A recent study has turned on its head the notion that getting naturally infected with SARS-CoV-2 virus would provide more protection from future infections. The study has found the complete opposite — a previous infection makes the next infection(s) worse. The study has been posted as a preprint in Research Square, which is yet to be peer-reviewed.
Compared with vaccination, first infection with SARS-CoV-2 virus is associated with increased risk of adverse health outcomes in pulmonary and extrapulmonary organ systems, hospitalisation and even death. And reinfection contributes to additional risk of deaths and adverse health outcomes in the pulmonary and several extrapulmonary organ systems, the study found.
Persistence of risks
“The risks were evident in those who were unvaccinated, had one shot, or two or more shots prior to the second infection; the risks were most pronounced in the acute phase, but persisted in the post-acute phase of reinfection, and most were still evident at six months after reinfection,” a three-member team led by Dr. Ziyad Al-Aly from the Washington University School of Medicine, U.S., says in the preprint.
The study was based on national health care databases of the United States Department of Veterans Affairs that included people with no infection (53,96,855), with one infection (2,57,427), and two or more reinfections (38,926). Among those with reinfection, 36,417 (12.29%) people had two infections, 2,263 (0.76%) people had three infections, and 246 (0.08%) people had four or more infections.
The study found that compared with those with first infection, people with reinfection had an elevated risk (hazard ratio or HR 2.14) of all-cause mortality. There was also increased risk of hospitalisation (HR 2.98) and at least one sequela of SARS-CoV-2 infection (HR 1.82) among people with a reinfection.
Compared to those with first infection, those with reinfection exhibited increased risk of sequelae — cardiovascular disorders (HR 2.36), hematologic disorders (HR 2.22), fatigue (HR 2.4), gastrointestinal disorders (HR 1.69), kidney disorders (HR 1.70), diabetes (HR 1.62), musculoskeletal disorders (HR 1.29), and neurologic disorders (HR 1.39).
Cumulative risk
“The risks were most pronounced in the acute phase, but persisted in the post-acute phase of reinfection, and risks for most sequelae were still evident at six months,” they write. “Compared to non-infected controls, assessment of the cumulative risks of repeated infection showed that the risk and burden of all-cause mortality and the prespecified health outcomes increased in a graded fashion according to the number of infections.”
Compared with the Delta variant, the Omicron variant that first caused a wave in almost all countries beginning late-December last year was perceived to be mild in people who were fully vaccinated and/or infected. The BA.5 Omicron sub-lineage that is currently spreading to many countries is more transmissive than the BA.1 sub-lineage and is also causing more hospitalisations and even deaths in Portugal, which has a very high percentage of the population fully vaccinated and even boosted.
“There was a popular narrative that after surviving COVID-19, the next infection will be milder. Anecdotal experience had however shown that’s not the case. Many people have said that their second bout was worse, while others have said it was mild,” Dr. Rajeev Jayadevan, Co-Chairman, National IMA COVID Task Force tells The Hindu.
“Now, this study has confirmed that with every subsequent bout of COVID-19, there are additional and cumulative health problems. In other words, it is not necessarily going to be a common cold the next time around. The SARS-CoV-2 virus is not a common cold virus, it can repeatedly affect organs such as blood vessels, immune system, heart, brain and the lungs. It has shown that it can infect people who were unvaccinated, vaccinated or boosted,” he adds.
Prevention is key
Unlike what was believed early during the pandemic, neither herd immunity using the currently available vaccines nor eliminating the virus seem possible. The emergence of highly transmissive variants endowed with greater immune escape makes the task of preventing reinfections a challenge. Currently available vaccines cannot protect against reinfection. “The totality of evidence suggests that prevention strategies of reinfection might benefit people regardless of prior history of infection and vaccination status,” they write.
“Although it is true that the chance of severe outcomes is smaller among those with prior immune memory either from vaccination or past infection, when a large number of people undergo frequent reinfections, it can be expected that several of them will have bad outcomes,” Dr. Jayadevan says.
The SARS-CoV-2 virus is here to stay and the threat posed by the virus will remain for years. Public health measures, particularly non-pharmaceutical interventions such as mask wearing, better ventilation, and use of air filters to name a few need to be embraced to reduce the risk of virus spread.
