 "Study on Covaxin should revise statement on conclusions for clarity")
We read the recently published study titled ‘Long term safety analysis of BBV152 Coronavirus vaccine (Covaxin) in adolescents and adults: Findings from a one-year prospective study in North India’ by Kaur and colleague, 2024 from the Institute of Medical Sciences, Banaras Hindu University, Varanasi. The authors concluded that the patterns of side effects developing after Covaxin differed from those reported with other Covid-19 vaccines, as well as between adolescents and adults. With the majority of side effects persisting for a significant period, extended surveillance of Covid-19-vaccinated individuals is warranted to understand the course and outcomes of late-onset side effects. Serious side effects might not be uncommon and necessitate enhanced awareness and larger studies to understand the incidence of immune-mediated phenomena post-COVID-19 vaccination. Several media houses published articles citing the study and raised concerns regarding the efficacy of this vaccine. However, we have few concerns regarding the findings of the paper.
The authors of the study appear to have reported common illnesses that occur frequently in the general population as adverse effects related to the Covid vaccine. This likely overstates the actual risks associated with the vaccine and conflates common illnesses with vaccine-related adverse effects. To improve the accuracy and clarity of their conclusions, the authors should revise their statement to acknowledge that their findings primarily document general illnesses. They should clarify that these illnesses are not necessarily caused by the vaccine, and that their study does not establish a causal relationship between the vaccine and any serious adverse events. This distinction is crucial to avoid misleading interpretations.
Several studies (Kaur S et al, 2022; Mand A et al, 2022; Parida SP et al, 2022 and Deb T et al, 2024) published in different parts of the country have shown that adverse effects following Covaxin are mild, self-limiting, and resemble those of other vaccines. All of these studies concluded that vaccine is safe to administer, and one study, particularly in adolescents, showed no immediate adverse effects in this group. A study by Yadav PD et al, 2024 showed that the neutralising antibody response was satisfactory after two and three doses of Covaxin at a six-month follow-up, and only the Omicron sub-variant, XBB.1, showed some possibilities of neutralization escape. The conclusions of the study by Kaur and colleagues, 2024 seem to be superfluous and likely to raise undue concern among the general public. The absence of a control group as one of the major shortcomings of the study by Kaur and colleagues.
The prevalence and annual incidence of the most common illnesses in adolescents and adults of Indian ethnicity, like dengue, stroke, and Guillain-Barré Syndrome (GBS), have been well documented in several studies. When we compared the incidence of these disorders in vaccine recipients with the general population from previous studies, we could not find statistical significance for even a single side effect.
Moreover, some of the side effects cited by the authors as “persistent” are naturally age-related illnesses, such as refractory error (most probably myopia, with onset in school age). While most laboratories and primary care physicians test for typhoid for any febrile illness in people in the Indian setting, most of these are actually anamnestic reactions. While the utility of the Widal test has been challenged for a long time, it is still used by many laboratories in rural and suburban areas. Hence, the authors should not have stressed so much the incidence of typhoid and Dengue as adverse effects of the Covaxin vaccine. This is likely to create undue fear among the general public without strong evidence attached to it. In contrast, Phadke et al, 2021 have previously published findings showing a decrease in the incidence of dengue cases during Covid-19.
Moreover, the causality established by the authors regarding the serious side effects also seems doubtful. For instance, the authors mentioned that the GBS case in an adolescent was “probably” causally related to the vaccine administration. Revised World Health Organization (WHO) causality assessment of adverse events following immunization states that probable causal association can only be established when the clinical event had a reasonable time relationship to vaccine administration and was unlikely to be attributed to concurrent disease or other drugs or chemicals. It is unclear how the authors ruled out other prodromal illnesses as attributors, as they themselves mentioned as high as half of the participants had recurrent upper respiratory infections (URIs), which are likely to trigger GBS. For all the serious side effects and deaths, the available data (participants were contacted merely telephonically, and when stroke or death occurred, the exact clinical details were not available to the investigators) would actually lead to one of these three causality terms: “unlikely,” “unrelated,” or “unclassifiable.” The WHO system also mentions that direct documentation of all clinical records and physical examination by a dedicated clinical trial or pharmacovigilance team are essential prerequisites for applying this system. Hence, in this case, the authors should have been more cautious in using the term causality and subjecting these to logistic regression to find out risk factors such as females and those with diabetes are likely to have more adverse effects. In fact, people with diabetes are more likely to have severe COVID-19 and require the vaccine more than the general population. Lastly, the authors themselves mentioned that a proportion of vaccine recipients reported overall improvement in health after the vaccine administration, which merely shows the placebo effect.
Singh is professor of pediatrics, executive director AIIMS Rishikesh and co-chair Cochrane India. Sherawat is additional professor of pediatrics, AIIMS Rishikesh
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