*Corresponding author
  1. Jindal Institute of Behavioral Sciences (JIBS), Jindal Global Institution of Eminence Deemed to be University, Sonipat 131001, India ; rama.jayaraj@jgu.edu.in and Director of Clinical Sciences, Northern Territory Institute of Research and Training, Darwin 0909, NT, Australia * Correspondence: Prof Rama Jayaraj, Email: jramamoorthi@gmail.com
  2. Department of Oral and Maxillofacial Surgery, College of Dental Sciences Manipal, Manipal Academy of Higher Education, A Constituent of MAHE, Mangalore, 575001, India; sameep.shetty@manipal.edu
  3. Department of Biotechnology, College of Engineering & Technology, Kattankulathur – Chennai, Tamil Nadu, India; devia@srmist.edu.in
  4. Bharathiar Univ, Dept Biochem, Coimbatore, Tamil Nadu, India; suja.s@buc.edu.in
  5. Dept Oral and Maxillofacial Surgery, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune, Maharashtra, Email:merchantyash@gmail.com
Excellent Clinical Research Approach and Adaptation of Systematic Review Guidelines and Registrations: It is with interest that we read the relevant systematic review and meta-analysis on the impact of alcohol consumption on severity of COVID-19 infection. We laud the efforts of the authors to contribute to this global research output and provide myth busting evidence on the contemporary issue. This study is of great clinical and timely relevance, also adhered the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Furthermore, it is also recommended that the Protocol OF A Systematic Review and Meta-Analysis be registered in the International Prospective Register of Systematic Reviews (PROSPERO) to identify any replication of the study and act as guide for other similar studies. We would like to take the opportunity to offer our perspective and constructive critique in their analysis.
Alcohol and confounding factors (tobacco in the smoked or smokeless form) : Patients partaking alcohol often smoke during drinking and alcohol as a solvent has a synergistic and additive deleterious effect. It is recommended to note that in the subset of patients partaking alcohol whether confounding factors like other habits (tobacco in the smoked or smokeless form) and co-morbidities were taken into consideration.
Contradicting findings of another impact of alcohol consumption on COVID-19 severity: It is undisputed that moderate to heavy alcohol consumption impairs immunity and has no benefits during a pandemic or otherwise. However, a recent prospective study noted that COVID-19 risk appears to vary across different alcoholic beverage subtypes, frequency, and amount. Red wine, white wine, and champagne may reduce the risk of COVID-19 when consumed in moderation and occasionally1.
Attempts to inform clinical decision making and Future directions: It is believed that the higher polyphenolic content of these beverages enhanced plasma antioxidant activity and reduces the level of low-density lipoprotein2. Authors of this study strongly proposed that people do not drink alcohol during the COVID-19 pandemic and attempts to inform clinical decision during this crisis. Public health guidance should focus on reducing the risk of COVID-19 by advocating healthy lifestyle habits and preferential policies among consumers of beer and cider and spirits.
Conceptual Interpretation of Conclusions from Literature-Based Meta-Analysis: We would like to recommend that conclusions by Wei and colleagues should better reflect the indecision of a literature based Systematic Review and Meta-Analysis. In this scenario, elaborating that “Alcohol consumption intensifies COVID-19 severity and deteriorates its clinical outcomes” should be potentially replaced by “alcohol consumption are likely associated with COVID-19 severity and may be or could be deteriorate its clinical outcomes.”
Publication bias of the included studies: Publication bias is a corollary of the publication process. Small sample studies or negative findings often fail to get published. Abiding the PRISMA, authors have piloted the publication bias analysis using Egger’s test for continuous variables but evaded other publication bias indicators in the manuscript or as supplementary material, which could derail peer-appraisal of the study (Figure 1). Therefore, a suggestion would be to inculcate Classic Fail-Safe N, Orwin Fail-Safe N, Duval and Begg and Mazumdar’s rank correlation test in such studies for comprehensive analysis of publication bias indicators (Table 1).3,4 Although this is the first systematic review and meta-analysis on Impact of alcohol consumption on COVID-19 severity, not assessing the full scale of publication bias leads to the findings being uncertain in term of actual clinical utility.
Comparison of Heterogeneity with Hypothesis testing: A robust statistical analysis can be interpreted with the addition of Tau- Square in addition to Chi-Square and I-Square static (measures of statistical heterogeneity). The authors have estimated the Z value, a test static for the null hypothesis and to obtain the P- value, but fail to compare the Heterogeneity with Hypothesis testing (Table 2). The ordered heterogeneity test, that permits testing against simply ordered alternative hypotheses in the context of almost any nondirectional test5. Therefore, we recommend comparing the results of all statistical syntheses including heterogeneity and hypothesis testing of the included study, conducted according to PRISMA.
We feel that above points should be addressed. Given the current relevance of this field to medical virology, it is important that this study that feeds it is free of any possible reproach when under scientific analysis.