About the vaccine developed in the United Kingdom (University of Oxford-AstraZeneca)

Abstract

Mr. Director of the Medical Journal of Uruguay

Prof. Dr. Hugo Rodríguez Almada

Present

Of our most consideration,

The COVID-19 pandemic, unlike others that occurred in the past, takes place in a highly communicated world. News flows faster than scientific research. This decoupling often causes information to be disseminated without the necessary support from scientific evidence. In the particular case of therapeutics and vaccines developed to reduce the risk of presenting the disease caused by the SARS-CoV-2 virus, this dizzying rate of disclosure of information conspires against its correct analysis and interpretation. Complex webs of confusion are generated with little technical support, often difficult to clarify, to which is added the generation of practically daily knowledge about this disease. The vaccine developed in the United Kingdom by the University of Oxford, in consortium with the pharmaceutical products laboratory AstraZeneca, is an example of this situation (hereinafter AZN vaccine). The vaccine consists of a viral vector (adenovirus) that contains glycoprotein S, which is part of the antigenic structure of the SARS-CoV-2 virus and which, schematically, is the spearhead that the virus uses to enter the respiratory system. It is given in two doses 4 to 12 weeks apart (optimal range 8 to 12 weeks) and is marketed under the name Vaxzevria. It is one of more than 50 vaccines tested for this virus and one of more than 10 approved for administration in the context of the ongoing pandemic (1). Shortly after its administration, at least two concerns began: its effectiveness against the risk variants of the SARS-CoV-2 virus and its adverse effects, mainly thromboembolic. The reports come mostly from European Union countries, which at least raises suspicions about the possible effect of Brexit on this web of information, inquisitions and communications (2). The reason for this communication is to synthetically provide a series of useful information about this vaccine in relation to its effectiveness and safety. We will refer to the announcements about the eventual prothrombotic effect. In this sense, we point out:

1. With two doses administered 12 weeks apart, the vaccine has an overall efficacy of 81% in preventing the disease caused by the SARS-CoV-2 infection, and close to 100% when considering the severe forms of the disease and the death (3).
2. The vaccine has completed all phases of development to the same extent as others have. The haste that the pandemic has imposed has determined that these phases are developing at an unusual speed. However, this does not imply that the usual requirements determined by the development of vaccines were not met.
3. The incidence of venous thrombosis in the general population is 0.9-1.76 cases per 1,000 person-years (4). The incidence of cerebral venous thrombosis is estimated at 0.22-1.57 per 100,000 person-years (5).
4. SARS-CoV-2 disease, in its severe presentation, per se increases the risk of venous thromboembolic disease. It is estimated that 25% of critical patients and 5% of non-critical patients hospitalized for COVID-19 will have a thromboembolic event. This risk is much higher than the eventuality of a thromboembolic event induced by the AZN vaccine (4).
5. Thromboembolic events have been reported in the context of decreased platelet count within 7 to 20 days after administration of the AZN vaccine. This event has been called VIPIT, by its English name (Virus / Vaccine Induced Prothrombotic Immune Thrombocytopenia), and its pathophysiological behavior is reminiscent of heparin-induced thrombocytopenia. These events have been fundamentally in unusual sites: cerebral venous sinus thrombosis, splanchnic thrombosis, and more than half of these occurred in female patients under 60 years of age. The frequency has been established in one case every 125,000 to one case every 1 million people exposed to the vaccine. Diagnostic and treatment criteria have been developed for this entity, the scope of which exceeds this note (6).
6. The analyzes on the imputability of causality between the vaccine and the aforementioned adverse event have allowed us to conclude that the relationship is biologically plausible and, consequently, the event is possible. Recent reports with the vaccine produced by Johnson & Johnson suggest that it could be a group effect of the vaccines produced with viral vector.
7. At the moment, no clear predisposing factors have been identified. Age less than 60 years and female sex could correspond to a bias rather than a clear risk factor. Indeed, it has not been determined that the history of previous thromboembolic events, being anticoagulated or the presence of hereditary or acquired thrombophilias, constitute risk factors for the appearance of this adverse effect. It is not recommended to carry out any type of study prior to the administration of this vaccine (7). It can be administered in patients who have a history of thrombosis, thrombophilia or who are anticoagulated.
8. More than 20 million doses of this vaccine have been administered. However, the relationship between AZN vaccine and this adverse effect is probably not fully established. Knowledge about adverse effects arises from pharmacovigilance. Pharmacovigilance feeds on reports of adverse effects: if they are not reported, they are not known. It is well known that there are fewer reports than events. Consequently, the magnitude of this adverse effect may not yet be defined.
9. No medical intervention is without risk. Indeed, in pharmacology the maxim is well known that establishes that an intervention that lacks adverse effects is highly probable that it also lacks beneficial effects. In this sense, pharmacovigilance is essential.
10. For all the foregoing and in light of the information available at the present time, it is reasonable to establish that the benefits of this vaccine far outweigh the risks. Notwithstanding the foregoing, given the existing reports, it is prudent to recommend that this vaccine be reserved for the population over 60 years of age.