COVID-19 Vaccine and Death: Causality Algorithm According to the WHO Eligibility Diagnosis

Abstract

The current challenge worldwide is the administration of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Even if rarely, severe vascular adverse reactions temporally related to vaccine administration have induced diffidence in the population at large. In particular, researchers worldwide are focusing on the so-called "thrombosis and thrombocytopenia after COVID-19 vaccination". This study aims to establish a practical workflow to define the relationship between adverse events following immunization (AEFI) and COVID-19 vaccination, following the basic framework of the World Health Organization (WHO). Post-mortem investigation plays a pivotal role to support this causality relationship when death occurs. To demonstrate the usefulness and feasibility of the proposed workflow, we applied it to two exemplificative cases of suspected AEFI following COVID-19 vaccination. Based on the proposed model, we took into consideration any possible causality relationship between COVID-19 vaccine administration and AEFI. This led us to conclude that vaccination with ChAdOx1 nCov-19 may cause the rare development of immune thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4), which clinically mimics heparin-induced autoimmune thrombocytopenia. We suggest the adoption of the proposed methodology in order to confirm or rule out a causal relationship between vaccination and the occurrence of AEFI.

Keywords: COVID-19; SARS-CoV-2; autopsy; deep vein thrombosis; disseminated intravascular coagulation; immune thrombocytopenia; post-mortem investigation; standard protocol; vaccination campaign; vaccine.

Figure 1

Structure of the causality assessment guidelines for AEFI following COVID-19 vaccine administration.

Figure 2

For each AEFI, this flowchart should be applied in order to define the causality assessment between the two events, vaccine administration and AEFI. The green answers reinforce the relationship.

Figure 3

IHC in the exemplificative cases of VITT demonstrated the activation of the innate immunity and of the complement pathway at the level of vascular and perivascular tissues of the major organs. (A) lung stained for the complement fraction C1r (20×); (B) Cephalic vein with deep vein thrombosis stained for the complement fraction C4d (10×); (C) liver positive for CD 163 cells infiltrates (20×); (D) clusters of activated CD66 cells in the lung (20×).