Immature Platelets and Disease Severity in Patients Hospitalized with Acute COVID-19 Who Are Vaccinated Against COVID-19
Authors: Lee Nicholas C.J. , Jeon-Slaughter Haekyung , Ibrahim Ibrahim F. , Bat Taha , Choi Sung-Hee 
Published: November 2021

Abstract
Introduction: COVID-19 has killed more than four million people worldwide and resulted in strained health resources globally(Dong Lancet ID 2020). There is a critical need for prognostic biomarkers to predict severity and outcomes in COVID-19 patients to allow more efficient resource allocation. Studies using pre-vaccination hospitalized patient data have demonstrated that elevated initial and peak immature platelet fraction (IPF), as well as related platelet indices, were associated with progression to severe COVID-19 outcomes (Welder Br J Haem 2021). This suggests the potential role of immature platelets as a cost-effective biomarker. The underlying pathophysiology of immature platelets in COVID-19 is unclear but these results support the hypothesis of higher inflammatory response, leading to thrombopoiesis mediated by pro-inflammatory cytokines and platelet hyper-reactivity in this population (Manne Blood 2021). It is unclear if this holds true in patients vaccinated against COVID-19. This study aims to assess the relationship between immature platelets in patients vaccinated against COVID-19 and hospitalized with acute COVID-19.
Methods: This study used a COVID-19 patient registry established by the University of Texas Southwestern that comprises patients between May 2020 to July 2021. The database was approved by the Institutional Review Board. The study included 22 fully vaccinated adult patients with the mRNA COVID-19 vaccines hospitalized with acute COVID-19 and had IPF measurements during the hospitalization as well as 519 non-intensive care unit (ICU) patients admitted with acute COVID-19 prior to availability of a COVID-19 vaccine (pre-vaccination era). The study conducted non-parametric tests to compare hospital outcomes and covariates of interest between vaccinated patients and pre-vaccination era non-ICU patients. Covariates included for analysis are age, gender, race, length of hospital stay (LOS), dexamethasone use, platelet count, immature platelet count (IPC), IPF, thrombotic events and mortality.
Results: All patients vaccinated against COVID-19 were alive without thrombotic events at the time of analysis. One out of 22 vaccinated patients required ICU admission and use of a ventilator. IPF and platelet counts at admission were similar between vaccinated patients and non-ICU patients from pre-vaccine era while IPC was significantly lower in the vaccinated group (Table 1). The vaccinated patient requiring ICU admission and mechanical ventilation was a heavy tobacco user with chronic obstructive pulmonary disease (IPF 6.1%, IPC 4x10 9/L, platelet count 66x10 9/L). There was a disproportionate number of Hispanic patients in the vaccinated cohort (44%, P = 0.02). The LOS was significantly shorter in vaccinated patients compared to pre-vaccination era non-ICU patients by a day and a half (P = 0.047). The admission IPF and IPC were not correlated with increased LOS (IPF Spearman ρ = 0.23, P = 0.31; IPC ρ = -0.34, P = 0.13), while platelet count at admission negatively correlated with LOS (ρ = -0.41, P = 0.06).
Discussion: IPF, IPC, and platelet count have previously been demonstrated to be a predictor of increased ICU and hospital LOS, ventilator duration, and in-hospital mortality. To our knowledge, this is the first study assessing the relationship between IPF and platelet indices in hospitalized patients vaccinated against COVID-19. Due to the lack of severe COVID-19 outcomes in these vaccinated patients, LOS was the only variable able to be analyzed and lower platelet count was found to be associated with increased LOS . These preliminary results demonstrated similar initial IPF and platelet counts but lower IPC in a small cohort of vaccinated COVID-19 patients compared with the pre-vaccination era patients with no severe outcomes. This suggests that the predictive value of these biomarkers may also apply to the vaccinated patient population. As IPC in this current study is derived from IPF and platelet counts, independent measure of IPC is needed to confirm this finding in a larger cohort. This study also potentially suggests the protective benefits of COVID-19 vaccines as reported in prior randomized trials (Polack NEJM 2020). Further research is needed to confirm these findings in a larger vaccinated cohort assessing severe outcomes, hospitalization, and death, especially with future infection waves with contagious COVID-19 variants rapidly emerging.
Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.