Current COVID-19 Infections Include Future Variants of Concern

Nowadays the question is not so much, “Have you gotten COVID-19?,” but rather, “Do you know what variant you contracted?” If your infection wasn’t in the early days of the pandemic, you may have a good guess as to which variant found you due to researchers discovering and reporting mass surges.

But now, a team of researchers at Case Western Reserve University (CWRU) say it’s not that black and white. Using genetic sequencing, they have shown that, among 360 patients, all infections include multiple variants of SARS-CoV-2. More importantly, they found that the genetic variants observed in low frequency in older infections morphed into new strains responsible for later transmission surges.

“Our work brings attention to the complexity of infectious diseases that is often over-simplified when considering only the most abundant virus in an infection, and we demonstrate the importance of examining the variations that are historically considered noise,” said Ernest (Ricky) Chan, director of the bioinformatics core with the Cleveland Institute for Computational Biology at the Case Western Reserve School of Medicine.

According to their paper published in PLOS Genetics, the CWRU team performed full genome sequencing of SARS-CoV-2 viruses from 250 patients in Northeast Ohio and used similar data from another 110 patients with full genetic sequences of infecting viruses provided through research collaborators.

These data were developed in the early days of the COVID-19 pandemic when the Alpha variant and then the Delta variant were of major concern. This work showed that mutations found in Omicron BA.1 and BA.2 were already present as relatively minor variations at least a year before Omicron and its iterations became variants of concern and led to a major COVID-19 resurgence last winter.

While the research team acknowledges focusing on majority variants is critical for the development of effective diagnostics, therapeutics and vaccines, they urge the research community to quantify and report variation for the betterment of public health.

For example, their study accurately identified two individuals who harbored mixed B.1.1.7/B.1.617.2 infections in mid-May 2021. The collection of these samples preceded by one month the first reports from the State of Ohio that B.1.617.2 was present in the Cleveland area—and occurred at a time when the city lifted its Civil Emergency Proclamation (May 28, 2021) and the state rescinded its masking mandate and social distancing orders (June 2, 2021).

“Communicating knowledge of B.1.617.2 infection and transmission in Cleveland ahead of relaxing mitigation measures may have contributed to a more cautious public health strategy,” explain the study authors.

During their genetic sequencing, the researchers observed numerous examples of alternate alleles that did not clear the 50% threshold for inclusion in conventional consensus sequences but have since become variants of concern, including multiple Omicron strains.

“These observations suggest that minority alleles in earlier SARS-CoV-2 infections may contribute to the continuing evolution of new variants of concern. Confirming this potential will require consideration of minor alternate alleles, as suggested, in more extensive whole genome analysis of SARS-CoV-2,” write the authors in their recently published paper.

Lastly, the authors point out it’s not just SARS-CoV-2 whose genetic diversity is underreported. They say it happens with most—if not all—infectious disease pathogens, including Yersinia pestis, Marburg virus, Ebola virus, Plasmodium and Mycobacterium tuberculosis.

“Adequately addressing the under-reporting of infection complexity represented in data repositories has significant potential to alter vitally important characteristics of infectious diseases, including assessment of drug treatment efficacy and resistance and vaccine escape,” conclude the study authors.  

 

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