key: cord-0709495-s9rc8383
authors: He, Jieyu; Wei, Yongyue; Chen, Jiao; Chen, Feng; Gao, Wei; Lu, Xiang
title: Dynamic trajectory of platelet-related indicators and survival of severe COVID-19 patients
date: 2020-10-14
journal: Crit Care
DOI: 10.1186/s13054-020-03339-x
sha: 99816f36a4b6a772099cec21878f411337b70c7f
doc_id: 709495
cord_uid: s9rc8383

nan

Previous studies have found approximately a 30% cumulative incidence for thrombosis in critically unwell patients, almost all whom already present impaired platelets function and activity, with COVID-19 in the intensive care unit (ICU) [1, 2] . We aimed to explore the association between platelet-related laboratory indicators and prognosis in critically ill patients with COVID-19.

All the severe and critically ill COVID-19 patients ( Table 1 ) diagnosed in Huangshi City, Hubei Province, China, till 6 March, 2020, were recruited in this study which were distributed in the three hospitals including Huangshi Central Hospital, Huangshi Hospital of Traditional Chinese Medicine, and Daye People's Hospital. Laboratory examinations including routine blood tests, lymphocyte subsets, inflammatory or infection-related biomarkers, cardiac, renal, liver and coagulation function tests were obtained at admission and during hospitalization. The baseline laboratory measures with over 40% missing value were excluded from the analysis. Death in 28 days after admission to the hospital was the primary end point of this study. Patients discharge from hospital within 28 days or kept in hospitalization after 28 days were considered as censored outcome. Time-to-event outcome was defined for the following statistical models.

The platelet-related indicators included platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), thrombocytocrit (PCT), and platelet large cell ratio (P-LCR). Baseline indicators were dichotomized by the median to low and high groups. For each plateletrelated indicator with repeated examinations during hospitalization, trajectory analysis was performed to cluster the patients based on the dynamic time-series trend of the corresponding indicator, using R package traj [3] . According to the requirement of the method, patients during hospitalization with less than four observations of the specific indicator were classified as a separate cluster. Cox proportional hazards model with adjustment for age, gender, number of comorbidities were applied to test the association between dynamic trajectory of plateletrelated indicators and overall survival of COVID-19 patients.

The patients at admission with high PLT (HR 0.28; 95% CI 0.11-0.69; P = 0.0057; Fig. 1a ) were associated with the preferred survival; however, patients with high PDW (HR 2.52; 95% CI 1.17-5.44; P = 0.0185; Fig. 1b ), high MPV (HR 3.73; 95% CI 1.55-9.02; P = 0.0034; Fig. 1c ), or high P-LCR (HR 3.00; 95% CI 1.40-6.41; P = 0.0046; Fig. 1d ) were significantly associated with the worse survival. On the other hand, dynamic trajectory of PLT couldn't distinguish patients' survival ( Fig. 1e) . However, a similar dynamic trajectory pattern with rapid acceleration in the first 2 weeks followed by a considerable deceleration, was identified for MPV, PLCR, and PDW; patients with such pattern were significantly associated with about 2 to 5 times increased death hazard (Fig. 1f h). All the above results remained significant after false discovery rate (FDR) control. The findings of this study were accordant with several evidences suggesting platelets as well as related indicators participating in inflammation and prothrombotic responses in many viral infections [4] . The damage to endothelial cells leads to activation, aggregation, and retention of platelets, and the formation of thrombus at the injured site, which may cause a depletion of platelets and megakaryocytes, resulting in decreased platelets production and increased consumption. In addition to their traditional role in thrombosis and hemostasis, platelets mediate key aspects of inflammatory and immune processes [5] . Platelets have been reported to express surface receptors able to mediate binding and entry of various viruses [6] . In brief, paying close attention to the dynamics of platelet-related indicators of COVID-19 patients will undoubtedly improve our knowledge on diseases progression, but could also bring the improvement in therapeutic options for severe or critically ill patients.

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Thrombotic complications of patients admitted to intensive care with COVID-19 at a teaching hospital in the United Kingdom

Statistical measures were proposed for identifying longitudinal patterns of change in quantitative health indicators

Platelets in immune response to virus and immunopathology of viral infections

The era of thromboinflammation: platelets are dynamic sensors and effector cells during infectious diseases

Human platelets and their capacity of binding viruses: meaning and challenges?

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We would like to thank all the medical staff for their efforts in collecting the data used in this study, and all the patients who consented to donate their data for analysis and the all medical staff members who are on the front line of caring for patients.

Authors' contributions Y.W. and J.H conducted drafting of the manuscript. Y.W., J.H., and F.C. performed statistical analysis and interpretation. Samples and data collection was done by J.C. and W.G. Study conception and supervision were done by X.L., W.G. All authors read and approved the final manuscript.

This work was supported by the National Natural Science Foundation of China (81770440 and 81970218 to XL, 81970217 to WG, 82041024 to FC, 81973142 to YW).

Dr. X. Lu had full access to all of the data in the study. After publication, the data will be made available to others on reasonable requests after approval from the author (luxiang66@njmu.edu.cn).

The ethics committee of the hospitals (Huangshi Central Hospital, Huangshi Hospital of Traditional Chinese Medicine, and Daye People's Hospital) waived the written informed consent from patients with COVID-19, and all the procedures being performed were part of the routine care.

The informed consents of patients were waived by the Ethics Commission of the hospitals (Huangshi Central Hospital, Huangshi Hospital of Traditional Chinese Medicine, and Daye People's Hospital) for the rapid emergence of this epidemic.

The authors declare no competing financial interests.Received: 7 October 2020 Accepted: 9 October 2020