Comorbidities Diminish the Likelihood of Seropositivity After SARS-CoV-2 Vaccination

Background: The impact of chronic health conditions (CHC) on serostatus post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is unknown. Methods: We assessed serostatus post-SARS-CoV-2 vaccination among fully vaccinated participants recruited between April 2021 through August 2021 in 18 years and older residents of Jefferson County, Kentucky, USA. Serostatus was determined by measuring SARS-CoV-2 Spike protein specific immunoglobulin (Ig) G (Spike IgG) antibodies via enzyme-linked immunoassay (ELISA) in peripheral blood samples. Results: Of the 5,178 fully vaccinated participants, 51 were seronegative and 5,127 were seropositive. Chronic kidney disease (CKD) (OR=13.49; 95% CI: 4.88, 37.3; P<0.0001) and autoimmune disease (OR=11.34; 95% CI: 5.21, 24.69; P<0.0001) showed highest association with negative serostatus in fully vaccinated participants. The absence of any CHC was strongly associated with positive serostatus (OR=0.37; 95% CI: 0.19, 0.73; P=0.003). The risk of negative serostatus increased in the presence of two CHCs (OR=2.82; 95% CI: 1.14, 7) to three or more CHCs (OR=4.52; 95% CI: 1.68, 12.14). Similarly, use of 2 or more CHC related medications was significantly associated with seronegative status (OR=6.08; 95%: 2.01, 18.35). Conclusions: Presence of any CHC, especially CKD or autoimmune disease, increased the likelihood of seronegative status among individuals who were fully vaccinated to SAR-CoV-2. This risk increased with a concurrent increase in number of comorbidities, especially with multiple medications. Absence of any CHC was protective and increased the likelihood of a positive serological response post-vaccination. These results will help develop appropriate guidelines for booster doses and targeted vaccination programs.