Perils of promoting an anti-vaccination scare

Two recent controversies featuring Covid-19 vaccines extensively employed in India have lessons for scientific research and media reporting. The virus vector vaccine manufactured and marketed by AstraZeneca used the spike protein antigen of SARS CoV-2 virus to stimulate immune response and a chimpanzee adenovirus as the carrier to transport that antigen to human cells. After approval for human vaccination in 2020, the vaccine was extensively used in several countries, including India.

In 2021, reports emerged of some vaccine recipients in Europe experiencing severe clotting disorders in their blood vessels. This had a peculiar feature. In affected individuals, clotting occurred despite a drop in platelet counts (cells that clump together to trigger blood clots). It was initially labelled as Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT). As other countries too started reporting similar complications in some recipients of this vaccine, the adverse event was renamed Thrombosis with Thrombocytopenia Syndrome (TTS). The complication was only noted with two virus vector vaccines (AstraZeneca; Johnson and Johnson) and not with other types of vaccines. The name was thus changed to avoid provoking public concern about all vaccines.

In 2021, this complication was widely discussed in scientific literature and global media. Questions about how much AstraZeneca knew about this from its own animal and human research, and to what extent concerns were shared with the general public, are now under judicial review in a court in the United Kingdom (UK) that is examining compensation claims. Recently, AstraZeneca admitted that evidence exists of this complication. While all who actually suffered such complications must be compensated, there is no cause for public anxiety among vaccine recipients who received their doses several months ago and did not experience such a complication soon after.

The mRNA vaccines too have had their share of “scare”, with myocarditis and pericarditis (inflammation of heart muscle and its covering layer) reported among some persons who received the vaccines. Young males were identified as a high-risk group. Both the virus vector vaccines and mRNA vaccines were specifically directed at the spike protein of the SARS-CoV-2 virus.

Inactivated virus vaccines have been around much longer and widely used. Vaccines against influenza and Hepatitis A are among the classic examples. They have been generally well tolerated, with no serious complications. Indigenously developed Covaxin too is an inactivated virus vaccine. Here, the inactivated SRS CoV-2 virus was combined with a United States (US) supplied adjuvant Alhydroxyquim-II that stimulates cellular immunity. Because Covaxin presents an array of antigens from the whole virus, it can provide broadband immunity, even against variants that emerged with changed spike protein configurations as the pandemic advanced.

A recent study reported a long list of adverse events of special interest (AESIs), in 635 adolescents and 291 adults one year after vaccination with Covaxin. This created a media stir in India, coming close on the heels of AstraZeneca’s admission. The report on Covaxin raised further concerns, stoking anti-vaccine sentiments that were hitherto at a low level in India.

The report on Covaxin is enfeebled by its weak scientific methodology. Information on a long list of possible adverse effects was obtained only through a telephonic survey. Based on those responses even diagnoses that required clinical or laboratory evidence were documented as present or absent. Such questioning is subject to recall bias (leading to inaccurate responses) and ascertainment bias (mode of questioning generating preferred responses). No corroborative clinical or laboratory evidence was presented, rendering diagnoses questionable.

More importantly, there was no control group of unvaccinated individuals for comparison. When respiratory infections are reported in the vaccinated group, we should also know about the concurrent prevalence of such infections among age and location-matched persons who were not vaccinated. When hypothyroidism is reported among vaccinated individuals, we need information on the prevalence of that disorder in a similar demographic group in the general population. Was hypothyroidism present in those who reported it even prior to their vaccination? When typhoid infections reported by telephonically interviewed persons are linked to the Covid-19 vaccine, it strains credulity. Did researchers check the incidence of typhoid among unvaccinated persons in that area? The Indian Council of Medical Research (ICMR) has rightly drawn attention to such serious design and analytical flaws.

Post-marketing studies of vaccine-related adverse effects are important because clinical trials designed to assess efficacy do not provide large enough sample sizes of vaccine recipients to identify an array of potential adverse effects. Late complications are especially likely to be missed in short-term efficacy trials. Discovery of the link between virus vector vaccines and TTS attests to the value of such studies. However, methodologically weak studies can derail scientific research and harm public health. A spurious link between the measles vaccine and autism, suggested by a publication in The Lancet, created a worldwide anti-vaccine movement. The link was found to be non-existent and the flawed study was later retracted but the damage continues with measles outbreaks among families who refuse to vaccinate their children.

Four groups have a duty to report accurately and responsibly on issues of public health importance involving vaccines: Researchers who must design methodologically strong studies, conduct them with scrupulous adherence to protocols and report them with integrity; manufacturers who must truthfully disclose all findings of clinical trial research plus provide alerts from continuing post-marketing surveillance; the government’s science agencies which must provide vigilant oversight of research and public accountability; media which must gain sufficient familiarity with research methodology to distinguish between scientifically strong and frail studies. Unless all of them play their roles with conviction and commitment, a confused public will be sceptical of science and suspicious of public health interventions.

K Srinath Reddy is honorary distinguished professor of public health, Public Health Foundation of India. The views expressed are personal