Associations of comorbidities and medications with COVID-19 outcome: A retrospective analysis of real-world evidence data

Abstract

Background: Hundreds of thousands of deaths have already been recorded for patients with the severe acute respiratory syndrome coronavirus (SARS-CoV-2; aka COVID-19). Understanding whether there is a relationship between comorbidities and COVID-19 positivity will not only impact clinical decisions, it will also allow an understanding of how better to define the long-term complications in the groups at risk. In turn informing national policy on who may benefit from more stringent social distancing and shielding strategies. Furthermore, understanding the associations between medications and certain outcomes may also further our understanding of indicators of vulnerability in people with COVID-19 and co-morbidities. Methods: Electronic healthcare records (EHR) from two London hospitals were analysed between 1st January and 27th May 2020. 5294 patients presented to the hospitals in whom COVID status was formally assessed; 1253 were positive for COVID-19 and 4041 were negative. This dataset was analysed to identify associations between comorbidities and medications, separately and two outcomes: (1) presentation with a COVID-19 positive diagnosis, and (2) inpatient death following COVID-19 positive diagnosis. Medications were analysed in different time windows of prescription to differentiate between short-term and long-term medications. All analyses were done with controls (without co-morbidity) matched for age, sex, and number of admissions, and a robustness approach was conducted to only accept results that consistently appear when the analysis is repeated with different proportions of the data. Results: We observed higher COVID-19 positive presentation for patients with hypertension (1.7 [1.3-2.1]) and diabetes (1.6 [1.2-2.1]). We observed higher inpatient COVID-19 mortality for patients with hypertension (odds ratio 2.7 [95% CI 1.9-3.9]), diabetes (2.2 [1.4-3.5]), congestive heart failure (3.1 [1.5-6.4]), and renal disease (2.6 [1.4-5.1]). We also observed an association with reduced COVID-19 mortality for diabetic patients for whom anticoagulants (0.11 [0.03-0.50]), lipid-regulating drugs (0.15 [0.04-0.58]), penicillins (0.20 [0.06-0.63]), or biguanides (0.19 [0.05-0.70]) were administered within 21 days after their positive COVID-19 test with no evidence that they were on them before, and for hypertensive patients for whom anticoagulants (0.08 [0.02-0.35]), antiplatelet drugs (0.10 [0.02-0.59]), lipid-regulating drugs (0.15 [0.05-0.46]), penicillins (0.14 [0.05-0.45]), or angiotensin-converting enzyme inhibitors (ARBs) (0.06 [0.01-0.53]) were administered within 21 days post-COVID-19-positive testing with no evidence that they were on them before. Moreover, long-term antidiabetic drugs were associated with reduced COVID-19 mortality in diabetic patients (0.26 [0.10-0.67]). Conclusions: We provided real-world evidence for observed associations between COVID-19 outcomes and a number of comorbidities and medications. These results require further investigation and replication in other data sets.

The Association Between Hypoglycemic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis

“…As reported in a retrospective cohort of hospitalized patients in the UK, long-term antidiabetic medications reduced COVID-19 mortality in diabetic patients(25), which was a very encouraging finding, especially as diabetic patients are particularly susceptible to cumulative organ injury by SARS-CoV-2 because of already compromised pulmonary, cardiac and renal functions. Therefore, furthering our understanding of antidiabetic medications can yield a practical and effective approach in dramatically improving outcomes in this vulnerable population disproportionately affected by COVID-19.…”

“…16 studies were included in qualitative synthesis. Among these, 12 studies related to metformin(15, 16, 25-35), 6 studies related to DPP-4i(27, 28, 33, 35-38), 3 studies related to sulfonylurea or glinides(27, 28, 33, 35), 2 studies related to SGLT-2i(33, 35) and 1 study related to GLP-1RA(27, 28). Some of these studies included multiple outcomes to different medications.…”

“…preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted January 27, 2021. ; https://doi.org/10.1101/2021.01.26.21250506 doi: medRxiv preprint 16 studies were included in qualitative synthesis. Among these, 12 studies related to metformin (15,16,(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), 6 studies related to DPP-4i (27,28,33,(35)(36)(37)(38), 3 studies related to sulfonylurea or glinides (27,28,33,35), 2 studies related to SGLT-2i (33,35) and 1 study related to GLP-1RA (27,28). Some of these studies included multiple outcomes to different medications.…”

Non-insulin anti-diabetic agents in patients with type 2 diabetes and COVID-19: A Critical Appraisal of Literature

“…Similarly, two smaller retrospective study by Abu-Jamous et al. [ 24 ] and Crouse et al. [ 25 ] involving 411 and 239 patients with diabetes also showed an 81% (OR: 0.19 (0.05–0.70), p = not reported) and 67% (OR 0.33; 95% CI 0.13–0.84; p = 0.02) relative risk reduction of death, respectively, in those who were metformin users compared to the non-users.…”

“…Meanwhile, several small to large retrospective studies and one large prospective study have reported the outcomes with metformin in patients of T2DM with COVID-19 [ [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] ]. While some studies [ [17] , [18] , [19] , [20] , [21] ] found neither any harm nor any benefit in metformin users when compared to non-users both in severity and mortality outcomes, majority [ [23] , [24] , [25] , [26] , [27] , [28] , [29] ] reported a significant reduction in mortality. Interestingly, one study reported even an increase in severity in metformin users [ 22 ].…”