Sex-specific hemostatic responses and alterations of Platelet Distribution Width (PDW) and D-dimer in mild COVID-19, Malaria, and co-infection in a tropical setting: A case-control study in Port Harcourt, Nigeria.

Abstract

In malaria-endemic tropical regions, overlapping coagulopathy in COVID-19 and malaria poses management challenges with potential sex differences. This STROBE-compliant case-control study evaluated sex-specific variations in platelet indices and assessed alterations of platelet distribution width (PDW) and D-dimer in mild cases. We studied 220 participants, 55 per group: healthy controls, malaria-positive, COVID-19-positive, and COVID-19 plus malaria co-infected, aged 20-65 years, balanced by sex (22 females and 33 males per group), conducted in Port Harcourt, Nigeria between November 2021 and March 2022. Platelet indices were measured using Sysmex XP-300 and D-dimer and fibrinogen by sandwich-ELISA. Data were analyzed using SAS 9.4 and JMP 14.3. PDW was significantly elevated in all infected groups versus controls: malaria 15.19 ± 1.47 fL, COVID-19 15.17 ± 1.51 fL, co-infection 15.58 ± 1.45 fL versus control 13.27 ± 1.20 fL; F = 25.850, p < 0.001. D-dimer was highest in co-infected group 552.80 ± 402.46 ng/mL; F = 2.816, p = 0.040. Two-way ANOVA showed no significant group×sex interaction for platelet indices but significant interactions for fibrinogen F = 18.42, p < 0.001 and D-dimer F = 3.14, p = 0.026. Sex-stratified analysis showed PDW higher in females in malaria p = 0.012 and co-infection p = 0.033, and D-dimer higher in males only in malaria p = 0.021. No significant correlations were observed between platelet indices and fibrinolytic markers. PDW was consistently elevated across mild infections and sex significantly modified fibrinolytic markers, indicating PDW and D-dimer are accessible indicators of hemostatic alterations in resource-limited tropical settings.