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Thromboembolic Events and Thrombosis With Thrombocytopenia After COVID-19 Infection and Vaccination in Catalonia, Spain

37 Pages Posted: 20 Jul 2021

See all articles by Edward Burn

Edward Burn

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol)

Elena Roel

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol)

Andrea Pistillo

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol)

Sergio Fernandez-Bertolín

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol)

Maria Aragón

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol)

Carlen Reyes

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol)

Katia Verhamme

Erasmus University Medical Center - Department of Medical Informatics

Peter Rijnbeek

Erasmus University Medical Center - Department of Medical Informatics

Xintong Li

University of Oxford - Centre for Statistics in Medicine

Victoria Strauss

University of Oxford - Centre for Statistics in Medicine

Daniel Prieto-Alhambra

University of Oxford - Centre for Statistics in Medicine

Talita Duarte-Salles

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol)

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Abstract

Background: Thromboembolism and thrombocytopenia have emerged as potential adverse events associated with vaccines against SARS-CoV-2. We compared rates of thromboembolism and thrombocytopenia following vaccination with BNT162b2 and ChAdOx1 with expected rates. Rates for people with COVID-19 were estimated to provide context.

Methods: Primary care data from Catalonia, Spain, informed the analysis. Study participants were vaccinated with BNT162b2 or ChAdOx1 (27/12/2020-19/05/2021), diagnosed with COVID-19 (1/09/2020-1/03/2021) or present as of 1/01/2017. Outcomes included venous thromboembolism (VTE), arterial thromboembolism (ATE), thrombocytopenia, and thrombosis with thrombocytopenia syndrome (TTS). Incidence rates were estimated in the 21 and 90 days after vaccination and COVID-19 diagnosis, respectively, and up to 31/03/2019 for background rates. Age indirectly standardised incidence ratios (SIR) were estimated.

Findings: We included 945,941 BNT162b2 (778,534 with 2 doses), 426,272 ChAdOx1, 222,710 COVID-19, and 4,570,149 background participants. SIRs for VTE were 1.29 [95% CI 1.13-1.48] and 0.90 [0.76-1.07] after first- and second-dose BNT162b2, and 1.15 [0.83-1.58] after first-dose ChAdOx1. The SIR for VTE in COVID-19 was 8.04 [7.37-8.78]. SIRs for thrombocytopenia were 1.35 (1.30-1.41) and 1.19 (1.14-1.25) after first- and second-dose BNT162b2, 1.03 (0.93-1.14) after first-dose ChAdOx1 and 3.52 (3.39 to 3.67) for COVID-19. Rates of ATE were similar to expected rates for BNT162b2 and ChAdOx1, as were rates of TTS for BNT162b2, while fewer than 5 such events were seen for ChAdOx1.

Interpretation: Safety profiles of BNT162b2 and ChAdOx1 were similar. A safety signal was seen for VTE after first-dose of BNT162b2. Although confidence intervals were wider, a similar estimate was seen for first-dose of ChAdOx1. The 1.3 fold increase in the rate of VTE after first-dose of BNT162b2 compared with an 8 fold increase after diagnosis of COVID-19. No safety signals were seen for ATE or TTS. Further research is needed to investigate the causality in the observed associations.

Funding Information: This study was funded by the European Medicines Agency in the form of a competitive tender (Lot ROC No EMA/2017/09/PE).

Declaration of Interests: DPA’s research group has received research grants from the European Medicines Agency, from the Innovative Medicines Initiative, from Amgen, Chiesi, and from UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen and UCB Biopharma. Peter Rijnbeek works for a research institute who receives/received unconditional research grants from Yamanouchi, Pfizer-Boehringer Ingelheim, GSK, Amgen, UCB, Novartis, Astra-Zeneca, Chiesi, Janssen Research and Development, none of which relate to the content of this work. Katia Verhamme works for a research institute who receives/received unconditional research grants from Yamanouchi, Pfizer-Boehringer Ingelheim, GSK, Amgen, UCB, Novartis, Astra-Zeneca, Chiesi, none of which relate to the content of this work .All other authors have no conflicts of interest to declare.

Ethics Approval Statement: This study was approved by the Clinical Research Ethics Committee of the IDIAPJGol (project code: 21/054-PCV).

Keywords: BNT162b2, ChAdOx1-S, SARS-CoV2, COVID-19, thrombosis, thrombocytopenia

Suggested Citation

Burn, Edward and Roel, Elena and Pistillo, Andrea and Fernandez-Bertolín, Sergio and Aragón, Maria and Reyes, Carlen and Verhamme, Katia and Rijnbeek, Peter and Li, Xintong and Strauss, Victoria and Prieto-Alhambra, Daniel and Duarte-Salles, Talita, Thromboembolic Events and Thrombosis With Thrombocytopenia After COVID-19 Infection and Vaccination in Catalonia, Spain. Available at SSRN: https://ssrn.com/abstract=3886421 or http://dx.doi.org/10.2139/ssrn.3886421

Edward Burn

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol) ( email )

Barcelona
Spain

Elena Roel

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol) ( email )

Barcelona
Spain

Andrea Pistillo

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol) ( email )

Barcelona
Spain

Sergio Fernandez-Bertolín

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol) ( email )

Barcelona
Spain

Maria Aragón

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol) ( email )

Barcelona
Spain

Carlen Reyes

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol) ( email )

Barcelona
Spain

Katia Verhamme

Erasmus University Medical Center - Department of Medical Informatics ( email )

Doctor Molewaterplein 40
Rotterdam, South Holland 3015 GD
Netherlands

Peter Rijnbeek

Erasmus University Medical Center - Department of Medical Informatics ( email )

Doctor Molewaterplein 40
Rotterdam, South Holland 3015 GD
Netherlands

Xintong Li

University of Oxford - Centre for Statistics in Medicine

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Victoria Strauss

University of Oxford - Centre for Statistics in Medicine ( email )

Oxford
United Kingdom

Daniel Prieto-Alhambra (Contact Author)

University of Oxford - Centre for Statistics in Medicine ( email )

Oxford
United Kingdom

Talita Duarte-Salles

Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol) ( email )

Barcelona
Spain

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