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Explained | Why are ‘breakthrough’ infections a concern?

Why are people who are double-vaccinated still getting COVID-19? Do vaccines work against variants?

September 05, 2021 02:45 am | Updated November 26, 2021 10:18 pm IST

A ‘breakthrough infection’ refers to the  virus being able to penetrate the protective barrier of antibodies. There are no official estimates of how many such cases have been reported in India.

A ‘breakthrough infection’ refers to the virus being able to penetrate the protective barrier of antibodies. There are no official estimates of how many such cases have been reported in India.

The story so far:India’s second wave has not fully dipped and over the past seven days, daily infections of COVID-19 have logged over 40,000 cases. The rise in daily infections is primarily seen in Kerala and Maharashtra, which paradoxically are also among the States which have a high rate of vaccination. In this context, there are concerns about the rise in ‘breakthrough infections’ or confirmed infections in those who have got the second dose of the vaccine at least two weeks earlier.

Are those who are doubly vaccinated getting COVID-19?

If a person gets infected with the SARS-CoV-2 virus 14 days after the second shot of the vaccine, it is called a ‘breakthrough infection’. The two-week window is the time it takes for the body to produce necessary antibodies following a shot of the vaccine. A ‘breakthrough infection’ refers to the virus being able to penetrate the protective barrier of antibodies. There are no official estimates, nationally, of how many ‘breakthrough infections’ have been reported in India but news reports in mid-August, quoting unnamed officials, estimated that 80,000-100,000 people got infected, nearly half in Kerala. The State has a COVID-19 genome surveillance programme that periodically monitors the prominent coronavirus variants as well as whether some variants are more closely linked to instances of ‘breakthrough infections’. According to the latest update on August 30, 7,202 coronavirus samples, or about 0.1% of its cumulative caseload of 400,000 confirmed cases, had been sequenced. A subset of those who tested positive in April, May and June had ‘breakthrough infections’. The total number is not known yet, but 155 such breakthroughs were analysed, 147 of whom were fully vaccinated with Covishield and eight with Covaxin.

Editorial | Breakthrough challenge: On vaccines and the virus variants

How significant are such infections?

It appears that so far breakthroughs are not translating into serious disease requiring hospitalisation. In the Kerala analysis, 151 were “mildly symptomatic” and four were asymptomatic. A third were healthcare workers, who because of prolonged and close exposure to a variety of patients are at a greater risk of contracting infection. In recent months, more studies are emerging on ‘breakthrough infections’. A preprint by researchers at the CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) and Max Hospitals in Delhi found that nearly a quarter of 600 fully vaccinated healthcare workers contracted the virus after vaccination. Earlier, studies from the CMC, Vellore, and PGIMER, Chandigarh, too had reported that between 1% and 10% of fully vaccinated healthcare workers had contracted the infection. Less than 5% needed hospitalisation and no lives were lost, indicating that vaccines were effective in preventing severe sickness and death. Internationally, the trend is not too different either. Israel and the U.S., despite high vaccination coverage, continue to report fresh cases, though the infection rate is much higher in the unvaccinated.

There was a qualitative difference between the CSIR study and the others. While the CMC and PGIMER reports showed ‘breakthrough infections’ as those confirmed by a gold-standard RT-PCR test, the CSIR study relied on a blood test that measured levels of antibodies directed towards the nucleocapsid region of the coronavirus, which is different from the region (spike protein) that vaccine-generated antibodies normally target. Currently, all the vaccines are designed to produce antibodies against the spike protein and so high levels of antibodies against the nucleocapsid region were presumed markers of a fresh coronavirus infection. None of the infections made the healthcare workers sick enough to warrant a test and so it could well be that the number of ‘breakthrough infections’ are much higher than those confirmed by RT-PCR tests. The bigger concern, however, is that those with a ‘breakthrough infection’, under the belief that they are fully protected, may be less stringent with using masks and could be carriers of infection. The U.S. Centers for Disease Control and Prevention reports that the viral load in those with a ‘breakthrough infection’ can be as much as those unvaccinated, which is why mask mandates are back despite significant vaccination coverage.

That ‘breakthrough infections’ occur is not a surprise. In clinical trials, all vaccines available have reported efficacy rates between 70% and 90%. This implies that between 10% and 30% of a vaccinated population will be vulnerable to infection. Vaccines, however, were premised on inuring the body to disease and so far the evidence is that they are overwhelmingly effective.


Is the Delta variant responsible for the rise in cases?

When the underlying coronavirus variants were analysed in the Kerala study, 126 were found to have the Delta variant (B.1.617.2), nine had the Kappa variant (B.1.617.1) and six had Delta-Plus variants, that is sub-lineages of the Delta with one or more of its defining mutations. These mutations mostly help the virus escape detection by antibodies. The India SARS-CoV-2 Genome Consortium (INSACOG), which monitors emerging variants nationally, has analysed 51,651 coronavirus genomes as of August 30. Of them, 31,721 cases were international variants of concern and among them 21,449 were Delta variants. A mere 393 cases were Delta-Plus, though many Delta variants are in the process of being reclassified as Delta-Plus (there are 13 such sublineages) because, while it does not necessarily make them more virulent or harmful, they serve as markers of an evolutionary change in the coronavirus and need to be tracked, say genome scientists. Delta has also been demonstrated to reduce antibody levels elicited by vaccines. Antibody levels are not the only measure of protection and immunity by T-cells, which cannot be easily evaluated in a lab, are also important for neutralising the virus. However, vaccine production technologies such as m-RNA and DNA are premised on their ability to be tweaked quickly for newer variants. The makers of Covaxin claim that their vaccine, being an inactivated whole virus, is geared up to be more effective against variants than other vaccines primarily targeted at the spike protein. An ICMR study showed a 65.2% protection against the Delta variant in a double-blind, randomised, multicentre, Phase 3 clinical trial of Covaxin.

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