Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China

Original Article: Joseph T. Wu, Kathy Leung, Mary Bushman, Nishant Kishore, Rene Niehus, Pablo M. de Salazar, Benjamin J. Cowling, Marc Lipsitch and Gabriel M. Leung, Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China, Nature Medicine

Author of summary: Paolo Colombo; Reviewer: Francesco Trapani

Original Article Published on March 19th, 2020

The symptomatic case fatality risk (sCFR) is the proportion of deaths from a certain disease compared to the total number of symptomatic people. In this paper the authors estimate the overall sCFR of COVID-19 in Wuhan to be 1.4% (0.9–2.1%).This measure is substantially lower than the corresponding naïve confirmed case fatality risk(4.5%). Comparing the epidemiological variables estimated separately on population groups stratified by age, it is shown that there is clear and considerable age dependency in symptomatic infection and fatality risks.

In this work, the authors used a mathematical model, integrated with real-world data, to assess the clinical severity of COVID-19.

Because the healthcare structure has been overwhelmed in Wuhan, certified data is probably unreliable (milder cases were unlikely to have been tested). As a consequence, the authors used the prevalence of infection in travelers to estimate the true prevalence of infection in Wuhan.
The epidemic growth was instead inferred based on numbers from only the first 425 cases in Wuhan (assuming hospital saturation was not yet reached). A probability of developing symptoms after infection (Psym) equal to 0.5 was chosen as a baseline.

The following set of clinical severity estimates was obtained :

Symptomatic case fatality risk (sCFR):

  • Overall sCFR = 1.4% (0.9%, 2.1%).
  • sCFR (age below 30y) = 0.3% (0.1–0.7%).
  • sCFR (age between 30y and 59y) = 0.5% (0.3–0.8%).
  • sCFR (age above 59y) = 2.6% (1.7–3.9%).

These results suggest that a person over 59 years has a probability to die 5 times higher than a patient in the age range of 30-59 years.

Susceptibility to symptomatic infection (SSI) :

As for sCFR, this measure also grows substantially with age. It is shown that:

  • SSI for people in the age range of 50-59 is doubled respect to people in the 30-39 range.
  • SSI for people in the age range of 60-79 is tripled respect to people in the 30-39 range.

These findings assess a significant age dependency in symptomatic infection and outcome (fatality) risks, by multiple folds in each case. This trend is observed also when choosing different values for Psym (0.5, 0.75, 0.95).

Other key epidemiological parameters estimated by the model:

  • R0 (basic reproductive number) = 1.94 (1.83–2.06).
  • The mean time from onset to death = 20 (17–24) days.
  • The doubling time (time it takes for daily incidence to double) = 5.2 (4.6-6.1) days.
  • The transmissibility reduction (due to public health interventions) = 48% (24–71%).

These results have been compared to fatality risks of other pandemics. In particular, SARS causes a moderate/serious disease requiring hospitalization. The infection fatality risk, symptomatic case fatality risk and hospitalization risk are then essentially the same. In contrast, as most COVID-19 infections do not cause a severe disease and hospitals in Wuhan have been overwhelmed, the symptomatic case fatality risk will be lower than the hospitalization fatality risk. The reported SARS case fatality risk is 9.6% worldwide and 6,4% in mainland China, significantly lower than the estimated sCFR for COVID-19 in Wuhan (1.4%).

Despite this, COVID-19 is likely to infect many more, given emerging evidence of presymptomatic transmission and growing evidence of extensive community spread in numerous countries.

These findings overall indicate that COVID-19 transmission is difficult to control. Perhaps the most important target of mitigation measures would be to ‘flatten out’ the epidemic curve, reducing the peak demand on healthcare services and buying time for better treatment pathways to be developed.

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