Inflammation parameters predict fatal outcome in male COVID-19 patients in a low case-fatality area–a population-based registry study

Abstract

Background: Male sex predicts case-fatality in SARS-CoV-2 (COVID-19)–a phenomenon linked to systemic inflammation. We compared sex-related associations of inflammation parameters and outcome in a population-based setting with low case-fatality prior to wide use of immunosuppressives. Methods: A population-based quality registry with laboratory-confirmed COVID-19 cases of specialized hospitals of the Capital Province of Finland were analysed to compare inflammatory parameters by sex during the first COVID-19 wave February–June 2020. Results: Altogether, 585 hospitalized patients (54% males) were included. Males required more often intensive care unit (ICU) treatment (26.9 vs. 17.5%) and had higher 90-d case-fatality (14.9 vs. 7.8%) compared with females. Highest association with case-fatality in males was seen for high neutrophil counts (median; interquartile range) (8.70; 7.10–9.10 vs. 5.60; 3.90–7.80) (E9/l), low monocyte (0.50; 0.20–1.50 vs. 0.70; 0.50–0.90) (E9/l) and lymphocyte (0.90; 0.70-1.40 vs. 1.50; 1.10-2.00) (E9/l) counts, and high levels of d-dimer (3.80; 1.80–5.30 vs. 1.10; 0.60–2.75) (mg/l) and C-reactive protein (CRP) (190; 85.5–290 vs. 77.0; 49.0–94.0) (mg/l). In females, low lymphocyte (0.95; interquartile range 0.60–1.28 vs. 1.50; 1.10–2.00) (E9/l) and thrombocyte counts (196; 132–285 vs. 325; 244–464) (E9/l) and high CRP values (95.0; 62.0–256 vs. 66.0; 42.5–89.0) (mg/l) were associated with case-fatality. In multivariable analysis for males, lymphocyte cut-off 0.85 (E9/l) (OR 0.02; 95% CI 0.002–0.260), d-dimer cut-off 1.15 (mg/l) (OR 7.29; 1.01–52.6) and CRP cut-off 110 (mg/l) (OR 15.4; 1.87–127) were independently associated with case-fatality. In female multivariable analysis, CRP cut-off 81 (mg/l) (OR 7.32; 1.44–37.2) was the only inflammatory parameter associated with case-fatality. Conclusions: COVID-19 results in higher inflammation parameter levels in male vs. female patients irrespective of outcome. This study suggests that low lymphocyte, high d-dimer and high CRP cut-off values may serve as potential markers for risk stratification in male patients.