Expansion of SARS-CoV-2-specific Antibody-secreting Cells and Generation of Neutralizing Antibodies in Hospitalized COVID-19 Patients

Abstract

26Coronavirus disease 2019 , caused by severe acute respiratory syndrome 27 coronavirus 2 (SARS-CoV-2), emerged in late 2019 and has since become a global 28 pandemic. Pathogen-specific antibodies are typically a major predictor of protective 29immunity, yet B cell and antibody responses during COVID-19 are not fully understood. 30 Here, we analyzed antibody-secreting cell (ASC) and antibody responses in twenty 31 hospitalized COVID-19 patients. The patients exhibited typical symptoms of COVID-19, and 32 presented with reduced lymphocyte numbers and increased T cell and B cell activation. 33 Importantly, we detected an expansion of SARS-CoV-2 nucleocapsid protein-specific ASCs 34 in all twenty COVID-19 patients using a multicolor FluoroSpot assay. Out of the 20 patients, 35 16 had developed SARS-CoV-2-neutralizing antibodies by the time of inclusion in the study. 36 SARS-CoV-2-specific IgA, IgG and IgM antibody levels positively correlated with SARS-37CoV-2-neutralizing antibody titers, suggesting that SARS-CoV-2-specific antibody levels 38 may reflect the titers of neutralizing antibodies in COVID-19 patients during the acute phase 39 of infection. Lastly, we showed that interleukin 6 (IL-6) and C-reactive protein (CRP) 40 concentrations were higher in serum of patients who were hospitalized for longer, supporting 41 the recent observations that IL-6 and CRP could be used to predict COVID-19 severity. 42Altogether, this study constitutes a detailed description of clinical and immunological 43 parameters in twenty COVID-19 patients, with a focus on B cell and antibody responses, and 44 provides tools to study immune responses to SARS-CoV-2 infection and vaccination. 45 46

Antibody response to SARS-CoV-2 infection in humans: a systematic review

“…Most studies, including all those considered high quality, suggested that neutralisation ability broadly correlated with total virus-specific IgG. 29,49,67,74,87,[99][100][101] Specifically, high quality studies found that neutralisation ability correlated positively with anti-S IgG 49,72,87,99 or anti-RBD IgG. 72,74,87,102 There was more limited evidence for correlation with anti-RBD IgM, including one high quality study, 51,84 and IgA.…”

“…72,74,87,102 There was more limited evidence for correlation with anti-RBD IgM, including one high quality study, 51,84 and IgA. 93,99 A number of basic science studies also identified specific neutralising antibodies. The majority of these studies were medium quality, and heterogeneity between assays limits comparability of findings.…”

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

“…Cells were continuously monitored for cytopathic effect (CPE). After days the cultures were harvested and supernatants were analyzed with RT-PCR specific for the SARS-CoV-2 E-gene and (rdrp)-gene (13). preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted September 13, 2020. ; https://doi.org/10.1101/2020.09.11.20191940 doi: medRxiv preprint…”

Laboratory diagnosis of coronavirus disease-2019 (COVID-19)

“…In addition, anti-S1-IgA, anti-S1-IgG and anti-N-IgM levels were also related to the neutralizing antibody titers of SARS-CoV-2. These studies indicating that SARS-CoV-2 antibody titers in COVID-19 patients may reflect the capacity of serum to neutralize SARS-CoV-2 [95].…”