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.

An evaluation of a FluoroSpot assay as a diagnostic tool to determine SARS-CoV-2 specific T cell responses

“…Blood samples were obtained from the ongoing COMMUNITY (COVID-19 Biomarker and Immunity) study [ 5 , 10 – 12 ]) which investigates long-term immunity after COVID-19 infection and vaccination. 2149 HCW and 118 COVID-19 patients were enrolled at Danderyd Hospital, Stockholm, Sweden, between April 15 th —June 8 th 2020.…”

“…Peripheral blood mononuclear cell (PBMC) isolation was performed using a Ficoll density gradient together with SepMate™ tubes, according to the manufacturer’s instructions (StemCell, Canada) and cells were cryopreserved in FBS (Gibco) with 10% DMSO (Tocris, England). SARS-CoV-2-specific T cell reactivity was evaluated by the dual IFN-γ and IL-2 (data from the IL-2 readout are not evaluated herein) FluoroSpot (Mabtech) using a commercial S1 peptide pool, referred to as P166, spanning the S1 domain of the S protein, a commercial peptide mixed pool, referred to as P47, with peptides derived from the S protein, N protein, membrane protein and the open reading frame (ORF)-3a and ORF-7a proteins (both from Mabtech) and an in-house designed SARS-CoV-2-specific pool, referred to as P16, with no more than 5 amino acid stretches aligning with endemic HCoVs previously used in a whole-blood assay assessing SARS-CoV-2 specific T cell responses [ 5 ]. The peptide sequences for the in-house pool as well as the overlapping sequencing with endemic HCoVs, SARS and MERS for all peptide pools used are presented in the S1 and S2 Tables.…”

“…However, the magnitude and duration of the cellular response have been difficult to clearly assess due to the presence of cross-reactive T cell responses owing to previous encounters with endemic human coronaviruses (HCoVs), thus affecting the assay’s specificity. Importantly, many peptide pools spanning the SARS-CoV-2 proteins include peptides overlapping with regions of endemic HCoVs, resulting in cross-reactive T cell responses to SARS-CoV-2 in pre-pandemic samples as shown by Mateus et al [ 8 ] as well as Le Bert et al [ 9 ] and our recent data [ 5 ], which provides a challenge when developing diagnostic tests based on T cell responses. Nonetheless, the large public interest for assays determining immunity against SARS-CoV-2 on an individual basis, along with more or less sensitive serological assays and limited PCR testing capacity early in the pandemic, has led to the launch of cellular immune response assays targeting the general public.…”

“…Since the outbreak of SARS-CoV-2 in Wuhan in 2019 and the subsequent global pandemic, major efforts have been invested into large, population-based immunological surveys assessing long-term immune responses after COVID-19 contraction. The vast majority of COVID-19 cases seroconvert (91–99%) [ 1 – 4 ] and neutralizing IgG levels remain relatively stable for at least eight months [ 2 , 5 ]. The majority of individuals infected with COVID-19 generate SARS-CoV-2-specific T cell responses [ 5 – 7 ].…”

“…The vast majority of COVID-19 cases seroconvert (91–99%) [ 1 – 4 ] and neutralizing IgG levels remain relatively stable for at least eight months [ 2 , 5 ]. The majority of individuals infected with COVID-19 generate SARS-CoV-2-specific T cell responses [ 5 – 7 ]. In an eight months follow-up study, levels of SARS-CoV-2 specific CD4+ T cells remained stable over time, whereas circulating CD8+ T cells were suggested to have a shorter half-life [ 7 ].…”