Assessing the association between antibody status and symptoms of long COVID: A multisite study

The association between SARS-CoV-2 humoral immunity and post-acute sequelae of COVID-19 (long COVID) remains uncertain. The objective of this population-based cohort study was to assess the association between SARS-CoV-2 seropositivity and symptoms consistent with long COVID. English and Spanish-speaking members ≥ 18 years old with SARS-CoV-2 serologic testing conducted prior to August 2021 were recruited from Kaiser Permanente Southern California and Kaiser Permanente Colorado. Between November 2021 and April 2022, participants completed a survey assessing symptoms, physical health, mental health, and cognitive function consistent with long COVID. Survey results were linked to SARS-CoV-2 antibody (Ab) and viral (RNA) lab results in electronic health records. Weighted descriptive analyses were generated for five mutually exclusive patient groups: (1) +Ab/+RNA; (2) +Ab/- or missing RNA; (3) -Ab/+RNA; (4a) -Ab/-RNA reporting no prior infection; and (4b) -Ab/-RNA reporting prior infection. The proportions reporting symptoms between the +Ab/+RNA and -Ab/+RNA groups were compared, adjusted for covariates. Among 3,946 participants, the mean age was 52.1 years old (SD 15.6), 68.3% were female, 28.4% were Hispanic, and the serologic testing occurred a median of 15 months prior (IQR = 12-18). Three quarters (74.5%) reported having had COVID-19. Among people with laboratory-confirmed COVID-19, there was no association between antibody positivity (+Ab/+RNA vs. -Ab/+RNA) and any symptoms, physical health, mental health, or cognitive function. As expected, physical health, cognitive function, and fatigue were worse, and palpitations and headaches limiting the ability to work were more prevalent among people with laboratory-confirmed prior infection and positive serology (+Ab/+RNA) compared to those without reported or confirmed prior infection and negative serology (-Ab/-RNA/no reported COVID-19). Among people with laboratory-confirmed COVID-19, SARS-CoV-2 serology from practice settings were not associated with long COVID symptoms and health status suggesting limited utility of serology testing for long COVID.