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

Olea, Beatriz; Albert, Eliseo; Torres, Ignacio; Amat, Paula; Remigia, María José; Gozalbo-Rovira, Roberto; Rodríguez-Díaz, Jesús; Buesa, Javier; Blasco, María Luisa; Redón, Josep; Signes-Costa, Jaime; Navarro, David

BACKGROUND: 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. PATIENTS AND 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. SARS-CoV-2-reactive CD69(+)-expressing-IFNγ-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-γ 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, 60–145 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 IFNγ 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.