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

Abstract

Current SARS-CoV-2 serological assays generate discrepant results, and the longitudinal characteristics of antibodies targeting various antigens after asymptomatic to mild COVID-19 are yet to be established. This longitudinal cohort study including 1972 healthcare workers, of which 386 participants exhibited antibodies against the SARS-CoV-2 spike antigen at study inclusion, reveal that these antibodies remain detectable in the vast majority of participants, 98%, at least four months post infection, despite having had no or mild symptoms. These antibody levels did not differ from those found in 59 convalescent COVID-19 patients (p=0.7). Virus neutralization capacity was confirmed by microneutralization assay in 93% of study participants at least four months post infection. Contrary to antibodies targeting the spike protein, antibodies against the nucleocapsid protein were only detected in 68% of previously anti-nucleocapsid IgG positive healthcare workers, and these four-month follow-up levels were substantially lower in healthcare workers than in convalescent COVID-19 patients (p=2*10-5). Our findings support a durable and functional humoral response after SARS-CoV-2 infection, even after no or mild symptoms. We further demonstrate differences in antibody kinetics depending on the antigen, arguing against the use of the nucleocapsid protein as target antigen in population-based SARS-CoV-2 serological surveys.

Monitoring of anti-SARS-CoV-2 IgG antibody immune response in infected and immunised healthcare workers in Hungary: a real-world longitudinal cohort study

“…Our findings partially confirm the results of Havervall and colleagues who followed-up 2300 previously SARS-CoV-2 infected healthcare workers in Sweden and found the average time for the reduction of anti-SARS-CoV IgG below the positive cut-off point between 4-6 months [22]. They also found the association between higher immune response levels and more severe symptoms statistically significant similar to the study by Long et al conducted earlier on 37 asymptomatic persons from China [4, 22]. The lack of statistical significance between symptom severity and level of immune response in our study is potentially linked to our limited sample size.…”

Seven-month kinetics of SARS-CoV-2 antibodies and protective role of pre-existing antibodies to seasonal human coronaviruses on COVID-19

“…Several studies have observed relatively stable levels of IgG to the spike (S) protein after three 11,6 , four 12,13 and six to eight months 2,9,14-16 . However, others reported that IgG only lasted around 3-4 months PSO 17,18 . Many studies consistently observe that IgG to the nucleocapsid (N) protein, found inside the virus or infected cells, decay faster than IgG to S, being a marker of a most recent infection but less sensitive for assessing population seroprevalence 2,13-20 .…”

The prevalence of adaptive immunity to COVID-19 and reinfection after recovery – a comprehensive systematic review and meta-analysis

“…Data from 26 studies (8, 9, 11, 12, 16, 17, 29, 47, 49-53, 56, 57, 60, 63, 64, 67, 69, 71, 75, 78, 81, 82, 84), with 3092 participants were available for evaluation of the prevalence of detectable IgG after recovery. The pooled prevalence of detectable IgG after recovery was 89.0% (95%CI 72.8 – 99.0, I 2 =89.7%, p<0.01, 8 studies) within 1 month, 92.6% (95%CI 86.9 – 96.9, I 2 =57.7%, p<0.01, 4 studies) at >1 - <3 months, 91.4% (95%CI 84.5-96.3, I 2 =84.3%, p<0.01, 9 studies) at 3-<6 months and 90.4% (95%CI 72.2-99.9, I 2 =89.0%, p<0.01, 5 studies) beyond 6 months (Fig 3 and Supplementary Figs.…”

“…Several studies have shown that individuals infected with SARS-CoV-2 develop neutralizing antibodies (7,8), and that, up to 8 months later, most individuals who recover from COVID-19 have evidence of immunological memory (9)(10)(11)(12)(13). However, many of these studies involve small numbers of participants and suffer from loss to follow up.…”