Title : Associations between premorbid platelet levels and hospitalizations due to SARS-CoV-2 and other common respiratory viral infections: A population-based cohort study
Abstract:
Background: Platelets have been found to play a crucial role in the immune response during infections, with a low platelet count at admission associated with adverse outcomes after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to investigate the effect of premorbid platelet levels on the risk of hospitalization due to SARS-CoV-2 infection, as well as hospitalizations related to six other common respiratory viral infections, including Influenza A, Influenza B, Parainfluenza, Respiratory Syncytial Virus (RSV), and Enterovirus/Rhinovirus.
Methods: We conducted a territory-wide cohort study on adults with normal platelet count and mean platelet volume (MPV) in Hong Kong from January 2018 to December 2019. The occurrence and outcomes of SARS-CoV-2 infection-related hospitalizations were followed up until December 2022. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographic characteristics and comorbidities. We also explored the associations between ABO blood type and SARS-CoV-2 infection-related hospitalizations to validate the robustness of our workflow. Additionally, Cox proportional hazard regression models were used to investigate the association between hospitalizations related to six other common respiratory viral infections from January 2018 to December 2019 and premorbid platelet levels within the two preceding years, from January 2016 to December 2017, within the same cohort.
Results: Among 995,256 eligible individuals included in the analysis, we found a negative association between MPV and SARS-CoV-2 infection-related hospitalizations (adjusted HR, 0.95; 95% CI, 0.94-0.96), with the lowest risks observed at the maximum value (11 fL). There were nonlinear associations between platelet count and SARS-CoV-2 infection-related hospitalizations (adjusted HR per 3×1010/L lower than 226.9 ×109/L of 0.93[0.91-0.96]), with the nadir at 226.9 ×109/L. These associations remained significant in all subgroups stratified by age, gender, and Charlson score, except for the 18-38 years age group and Charlson score >3 group. Furthermore, the results of the ABO blood type analysis in our cohort were consistent with previously published findings, showing that the O blood group had a lower risk of SARS-CoV-2 infection-related hospitalization compared to non-O blood groups (adjusted HR, 0.79[0.64 to 0.97]). The associations between premorbid platelet levels and hospitalizations due to other common respiratory viral infections were significant and linear for MPV (adjusted HR, 0.94[0.91-0.97] for Influenza A, 0.92[0.88-0.96] for Influenza B, 0.94[0.89-0.999] for RSV, 0.92[0.90-0.95] for Enterovirus/Rhinovirus), and weaker for platelet count (adjusted HR:1.02-1.03 per 3×1010/L).
Interpretation: Within the normal range of platelet values, we observed a linear decrease in the risk of COVID- 19-related hospitalizations across the entire MPV range, which is not attributable to excess risks of related diseases. This association was also observed in hospitalizations due to other common respiratory viral infections (Influenza A, Influenza B, RSV, Enterovirus/Rhinovirus). We found that the association between platelet count and COVID-19-related hospitalization was nonlinear, but linear for hospitalizations due to other common respiratory viral infections (Influenza A, Parainfluenza, Enterovirus/Rhinovirus). This study provides the first clinical evidence on the associations between premorbid platelet levels and the risk of hospitalization due to SARS-CoV- 2 and six other common respiratory viral infections.
