Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2

As an emerging infectious disease, coronavirus disease 2019 (COVID-19) pneumonia, which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a severe global public health emergency. According to the World Health Organization (WHO) COVID-19 epidemic interactive dashboard, as of 19 June 2020, there have been 8 385 440 confirmed cases all over the world, including 450 686 deaths. Under such urgent conditions, it is of great clinical significance to distinguish patients with poor clinical outcome (such as severe, critical or death) from within the large number of patients with COVID-19 using regular parameters (such as demographic data, past health history, and common laboratory examination results). Du et al. [1] performed a single centre prospective cohort study to investigate the possible risk factors associated with the poorest clinical outcome (dying from COVID-19 pneumonia). They reported that age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL⁻¹ and cardiac troponin I ≥0.05 ng·mL⁻¹ in patients with COVID-19 pneumonia were associated with increased risk of death from this disease [1]. They further identified that CD3+CD8+ T-cells ≤75 cells·μL⁻¹ and cardiac troponin I especially ≥0.05 ng·mL⁻¹ could be used as predictors for mortality of patients with COVID-19 pneumonia using a matched case–control study [1]. With great interest, we have read the full text of the paper and found that there are several issues which are worth clarifying.

Short abstract

There are several issues which are worth clarifying in the paper “Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study” published in the European Respiratory Journal https://bit.ly/336rv2Y

To the Editor:

As an emerging infectious disease, coronavirus disease 2019 (COVID-19) pneumonia, which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a severe global public health emergency. According to the World Health Organization (WHO) COVID-19 epidemic interactive dashboard, as of 19 June 2020, there have been 8 385 440 confirmed cases all over the world, including 450 686 deaths. Under such urgent conditions, it is of great clinical significance to distinguish patients with poor clinical outcome (such as severe, critical or death) from within the large number of patients with COVID-19 using regular parameters (such as demographic data, past health history, and common laboratory examination results). Du et al. [1] performed a single centre prospective cohort study to investigate the possible risk factors associated with the poorest clinical outcome (dying from COVID-19 pneumonia). They reported that age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL⁻¹ and cardiac troponin I ≥0.05 ng·mL⁻¹ in patients with COVID-19 pneumonia were associated with increased risk of death from this disease [1]. They further identified that CD3+CD8+ T-cells ≤75 cells·μL⁻¹ and cardiac troponin I especially ≥0.05 ng·mL⁻¹ could be used as predictors for mortality of patients with COVID-19 pneumonia using a matched case–control study [1]. With great interest, we have read the full text of the paper and found that there are several issues which are worth clarifying.

First, both in the Abstract and Results sections, Du et al. [1] reported that pre-existing cardiovascular or cerebrovascular diseases in patients with COVID-19 pneumonia was associated with elevated risk of dying from this disease using multivariate logistic regression analysis, with odds ratio and 95% confidence interval being equal to 2.464 (0.755–8.044) and p-value being equal to 0.007. Obviously, the 95% confidence interval includes 1, indicating that the estimated population odds ratio is possible to be equal to 1. According to the principle of statistics, the conclusion made from parameter estimation and hypothesis test should be consistent. In other words, if the p-value for odds ratio of pre-existing cardiovascular or cerebrovascular disease is 0.007, the lower limit of the 95% confidence interval should at least be more than 1, considering this factor is risk one for poor clinical outcome. Thus, we suggest that the authors should check the data and to ascertain whether there were typography errors or an incorrectly interpreted statistical result.

Second, in the Methods section, Du et al. [1] state “The information for all patients, including demographic data, clinical characteristics, laboratory parameters and outcomes, were collected prospectively.” And in the Results section, the authors showed the summary statistics for demographic data, life sign data and laboratory examination data in tables 1 and 2 of their original article [1]. However, the authors did not denote definitively, in the summary statistics for laboratory findings and life sign data, on which time of the patients’ examination the results were based. In clinical practice, it is common that one patient with COVID-19 pneumonia receives laboratory examinations (such as blood regular test) several times, and the results of the same test for the same patient may be different from one time to another.

Third, in the Discussion section, the authors state “As of midnight on 24 March 2020, the numbers of Chinese confirmed COVID-19 pneumonia cases and deaths were 81 218 and 3281, respectively, indicating that the overall death rate from COVID-19 pneumonia was 4%.” Obviously, the so-called overall death rate of 4% was calculated using the formula: number of cumulative deaths/cumulative number of confirmed cases, i.e. 3281/81218. This simple formula is problematic, especially considering the COVID-19 epidemic was ongoing then. As such there was still a certain proportion of COVID-19 patients (confirmed on or before 24 March 2020) whose clinical outcomes were unknown. As the authors said in the latter part of their Discussion section, “On 24 March 2020, China had 4287 current cases with confirmed COVID-19 pneumonia, and 1399 (32.6%) of them were very severe cases.” We think that using case fatality rate (CFR) to replace death rate or mortality rate in the Discussion section of the report by Du et al. [1] is appropriate. Death rate or mortality rate of a certain disease is often defined as the ratio of deaths from a certain disease in an area to the population of that area. CFR refers to the proportion of cases who eventually die from the disease. To estimate the CFR of COVID-19 pneumonia, Du et al. [1] can refer to the methods proposed by Ghani et al. [2].

Taken together, the findings of the study reported by Du et al. [1] are of great significance, though some possible error and inappropriate expression were found. We hope our comments will be helpful to improve the expression and increase the quality of the published paper.

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