Lightening the load: reduce viral transmission dose to lessen Covid-19 severity Adherence to separation measures is key

While the number of positive tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across many European countries has risen sharply, increases in the number of hospitalizations and deaths due to coronavirus disease 2019 (Covid-19) have not been as steep. The case fatality rate (the proportion of deaths per positive test) in the UK was lower in May and June than in March and April¹, and appears to be have been declining steadily throughout July and August². Reductions were also observed in the early stages of the outbreak across many countries³. Case fatality rates have varied in different countries, with relatively lower estimates observed in several African countries⁴. Why have case fatality rates decreased, and how does this relate to measures used to control the epidemic?

Possible reasons

The first reason for reductions in the Covid-19 case fatality rate is the changing demographic of cases⁵. Age is a strong predictor of Covid-19 mortality⁶. In many Western countries, while the absolute number of cases in over-60s is increasing, the proportion of cases in over-60s is decreasing⁵. This suggests that public health measures to curb the spread of SARS-CoV-2 have been successful in reducing the relative burden of disease in elderly individuals, who are the most vulnerable demographic group.

The second reason is improved treatment. This includes pharmacological agents such as systemic corticosteroids, which have recently been shown to improve outcomes in Covid-19 patients⁷. Further, clinical management of cases is likely also improving, through accumulated experience of the disease.

A third reason may relate to the number of infectious viral particles to which a case is exposed at the point of their infection (the “inoculum”). While SARS-CoV-2 human challenge trials to investigate this are in early stages of development, studies of influenza A virus in humans have demonstrated that initial exposure to a lower inoculum results in fewer and shorter symptoms as well as lower likelihood of viral shedding^{8 9}. This parallels animal experiments for influenza and for other viral diseases¹⁰, and more recently for SARS-CoV-2 in Syrian hamsters¹¹ and ferrets¹², in which inoculum size correlated with severity of ensuing disease. Viral load in patients with Covid-19 has been shown to be greater in those with more severe illness¹³.

In humans, randomized trials of patients with viral upper respiratory tract infections have shown reductions in viral droplet emissions from mask wearing¹⁴. Furthermore, masks have been demonstrated to reduce inhalation of particles¹⁵. Several epidemiological studies have indicated benefits of mask wearing and other social distancing measures in reducing the severity of Covid-19^{16 17}. Additionally, the use of masks has been shown in a laboratory setting to reduce both disease transmission and severity of SARS-CoV-2 infection in hamsters¹⁸. A case series in humans comparing three transmission clusters with different degrees of social distancing showed differences in outcome severity between the clusters¹⁹. Differences in social practices and living conditions that lead to variation in the inoculum may partly explain discrepancies in case fatality rates between countries.

Successful measures

The relation of inoculum size to infection severity has clear public health implications. As the northern hemisphere winter draws in and more time is spent in confined spaces, it is important to emphasize that separation measures such as mask wearing, ventilation, and social distancing may not only reduce the spread of the virus, but also disease severity. Even imperfect adherence to such measures is likely to be beneficial. A question that remains open is the relative contribution of droplet versus aerosol transmission²⁰. Although measures such as screens and face-shields intercept droplets, they are less likely to reduce aerosol transmission in poorly ventilated spaces. While no approach is without risk, prioritizing those measures that are most effective in reducing substantial viral transmission events enables a balance between managing the Covid-19 pandemic and allowing society to continue to function.

Although the increased number of cases is alarming, the relatively lower fatality rate is a sign that current public health measures have had some success in protecting the most vulnerable, as well as potentially reducing disease severity in those that are infected. Ensuring adherence to control measures that reduce viral exposure is critical to minimizing the severity of the pandemic, particularly in the knowledge of the severe harm that is caused by a hard lockdown.

Data sharing

The manuscript does not contain primary data.