key: cord-1003572-hpfyc5rt
authors: Pan, An; Wu, Tangchun
title: Wuhan COVID-19, data – an example to show the importance of public health interventions to fight against the pandemic
date: 2020-06-12
journal: Toxicology
DOI: 10.1016/j.tox.2020.152523
sha: 94b5126a722efc507e8b3018fc557f703b13fa3d
doc_id: 1003572
cord_uid: hpfyc5rt

nan

Journal Pre-proof This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. We appreciate Dr Walach and Dr Hockertz's interest in our recent publication in JAMA (Pan et al. 2020 ). However, we respectfully disagree with their arguments about the data in our paper. Here we want to further clarify the analysis approaches in our study and provide the readers with a clear understanding of the findings.

First, we have used the symptom onset date instead of disease confirmation date (or diagnosis date) in all analyses, while Dr Walach and Dr Hockertz thought that we used diagnosis date for the analyses and thus led to misunderstanding of our results. The delay between symptom onset date and diagnosis date is very common for an infectious disease, especially for an emerging disease due to the following reasons: 1) people may not seek medical care immediately after symptom onset; 2) there was no diagnosis kit at the beginning of the outbreak of an emerging infectious disease, which was exactly the case for the COVID-19, and thus many early cases were retrospectively tested or were tested after the patients were already in hospitals for weeks; 3) testing capacity was also a major determinant for the delay, again, because this was an emerging infectious disease, the testing capacity at the beginning of the epidemic curve was low; we have already described the increasing testing capacity over time in the supplemental methods; 4) some patients got multiple tests before the final diagnosis because of the relatively high false negative rate of the PCR tests. In consideration of those issues, we have provided an analysis to show the delay between symptom onset date and diagnosis date (eFigure 3). We described in the text that "There was a substantial delay between symptom onset date and laboratory confirmation date in the early periods, with the lag decreasing over time (median, 26, 15, 10, 6 , and 3 days for the 5 periods, respectively)." That was exactly why we have used the symptom onset date in our analyses to avoid the influence of such delays in the results; therefore, Dr Walach and Dr Hockertz's arguments about our date were based on misinterpretation. In addition, there were already some "interventions" that happened before the city lockdown: 1) almost all schools were closed because of the winter break since the early and middle January; 2) many people wore facial masks J o u r n a l P r e -p r o o f after the official announcement of human-to-human transmission on January 20, and some wore masks even earlier because of the flu season.

In terms of the reduced severity of confirmed cases in the second period before city lockdown, again, Dr Walach and Dr Hockertz misinterpreted the data. In an outbreak of an emerging infectious disease like COVID-19, no one knew about the disease and no large-scale diagnosis test was available in the first period. Furthermore, because many patients with COVID-19 presented similar symptoms as seasonal flu or common cold, those with mild symptoms might not seek medical care and now we also know that there are substantial proportion of cases with mild/moderate symptoms who could recover without medical treatment as well as the asymptomatic cases. Therefore, it was highly possible that only those with severe symptoms came to the hospitals and thus the proportion of severe/critical cases would be high at the beginning of the COVID-19 epidemic. With increasing testing capacity and also awareness and knowledge of the disease in the medical community and the general public, more and more cases with mild/moderate symptoms would come to the hospital for medical care. Therefore, even without any public health interventions, the proportion of severe/critical cases would reduce. Finally, we did not interpret the reduction of proportion of severe/critical cases over time as a result of the public health interventions in our paper. Therefore, we could not agree with Dr Walach and Dr Hockertz's argument "Why would a person have a 29 % lower chance during the second period to become a severe or critical case, when no public health measures were in place, if the lockdown and following measures were in fact causal for not only containing the virus but also preventing severe cases?" Whether a person developed to be a severe case at the admission to the hospital might not be largely influenced by the interventions, but depend on their own characteristics. The severe cases were mostly those with comorbidities and older people, and they should and must be protected. The "stay-at-home" order is a strategy to protect the vulnerable populations.

Dr Walach and Dr Hockertz also argued that "the infection runs its course", "once the epidemic is visible it runs its course and then falls off." Although our data could not provide information for this issue, there have been many studies demonstrating the importance of non-pharmaceutical interventions (NPIs) against the respiratory infectious diseases, such as the SARS and MERS, and of course, the COVID-19. We want to emphasize that public health interventions are extremely important in fighting against the pandemic, when effective drugs and vaccines are not available. Just as the Editorial in the JAMA said "Regardless, for the time being, NPIs are the only tool in the armamentarium for controlling COVID-19, and this report in JAMA serves to quantify important metrics suggesting their potential effectiveness." (Hartley and Perencevich, 2020) It is true that everything runs its course, so as the infectious diseases including COVID-19. The question is when is the peak of the course if we do nothing? How big is the problem? No one knows the answers. However, if we look at the epidemic curve in different countries, particularly US and many European countries (https://epiforecasts.io/covid), the effective reproduction number has been stuck at 1.0 for weeks, even after a series of public health interventions. What will happen if we did nothing? The things happened in the US have clearly given us some clues if we did little at the beginning of the course. The next question is: can we let the virus run its own course? The answer is absolutely no. We have to protect the people's health and save lives, particularly those disadvantaged populations, by acting as early as possible in the epidemic.

They cited an analysis by an Israel scientist who claimed on April 13 that "the spread of the coronavirus declines to almost zero after 70 daysno matter where it strikes, and no matter what measures governments impose to try to thwart it." We have seen the global pandemic since early this year and it has clearly passed the 70 days. Almost no country in the world has claimed that the number of incident cases has decline to zero or almost zero. Even we look at the data in Israel itself (https://epiforecasts.io/covid/posts/national/israel), the effective reproduction number declined to below 1.0 for a while, but it started to go up in middle of May and now it is above 1.0 again. They also talked about Sweden, but Sweden has the largest number of cases and deaths compared to its neighboring countries, and the effective reproduction number has been around 1.0 since early April (https://epiforecasts.io/covid/posts/national/sweden/). Where is the peak and where is the "fall off"?

Taken together, we warmly welcome more discussions about our data and also public health interventions for controlling the pandemic. Right and timely information exchanges are equally important in the fight against the COVID-19 pandemic.

Wuhan Covid19 data -More questions than answers

Association of public health interventions with the epidemiology of the COVID-19 outbreak in Wuhan

Public Health Interventions for COVID-19: Emerging Evidence and Implications for an Evolving Public Health Crisis