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There is limited information regarding the severity of COVID-19 in immunocompromized patients. We conducted a retrospective cohort study considering the period from 1 March 2020 to 31 December 2020 to determine whether previously existing lymphopenia increases the risk of hospitalization and death after SARS-CoV-2 infection in the general population. The laboratory and hospital discharge databases of the Azienda Sanitaria Universitaria Friuli Centrale were used, and 5415 subjects infected with SARS-CoV-2 and with at least one recent absolute lymphocyte count determination before SARS-CoV-2 positivity were included. In total, 817 (15.1%) patients had severe COVID-19. Patients developing severe COVID-19 were more frequently males (44.9% of the severe COVID-19 group vs. 41.5% in the non-severe COVID-19 group; p &lt; 0.0001) and were older (73.2 ± 13.8 vs. 58.4 ± 20.3 years; p &lt; 0.0001). Furthermore, 29.9% of the lymphopenic patients developed severe COVID-19 vs. 14.5% of the non-lymphopenic patients (p &lt; 0.0001). In a logistic regression model, female sex remained a protective factor (OR = 0.514, 95%CI 0.438–0.602, p &lt; 0.0001), while age and lymphopenia remained risk factors for severe COVID-19 (OR = 1.047, 95%CI 1.042–1.053, p &lt; 0.0001 for each additional year of age; OR = 1.715, 95%CI 1.239–2.347, p = 0.0011 for lymphopenia). This provides further information to stratify the risk of COVID-19 severity, which may be an important element in the management of immunosuppressive therapies.

Pre-Existing Lymphopenia Increases the Risk of Hospitalization and Death after SARS-CoV-2 Infection