key: cord-1011263-n4c3b44b
authors: Schiller, Martin; Solger, Kim; Leipold, Stefanie; Kerl, Hans Ulrich; Kick, Wolfgang
title: Diabetes-associated nephropathy and obesity influence COVID-19 outcome in type 2 diabetes patients
date: 2021-09-20
journal: J Community Hosp Intern Med Perspect
DOI: 10.1080/20009666.2021.1957555
sha: 28d4bd350780de743e43399234374a41fe324738
doc_id: 1011263
cord_uid: n4c3b44b

Coronavirus disease 2019 has rapidly spread around the globe and various comorbidities, such as diabetes have been recognized as risk factors for an unfavorable outcome. We analyzed a cohort of COVID-19 patients (n = 75) treated at a German community hospital. With a focus on diabetes mellitus, we evaluated the impact of distinct comorbidities on the COVID-19 disease course. The duration of hospital stay was prolonged if diabetes was present. An older age was associated with a poor outcome. The percentage of non-survivors increased in the presence of congestive heart failure or chronic kidney disease. In the group of diabetes patients, mortality was increased if any organ complication was present and diabetic nephropathy or the combination of obesity plus diabetes were by far the most important risk factors. Taken together, an older age, congestive heart failure, and chronic kidney disease significantly influenced COVID-19 disease course and survival. Diabetic nephropathy or the combination of obesity plus diabetes had the strongest impact on patients’ outcome.

Coronavirus disease 2019 (COVID-19) is a novel disease caused by the SARS-CoV-2 virus. Since its first recognition in December 2019 (in Whuan), this virus has now spread worldwide causing a global health emergency. The disease mainly affects the respiratory tract [1] . Other manifestations and complications include cytokine release syndrome, involvement of the central nervous system, acute kidney injury, myocardial damage, and secondary infections [2, 3] . Several diagnostic and prognostic markers have been described, such as sofa score (Sepsis-related organ failure assessment score), lymphocytopenia, and d-dimer levels [4] [5] [6] . Radiologic findings include ground glass opacity, posterior/peripheral involvement of the lung, or bilateral infiltration [7, 8] .

Various conditions have been reported as predictors of an unfavorable outcome in COVID-19 patients. Thus, most severe cases seem to occur in the elderly or in patients with distinct comorbidities including cardiovascular disease or diabetes [9] [10] [11] .

Diabetes is also a risk factor in patients infected with viruses other than SARS-CoV-2. An increased mortality has been discussed in influenza, respiratory syncytial virus, SARS-coronavirus, and MERScoronavirus infected patients [12] [13] [14] . We investigated the outcome of COVID-19 patients treated at a German community hospital with the focus on diabetes mellitus as a relevant comorbidity. Our patient cohort is representative for elderly patients who are typically treated by primary health care providers. Diabetes patients required a significantly prolonged in-hospital treatment, when compared to the non-diabetes group. The percentage of diabetes patients who did not survive COVID-19 infection was elevated if any diabetes-associated organ complication was present. Most importantly, patients with an established diabetic nephropathy or obese diabetes patients had the worst outcome, with more than 70% of non-survivors.

This work was conducted at the Kliniken Hochfranken Munchberg, a German community hospital. Laboratory and radiologic findings from 75 hospitalized COVID-19 patients, as well as their respective comorbidities were analyzed. COVID-19 was diagnosed by a positive PCR-result (Real Star SARS-CoV-2 PCR Kit, Altona Diagnostics GmbH, Hamburg, Germany) and/or typical radiologic findings. All patients showed COVID-19 symptoms, such as fever, cough, and shortness of breath. . Samples for PCR were obtained from throat swabs or qualified sputum. COVID-19 patients were treated in our hospital from March 2020 to August 2020. Mean values and graphs were calculated using Microsoft Excel software. Statistical analysis was performed using 

The mean age of hospitalized COVID-19 patients was 74.2 years (22-99 years), with 35 female and 40 male patients. In total, 23 of the patients did not survive (30.7%) and the death rate in male patients was higher than in female ones (37.5% vs. 22.9%; p = 0.315). Eleven patients (out of which 10 required mechanical ventilation) were treated at our intensive care unit. The average age of patients who survived was 71 years, while non-survivors were significantly older (81.6 years; p < 0.0005; for details see Table 1 ).

