Risk of Immune Associated Thrombocytopenia after COVID-19 Infection

Abstract

Background: Thrombocytopenia is increasingly documented as having an elevated risk of occurrence among individuals infected with COVID-19. This study further investigates the relationship between COVID-19 and immune associated thrombocytopenia, including ITP, APS, TMA, and MDS, highlighting variations among participants based on gender, age, race, and vaccination status. Additionally, it examines the risk of thrombocytopenia in individuals with connective tissue diseases post-COVID-19 infection.

Methods: This retrospective cohort study utilizes the TriNetX US collaborative network. The patients who had COVID-19 infection were identified, while the individuals who did not have COVID-19 infection were matched at a 1:1 ratio using propensity score matching based on age, gender, race, adverse socioeconomic status, lifestyle-related factors, and comorbidities. The primary outcome was the incidence of immune associated thrombocytopenia, encompassing ITP, APS, TMA, and MDS. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for thrombocytopenia were calculated between the propensity score-matched groups using the Cox proportional hazards regression models.

Findings: Between January 1, 2020, and July 1, 2023, the study identified 1,308,189 paired COVID-19 positive patients and COVID-19 negative patients for analysis. During a 6-month follow-up, COVID-19 patients exhibited a significantly higher risk of thrombocytopenia (HR=1.649 [1.621-1.678]). Furthermore, COVID-19 patients faced an increased risk of ITP (HR=2.647 [2.197-3.189]), APS/Lupus Anticoagulant Syndrome (HR=2.254 [2.033-2.499]), TMA (HR=2.222 [2.103-2.348]), and MDS (HR=1.923 [1.629-2.268]). COVID-19 vaccination was associated with a reduced risk of thrombocytopenia following infection, while the risk increased in patients with connective tissue diseases after COVID-19 infection.

Interpretation: This study elucidates the risk of thrombocytopenia, ITP, APS, TMA and MDS following COVID-19 infection, particularly among specific high-risk populations. Enhanced early monitoring is recommended, with particular attention to patients with CTDs, who should take extra precautions to prevent infection during the pandemic and closely monitor their platelet levels post-infection.

Funding: Central High-Level Hospital Clinical Research Business Fee (BJ-2021-235), CAMS Innovation Fund for Medical Science (2021-12 M-1–050), and Natural Science Foundation of China (31140008) .

Declaration of Interest: We declare no competing interests.

Ethical Approval:  The Institutional Review Board of the Beijing Hospital approved this study (2023BJYYEC-101-02), and the use of TriNetX in this research was approved by the Institutional Review Board of Chung Shan Medical University Hospital (CSMUH), under approval number CS2-21176.

Keywords: immune associated thrombocytopenia, COVID-19, ITP, APS, TMA, MDS, CTDs