Robust humoral and cellular immune responses and low risk for reinfection at least 8 months following asymptomatic to mild COVID-19

Abstract

Background: Emerging data support detectable immune responses for months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, but it is not yet established to what degree and for how long protection against reinfection lasts.

Methods: We investigated SARS-CoV-2-specific humoral and cellular immune responses more than 8 months post-asymptomatic, mild and severe infection in a cohort of 1884 healthcare workers (HCW) and 51 hospitalized COVID-19 patients. Possible protection against SARS-CoV-2 reinfection was analyzed by a weekly 3-month polymerase chain reaction (PCR) screening of 252 HCW that had seroconverted 7 months prior to start of screening and 48 HCW that had remained seronegative at multiple time points.

Results: All COVID-19 patients and 96% (355/370) of HCW who were anti-spike IgG positive at inclusion remained anti-spike IgG positive at the 8-month follow-up. Circulating SARS-CoV-2-specific memory T cell responses were detected in 88% (45/51) of COVID-19 patients and in 63% (233/370) of seropositive HCW. The cumulative incidence of PCR-confirmed SARS-CoV-2 infection was 1% (3/252) among anti-spike IgG positive HCW (0.13 cases per 100 weeks at risk) compared to 23% (11/48) among anti-spike IgG negative HCW (2.78 cases per 100 weeks at risk), resulting in a protective effect of 95.2% (95% CI 81.9%-99.1%).

Conclusions: The vast majority of anti-spike IgG positive individuals remain anti-spike IgG positive for at least 8 months regardless of initial COVID-19 disease severity. The presence of anti-spike IgG antibodies is associated with a substantially reduced risk of reinfection up to 9 months following asymptomatic to mild COVID-19.

Keywords: COVID-19; SARS-CoV-2; humoral response; long-term immunity; reinfection.

Fig. 1

Long‐term humoral and cellular immune responses in healthcare workers (HCW) and COVID‐19 patients. Normalized anti‐spike IgG levels (a) and concentration of background‐adjusted interferon‐gamma (IFN‐γ) levels after SARS‐CoV‐2‐specific peptide stimulation of whole blood (b) in HCW less than or equal to 4 months post‐infection (HCW ≤ 4 MPI), n = 259, HCW 5–8 months post‐infection (HCW 5–8 MPI), n = 116, HCW at least 8 months post‐infection (HCW ≥ 8 MPI), n = 370, hospitalized COVID‐19 patients at least 8 months post‐infection (Cov19 Pat ≥ 8 MPI), n = 51, and anti‐spike IgG negative HCW at all sampling time points, n = 1076. Purple and orange: Anti‐Spike IgG seropositive and seronegative, respectively. Blue and green: Positive and negative IFN‐γ response to the SARS‐CoV‐2‐specific peptide pool, respectively. p‐values are shown with brackets

Fig. 2

Incidence of three‐month weekly qPCR screening. The cumulative incidence of qPCR‐confirmed SARS‐CoV‐2 infection in healthcare workers who had seroconverted (anti‐spike IgG; red line) 7 months prior to initiation of the qPCR screening, and in anti‐spike IgG negative healthcare workers (blue line)

Fig. 3

Study timeline. Flow chart depicting number of healthcare workers (HCW) and COVID‐19 patients at each follow‐up and qPCR screening sub‐study. Patients indicate COVID‐19 patients