SARS-CoV-2 infection can be a life-threatening disease. The optimal treatment of patients is not yet standardized. We use a serology-based therapeutic strategy based on the presence of antibodies against the SARS-CoV-2 virus, in which patients with positive serology receive aggressive anti-inflammatory treatment with high-dose dexamethasone and/or tocilizumab and patients with negative serology receive early convalescent plasma therapy. We also analyze the immunological impact of this therapy in the recovery of T cells, B cells and NK cells during hospitalization in a COVID-19 infectious ward. Our results suggest that aggressive therapy with early administration of convalescent plasma and high-dose dexamethasone may be of benefit in patients with SARS-CoV-2 infection and might avoid progression of lung damage or need of admission in intensive care. This strategy did not impair immune responses against SARS-CoV-2, as 93% of the patients generated antibodies against the virus. Independently of previous immunological status of the patients, serology-guided therapy might benefit even patients with a high CIRS-G score, immunosuppressed or medically debilitated individuals and elderly patients. T cell disturbances were most frequent in patients who required high-dose dexamethasone, and B cell depletion was most frequent in patients who received tocilizumab. Early passive immunotherapy with convalescent plasma does not affect lymphoid recovery.