Lightening the viral load to lessen covid-19 severity
BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4763 (Published 10 December 2020) Cite this as: BMJ 2020;371:m4763
- Stephen Burgess, statistician1,
- David Smith, clinician2,
- Julia C Kenyon, virologist3,
- Dipender Gill, clinician scientist4
- 1MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK
- 2Institute for Infection and Immunity, St George’s, University of London, London, UK
- 3Department of Medicine, University of Cambridge, Cambridge, UK
- 4Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Correspondence to: S Burgess sb452{at}medschl.cam.ac.uk
Although the number of positive tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across many European countries has risen sharply in recent weeks, increases in the number of hospital admissions and deaths from 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 seemed to steadily decline throughout July and August.2 Reductions were also observed in the early stages of the outbreak across many countries.3 Case fatality rates have varied in different countries, with relatively lower estimates observed in several African countries.4 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 cases.5 Age is a strong predictor of covid-19 mortality.6 In many Western countries, the absolute number of cases in people older than 60 is increasing but the proportion of cases in that age group is decreasing.5 This indicates that public health measures to curb the spread of SARS-CoV-2 have been successful in reducing the relative burden of disease in older people, who are the most vulnerable demographic group.
The second reason is improved treatment. Systemic corticosteroids have been shown to improve outcomes in patients with covid-19,7 and clinical management of cases may also be improving through accumulated experience of the disease.
A third reason may relate to the number of infectious viral particles to which people are exposed at the point of infection (the “inoculum”). Although human challenge trials for SARS-CoV-2 are in early stages of development, studies of influenza A virus in humans have shown that initial exposure to a lower inoculum results in fewer and shorter symptoms as well as lower likelihood of viral shedding.89 This parallels animal experiments for influenza and for other viral diseases,10 and more recently for SARS-CoV-2 in Syrian hamsters11 and ferrets,12 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 illness.13
Protective measures
In humans, randomised trials of patients with viral upper respiratory tract infections have shown mask wearing reduces viral droplet emissions.14 Furthermore, masks have been found to reduce inhalation of particles.15 Several epidemiological studies have indicated mask wearing and other social distancing measures reduce the severity of covid-19.1617 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 hamsters.18 A case series in humans comparing three transmission clusters with different degrees of social distancing showed differences in outcome severity between the clusters.19 Differences in social practices and living conditions that lead to variation in the inoculum may partly explain discrepancies in case fatality rates between countries.
The relation of inoculum size to infection severity has clear public health implications. As the northern hemisphere enters winter and more time is spent in confined spaces, it is important to emphasise that separation measures such as mask wearing, ventilation, and social distancing may reduce not only 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 transmission.20 Although measures such as screens and face shields intercept droplets, they are less likely to reduce aerosol transmission in poorly ventilated spaces. No approach can eliminate risk, but prioritising 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 current high number of cases is alarming, the lower fatality rate is a sign that public health measures have had some success in protecting the most vulnerable, as well as potentially reducing disease severity in people who are infected. Ensuring adherence to control measures that reduce viral exposure is critical to minimising the severity of the pandemic, particularly given the severe harm that is caused by a hard lockdown.
Footnotes
Competing interests: We have read and understood BMJ policy on declaration of interests and declare that DG is employed part-time by Novo Nordisk, unrelated to the submitted article.
Provenance and peer review: Not commissioned, externally peer reviewed.