Timing of exposure critical for SARS-CoV-2 transmission according to animal study

Transmission efficiency determines the size of an infectious outbreak, as demonstrated by the tendency of severe acute respiratory syndrome coronavirus 2  (SARS-CoV-2) to transmit among humans and sustain the coronavirus disease 2019 (COVID-19) pandemic.

Study: Timing of exposure is critical in a highly sensitive model of SARS-CoV-2 transmission. Image Credit: olgers/Shutterstock

In a recent pre-print study posted to the bioRxiv* server, a team of researchers gathered data from detailed animal studies to show that exposure to SARS-CoV-2 for about one hour is sufficient to support vigorous SARS-CoV-2 transmission. In addition, the time-lapse after SARS-CoV-2 exposure alters transmissibility, with the highest transmission frequency observed in contacts occurring at times of peak viral load. Furthermore, they demonstrated that viral load determines the infectious period.

The study

In the present study, the researchers assessed the spread of SARS-CoV-2 in golden Syrian hamsters to get a perspective on spatio-temporal conditions impacting the transmission efficiency of SARS-CoV-2 through the air. The researchers hypothesized that viral densities in the air or inside the recipients' respiratory tract increase with time. Therefore, they exposed naïve hamsters to infected hamsters at different time-points - five days, eight hours, four hours, and one hour and at 24 hours post-inoculation (hpi) of donor hamsters.

To check the transmission potential early and late in the course of SARS-CoV-2 infection, naïve hamsters were exposed to infected hamsters for one or two hours at 10–12, 12–14, 14–16, 16–17, or 24–25 hpi, and then for two hours on days two, four, and six post-inoculation (pi).

After each exposure window, the nasal lavage samples of the donor hamsters were collected and used to assess viral loads at the time of exposure. These samples, collected across multiple time points, were later used to evaluate the dependence of transmission efficiency on viral load.

Timing of exposure

The study results showed that for all the exposure time durations tested during the study, the SARS-CoV-2 transmission in hamsters was quite vigorous, suggesting that a minimal infectious dose reaches naïve hamsters within one hour. Hence the timing of exposure emerged as the strongest determinant of SARS-CoV-2 transmission success.

They observed that high viral loads were reached by 17 hours and sustained at 48 hpi, but titers declined below this range by four days post-inoculation (dpi). Naïve hamsters exposed to donor hamsters for two hours beginning at 10, 12, or 14 hpi were not infected.

In contrast, viral transmission was seen in two of the four animals exposed for 1 hour beginning at 16 hpi and all the four animals exposed for one hour beginning at 24 hpi. Exposure at late time points showed appreciable transmission only at 2 dpi, with five of eight hamsters contracting infection when exposed for two hours beginning at 2 dpi. Overall, the study data revealed that the opportunity for transmission was from 17 hours to two days after infection in the donor hamsters.

The results also suggested that viral load most likely determines the infectious period, since the nasal lavage titers of animals that transmitted to contacts showed significantly higher viral loads in comparison to those that did not transmit the virus.

When exposures were carried out with optimal timing, relative humidity and temperature did not impact transmission. However, there was an improvement in transmission efficiency at high relative humidity or high temperature.

Conclusions

The study results showed that when naïve and infected animals are not in direct contact and only share air space, SARS-CoV-2 transmission is highly efficient under a wide range of humidity and temperature conditions. Subsequently, many hamsters with exposure periods as short as one hour were infected. Peak transmission was observed between 16h and 48h after inoculation, revealing an early and narrow period during which transmission occurs. This period also corresponds with high viral titers in the nasal tract. The authors recommended active investigation of the dependence of respiratory virus transmission on disease symptoms and limitations imposed by antiviral responses in future studies.

When translating the hamster study results to humans, there is a difference between the peak viral loads. In humans, peak viral loads are observed three to four– days after infection, while peak titers in hamsters were observed at 24 hpi. This is because hamsters were inoculated with a dose higher than the typical dose in humans.

However, the association between infectious period and higher viral load is likely true for humans as well. To conclude, a detailed understanding of the host, viral, and environmental factors that shapes and drives SARS-CoV-2 transmission dynamics is vital for devising effective strategies to interrupt transmission.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Neha Mathur

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.

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