Mucosal versus systemic antibody responses to SARS-CoV-2 antigens in COVID-19 patients

Abstract

While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the antibody response in the oral cavity is likely an important parameter that influences the course of infection. We developed enzyme linked immunosorbent assays to detect IgA and IgG antibodies to the SARS-CoV-2 spike protein (full length trimer) and its receptor binding domain (RBD) in serum (n=496) and saliva (n=90) of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared to negative controls. Anti-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16-30 days PSO. Whereas anti-CoV-2 IgA antibodies rapidly decayed, IgG antibodies remained relatively stable up to 115 days PSO in both biofluids. Importantly, IgG responses in saliva and serum were correlated, suggesting that antibodies in the saliva may serve as a surrogate measure of systemic immunity.

SARS-CoV-2 vaccines in development

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 in China and caused a coronavirus disease 2019 (COVID- 19) pandemic. To mitigate the public health, economic and societal impacts of the virus, a vaccine is urgently needed.…”

“…The causative agent was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a betacoronavirus closely related to the SARS-CoV-1 from 2002-2004 2 . SARS-CoV-2 caused a sizable epidemic of coronavirus disease 2019 (COVID- 19) in China and then spread globally and caused a pandemic. Coronaviruses are enveloped viruses with a large, single stranded positive sense RNA genome.…”

“…Antibodies directed to S, including ones targeting the RBD and with targets outside of the RBD, have been shown to neutralize the virus [14][15][16][17][18] . In addition, while the magnitude of the antibody response to S is very heterogenous, it looks so far like a normal antibody response to a respiratory virus with an initial plasmablast-derived boost of antibodies, followed by some decline and then a potential stabilization at a baseline maintained by long lived plasma cells 17,19,20 . Mucosal antibody responses are also induced by natural infection in humans 19,21 .…”

“…In addition, while the magnitude of the antibody response to S is very heterogenous, it looks so far like a normal antibody response to a respiratory virus with an initial plasmablast-derived boost of antibodies, followed by some decline and then a potential stabilization at a baseline maintained by long lived plasma cells 17,19,20 . Mucosal antibody responses are also induced by natural infection in humans 19,21 . In addition, it has been demonstrated that S is a strong target of CD4+ T-cells, while fewer CD8+ T-cells are induced by natural infection with SARS-CoV-2 in general 22 .…”

Viruses That Can and Cannot Coexist With Humans and the Future of SARS-CoV-2

“…Short immunity periods are the case for seasonal human coronaviruses (Callow et al, 1990;Galanti and Shaman, 2020;Kissler et al, 2020). Although natural infection with SARS-CoV-2 can induce neutralizing antibodies in humans (Brouwer et al, 2020;Chi et al, 2020;Ju et al, 2020;Shi R. et al, 2020), we still do not know if the infection confers immunity to prevent reinfection and, if so, for what duration (Altmann and Boyton, 2020;Ibarrondo et al, 2020;Isho et al, 2020;Kirkcaldy et al, 2020;Long et al, 2020;Robbiani et al, 2020;Staines et al, 2020). Many cases that tested positive after once turning negative are currently considered as reactivation, long-term shedding, or detection of residual genetic material Mahase, 2020b;Xiao A. T. et al, 2020) although a few cases of possible reinfection have been reported (Bloomberg, 2020).…”