key: cord-0812295-djs0yjts
authors: Lazor-Blanchet, C.; Zygoura, P.; Dafni, U.; Lamoth, F.; Tsourti, Z.; Lobritz, M.A.; Regina, J.; Grandbastien, B.; Fenwick, C.; Pantaleo, G.; Calandra, T.; Meylan, S.D.
title: Low neutralizing antibody titers after asymptomatic or non-severe SARS-CoV-2 infection over a 6-month assessment period
date: 2022-02-05
journal: J Infect
DOI: 10.1016/j.jinf.2022.02.001
sha: 316c5e97c3fd07998eb5fb998b50b0d689f5b8d9
doc_id: 812295
cord_uid: djs0yjts

nan

Low neutralizing antibody titers after asymptomatic or non-severe SARS-CoV-2 infection over a 6-month assessment period

Lazor-Blanchet C. a , Zygoura P. b  Patients with asymptomatic and mild SARS-CoV-2 infections are at risk of re-infection within the same year  Neutralizing capacity remains more stable over time than do anti-S IgG titers.

In their recent publication, Hanrath and co-workers describe protection against SARS-CoV-2 re-infection conferred by prior SARS-CoV-2 infection, as assessed by PCR over 6 months in healthcare workers (HCW) with a prior history COVID-19. 1 Neutralizing antibodies against SARS-CoV-2 are a key determinant of immunity following infection. 2,3 Data in convalescent patients who experienced moderate to severe disease suggest that this immune response may last for months, and generally correlates with disease severity. [4] [5] [6] However, serological responses in patients with asymptomatic or mild SARS-CoV-2 infections are less well defined. 7 We characterized serological responses to SARS-CoV-2 in asymptomatic or non-severe SARS-CoV-2 infections over a 6-month period. Specifically, we monitored the magnitude and kinetics of serological responses in 335 healthcare workers (HCW) found to be seropositive for SARS-CoV-2 using a Luminex-based technology targeting the trimeric spike protein. 8 This study group was composed of 198 (59%) seropositive HCW randomly selected throughout our institution 9 without a prior SARS-CoV-2 polymerase chain reaction positive test (PCR+) and 137 (41%) seropositive HCW recruited on the basis of a prior SARS-CoV-2 PCR+ test. SARS-CoV-2-specific antibody response was measured at baseline (end of May 2020), 3-and 6 months thereafter using the luminex-based quantitative anti-spike trimer protein assay to determine quantitative antibody responses, and a cell-free neutralization assay based on the competitive inhibition of trimeric SARS-CoV-2 spike protein binding to the angiotensin-converting enzyme 2 (ACE2) receptor to determine neutralizing capacity of the antibodies developed. 8, 10 Importantly, in this neutralizing activity assay a value of 50 percent is predictive of robust neutralisation capacity in cell assays. 10 re-infection, we observe that re-infection risk varies according to initial infection severity. 1 Consistent with recent data, we find that antibody titers can be influenced by infection severity and that neutralizing capacity remains more stable over time than does quantitative anti-S IgG titer. [4] [5] [6] However, in this cohort of seropositive HCWs, participants with asymptomatic and mild SARS-CoV-2 infections had relatively lower antibody titers and experienced higher rates of re-infection. We acknowledge that the subset of re-infected participants is small (possibly due to the timing of the survey) and results are only hypothesis generating. Nevertheless our findings strengthen the recommendation to boost by vaccination persons who are seropositive following natural infection with SARS-CoV-2, particularly those who experienced asymptomatic or mild infections in light of the low overall neutralizing activity observed over time in this subgroup.

The study was approved by the local institutional review board (Research Ethics Committee of the Canton de Vaud -CER-VD, Switzerland, Req-2020-00990).

Prior SARS-CoV-2 infection is associated with protection against symptomatic reinfection

Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers

Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults

Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

Evolution of antibody immunity to SARS-CoV-2

Robust neutralizing antibodies to SARS-CoV-2 infection persist for months

Early and long term antibody kinetics of asymptomatic and mild disease COVID-19 patients

Changes in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence Studies

SARS-CoV-2 seroprevalence in healthcare workers of a Swiss tertiary care centre at the end of the first wave: a cross-sectional study

Legends: Figure 1: Evolution of Anti-S IgG titers and neutralization capacity in HCWs across time (A): HCWs assayed for Anti-S protein (red) expressed in mean fluorescence intensity and mean neutralization values (green) expressed in percent of inhibition at 0, 3 and 6 months: 335/334, 302/289 and 294/294 HCWs Evolution of median neutralization activity

presenting for follow-up visits at 3-and 6-months, respectively. Participants were segregated according to disease severity at baseline, as per NIH classification (asymptomatic -blue, mild [myalgia, anosmia, cough, ageusia, fever, sore throat, diarrhea, common cold but without shortness of breath] -purple, moderate to severe [shortness of breath with or without hospitalization] -green). Units of neutralizing activity are expressed as inverse of the serum dilution required for 50 percent inhibition. Distribution according to disease severity at 0/3/6 months: Asymptomatic 105/91/88 HCWs