Published online Dec 15, 2022. doi: 10.4239/wjd.v13.i12.1154
Peer-review started: August 10, 2022
First decision: October 5, 2022
Revised: October 18, 2022
Accepted: December 1, 2022
Article in press: December 1, 2022
Published online: December 15, 2022
Several risk factors for severe coronavirus disease 2019 (COVID-19) disease have been described, including: Advanced age, male sex, smoking history, and underlying chronic diseases such as cardiovascular disease, diabetes mellitus, obesity, underweight, and chronic kidney disease (CKD). This case-control study was conducted to identify risk factors for severe COVID-19 pneumonia in patients with type 2 diabetic mellitus hospitalized at the Galilee Medical Center (Nahariya, Israel).
We aimed to characterize differences between hospitalized diabetic patients with vs patients without COVID-19, and parameters associated with COVID-19 severity for prediction.
Similar to previous reports, multivariable logistic regression showed higher body mass index (BMI) and neutrophil:lymphocyte ratio (NLR) were significantly associated with severe COVID-19. Surprisingly, pre-hospitalization albuminuria, mostly moderate-range (albumin:creatinine 30-300 mg/g), was associated with reduced risk for severe COVID-19 pneumonia. The counterintuitive protective association in patients with stage II CKD was not described before. Given the causative association between type I interferon (IFN) signaling and proteinuria, we hypothesize that the presence of moderate-range albuminuria may represent an intact type I IFN signaling, which confers protection from severe COVID-19 pneumonia and its complications.
This case-control study included 209 patients with type 2 diabetic mellitus hospitalized at the Galilee Medical Center (Nahariya, Israel) and recruited between September 2020 and May 2021, 65 patients with COVID-19 infection in dedicated wards and 144 COVID-19-negative patients in internal medicine wards hospitalized due to other reasons. Clinical parameters – including age, type of antiglycemic medications, presence of retinopathy, smoking history, BMI, glycosylated hemoglobin, maximum NLR (NLRmax), C-reactive protein (CRPmax), estimated glomerular filtration rate (eGFR), and albumin (blood and urine) - were compared between the two primary patient groups, and then between COVID-19-negative patients hospitalized due to infectious vs non-infectious disease. Finally, we explored which parameters were associated with severe COVID-19 pneumonia.
COVID-19-negative patients were older and had longer duration of diabetes, lower eGFR, higher albumin, lower CRP, greater smoking history, and more baseline albuminuria at admission. 70% of COVID-19 patients with albuminuria had moderate-range albuminuria. Most of the patients with albuminuria had CKD II. Oral antiglycemic therapies were not significantly different between the two groups. As previously reported, multivariable logistic regression showed higher BMI and higher NLR were significantly associated with severe COVID-19. Surprisingly, pre-hospitalization albuminuria, mostly moderate-range, was associated with reduced risk for severe COVID-19 pneumonia. This protective association was specific to COVID-19 infection and was not observed in bacterial infections.
Moderate-range albuminuria in COVID-19-positive diabetic patients with CKD II is associated with less severe COVID-19. We hypothesize that this counterintuitive association may represent intact IFN signaling that on the one hand can lead to harmful proteinuria via podocyte injury, and on the other hand can serve as a protective cytokine with the potential to mitigate COVID-19 infection and complications. Given the importance of intact type I IFN response in controlling COVID-19, we suggest that moderate-range albuminuria in diabetic patients with mild CKD may serve as a biomarker for intact IFN signaling and therefore is associated with reduced risk for severe COVID-19 pneumonia.
Further studies should explore the potential role of albuminuria in the presence of mild CKD as a biomarker for reduced risk of COVID-19-related deterioration that may translate to therapeutic interventions.