Humoral Responses and Serological Assays in SARS-CoV-2 Infections

Abstract

In December 2019, the novel betacoronavirus Severe Acute Respiratory Disease Coronavirus 2 (SARS-CoV-2) was first detected in Wuhan, China. SARS-CoV-2 has since become a pandemic virus resulting in hundreds of thousands of deaths and deep socioeconomic implications worldwide. In recent months, efforts have been directed towards detecting, tracking, and better understanding human humoral responses to SARS-CoV-2 infection. It has become critical to develop robust and reliable serological assays to characterize the abundance, neutralization efficiency, and duration of antibodies in virus-exposed individuals. Here we review the latest knowledge on humoral immune responses to SARS-CoV-2 infection, along with the benefits and limitations of currently available commercial and laboratory-based serological assays. We also highlight important serological considerations, such as antibody expression levels, stability and neutralization dynamics, as well as cross-reactivity and possible immunological back-boosting by seasonal coronaviruses. The ability to accurately detect, measure and characterize the various antibodies specific to SARS-CoV-2 is necessary for vaccine development, manage risk and exposure for healthcare and at-risk workers, and for monitoring reinfections with genetic variants and new strains of the virus. Having a thorough understanding of the benefits and cautions of standardized serological testing at a community level remains critically important in the design and implementation of future vaccination campaigns, epidemiological models of immunity, and public health measures that rely heavily on up-to-date knowledge of transmission dynamics.

Short-term antibody response after 1 dose of BNT162b2 vaccine in patients receiving hemodialysis

“…In an RCT, the BNT162b2 vaccine was shown to be greater than 80% clinically efective by 3 weeks afer the first dose in healthy individuals. 5 In the absence of internationally accepted surrogate measures of vaccine eficacy against SARS-CoV-2, 13 our healthy control group serves as a benchmark representing the expected "optimal" antibody response. Indeed, 98% of our controls developed anti-RBD IgG within 3 weeks of a single dose of this vaccine, irrespective of previous SARS-CoV-2 infection, which is consistent with recent studies.…”

“…10 With respect to the novel coronavirus SARS-CoV-2, although there is increasing understanding of the antibodies that best correlate with viral neutralization and T-cell responses, 11,12 assays vary from laboratory to laboratory and as yet there are no internationally accepted standards defining what antibody levels constitute immunity. 13 The only way to evaluate vaccine efficacy using antibody levels, therefore, is through direct experimental comparison with controls who are known to reliably develop immunity after vaccination (i.e., healthy individuals similar to those enrolled in the RCT showing vaccine eficacy 5 ) or who have developed immunity afer natural infection (i.e., survivors of .…”

Prior infection by seasonal coronaviruses, as assessed by serology, does not prevent SARS-CoV-2 infection and disease in children, France, April to June 2020

“…This was not associated with differences in quantitative anti-N or anti-S antibody responses. Higher N antibody frequency in MIS-P may have originated from back-boosting cross-reactivity for HCoV N-specific responses as epitopes are shared between HCoV and SARS-CoV2 [ 38 ], and anamnestic responses to HCoV may influence the antibody response to SARS-CoV-2 [ 39 ]. Isotype or avidity of these responses was not tested here but could help to assess functional maturation of N-specific antibodies in future studies.…”

Immune profiling of COVID-19: preliminary findings and implications for the pandemic

“…Antibody responses are the most-studied aspect of the immune system, and have certainly been well characterized in COVID-19. 18 They can be measured by ELISA as well as by multiplexed immunoassays, using bead-based fluorescent or microtiter plate electrochemiluminescence readouts. Even higher multiplexing can be achieved with protein/peptide microarrays.…”

“…Most infected individuals raise a detectable antibody response to SARS-CoV-2, including IgM, IgG, and IgA antibodies to the spike protein and its receptor-binding domain. 18 22 These responses tend to be higher in more severe cases, though there is considerable population heterogeneity. Antibody levels generally peak within 2 weeks for IgM and 3 weeks for IgG, 23 for both nucleocapsid and spike protein targets.…”