Variants are of concern because of increased transmissibility, increased disease severity, and immune escape resulting in the risk of reinfection in convalescent individuals or infection in vaccinated individuals.
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The patient had an Alpha variant infection despite past
infection, complete vaccination, and seroconversion.

Despite enhancement after this infection, the patient subsequently had severe Delta variant infection.

This was also a proven reinfection by WGS . The patient acquired the infection from a fully vaccinated family member.

A year and a half after the 2019 Coronavirus Disease (COVID-
19) pandemic, we are at the heartbreaking milestone of four million recorded deaths from COVID-19. Estimates of the true number of deaths based on excess deaths are incredibly higher at more than ten million (1). The true number of infections is estimated
to be five to twenty times higher than the number of confirmed cases (2) and is in the billions. Fortunately, we have several effective vaccines with which we can potentially contain the COVID-19 pandemic. Unfortunately, our vaccination efforts must contend with the rapid spread of Severe Acute Respiratory Coronavirus 2 from Severe Acute Respiratory Syndrome (SARS-CoV-2), and this is a monumental challenge.
In December 2020, the Alpha variant was identified in the United Kingdom (3) and designated the first variant of concern (VOC). Since then, it has been a race between the speed of VOCID-19 vaccine distribution and the emergence and spread of SARSCoV-2.
As the number of vaccinated individuals has surpassed 1 billion worldwide, new variants of concern have emerged that are more worrisome than their predecessors. The Delta variant is the most worrisome variant to date. The
variants are of concern because of increased transmissibility, increased disease severity, and immune escape resulting in risk of reinfection in convalescent individuals or infection in vaccinated individuals (4).
Between February and June 2021, India experienced a second wave of COVID-19, partially attributable to VOCs (5). Both Alpha and Delta variants have been identified in India and have contributed to the second wave in India (5).
With the Delta variant poised to become the dominant lineage worldwide, the combination of increased transmissibility and immune escape is dangerous.
Breakthrough infections are mitigated by vaccines and are generally mild (5). Vaccines also reduce the risk of transmission transmission (6), but it is unclear whether this applies to the Delta variant and all vaccines. Reinfections are
thought to be relatively rare, but the difficulty of recovering paired samples
from different episodes for whole genome sequencing (WGS) makes it difficult to establish reinfection. In the context of VOCs, reinfections are possible and probably more common than previously thought. Even when reinfections are proven by WGS, serial serology, inflammatory markers, and radiological imaging are usually unavailable. This limits our understanding of these rare but immunologically significant episodes.
Individuals with immunity from natural infection and vaccination are said to have hybrid immunity. The combination of postinfection and postvaccination immunity
results in antibody responses that are 25- to 100-fold higher, improved memory B-cell and CD4+ T-cell responses, and improved cross-protection against variants (7). SARS-CoV-2 infection in an individual with such hybrid immunity should be very rare, severe infection even rarer. However, demonstrating that a breakthrough infection was also a reinfection is subject to
difficulties in identifying such rare cases and recovering samples.
So such cases are difficult to demonstrateThe patient in our study had two WGS breakthrough infections proven with Alpha and Delta variants, with the second
breakthrough infection resulting in hospitalization. The patient had serial serology, blood investigations, inflammatory markers, and radiological imaging giving us a unique opportunity to study this breakthrough reinfection.