key: cord-0995408-21svrhh6 authors: Konstantinides, Stavros title: Thrombotic complications of vaccination against SARS-CoV-2: what pharmacovigilance reports tell us – and what they don't date: 2021-04-22 journal: Eur Respir J DOI: 10.1183/13993003.01111-2021 sha: 44973b4031b773982db27ccf85a9a6aba576a72e doc_id: 995408 cord_uid: 21svrhh6 Thrombotic complications of COVID-19 vaccination are very rare, but awareness is needed. From the beginning of the COVID-19 pandemic, this disease has been associated with frequent thrombotic complications, resulting both from direct effects of the virus on the endothelium and from the 'cytokine storm' resulting from the host's immune response (2, 3) . In a recent meta-analysis of 102 studies involving 64,503 patients, the frequency of COVID-19-related venous thromboembolism was as high as 14.7% (95% CI 12.1% to 17.6%) and that of COVID-19-related arterial thrombotic events 3.9% (95% CI 2.0% to 3.0%) (4). The cumulative rate of thromboembolic events is particularly high among critically ill patients necessitating admission to an intensive care unit (5, 6) . Very recently, a small study reported a 14.2% (95% CI 7.5 to 20.8) prevalence of pulmonary embolism at the time of hospital admission for COVID-19, further underscoring the thromboembolic risk in this setting (7) . Consequently, since the COVID-19 vaccines mentioned above have been shown to effectively prevent symptomatic infection including hospital admissions and severe disease The pathomechanisms are reminiscent of autoimmune heparin-induced thrombocytopenia, although none of the patients included in the report had received heparin (11) . An analysis of the samples from five patients in Norway, who presented with venous thrombosis and thrombocytopenia 7 to 10 days after receiving the first dose of the same vaccine, yielded similar findings (12), as did a report on 23 cases from the United Kingdom (13) . Overall, approximately 40% of the studied patients died, either from ischaemic brain injury or from (1) should be interpreted with extreme caution due to numerous important limitations, which are highlighted by the authors. Pharmacovigilance reports contain administrative, nonadjudicated data which can help to generate hypotheses, but they cannot, and should not, support speculation on causal relations. In addition, the present analysis does not permit any direct comparisons between the three studied vaccines with regard to the risk for VITT, since only the numerator, i.e. the number of thrombosis reports, but not the denominator for each vaccine, i.e. the total number of the recipients of the particular vaccine for which thrombotic events were reported, is given. This must always be kept in mind when reading Table 1 of the report by Smadja et al (1) . Finally, the likelihood of both underreporting and overreporting of adverse events to the WHO is not to be underestimated. Thus, in view of all the things that the present publication does not tell us, it must not be interpreted as challenging the safety of any COVID-19 vaccine and should not be used as an argument to halt or slow the life-saving global vaccination programme. On the other hand, the results of Smadja et al do highlight the importance of continuing pharmacovigilance after the approval of any vaccine (and any drug), in everyday clinical practice. Analysing pharmacovigilance reports helps to increase awareness of authorities and physicians to specific alarming clinical symptoms and signs, so that these can be detected and managed early, however rare they may be. In the future, improving insights into the pathogenesis of VITT may help us to better select candidates for specific vaccines, minimise uncertainty in the medical community and the lay public, and help us to further accelerate the global vaccination programme with safety with the aim of liberating the population from the COVID-19 pandemic. Vaccination against COVID-19: Insight from arterial and venous thrombosis occurrence using data from VigiBase Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19 COVID-19 and its implications for thrombosis and anticoagulation Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis Prevalence of pulmonary embolism in patients with COVID 19 at the time of hospital admission Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine Singledose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination The work of Stavros Konstantinides was supported by the German Federal Ministry of Education and Research (BMBF 01EO1003 & 01EO1503). The author is responsible for the contents of this publication.