Reply to the letter of Singh and Singh in response to the article: “Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis” (Kumar et al.)

Dear Sir,

We appreciate the keen interest taken by Drs. Singh and Singh for sending a correspondence in response to our article titled “Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis” [1]. The authors have raised three questions in the correspondence, mainly related to the methodology of our meta-analysis and the conclusion. Our reply to their questions is given below:

• 1.The authors have questioned why we have used odds ratio instead of risk ratio or hazard ratio as the effect size for association of diabetes with severity and mortality of COVID-19. However, the authors failed to note that all the included studies in our meta-analysis were retrospective case-control studies, in which the outcome of interest (mortality/severity) had already occurred. In case-control studies only odds ratio can be calculated, and relative risk cannot be calculated. For calculating relative risk cohort studies are more suitable which gives the incidence of the outcome in both the cohorts [2]. Similarly we could not use hazard ratio (which is also a type of relative risk) because in case-control studies time-to-event analysis is usually not there.
• 2.The authors have raised the doubt that many of the included studies would have overlapping patient data. However, the authors have failed to note that in the method section as well as in the discussion, we have diligently tried to avoid including any duplicate studies by limiting our search to single database, limiting search to English articles only, and carefully going through each included article’s study setting and author list. We do agree that there could have been still some overlapping patients from USA in the CDC study [3] and from China in the study by Guan et al. [4], however, in our large meta-analysis of 16,003 patients, this small overlap is inevitable and inconsequential.
• 3.The authors have objected to our conclusion of “Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics”; and have suggested that we should have concluded as “patients who have severe COVID-19, or who die from the disease, are more likely to have diabetes”. The reason for their objection is that we have calculated the odds ration and not the relative risk. While we partially agree with the change of wording as suggested by the authors; however, when the outcome of interest is rare, as the case of mortality/severity in patients with COVID-19, the odds ratio is very close to the relative risk [5], and our conclusion will still hold good.

We would like to reiterate that until we have large cohort studies available which provides relative risk of severity/mortality of COVID-19 in diabetic patients versus non-diabetic patients; as of now, our meta-analysis gives the best estimate of the association between severe/fatal COVID-19 and diabetes. Moreover, the implication of our meta-analysis that the diabetic population needs to be protected from COVID-19 infection, and if infected, needs closer monitoring for severe diseases and adverse outcome, cannot be overemphasized.

Funding

None.

Declaration of competing interest

None to declare.