Immune response after SARS-CoV-2 infection with residual post COVID symptoms

ABSTRACT BACKGROUND In a number of patients, post-acute COVID syndrome develops after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Long COVID [LC]). Here, we examined the immune responses and clinical characteristics of individuals with LC compared to age- and gender-matched healthy recovered COVID individuals (HC) during the Omicron pandemic. Immune responses following BNT162b2 (Pfizer) booster are also determined. METHODS This retrospective cohort study included 292 patients (LC, 158; HC, 134) confirmed to have SARS-CoV-2 infection from January to August 2022. We determined anti-SARS-CoV-2 receptor-binding domain immunoglobulin G (anti-RBD IgG), surrogate virus neutralization test (sVNT), T-cell subsets, and neutralization of wild-type, BA.1 and BA.5. A subset of patients was voluntarily recruited for booster vaccination with BNT162b2 vaccine and immunogenicity was assessed 4weeks after vaccination. RESULTS Cycle thresholds were higher in the HC group than in the LC group (20.7 vs. 19.7; P<0.039). Anti-RBD IgG was higher at ≤56 days after COVID-19 onset (PC) in 3-dose vaccines compared with 2-dose vaccines in the LC group (P=0.02) and after 57-84 days PC in 3-dose vaccines in the HC group (P<0.001). The sVNT in LC was significantly high against Wuhan and sVNT was 30% lower against the Omicron than the Wuhan. sVNT was relatively sustained in 3-dose vaccines than ≤ 2-dose vaccines. sVNT in the HC group reached its peak at 57-84 days PC as compared with the LC group. CONCLUSIONS These findings imply that LC produced increased neutralizing antibody responses than those with HC. During the Omicron pandemic, immunity after LC has still waned; therefore, a booster vaccine may be needed after 2-3 months from last infection. ( ClinicalTrials.gov number, NCT05484700 )