Ambient carbon dioxide concentration correlates with SARS-CoV-2 aerosolability and infection risk

The airborne transmission of SARS-CoV-2, the virus causing COVID-19, is a significant factor in its spread. Understanding how environmental factors influence the aerosolization and infectivity of the virus is crucial for developing effective mitigation strategies. Previous research highlighted the role of respiratory aerosol pH in reducing SARS-CoV-2 infectivity, with changes in gas-particle partitioning of bicarbonate ions and CO2 being key. This study builds upon this foundation by examining the direct effect of ambient CO2 concentration on SARS-CoV-2 aerosolability and its subsequent impact on transmission risk. The study's hypothesis is that elevated CO2 levels will increase the aerosolability and thus the transmission potential of SARS-CoV-2. This is important because it directly relates to indoor air quality and ventilation strategies. Poor ventilation in indoor spaces leads to CO2 buildup, potentially creating environments conducive to increased viral transmission. Therefore, understanding this relationship is vital for informing public health interventions aimed at minimizing COVID-19 spread and reducing the risk of future outbreaks of similar respiratory viruses. The study aims to quantify the impact of CO2 concentration on viral aerosolability and utilize a transmission model to assess the increased risk of infection in real-world settings, such as classrooms.

The literature review section summarizes existing knowledge on SARS-CoV-2 transmission, focusing on airborne transmission as a major route. It reviews previous studies demonstrating the correlation between respiratory aerosol pH and SARS-CoV-2 infectivity, emphasizing the role of bicarbonate ions and CO2 in this process. The review also incorporates research on the various SARS-CoV-2 variants, their differing stabilities, and the influence of environmental factors like relative humidity on viral aerosolization. Studies on non-pharmaceutical interventions like ventilation, social distancing and mask-wearing are also reviewed within the context of reducing airborne viral load and transmission risk. Finally, existing mathematical models used to estimate transmission risk, such as the Wells-Riley model, are discussed, laying the foundation for the study's use of a similar framework.

The study employed a novel technique called CELEB5 (Controlled Environment Levitated Electrodynamic Balance System) to measure the airborne longevity of SARS-CoV-2 variants. This technology allows for precise control over environmental factors like relative humidity (RH) and CO2 concentration while monitoring the infectivity of aerosolized viral particles over time. The study used both Delta and Omicron (BA.2) variants to explore potential differences in their aerosolization characteristics. The CELEB5 system generates and levitates individual droplets containing the virus, allowing for detailed observation of viral decay under controlled conditions. The researchers also performed bulk stability measurements using TCID50 assays and immunostaining to assess viral stability in solutions with varying pH levels. The study used Dulbecco's Modified Eagle Medium (DMEM) as a proxy for respiratory fluids, considering its similar physicochemical properties, including bicarbonate content. The experimental data on viral decay was then incorporated into a Wells-Riley model to estimate the risk of COVID-19 transmission in different indoor environments with varying CO2 concentrations and ventilation rates. Statistical analyses, including t-tests and ANOVA, were used to assess the significance of the findings. The study meticulously describes the cell culture methods, virus preparation, and the experimental procedures involved in both the airborne longevity measurements and the bulk stability assays.

The study's key findings demonstrate a strong correlation between ambient CO2 concentration and SARS-CoV-2 aerosolability. Specifically, increasing CO2 concentration, even moderately (from 500 to 800 ppm), led to a significant increase in the aerosolized viral load, particularly at RH levels below 80%. The Omicron BA.2 variant was found to be more aerosolizable and more resistant to high-pH conditions compared to the Delta variant. The researchers observed a triphasic decay profile for aerosolized SARS-CoV-2, consisting of a lag phase, a dynamic phase, and a slow decay phase. The duration of these phases was influenced by both microbiological factors (viral pH sensitivity) and aerosol dynamics (RH, CO2 concentration). Incorporating the experimental data into a Wells-Riley model, the study showed a significant increase in the risk of COVID-19 transmission with even a moderate increase in CO2 concentration, particularly in poorly ventilated environments. The model predicted that the time until a 50% chance of at least one infection occurs is approximately halved by raising the CO2 levels in a poorly ventilated space. These results highlight the critical role of ventilation in mitigating airborne transmission, even in the short term.

The study's findings strongly support the hypothesis that elevated CO2 concentrations contribute to increased SARS-CoV-2 aerosolability and transmission risk. The observed triphasic decay profile provides insights into the complex interplay between viral properties and environmental conditions governing viral longevity in aerosols. The increased aerosolability at higher CO2 levels is likely due to the effect of CO2 on the pH of respiratory droplets, reducing the rate of viral inactivation. This has significant implications for indoor environments, particularly poorly ventilated spaces where CO2 tends to accumulate. The integration of experimental data with the Wells-Riley model provides a powerful tool for assessing transmission risk under realistic scenarios. The study's results underscore the crucial role of effective ventilation strategies in minimizing COVID-19 transmission. These findings have broader implications for understanding the seasonality of respiratory viral infections, suggesting that variations in indoor CO2 concentrations may play a significant role. It also highlights the importance of considering CO2 levels when interpreting the results of previous aerosol studies on viral stability and infectivity.

This study demonstrates a significant positive correlation between ambient CO2 concentration and SARS-CoV-2 aerosolability, leading to increased infection risk, especially in poorly ventilated spaces. The triphasic decay model offers a more nuanced understanding of viral decay dynamics. The study underscores the critical importance of ventilation in mitigating COVID-19 transmission and suggests potential links between indoor CO2 levels and the seasonality of respiratory viral infections. Future research should investigate the interplay of CO2, RH, and other factors on short-distance transmission and expand this work across a wider range of respiratory viruses and environmental conditions.

The study used DMEM as a surrogate for respiratory fluids, which may not perfectly capture the complexity of real-world respiratory secretions. The Wells-Riley model used is based on assumptions of well-mixed environments, which might not always hold true in real-world settings. Further research is needed to explore the influence of droplet size on viral inactivation rates and examine the applicability of these findings across different respiratory viruses and varying environmental conditions. Additional research using more sophisticated models that can account for both short and long-range transmission are needed.