With input from Dr Monica Vasudev

What can be the reasons in India

1. Overuse of antibiotics and anti-virals leading to NSP 14 inhibition and new strains of the viruses, resulting in breakthrough cases.
2. Breakthrough infections means that the virus has been able to break through the defences created by the vaccine.
3. Breakthrough infections are expected in a small number of people after vaccination.
4. Some may have been infected before the shot but some strains may evade vaccine protection. These strains (newer strains in India) may aggravate or facilitate COVID (also, Israel observation).
5. In India also, we are clinically seeing a lot of early breakthrough cases.

A study by Kustin et al, titled ‘Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals’:  

1. The BNT162b2 mRNA vaccine has shown high levels of protection, but there is still apprehension that the variants of concerns (VOCs) can overcome the immune response generated by the vaccines.
2. Neutralization assays have demonstrated some reduction in neutralization of VOCs B.1.1.7 and B.1.351; however, the relevance of these assays in real life scenario is not clear.
3. A case-control study was conducted to assess whether BNT162b2 vaccine recipients with confirmed SARS-CoV-2 infection had increased likelihood of getting infected with B.1.1.7 or B.1.351 compared with unvaccinated individuals.
4. Vaccine recipients infected at least one week after the second dose were disproportionally infected with B.1.351 with an odds ratio of 8:1.
5. Individuals infected between two weeks following the first dose and one week after the second dose, were found to be disproportionally infected by B.1.1.7 (odds ratio of 26:10). This pointed to decreased vaccine effectiveness against both VOCs under different dosage/timing conditions.

Discussion

1. The study results point to an increased incidence of VOC B.1.351 in vaccine breakthrough infections in fully vaccinated individuals with BNT162b2, as well as a heightened incidence of VOC B.1.1.7 in partially vaccinated people.
2. The results appear to be in line with those from in vitro neutralization assays that have demonstrated reduction in neutralization against B.1.351, and little to no reduction against B.1.1.7 in fully vaccinated individuals.
3. The findings indicate that serum-based neutralization studies that consider individual monoclonal antibody responses may serve as a good proxy for real life protection in the case of COVID-19.
4. Sequencing limitations prevented the researchers from sequencing very low viral load samples. Therefore, the focus of the study was on vaccine recipients who generated higher viral loads.
5. It has been shown that cases with low viral load may present a lesser concern from a public health perspective. They are linked with less symptoms and reduced transmission.
6. The full effectiveness (FE) cohort is based on infections shown seven or more days after the second vaccine dose.
7. Some individuals in this cohort may have been infected before the immunity from the boost was fully developed, and it seems possible that increased immunity from the boost may be more effective at prevent infection with the B.1.351 variant.
8. This study may suggest a somewhat lower protection against B.1.1.7 in the first weeks after the first vaccine dose.
9. From a biological viewpoint, the breakthrough cases in this study might have occurred either as a result of immune evasion of both strains, or the ability of B.1.17 to create higher viral loads.

(https://www.medrxiv.org/content/10.1101/2021.04.06.21254882v1.full.pdf+html)

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA