Prospective studies are required for assessing the outcome of a SARS-CoV-2 infection based on the symptoms at onset

KEYWORDS:

•  SARS-CoV-2
• onset
• outcome prediction
• symptoms
• COVID-19

We read with interest the article by Zhou et al. who reported on a retrospective, multi-centre study of the difference in outcome of symptomatic SARS-CoV-2 infected patients with initial respiratory symptoms (group-1) compared to patients with extra-pulmonary symptoms at onset (group-2) [1]. It was found that group-1 patients compared to group-2 patients were more likely to develop severe or very severe COVID-19, were on steroids and antibiotics more often, required intensive care unit (ICU) admissions more often, required non-invasive or invasive ventilation more likely, developed acute, respiratory distress syndrome (ARDS) more often, had secondary bacterial infections more often, and recovered longer [1]. The study is excellent, but has limitations that are cause for concerns and should be discussed.

The major limitation of the study is its retrospective design. Such a design does not allow for control over the extracted data, does not allow the addition of missing data, and does not allow for an assessment of the reliability of the analysis. The quality of the data and the accuracy of their processing cannot be reliably assessed.

Another limitation of the study is that the number of extrapulmonary symptoms was limited to fever, headache, fatigue, myalgia, diarrhoea, palpitation, nausea, vomiting, loss of appetite [1]. There is ample evidence that SARS-CoV-2 may initially manifest with many more extrapulmonary symptoms than considered in the index study. A recent review of the extrapulmonary onset manifestations of SARS-CoV-2 infection found that COVID-19 is also commonly associated with hypogeusia, hyposmia, abdominal pain, hepatopathy, and deep venous thrombosis [2].

A third limitation of the study is that it did not define how extrapulmonary symptoms are due to COVID-19 and not to any of the comorbidities. Since 173 patients had comorbidities, it is important to rule out these comorbidities as the cause of the symptoms considered SARS-CoV-2-related. We should know if those in group-1 had more comorbidities than those in group-2. It remains unclear why patients with comorbidities are less likely to develop ARDS than patients without comorbidities. One would expect ARDS would develop more frequently in severely ill cases.

Unexpectedly, there were no differences in laboratory parameters between the two groups, although group-1 patients were more severely ill. How do the authors explain this surprising finding?

We should know how many of the patients in group-2 developed respiratory symptoms as the disease progressed. In other words, how many would move from group-2 to group-1 over the course of the disease? This is important because some patients in group-2 developed ARDS.

Overall, the interesting study has limitations that call the results and their interpretation into question. Addressing these issues would strengthen the conclusions and could improve the status of the study. Prospective studies would be more reliable than retrospective studies to assess the outcome of SARS-CoV-2 infections based on symptoms at onset.

Author contribution

JF: design, literature search, discussion, first draft, critical comments, final approval.

Compliance with ethics guidelines

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Data access statement

All data are available from the corresponding author.

Disclosure statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.