We read with great interest the meta-analysis by Pan et al  entitled “Metabolic
associated fatty liver disease increases the severity of COVID-19” published in Digestive
and Liver Disease. The article provides new information on the risk of severe COVID-19.
There is evidence suggesting that comorbidities such as hypertension, diabetes mellitus,
and cardiovascular diseases are associated with COVID-19 severity (https://covid19.who.int/).
In their article, the authors found that individuals with metabolic associated fatty
liver disease (MAFLD) also have a high risk to develop a severe condition when infected
by COVID-19, [odds ratio (OR): 2.93; 95% confidence interval (95%CI): 1.87, 4.60].
We found that the study has several limitations that should be clarified. First, the
article includes several letters to the Editor. At least four , , ,  out
of six papers , , , , ,  are letters to the Editor. Although the
Newcastle-Ottawa scale (NOS) was used to assess the quality of the included papers,
which had moderate to high quality, the vast majority of meta-analysis studies excluded
letters to the Editor. Referring to guideline from Preferred Reporting Items for Systematic
Reviews and Meta-analyses (PRISMA) , reviews, commentaries, and letters to the
Editor should be excluded. Nevertheless, since they have moderate-high quality based
on the NOS criteria, these articles might be tolerable for inclusion in the meta-analysis.
Second, two [2,4] out of six papers , , , , ,  do not provide sufficient
data for meta-analysis. The data of MAFLD prevalence in both severe and mild-moderate
COVID-19 are insufficient to calculate the correlation and effect estimates. In the
study by Zou et al  for example, the data are presented as total cases of severe
COVID-19 and total cases of MAFLD. The data on how many MAFLD patients developed severe
and mild - moderate COVID-19 were not presented. Therefore, the calculation of cumulative
effect estimates, and the correlation was impossible to perform, and this article
should be excluded. Moreover, in the study by Targher et al , the available data
are only the number of MAFLD patients with neutrophil-to-lymphocyte ratio (NLR) ≤
2.8 and NLR > 2.8. NLR is not the indicator of COVID-19 severity. The indicators of
COVID-19 severity include any of the following criteria: respiratory distress (RR
≥ 30/min), oxygen saturation ≤ 93% at rest, and arterial partial pressure of oxygen
(PaO2) / fraction of inspiration O2 (FiO2) ≤ 300 mnHg . Therefore, we consider
that this article does not meet the criteria to define severe COVID-19 and should
be excluded. We re-analyzed the data after excluding those two papers and found that
patients with MAFLD had a 6-fold higher risk of developing severe COVID-19 compared
to those without MAFLD,(OR: 6.66; 95%CI: 2.84, 15.64) (Fig 1
). Although our analysis is consistent with Pan et al , our analysis highlights
a higher risk.
Forest plot of the association between MAFLD and the risk of severe COVID-19 (OR:
6.66; 95%CI: 2.84, 15.64; p: <0.0001; p Heterogeneity: 0.0810; I squared: 56%; p Egger:
We believe that study by Pan et al  provides important information on COVID-19
management, particularly in patients with MAFLD. This study suggests that MAFLD patients
should be allocated to high monitoring due to the high likelihood of developing severe
The authors received no financial support for the research, authorship, and/or publication
of this article.
Declaration of Competing Interest
None of the authors has any conflicts to declare.