVID-19 patients in relation to serum antibody responses

Abstract

Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic. The understanding of the transmission and the duration of viral shedding in SARS-CoV-2 infection is still limited. Objectives To assess the timeframe and potential risk of SARS-CoV-2 transmission from hospitalized COVID-19 patients in relation to antibody response. Method We performed a cross-sectional study of 36 COVID-19 patients hospitalized at Karolinska University Hospital. Patients with more than 8 days of symptom duration were sampled from airways, for PCR analysis of SARS-CoV-2 RNA and in vitro culture of replicating virus. Serum SARS-CoV-2-specific immunoglobulin G (IgG) and neutralizing antibodies titers were assessed by immunofluorescence assay (IFA) and microneutralization assay. Results SARS-CoV-2 RNA was detected in airway samples in 23 patients (symptom duration median 15 days, range 9–53 days), whereas 13 patients were SARS-CoV-2 RNA negative (symptom duration median 21 days, range 10–37 days). Replicating virus was detected in samples from 4 patients at 9–16 days. All but two patients had detectable levels of SARS-CoV-2-specific IgG in serum, and SARS-CoV-2 neutralizing antibodies were detected in 33 out of 36 patients. Total SARS-CoV-2-specific IgG titers and neutralizing antibody titers were positively correlated. High levels of both total IgG and neutralizing antibody titers were observed in patients sampled later after symptom onset and in patients where replicating virus could not be detected. Conclusions Our data suggest that the presence of SARS-Cov-2 specific antibodies in serum may indicate a lower risk of shedding infectious SARS-CoV-2 by hospitalized COVID-19 patients.

Release of infectious virus and cytokines in nasopharyngeal swabs from individuals infected with non-alpha or alpha SARS-CoV-2 variants: an observational retrospective study

“…This strongly suggests that the antibodies locally present in nasopharyngeal secretions can neutralize viral infectivity. These results further support previous reports indicating that infectious SARS-CoV-2 could only be isolated in individuals with low or undetectable neutralizing antibodies in their serum [ 17 , 18 ]. We did not have access to serum samples in this cohort to compare levels of mucosal and circulating antibodies.…”

“…The extent and duration of shedding of infectious virus in nasopharyngeal swabs of COVID-19 patients are only partially characterized. Some studies have corelated RT-qPCR levels, or a positive lateral flow antigenic rapid diagnostic test (RDT), with viral outgrowth assays [ [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] ]. Assessment of viral infectivity is classically performed using subclones or derivatives of the Vero cell line, which is naturally sensitive to infection and does not mount a type-I Interferon response [ [12] , [13] , [14] , [15] , [16] , [17] , [18] , 22 ].…”

“…Some studies have corelated RT-qPCR levels, or a positive lateral flow antigenic rapid diagnostic test (RDT), with viral outgrowth assays [ [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] ]. Assessment of viral infectivity is classically performed using subclones or derivatives of the Vero cell line, which is naturally sensitive to infection and does not mount a type-I Interferon response [ [12] , [13] , [14] , [15] , [16] , [17] , [18] , 22 ]. In these cells, the presence of replicating virus is generally detected by visualisation of a cytopathic effect after 2-10 days of culture, or by immunofluorescence staining or RT-qPCR measurement at an earlier time point.…”

Risk of SARS-CoV-2 transmission upon return to work in RNA-positive healthcare workers

“…Furthermore, the presence of SARS-CoV-2 specific antibodies has been negatively correlated with the presence of infectious virus. [ 14 , 15 ] Therefore, antibody dynamics could be valuable in determining the risk of transmission upon return to work and subsequent re-infection in this population with an increased occupational risk.…”

Estimating SARS-CoV-2 Seroprevalence in Canadian Blood Donors, April 2020 to March 2021: Improving Accuracy with Multiple Assays

“…During the SARS-CoV-2 pandemic, serological studies have provided a number of key insights into this newly emerged infection; they have affirmed that development of an antibody response correlates with clearance of viral shedding ( 11 ); they have helped delineate the fraction of infections that are identified as cases ( 12 ); have permitted estimation of infection fatality ratios and have facilitated identification of groups and regions with elevated infection risks and ongoing vulnerabilities to infection ( 13 – 16 ). However, seroprevalence studies rely on assays with imperfect sensitivity and specificity ( 16 ).…”