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

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. 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. 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%). 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.

Havervall S ，Ng H ，Jernbom Falk A ，Greilert-Norin N ，Månberg A ，Marking U ，Laurén I ，Gabrielsson L ，Salomonsson AC ，Aguilera K ，Kihlgren M ，Månsson M ，Rosell A ，Hellström C ，Andersson E ，Olofsson J ，Skoglund L ，Yousef J ，Pin E ，Lord M ，Åberg M ，Hedhammar M ，Tegel H ，Dönnes P ，Phillipson M ，Nilsson P ，Klingström J ，Mangsbo S ，Hober S ，Thålin C ... -  《-》

Evolution of antibody responses up to 13 months after SARS-CoV-2 infection and risk of reinfection.

Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11-13 of 283 days (95% CI 231-349) for anti-N and 725 days (95% CI 623-921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42-1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants. FUN1DING: None.

Gallais F ，Gantner P ，Bruel T ，Velay A ，Planas D ，Wendling MJ ，Bayer S ，Solis M ，Laugel E ，Reix N ，Schneider A ，Glady L ，Panaget B ，Collongues N ，Partisani M ，Lessinger JM ，Fontanet A ，Rey D ，Hansmann Y ，Kling-Pillitteri L ，Schwartz O ，De Sèze J ，Meyer N ，Gonzalez M ，Schmidt-Mutter C ，Fafi-Kremer S ... -  《EBioMedicine》

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

The relationship between the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of subsequent reinfection remains unclear. We investigated the incidence of SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) in seropositive and seronegative health care workers attending testing of asymptomatic and symptomatic staff at Oxford University Hospitals in the United Kingdom. Baseline antibody status was determined by anti-spike (primary analysis) and anti-nucleocapsid IgG assays, and staff members were followed for up to 31 weeks. We estimated the relative incidence of PCR-positive test results and new symptomatic infection according to antibody status, adjusting for age, participant-reported gender, and changes in incidence over time. A total of 12,541 health care workers participated and had anti-spike IgG measured; 11,364 were followed up after negative antibody results and 1265 after positive results, including 88 in whom seroconversion occurred during follow-up. A total of 223 anti-spike-seronegative health care workers had a positive PCR test (1.09 per 10,000 days at risk), 100 during screening while they were asymptomatic and 123 while symptomatic, whereas 2 anti-spike-seropositive health care workers had a positive PCR test (0.13 per 10,000 days at risk), and both workers were asymptomatic when tested (adjusted incidence rate ratio, 0.11; 95% confidence interval, 0.03 to 0.44; P = 0.002). There were no symptomatic infections in workers with anti-spike antibodies. Rate ratios were similar when the anti-nucleocapsid IgG assay was used alone or in combination with the anti-spike IgG assay to determine baseline status. The presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months. (Funded by the U.K. Government Department of Health and Social Care and others.).

Lumley SF ，O'Donnell D ，Stoesser NE ，Matthews PC ，Howarth A ，Hatch SB ，Marsden BD ，Cox S ，James T ，Warren F ，Peck LJ ，Ritter TG ，de Toledo Z ，Warren L ，Axten D ，Cornall RJ ，Jones EY ，Stuart DI ，Screaton G ，Ebner D ，Hoosdally S ，Chand M ，Crook DW ，O'Donnell AM ，Conlon CP ，Pouwels KB ，Walker AS ，Peto TEA ，Hopkins S ，Walker TM ，Jeffery K ，Eyre DW ，Oxford University Hospitals Staff Testing Group ... -  《-》

Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark.

Johannesen CK ，Rezahosseini O ，Gybel-Brask M ，Kristensen JH ，Hasselbalch RB ，Pries-Heje MM ，Nielsen PB ，Knudsen AD ，Fogh K ，Norsk JB ，Andersen O ，Jensen CAJ ，Torp-Pedersen C ，Rungby J ，Ditlev SB ，Hageman I ，Møgelvang R ，Dessau RB ，Sørensen E ，Harritshøj LH ，Folke F ，Sten C ，Møller MEE ，Engsig FN ，Ullum H ，Jørgensen CS ，Ostrowski SR ，Bundgaard H ，Iversen KK ，Fischer TK ，Nielsen SD ... -  《Microbiology Spectrum》

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

Havervall S ，Jernbom Falk A ，Klingström J ，Ng H ，Greilert-Norin N ，Gabrielsson L ，Salomonsson AC ，Isaksson E ，Rudberg AS ，Hellström C ，Andersson E ，Olofsson J ，Skoglund L ，Yousef J ，Pin E ，Christ W ，Olausson M ，Hedhammar M ，Tegel H ，Mangsbo S ，Phillipson M ，Månberg A ，Hober S ，Nilsson P ，Thålin C ... -  《-》