Kinetics of humoral immune response over 17 months of COVID-19 pandemic in a large cohort of healthcare workers in Spain: the ProHEpiC-19 study

Abstract

Background Understanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and control strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months. Methods We established a cohort of 769 healthcare workers including healthy and infected with SARS-CoV-2 in northern Barcelona to determine the kinetics of the IgM against the nucleocapsid (N) and the IgG against the N and spike (S) of SARS-CoV-2 in infected healthcare workers. The study period was from 5 May 2020 to 11 November 2021.We used non-linear mixed models to investigate the kinetics of IgG and IgM measured at nine time points over 17 months from the date of diagnosis. The model included factors of time, gender, and disease severity (asymptomatic, mild-moderate, severe-critical) to assess their effects and their interactions. Findings 474 of the 769 participants (61.6%) became infected with SARS-CoV-2. Significant effects of gender and disease severity were found for the levels of all three antibodies. Median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease at day 270 after the diagnosis, while IgG(N and S) levels remained positive at least until days 450 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay with a rate depending on disease severity. IgG(S) levels remained relatively constant from day 15 over time. Interpretation IgM(N) and IgG(N, S) SARS-CoV-2 antibodies showed a heterogeneous kinetics over the 17 months. Only the IgG(S) showed a stable increase, and the levels and the kinetics of antibodies varied according to disease severity. The kinetics of IgM and IgG observed over a year also varied by clinical spectrum can be very useful for public health policies around vaccination criteria in adult population. Funding Regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478).

Seroprevalence of IgG and Subclasses against the Nucleocapsid of SARS-CoV-2 in Health Workers

“…The seroprevalence of IgG antibodies against SARS-CoV-2 varied according to the study population and geographic region. We reported a seroprevalence of 42.69% of anti-N IgG antibodies; similar studies have reported a seroprevalence from 16.9% to 41.7% [14,17,18], associated with the constant exposition of health workers to COVID-19 patients and asymptomatic infections. In our studied population, patients reported obesity, hypertension, and diabetes.…”

“…The prevalence of IgG antibodies against the N protein varied according to the geographic region, disease severity, group, and occupational exposition [13][14][15]; specifically in health workers, the reported prevalence went from 4.14% to 41.7% [14,[16][17][18]. Health workers had a higher risk of infection due to direct contact with infected patients and the development of asymptomatic disease [19].…”

Determinants of Anti-S Immune Response at 9 Months after COVID-19 Vaccination in a Multicentric European Cohort of Healthcare Workers—ORCHESTRA Project

“…Anti-N and anti-S antibodies detected with the ECLIA method have been reported to persist at 9 months in ≥ 90% of subjects who were infected by COVID-19 [11]. Additionally, a recent study conducted in Spain (the ProHEpiC-19 cohort study) demonstrated the persistence of positive anti-N antibodies until 450 days (15 months) [21].…”

Antibody response to the COVID-19 ChAdOx1nCov-19 and BNT162b vaccines after temporary suspension of DMARD therapy in immune-mediated inflammatory disease: an extension study (RESCUE 2)

“…The most important factor in influencing the SARS-CoV2 level at 6 months was the peak antibody level following the second vaccination of the primary vaccine regimen. Studies examining the antibody decay kinetics in participants following COVID-19 infection showed that the height of the peak is dependent on disease severity with antibodies for IgG remaining above the positivity threshold for up to 500 days 15–17. Following vaccination our study showed that SARS-CoV2-Ig Ab persistence (≥7.0 U/mL) was 62 days for the AZ and 210 days for the Pfizer vaccine.…”