Adaptive immune responses to SARS-CoV-2 in recovered severe COVID-19 patients

Olea, B.; Vicent, E. A.; Torres, I.; Amat, P.; Remigia, M. J.; Gozalbo, R.; Rodriguez, J.; Buesa, J.; Blasco, M. L.; Redon, J.; Signes, J.; Navarro, D.

Objectives: There is an imperative need to determine the durability of adaptive immunity to SARS-CoV-2. We enumerated SARS-CoV-2-reactive CD4+ and CD8+ T cells targeting S1 and M proteins and measured RBD-specific serum IgG over a period of 2-6 months after symptoms onset in a cohort of subjects who had recovered from severe clinical forms of COVID-19. Methods: We recruited 58 patients (38 males and 20 females; median age, 62.5 years), who had been hospitalized with bilateral pneumonia, 60% with one or more comorbidities. IgG antibodies binding to SARS-CoV-2 RBD were measured by ELISA. SARSCoV-2-reactive CD69+ -expressing-IFN{gamma}-producing-CD4+ and CD8+ T cells were enumerated in heparinized whole blood by flow cytometry for ICS. Results: Detectable SARS-CoV-2-S1/M-reactive CD69+ -IFN-{gamma} CD4+ and CD8+ T cells were displayed in 17 (29.3%) and 6 (10.3%) subjects respectively, at a median of 84 days after onset of symptoms (range, 58-191 days). Concurrent comorbidities increased the risk (OR, 3.15; 95% CI, 1.03-9.61; P=0.04) of undetectable T-cell responses in models adjusted for age, sex and hospitalization ward. Twenty-one out of the 35 patients (60%) had detectable RBD-specific serum IgGs at a median of 118 days (range, 60 to 145 days) after symptoms onset. SARS-CoV-2 RBD specific IgG serum levels were found to drop significantly over time. Conclusion: A relatively limited number of subjects who developed severe forms of COVID-19 had detectable SARS-CoV-2-S1/M IFN{gamma} CD4+ and CD8+ T cells at midterm after clinical diagnosis. Our data also indicated that serum levels of RBD specific IgGs decline over time, becoming undetectable in some patients.