Variants of SARS-CoV-2 and Their Association With Disease Severity

The COVID-19 pandemic caught us all off guard. But since the emergence of SARS-CoV-2, the virus that causes COVID-19, Cleveland Clinic epidemiologists have been investigating the evolution of the virus in an attempt to help determine which patients are at risk for severe disease. Now they are sharing the results of their study of the genomics of SARS-CoV-2, which may help with surveillance as well as in the prediction of severe disease in particular patients.

“We started this study when very little was known about the virus,” says Frank Esper, MD, an infectious disease specialist at Cleveland Clinic Children’s. “We were interested in determining to what extent the genetic makeup of the virus itself influenced clinical outcomes such as disease severity, hospitalization, admission to intensive care units (ICU) and death.”

The article is published today in JAMA Network Open.

Viral variation, in addition to host factors, contributes to disease severity

Researchers performed next generation sequencing on 302 representative nasopharyngeal specimens that were positive for SARS-COV-2 from March 11, 2020 through April 22, 2020. This viral genome analysis identified variants and clades, which the team then compared with severity of disease and patient outcomes using information in the Cleveland Clinic COVID-19 Registry.

Within the study population, 58.3% (n = 176) were female, 64.6% (n = 195) were white, and the median age was 52.6 years. Thirty percent (n = 91) of these patients required hospitalization, and 39.5% (n = 35) of those hospitalized were admitted to an intensive care unit. There were 17 deaths (18.7% of those admitted and 5.6% overall). The researchers found correlations between certain SARS-CoV-2 variants or clades and lower hospitalization rates, increased patient survival when hospitalized, higher overall mortality, as well as levels of IL-6, creatinine and d-dimer.

This study is unique in that it follows strains within a confined community, allowing much more precise analysis of how the genomics of the virus changed over time. Additionally, Dr. Esper notes that while larger genomic studies look at the virus and how it mutates, this study takes that analysis further by addressing what those variants may mean for patients.

The impact of lockdown

“Our focus on the first wave of cases in Northeast Ohio allowed us to look for associations without some of the confounding variables of emerging treatments and public health and safety measures,” says Dr. Esper. “We started seeing variants and subpopulations of viruses – and the dance that they were doing – in our community.”

In the first six weeks of viral spread in Northeast Ohio, there was significant diversity in the strains that circulated in the community, says Dr. Esper. “Just before lockdown, people were still traveling: they were coming back from travel abroad or out-of-state. We saw strains from Wuhan, Italy, the UK and New York. Specifically, we found six of the seven different clades established within our community In the first six weeks of viral spread in Northeast Ohio, there was significant diversity in the strains that circulated in the community,” says Dr. Esper.

“The first strains out of the gate were much more severe, and were responsible for more hospitalization, more ICU admissions and, in some instances, death. This was one of the most surprising aspects of our study: how quickly SARS-CoV-2 changed, even within a confined community. Going on lockdown and allowing this strain to overgrow may have aided in reducing the overall severity of illness within the community,” Dr. Esper says.

Looking to the next pandemic

This research also provides important information about what to expect in the next pandemic.

“This is the third global outbreak of a coronavirus in the last 20 years. The world is becoming a smaller place, allowing germs to spread in a way that just wasn’t possible not too long ago. With SARS in 2003, MERS in 2012 and now SARS-CoV-2, we are averaging a new global coronavirus outbreak nearly every 8 years. Our research helps us better understand what to expect next time in terms of disease severity and how different variants evolve. It may help us identifying, and perhaps even selecting for, less severe variants,” Dr. Esper concludes.