Isolation measures during pandemic drove faster, more transmissible SARS-CoV-2 variants, study reveals

In a study published in the journal Nature Communications, an international team of researchers investigated the impact of human behavioral changes such as isolation during the coronavirus disease 2019 (COVID-19) pandemic on the evolution of the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They found that as SARS-CoV-2 evolved from its original form to variants like Alpha and Delta, the changes in the virus led to a pattern where the peak amount of virus in the body occurred earlier and was higher. However, the overall duration of infection was reduced. This evolution, driven by the virus's need to increase its ability to spread from person to person, was influenced by factors such as isolation practices.

Additionally, the research indicates that as the virus adapted to these human behaviors, there was a trend towards shorter incubation periods and a higher chance of the infection being asymptomatic, particularly noticeable in variants like Omicron. The findings indicate the potential role of isolation in inducing directional selection for increased transmissibility of the virus.

Study: Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution. Image Credit: Alonafoto / ShutterstockStudy: Isolation may select for earlier and higher peak viral load but shorter duration in SARS-CoV-2 evolution. Image Credit: Alonafoto / Shutterstock

Background

Given the current density and activities of the global population, human-mediated selection drives substantial evolutionary changes in organisms. The COVID-19 pandemic led to a significant slowdown in human activities and their environmental impact.

Changes in population size, immunity, and behavior, driven by public health policies, contribute to the rapid evolution of viruses. The ongoing evolution of SARS-CoV-2, from the initial Wuhan-Hu-1 strain to variants like Alpha, Delta, and the newly emerged Omicron, highlights the dynamic nature of the virus. The continuous emergence and adaptation of SARS-CoV-2 variants suggest an evolutionary trajectory, emphasizing the need for ongoing vigilance and adaptive responses.

Understanding the epidemiological and clinical aspects of emerging infectious diseases is crucial for developing adaptive treatments and strategies. Forces such as pharmaceutical interventions (the infection and response to vaccines and antiviral drugs), as well as non-pharmaceutical interventions or NPIs (isolation measures, social distancing, the use of masks, etc.), are known to act as selection pressures on the virus. Researchers in this study analyzed SARS-CoV-2 data to examine the impact of isolation as an NPI on SARS-CV-2 variant evolution. For the first time, they quantified and compared viral load dynamics as well as viral shedding among the variants in response to isolation measures.

About the study

In the present study, longitudinal viral load data were obtained from published papers on patients with COVID-19. Data with at least two time points for viral load measurements via samples from the upper respiratory tract were used. Among the four chosen studies, three were conducted in the United States of America (USA), and one was conducted in the United Kingdom (UK). An estimation model was developed using viral load data from patients infected with pre-Alpha variants (n = 86), Alpha variant (n = 59), Delta variant (n = 80), and Omicron (BA.1) variant (n = 49).

A nonlinear mixed-effect model was developed and tested to describe SARS-CoV-2 infection dynamics in target cells. This individual-level infection model was combined with a population-level transmission model to form a probabilistic multi-level population dynamics model to understand SARAS-CoV-2 evolution. The model included parameters such as the duration of viral shedding and the time and amount of peak viral load. Additionally, the transmission potential of the virus was estimated to understand the epidemiological consequences of the variants. The modeling and analysis were performed using Python and R as coding languages. The data and code were made publicly available at Zenodo.

Results and discussion

As per the study, no significant difference was found in (1) the peak time among pre-Alpha and Alpha variants and (2) the peak viral load among Alpha and Delta variants. However, the peak viral loads for Alpha and Delta were found to be higher than pre-Alpha variants. Additionally, the peak duration and time of viral shedding were found to be shorter for Delta than pre-Alpha or Alpha variants. The findings suggest that SARS-CoV-2 was evolving to form a more acute phenotype with a shorter shedding duration and a higher peak viral load.

In the transmission analysis, the researchers found that the transmission potential of the Alpha variant remained at a high value for a longer duration than pre-Alpha variants. In the Delta variant, the transmission potential was found to peak and fall rapidly within eight days of infection.

When viral shedding dynamics were compared, the peak load of the Alpha variant was found to be higher than pre-Alpha variants but with a lower duration and higher transmissibility. Although a similar effect was observed between pre-Alpha and Delta variants, no such effect was seen among Alpha and Delta variants. In response to human behavior changes such as isolation, the incubation period was found to decrease while the number of asymptomatic infections wer found to increase.

The effect of prior immunity induced by vaccination or prior infections was also investigated on the isolation-driven evolution of SARS-CoV-2. The original findings of the model remained consistent even when prior immunity among individuals was considered.

The model was further validated using data from the Omicron BA.1 subvariant. It was found that the evolution of SARS-CoV-2 towards an advanced peak viral load was maintained but at a slower pace.

However, as a limitation, the study did not consider the relationship between clinical phenotypes and viral evolution or the dynamics between hosts and viruses.

Conclusion

In conclusion, the findings demonstrate that SARS-CoV-2 variants evolved towards a more acute phenotype in response to isolation, with an earlier and higher peak viral load but a shorter duration. Further research is required to confirm these findings and understand the effect of other interventions on SARS-CoV-2 evolution to aid the development of improved public health strategies.

Journal reference:
Dr. Sushama R. Chaphalkar

Written by

Dr. Sushama R. Chaphalkar

Dr. Sushama R. Chaphalkar is a senior researcher and academician based in Pune, India. She holds a PhD in Microbiology and comes with vast experience in research and education in Biotechnology. In her illustrious career spanning three decades and a half, she held prominent leadership positions in academia and industry. As the Founder-Director of a renowned Biotechnology institute, she worked extensively on high-end research projects of industrial significance, fostering a stronger bond between industry and academia.  

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