Three people who received coronavirus vaccines in India between February 5 and March 31 developed a serious adverse effect called anaphylaxis, and one of them died, the Hindustan Times reported on Tuesday, citing a government review of side effects of the Covid-19 shots. The finding is significant as this is the first instance in which a death has been directly linked to vaccination.

Anaphylaxis is a severe, potentially life-threatening, allergic reaction. The United States’ Centers for Disease Control and Prevention has listed it as one of the adverse effects of Covid-19 immunisation. According to the CDC, anaphylaxis has been “reported rarely” following vaccination, and can show respiratory, gastrointestinal, cardiovascular, mucosal or neurological symptoms.

Data from government releases on vaccination show that more than 5.9 lakh beneficiaries received a shot between February 5 and March 31. A total of 28 people died after receiving a vaccine dose during this period. However, in most cases, there appeared to be no link between the death and inoculation, while in nine cases, the cause could not be determined, according to the Hindustan Times.

The person who died of anaphylaxis was a 68-year-old man who received his shot on March 8, 2021, the government review showed. The other two cases of adverse effect linked directly to vaccination were detected among a 21-year-old woman and a 22-year-old man, who received their shots on January 19 and 16, respectively. Both recuperated after treatment in a hospital.

“This is the first death where causality has been established with vaccine resulting in an anaphylaxis reaction,” NK Arora, Chairperson of the National Adverse Events Following Immunisation Committee, told the newspaper.

Of the 31 cases that were assessed, 18 were classified as coincidental cases of stroke, heart attack, septic shock and chronic obstructive pulmonary disease. Coincidental cases are those that are reported following immunisation but for which a clear cause other than vaccination is found on investigation.

Seven cases were classified as indeterminate, which means that the adverse effects occurred soon after vaccination but there was no definitive evidence, or clinical trial data. One case was classified as an anxiety-related reaction, while two were found to be unclassifiable.

Experts quoted in the government data said that mere reporting of deaths and hospitalisation as serious adverse events did not automatically imply that these events were caused due to the vaccines. “Only properly conducted investigations and causality assessments can help in understanding if any causal relationship exists between the event and the vaccine,” the report said.

The government has formed a special group to conduct causality assessment of adverse effects following immunisation. The results of the assessment are discussed in a meeting of the National AEFI Committee, headed by Arora, for final approval.

As per data in the first week of April 2021, the reporting rate is 2.7 deaths per million doses administered and 4.8 hospitalisations per million vaccine doses administered, according to the Hindustan Times.