Persistence of anti-SARS-CoV-2 antibodies in non-hospitalized COVID-19 convalescent health care workers

Abstract

Background. Coronavirus disease-19 (COVID-19) is a respiratory illness caused by the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), a novel beta-coronavirus. Although antibody response to SARS-CoV-2 can be detected early during the infection, several outstanding questions remain to be addressed regarding magnitude and persistence of antibody titer against different viral proteins and their correlation with the strength of the immune response, as measured by serum levels of pro-inflammatory mediators. Methods. An ELISA assay has been developed by expressing and purifying the recombinant SARS-CoV-2 Spike Receptor Binding Domain (RBD), Soluble Ectodomain (Spike), and full length nucleocapsid protein (N protein). Sera from healthcare workers affected by non-severe COVID-19 were longitudinally collected over four weeks, and compared to sera from patients hospitalized in Intensive Care Units (ICU) and SARS-CoV-2-negative subjects for the presence of IgM, IgG and IgA antibodies as well as soluble pro-inflammatory mediators in the sera. Results. Specificity and sensitivity of the ELISA assays were high for anti-RBD IgG and IgA (92-97%) and slightly lower for IgM and the Spike and N proteins (70-85%). The ELISA allowed quantification of IgM, IgG and IgA antibody responses against all the viral antigens tested and showed a correlation between magnitude of the antibody response and disease severity. Non-hospitalized subjects showed lower antibody titers and blood pro-inflammatory cytokine profiles as compared to patients in Intensive Care Units (ICU), irrespective of the antibodies tested. Noteworthy, in non-severe COVID-19 infections, antibody titers against RBD and Spike, but not against the N protein, as well as pro-inflammatory cytokines decreased within a month after viral clearance. Conclusions. Rapid decline in antibody titers and in pro-inflammatory cytokines may be a common feature of non-severe SARS-CoV-2 infection, suggesting that antibody-mediated protection against re-infection with SARS-CoV-2 is of short duration. These results suggest caution in use serological testing to estimate the prevalence of SARS-CoV-2 infection in the general population.

SARS-CoV-2 induces a durable and antigen specific humoral immunity after asymptomatic to mild COVID-19 infection

“…Anti-nucleocapsid IgG, however, declined in individuals with asymptomatic to mild COVID-19 disease, implying that this antigen may not be a useful target in long-term serological population studies.Our findings of a durable IgG response are consistent with recent studies showing stable antibody levels for up to 2-6 months(16)(17)(18)(19). Several other studies, however, report a rapid decline in circulating SARS-CoV-2 antibodies (10-12), especially after mild disease(13)(14)(15).Since the onset of the COVID-19 pandemic a plethora of serological assays have emerged, using different methods such as ELISA, CLIA, lateral flow and multiplex systems(23).Although the discrepancies regarding the longevity of SARS-CoV-2 antibodies may well stem from variations in sensitivity and specificity of these assays, the target antigen of choice is a likely contributing factor. Notably, many of the widely used commercially available serological assays target the SARS-CoV-2 nucleocapsid antigen or linear peptides of the protein(23,24).…”

“…The kinetics, duration and efficacy of circulating SARS-CoV-2 antibodies are however, due to the novelty of the virus, less established. In fact, conflicting studies provide data on a rapid decline in circulating IgG antibodies within weeks after COVID-19 (10)(11)(12), especially after mild disease (13)(14)(15), while others report detectable antibodies up to two to six months after symptom onset (16)(17)(18)(19).…”

Symptomatic recurrence of SARS-CoV-2 infection in healthcare workers recovered from COVID-19

“…Another notable result from the study was that, in non-severe COVID-19 infections, antibody titers as well as proinflammatory cytokines decreased within a month after viral clearance. Thus, rapid decline in antibody titers may be a common feature of non-severe SARS-CoV-2 infection, suggesting that antibody-mediated protection against re-infection with SARS-CoV-2 is of short duration [8]. The lack of data about the SARS-CoV-2 antibodies and the viral load of the cases is the main limitation of our study.…”

Performance of 30 commercial SARS-CoV-2 serology assays in testing symptomatic COVID-19 patients

“…However, close to what was previously reported, in our study, most assays achieved sensitivity higher than 90%, both for RDTs and IAs, for sera collected more than 15 days after onset of symptoms [ 10 – 17 ]. Even if some current reports show that neutralizing antibodies decline in convalescent individuals in 2 to 5 months after infection, identifying patients with an history of SARS-CoV-2 infection might be particularly interesting to spare vaccine doses as it was recently described those patients presented high titers of neutralizing antibodies after receiving only one vaccine dose, with titers similar or higher than uninfected individuals that received two vaccine doses [ 18 – 21 ] (10.1101/2021.01.29.21250653).…”