COVID-19 patients with an established diagnosis of type 2 diabetes (according to the criteria of the German diabetes society) were compared to nondiabetes patients. As expected, diabetes patients had higher blood glucose and HbA1c levels. Further, diabetes patients showed an impaired renal function and higher CRP levels, when compared to the nondiabetes group (Figure 1 ). No significant differences were found for troponin, d-dimer levels, white blood cells counts, or lactate dehydrogenase (LDH).

Analyzing the comorbidities of COVID-19 patients, the most common diagnoses were arterial hypertension (66.7%) and diabetes mellitus (34.7%). All diabetes patients in this cohort had been diagnosed with type 2 diabetes. Comorbidities are summarized in Table 1 . We observed an increased mortality in patients suffering from congestive heart failure (p = 0.0406) and chronic kidney disease (p = 0.0182).

The group of diabetes patients also showed an increased death rate (46.2% vs. 30.7%; p = 0.1317). However, this was only statistically significant if any diabetes-associated organ complication was present (57.9% vs. 30.7%; p = 0.0406). Importantly, diabetic nephropathy was by far the most substantial risk factor for an unfavourable outcome (73.3% nonsurvivors in this group; p = 0.0082).

Type 2 diabetes is often associated with metabolic syndrome, and an increased death rate in respiratory infections has been described for obese patients [15, 16] . Thus, we were interested, whether obesity (BMI > 30 kg/m 2 ) alone or in combination with diabetes has an impact on survival in our cohort.

While obesity itself caused only a non-significant increase in the percentage of non-survivors (55%; p = 0.0563), we observed a substantial increase in mortality, if obesity was present together with type 2 diabetes (71.4%; p = 0.0155, see Table 1 ).

At the time of admission, all COVID-19 patients (diabetes and non-diabetes) showed a relative lymphocytopenia (lymphocytes: 14.49% normal range: 20.5-51.1%), elevated CRP (82,36 mg/L; normal range: < 5 mg/L), troponin (42.9 pg/mL; normal range: < 14 pg/mL), LDH (351.82 U/L; normal range < 250 U/L), and d-dimer levels (1146.86 ng/mL; normal range: < 250 ng/mL). The elevation of CRP levels was pronounced in patients who did not survive, and these patients showed a significant increase in procalcitonin levels (0.65 ng/mL vs. 0.98 ng/mL; p = 0.1374) and neutrophil counts (73.59% vs. 81.92%; p = 0.0065). Moreover, mortality was associated with a pronounced lymphocytopenia (p = 0.0031) and an impaired renal function (p < 0.001). Laboratory results at the time of admission are shown in Table 2 .

Interestingly, while blood glucose was elevated in the diabetes group (p < 0.001), we found no differences in blood glucose levels when we compared the group of diabetic non-survivors to surviving diabetes patients ( Figure 2 ). Renal function was impaired in the diabetes group (p < 0.001; compared to nondiabetes patients) and a further significant impairment of glomerular filtration rate was observed in diabetes patients who did not survive ( Figure 2 ).

Lymphocytopenia was highly pronounced in the group of diabetic non-survivors (p = 0.046).

Diabetes patients who survived COVID-19 required a significantly prolonged hospital treatment (22.3 days vs. 11 days; p = 0.0096), when compared to non-diabetes patients. Diabetes-specific medication had no significant effects on patients' outcome (see Table 3 ).

As an impact of blood glucose levels on radiologic findings in COVID-19 has been discussed previously [17] , we analyzed and compared chest computed tomography (CT) images obtained from our patients. We did not observe any striking differences comparing diabetes patients to the non-diabetes group. Figure 3 shows representative chest CT images of diabetes and non-diabetes patients diagnosed with COVID-19 pneumonia.

Diabetic nephropathy or the combination of obesity plus diabetes were associated with a substantial increase in COVID-19 mortality. These comorbidities were the strongest risk factors with a death rate of more than 70%. Prominent laboratory findings were an impaired kidney function and lymphocytopenia, which were significantly pronounced in the group of diabetes patients with a poor outcome.

No potential conflict of interest was reported by the author(s). 

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Figure 2. Lymphocyte counts and glomerular filtration rate are impaired in diabetic COVID-19 non-survivors

glomerular filtration rate (GFR) and percentage of lymphocytes (LC) are shown. Diabetes patients showed elevated BG levels, however no difference was observed comparing survivors and non-survivors. GFR was diminished in diabetes, with a further decrease in the population of non-survivors. Lymphocytopenia was mostly pronounced in diabetic non-survivors. Statistical significance was calculated using the students t-test. factors based on 4-week follow-up

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