Determinants of IgG antibodies kinetics after severe and critical COVID‐19

Abstract

The kinetics of IgG antibodies after coronavirus disease 2019 (COVID‐19) remain poorly understood. We investigated factors influencing severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) IgG antibody levels and time to seronegativation during the follow‐up of severe and critically ill patients. We retrospectively reviewed serological evaluations drawn during the follow‐up of severe or critical laboratory‐proven COVID‐19 patients hospitalized at a large academic hospital. Specific IgG titers were measured using a chemiluminescent assay targeting anti‐spike and anti‐nucleocapsid protein IgG. The influence of time, demographic factors, clinical and paraclinical characteristics, and COVID‐19 therapeutics on IgG levels were assessed through linear regression using a mixed‐effect model, and delay until IgG negativation through a Weibull regression model. The cohort included 116 patients with a total of 154 IgG measurements drawn at a median of 79 days after diagnosis. IgG antibodies were increased with age ( p = 0.005) and decreased significantly over time ( p = 0.0002). Using elapsed time and age as covariates, we demonstrated higher IgG levels in patients with a higher body mass index (BMI) ( p = 0.0026) and lower IgG levels in immunocompromised patients ( p = 0.032). A high BMI was further found to delay and immunodeficiency to hasten significantly seronegativation, whereas no significant effect was observed with corticosteroids. These data highlight the waning over time of IgG antibodies after severe or critical COVID‐19. Age, BMI, and immunosuppression also appear to influence the IgG kinetics, while short‐term corticotherapy does not. Those data improve the understanding of SARS‐CoV‐2 serology while further research should determine the determinants of long‐term seroprotection.

Defining Antibody Seroprevalence and Duration of Humoral Responses to SARS-CoV-2 Infection and/or Vaccination in a Greek Community

“…Varona et al, found that seropositive healthcare workers of the Spanish Hospitals Group remained seropositive after 9 months but with a significant decline in antibody titers and two distinct antibody dynamic profiles were identified (declining vs. stable). Independent factors associated with longer persistence of antibodies were symptomatic infection and higher exposure to COVID-19 patients [ 24 , 28 , 29 ], age, BMI, and immunosuppression [ 30 ].…”

Decline of Anti-SARS-CoV-2 IgG Antibody Levels 6 Months after Complete BNT162b2 Vaccination in Healthcare Workers to Levels Observed Following the First Vaccine Dose

“…The analysis of specific antibodies in patients with a history of COVID-19 linked the immune response to various factors, including disease stage and severity, age, and comorbidities. While IgG antibodies can be detected in a vast majority of COVID-19 patients 10 days after the infection, their levels generally decrease over time [4][5][6][7]. Similar patterns in antibody dynamics could be predicted after vaccination [15][16][17][18][19][20][21].…”

“…Following SARS-CoV-2 infection, immunocompetent patients rapidly develop specific antibodies, whose levels generally show a positive correlation with disease severity [3][4][5][6][7]. Relatively high antibody levels in severe COVID-19 raise the question of their efficiency in immune defense.…”

“…Assuming that levels of anti-SARS-CoV-2 IgG correlate with the duration of effective immunity, antibody kinetics monitoring could prove useful as a possible predictor for revaccination planning. While neutralizing antibodies could play an important role in the clinical course of COVID-19, cellular immunity appears to be even more significant [2,7,[12][13][14].…”

Qualification of ELISA and neutralization methodologies to measure SARS-CoV-2 humoral immunity using human clinical samples

“…Early investigations of infection-induced responses for diagnostic purposes included evaluation of IgA, IgM and IgG humoral immunity ( Ma et al, 2020 ; Bichara et al, 2021 ; Maeda et al, 2021 ) and many commercial kits have been developed for these endpoints. SARS-CoV-2 specific IgA seems to be a high performing early diagnostic endpoint ( Ma et al, 2020 ; Sterlin et al, 2021 ), while the kinetics of post-infection IgM and IgG better reflect peak and waning immunity in convalescent cohorts ( Bichara et al, 2021 ; Duysburgh et al, 2021 ; De Greef et al, 2021 ). Interestingly, some studies have observed pro-inflammatory IgG subsets (IgG1 and IgG3) trend higher with severity of clinical COVID-19 disease while others (IgG2 and IgG4) are rarely detected ( Yates et al, 2021 ; Luo et al, 2021 ).…”