Anti‐SARS‐CoV‐2 mRNA vaccines, their efficiency, side effects and controversies

Dear Editor, I recently read the letter to your journal: ‘Role of the antigen presentation process in the immunization mechanism of the genetic vaccines against COVID19 and the need for biodistribution evaluations’ by P. Polykretis.1 The author suggests that antiSARSCoV2 mRNA vaccines may cause SARSCoV2 spike protein expression not only in regional lymph nodes but also in many organs including spleen, liver, pituitary gland, thyroid, ovaries and in other tissues. Polykretis further suggests that this expression may induce autoimmune disease and as such lead to dangerous and harmful side effects. The statement that the biodistribution and expression of the spike protein is significant in many different tissues is, however, contradicted even by specific references cited in the letter itself. As an example, it is stated in references 6 and 7 that in experimental rats, lipid nanoparticles, containing mRNA vaccine, were distributed mainly to the liver, which plays a role in detoxification of organism and is therefore necessary to neutralize the drugs. If any pathogenic effects were visible in liver, they were mild, transient and reversible, and no autoimmunity was observed in this organ. Other organs and tissues were not endangered. Furthermore, reference 9 refers to a large panel of publications describing single cases of severe adverse effects of mRNA vaccination, out of thousands healthy vaccinees, and reference 10 is not a peerreviewed article, but an internet site with links to ‘FDA documents’ that is impossible to open, at least for this author. Reports on adverse events show that they are rare and transient2,3 (see below). SARSCoV2 infection and COVID19 may pose higher risk of autoimmune diseases4– 6 than mRNA vaccination. Severe COVID19 may be associated with autoimmune phenomena in predisposed patients, although these may be only epiphenomena.4 Indeed, different neurological symptoms were observed in postacute COVID19 patients, including Guillan– Barre syndrome.5 Among antiCOVIDvaccinated patients, Guillan– Barre syndrome had increased frequency in Ad26.COV2.S vaccine but not in mRNA vaccines BNT162b2 and mRNA1273 groups.6 Therefore, although COVID19 may bring signs of autoimmunity in some patients, mRNA vaccination is rather neutral in this respect. Furthermore, Świerkot et al.7 did not find any relations between humoral or cellular immune response of mRNA antiSARSCoV2 vaccination and a panel of autoantibodies; only a weak possible association between the severity of vaccineinduced adverse effects and antinuclear antibody titres was observed. Phase III studies, as well as reallife data published in multiple peerreviewed reports in established journals, document the safety and overwhelming beneficial effects of PfizerBioNTech and Moderna mRNA vaccines in limiting severe disease and death from COVID19. Alesci et al.8 report that although adverse events (myalgia, headache and fatigue) exist, they tend to be of moderate or mild severity and are usually limited to the first 2 days after vaccination. Anaphylaxis after vaccination has been reported with a ratio of about 5 cases per 1 million doses. It is worth to be emphasized here that a group (65 years or older) with the highest risk of death from COVID19 has the lowest risk of developing side effects after vaccination!2 Polykretis further proposes that once mRNA is introduced into the cell, it persists there and is used for production of viral antigen, expressed on the cell surface and inducing killing of all such cells by the immune system. This is an unlikely assumption, since mRNA is shortlived and not expected to persist for too long. After fulfilling its function, the mRNA is instead degraded by ribonucleases.9 Longer mRNA persistence may be seen in cells devoid of a nucleus, for example in erythrocytes, in which longlived mRNA may be needed for the production of hemoglobin.10 In a new letter, following critical comments by Gül and Öztürk,11 Polykretis and McCullough12 argue further for the risk of symptomatic injury in terminally differentiated cells due to aberrant expression of mRNAencoded spike protein. Two references are cited, one describing 15 patients with suspected myocarditis and one including a single case report of encephalitis. In a recent study, Barda et al.13 not only confirms an increased risk of myocarditis after vaccination but also shows that natural infection itself conveys an even stronger risk for this condition (and of many more). Polykretis and McCullough further write: