Many viral infections are seasonal in nature, including the influenza virus, which makes an appearance every winter. In the early days of the COVID-19 pandemic, researchers and public health officials suggested that SARS-CoV-2 might behave like other endemic coronaviruses, peaking in the fall and winter seasons.

However, this claim was lacking scientific evidence, especially on the global scale. This question provided the impetus for researchers at the University of Illinois at Urbana-Champaign to conduct work that would fill this specific knowledge gap.

Taking into consideration all the similarities with influenza infection, the team investigated if COVID-19 infection is seasonal. They hypothesized that COVID-19 epidemiology and genetic makeup are affected by the seasonality phenomenon. For instance, they postulated that high temperatures and humidity would negatively affect viral transmission, as well as the resulting cases and death rates.

Does temperature and location affect COVID-19 disease?

First, the researchers downloaded relevant epidemiological data (disease incidence, mortality, recovery cases, active cases, testing rate, and hospitalization) from 221 countries, along with their latitude, longitude, and average temperature. They used Pearson correlation analyses to test if temperature and geographic location were associated with population-normalized data of incidence, mortality, recovery of patients, active cases, and testing rate in each country.

"One conclusion is that the disease may be seasonal, like the flu. This is very relevant to what we should expect from now on after the vaccine controls these first waves of COVID-19," said senior author Gustavo Caetano-Anollés, PhD, professor in the department of crop sciences, affiliate of the Carl R. Woese Institute for Genomic Biology at Illinois, in a statement.

"Indeed, our worldwide epidemiological analysis showed a statistically significant correlation between temperature and incidence, mortality, recovery cases, and active cases," noted Caetano-Anollés. "The same tendency was found with latitude, but not with longitude, as we expected."

Do viral mutations affect COVID-19 disease?

The team also sought to establish a link between temperature-location effects with genomic changes of SARS-CoV-2 to determine if temperature-related epidemiological effects are controlled by the virus in its interaction with the host. For this analysis, genomic change, and genomic change per unit time were computed from an alignment of 55, 453 SARS-CoV-2 genome sequences to determine if there were significant statistical correlations with temperatures and geographic coordinates of the various countries. Mutation accumulation and rates were calculated for the entire genome and for specific regions known for significant pathways of mutational change.

Mutational changes were based on results from a parallel study of 15,342 indexed virus genome sequences that revealed novel pathways of mutational change during the early stages of the COVID-19 pandemic. The analysis predicted mutational shift from spike and replication proteins to other regions of the proteome, including the nucleocapsid protein and the viroporin 3a protein. A lack of significant correlations indicates that mutational changes in the virus genomic makeup appear unrelated to the temperature modulation of the COVID-19 disease.

"Our results suggest the virus is changing at its own pace, and mutations are affected by factors other than temperature or latitude," said Caetano-Anollés. "We don't know exactly what those factors are, but we can now say seasonal effects are independent of the genetic makeup of the virus."

Host immune system and seasonality of COVID-19

The researchers noted that the host immune system could be in part responsible for the pattern of seasonality. While unconfirmed, some studies suggest that high environmental temperatures, host nutritional status, and vitamin D levels play a crucial role in the regulation of adaptive immune responses following respiratory viral infection, as is the case with influenza. The researchers recommend that the interaction of the environment and SARS-CoV-2 epidemiological data merits further investigation.

"We know the flu is seasonal, and that we get a break during the summer. That gives us a chance to build the flu vaccine for the following fall," explained Caetano-Anollés. "When we are still in the midst of a raging pandemic, that break is nonexistent. Perhaps learning how to boost our immune system could help combat the disease as we struggle to catch up with the ever-changing coronavirus."

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