Nearly one-third of 926 individuals who received Bharat Biotech's anti-Covid vaccine Covaxin reported 'adverse events of special interest,' or AESI, according to a one-year follow up study conducted by a team of researchers at BHU.
Serious AESI, which included stroke and Guillain-Barre syndrome, were reported in one per cent of individuals, the study conducted by researchers from the Banaras Hindu University (BHU), which looked at long-term safety of the BBV152 (Covaxin) vaccine in adolescents and adults, claimed.
Guillain-Barre syndrome is an autoimmune disorder which causes weakness in nerves in arms and legs.
The study, conducted from January 2022 to August 2023, stated that nearly 50 per cent of the sample size complained of infections during the follow-up period, predominated by viral upper respiratory tract infections.
However, Bharat Biotech in a statement in response to the study, said, "several studies have been executed on the safety of Covaxin, and published in peer-reviewed journals, demonstrating an excellent safety track record". The study involved 635 adolescents and 291 adults, who received the BBV152 vaccine.
Published in the journal Springer Nature recently, the study comes against the backdrop of UK pharmaceutical giant AstraZeneca admitting its Covid vaccine can cause rare side-effects of blood clotting and lowering of platelet count in a UK court.
"Close to one-third of the individuals developed AESIs. New-onset skin and subcutaneous disorders, general disorders, and nervous system disorders were the three most common disorders observed in adolescents after receiving the vaccine," the study said.
The participants were interviewed telephonically about long-term adverse events of special interest after one year of vaccination.
New-onset skin and subcutaneous disorders (10.5 per cent), general disorders (10.2 per cent), and nervous system disorders (4.7 per cent) were the common AESIs in adolescents.
General disorders (8.9), musculoskeletal disorders (5.8 per cent), and nervous system disorders (5.5 per cent) were the common AESIs in adults.
Menstrual abnormalities were noticed in 4.6 per cent of female participants.
Ocular abnormalities and hypothyroidism were observed in 2.7 per cent and 0.6 per cent of participants. Four deaths (three female individuals, one male individual) were reported in adults, the study added.
All four had diabetes, while hypertension in three, and a history of pre-vaccination COVID-19 was present in two of them.
Stroke was the main contributor in two deaths and one fatality was due to post-COVID-19 rhinocerebral mucormycosis, which supposedly disseminated after vaccination as reported by the caregivers.
The fourth death happened in a woman with multiple episodes of unconsciousness post-vaccination, the etiology of which remained unidentified till death. In the absence of a definite causality association, no conclusions can be drawn from these events, the study said.
"Interestingly, adults receiving three doses and those receiving one dose of BBV152 were respectively at four and two times higher risk of AESIs compared with adults receiving two doses of the Covaxin," the study said. A booster dose mechanistically enhances the production of anti-Spike antibodies above that produced by the second dose. Significant cross-reactivity has been shown between anti-SARS-CoV-2 antibodies and diverse human antigens and this can explain the multi-system AESIs witnessed in the study participant, it said.
However, it said that whether the one-dose group is more vulnerable to AESIs also is worth exploring. The results concerning the boosters need corroboration from larger studies owing to the limited number of adults receiving the third dose of vaccine.
The BHU researchers called for an extended surveillance of COVID-19-vaccinated individuals to understand the course and outcomes of late-onset AESIs, given the majority of AESIs persisting for a significant period.
Female individuals, adolescents with pre-vaccination COVID-19, those with co-morbidities, and those with post-vaccination typhoid had respectively 1.6, 2, 2.7, and 3.2 times higher odds of persistent AESIs.
Adults with co-morbidities had more than two times higher odds of AESIs and persistent AESIs, the study stated.
Bharat Biotech in its statement listed some data points which it said are required for such a study in "safety to be effective, informative and to avoid investigator bias".
It said that the AESI safety profile of the subjects prior to participation in the study should be assessed and that there should be a comparison of safety profile of non-vaccinated subjects during the course of the study.
All study participants should be followed during the course of the study, instead of only a subset, it further said.
The BHU study noted that the patterns and incidence of AESIs differ with respect to the type of vaccine and study population.
"In a predominantly adult-based population receiving the ChAdOx1-nCov-19 (Covishield) vaccine, nearly 14 per cent developed AESIs contrary to the one-third rates of AESIs observed in the present study," it said.
Musculoskeletal disorders, general disorders, and cardiovascular disorders were the common AESIs in that study, but the incidence reported was low, being 3.7 per cent, 2.1 per cent, and 1.4 per cent.
Reproductive system disturbances and ocular disturbances were less common and were documented in 0.7 per cent (2 per cent of female individuals) and 0.26 per cent of participants.
Three out of five mortalities reported with Covishield vacine happened because of cardiac causes, in contrast with the neurological events such as stroke reported in the present study, it said.
In the absence of a definite causality association, no conclusions can be drawn from these events, the study said.
"Still, it is noteworthy that more deaths in our ChAdOx1 long-term safety study were reported due to cardiac events whereas with BBV152, more stroke deaths were reported," it claimed. The researchers said that to understand the link of AESIs with COVID-19 vaccines, a control arm of unvaccinated individuals is needed to compare the rates of AESIs between the two groups.
In the absence of data on background rates of the observed AESIs, no comments can be made on changes in the incidence of the observed events in the post-vaccination period.
"The findings of our study are confined to BBV152 and should not be extrapolated to viral vector or mRNA vaccines. The study primarily involved adolescents and the sample size of adults was relatively small.
"Larger adult-based studies are needed to understand the long-term safety of BBV152 in adults. The study participants belonged to the northern belt of India and ethnicity-related diferences in vaccine tolerability should be explored," it said.
