Cross-Sectional Evaluation of Humoral Responses against SARS-CoV-2 Spike

Abstract

SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoproteins of SARS-CoV-2 mediate viral entry and are the main targets for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic, and public health interventions. Here, we perform a cross-sectional study on 106 SARS-CoV-2-infected individuals to evaluate humoral responses against SARS-CoV-2 Spike. Most infected individuals elicit anti-Spike antibodies within 2 weeks of the onset of symptoms. The levels of receptor binding domain (RBD)-specific immunoglobulin G (IgG) persist over time, and the levels of anti-RBD IgM decrease after symptom resolution. Although most individuals develop neutralizing antibodies within 2 weeks of infection, the level of neutralizing activity is significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.

Decline of Humoral Responses against SARS-CoV-2 Spike in Convalescent Individuals

“…Neutralizing activity against pseudoparticles bearing the SARS-CoV S glycoprotein was detected in only 25% of convalescent plasma and exhibited low potency, as previously reported (Fig. 2) (14). As recently shown, plasma samples from prepandemic SARS-CoV-2-negative and SARS-CoV-negative individuals showed no neutralization activity against pseudoparticles bearing the SARS-CoV-2 or SARS-CoV Spike protein (not shown).…”

“…Moreover, while the loss of neutralizing activity on the WT and D614G pseudoparticles over time correlated with the loss of anti-RBD IgM, IgA, and IgG antibodies, the correlation was higher for IgM than for IgG and IgA (Fig. S4C and D), suggesting that at least part of the neutralizing activity could be mediated by IgM, as recently proposed (13,14). Therefore, if plasma neutralization activity is shown to be required for protection from SARS-CoV-2 infection, then our results suggest that this protection could be limited in time and that, in the context of vaccination, multiple boosts might be necessary to mount a durable and effective anti-SARS-CoV-2 humoral response.…”

“…We first evaluated the presence of receptor-binding-domain (RBD)-specific IgG, IgM, and IgA antibodies by enzyme-linked immunosorbent assay (ELISA) as we had recently described (14). In agreement with a recent report (16,23), we observed that all RBD-specific IgG, IgM, and IgA titers significantly decreased between 6 and 10 weeks after the onset of symptoms.…”

“…It was recently reported that the humoral responses against SARS-CoV-2 are built rapidly, peaking at week 2 or week 3 after the onset of symptoms but steadily decreasing thereafter (13)(14)(15). Moreover, in a previous cross-sectional study, we reported that the neutralization capacity decreased between the third and the sixth week after the onset of symptoms (14). Since convalescent patients are generally required to wait for 14 days after recovery to start plasma donations and since they may donate plasma multiple times in the ensuing weeks, most donations are likely to occur even later than this.…”

COVID-19: Rethinking the Lockdown Groupthink

“…Third, and most importantly, there is a lack of sensitivity of serology. [20][21][22][23][24][25] Many reports now document there is often a rapid loss of antibody in COVID-19 patients that were less severely ill. [20][21][22][23][24][25][26] Moreover, at least 10% of COVID-19 patients never seroconvert, and many more may only develop a mucosal IgA response, 27,28 or only a T-cell response [which may be the case in up to 50% of mild infections]. 29,30 Finally, most data come from unusual epicenters where "infection finds its way into killing predominantly elderly citizens" in nursing homes and hospitals, 18 and where "[in Italy, Spain, France] an underfunded, understaffed, overstretched and increasingly privatized and fractured healthcare system contribute to higher mortality rates… [Lombardy] has long been an experimental site for healthcare privatization."…”