Abstract

Introduction
The persistence of the SARS-CoV-2 virus is related to inflammation and lymphopenia  in severe Covid-19. Longitudinal follow-up of patients is scarce and would be of help to determine if the different immune responses lead to different clinical presentations

Methods
Longitudinal prospective observational study of 91 patients. They were classified into viral phase, early inflammatory, and late inflammatory. We included clinical data, immune cell count, proinflammatory cytokine levels, serum inflammatory markers and tissue damage.

Results
Lymphocyte count was lower with greater severity, and double in survivors. It remained stable during evolution, but with variations depending on the level of severity: critical and deceased patients, had a very low initial count (500/mm3) that did not increase; severe patients the initial lymphopenia (900/mm3) normalized during hospitalization; and moderate, showed a normal and stable count. 
The correlation of the initial innate immune response cytokine TNF-a with the T-cell-derived (CD4+) cytokines, IFN-g and IL-17A, was significant at all severity levels, although this correlation decreased in the late inflammatory phase. Furthermore, in patients who reached critical status or died, there was not the sustained increase in IFN-g levels observed in less severe Covid-19 (p<0.001), coinciding with the persistent lymphopenia in those patients.

Conclusion
Our results confirm a drop in lymphocyte counts and decreased production of effector T-cell cytokines in the most severe patients, especially in the late phase of evolution, in line with the lymphocyte depletion described in critical and fatal Covid-19 disease.