Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, first appeared in Wuhan, China, and quickly spread throughout the world. We aimed to understand the relationship between diabetes mellitus and the prognosis of COVID-19.
Demographic, clinical, laboratory, radiologic, treatments, complications, and clinical outcomes data were extracted from electronic medical records and compared between diabetes (n=84) and non-diabetes (n=500) groups. Kaplan-Meier method and multivariate Cox analysis were applied to determine the risk factors for the prognosis of COVID-19.
Compared to non-diabetic patients, diabetic patients had higher levels of neutrophils (p = 0.014), c-reactive protein (p = 0.008), procalcitonin (p < 0.01), and D-dimer (p = 0.033), and lower levels of lymphocytes (p = 0.032) and albumin (p = 0.035). Furthermore, diabetic patients had a significant higher incidence of bilateral pneumonia (86.9%, p = 0.020). In terms of complications and clinical outcomes, the incidence of respiratory failure (36.9% vs. 24.2%, p = 0.022), acute cardiac injury (47.4% vs. 21.2%, p < 0.01) and death (20.2% vs. 8.0%, p = 0.001) in the diabetes group was significantly higher than that in non-diabetes group. Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time. Multivariate Cox analysis indicated that diabetes (HR 2.180, p = 0.031) was an independent risk factor for COVID-19 prognosis. In subgroup analysis, we divided diabetic patients into insulin required and non-insulin required groups according to whether they needed insulin, and found that diabetic patients requiring insulin may have a higher risk of disease progression and worse prognosis after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Diabetes is an independent risk factor for the prognosis of COVID-19. More attention should be paid to the prevention and treatment for diabetic patients, especially those who require insulin therapy.
The pathogen was identified to be a unique clade from the β-coronaviruses related to severe acute respiratory syndrome (SARS) and Middle East syndrome (MERS), and was officially named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Subsequently, this coronavirus-caused pneumonia was defined as coronavirus disease 2019 (COVID-19) by World Health Organization (WHO) on February 12.
On April 18, 2020, SARS-CoV-2 had caused 84,180 confirmed cases, and more than 4,000 death in China. Globally, this virus has spread to more than 200 countries, including the United States, Britain, Italy, South Korea and Japan.
Diabetes mellitus is one of the most common conditions among the elderly and contributes greatly to the morbidity worldwide. Moreover, numerous studies have shown that diabetic patients are more susceptible to various pathogens, such as Mycobacterium tuberculosis, Streptococcus pneumoniae, and Staphylococcus aureus.
Several retrospective studies in Wuhan indicated that diabetes was one of the most prevalent comorbidities in COVID-19 patients,
and suggested that diabetics were probably more susceptible to SARS-CoV-2 and these patients might have a worse prognosis.
In order to understand whether COVID-19 patients with diabetes have a more severe disease progression and a worse prognosis, 584 COVID-19 patients were studied. The data of demographic, clinical, laboratory, radiologic, treatments, complications, as well as clinical outcomes were carefully collected and analyzed. Our results indicate that diabetes mellitus is significantly associated with poor prognosis of COVID-19.
The relationship between diabetes and infection has always been an important concern of clinicians. Infectious diseases, especially influenza and pneumonia are very common among elderly diabetic patients. In addition, previous studies had shown that diabetes was a risk factor for the morbidity and mortality of multiple viral infections, including 2009 influenza A (H1N1), MERS-CoV and SARS-CoV.
However, the relationship between diabetes and COVID-19 prognosis is rarely reported.
Therefore, a high proportion of elderly patients in diabetes group might suggest a poor clinical outcome. Furthermore, we analyzed the symptoms of the patients at the first visit and found that diabetic patients were more likely to have symptoms of fatigue and anorexia, which might eventually lead to poor nutritional status of the patients. According to the criteria in the methods, we evaluated the disease severity of all the patients and found that there were more critical ill patients in the diabetes group, which suggest that diabetic patients are more likely to progress to a severe condition after the infection with SARS-CoV-2.
Previous studies have shown that COVID-19 patients, especially those with severe conditions, have significantly increased levels of serum inflammation-related biomarkers, including interleukin 6, C-reactive protein, and procalcitonin, and these indicators are closely related to the prognosis of the disease.
In diabetes, hyperglycemia and insulin resistance can promote the synthesis of numerous pro-inflammatory cytokines and adhesion molecules, which can exacerbate oxidative stress and inflammation in the body.
However, it is not clear whether diabetes will further aggravate the inflammatory response in COVID-19 patients. In order to clarify this question, laboratory data was analyzed in our study, and the results showed that diabetic patients had higher levels of neutrophils, c-reactive protein and procalcitonin, and a lower level of lymphocytes in comparison with non-diabetic patients. Besides lab findings, we also analyzed the radiologic data and found that diabetic patients had a significant higher incidence of bilateral pneumonia than non-diabetic patients. These results indicate that COVID-19 patients with diabetes had more severe inflammatory responses and lung infiltration, which might contribute to the worse prognosis of SARS-CoV-2’s infection.
The high concentration of serum D-dimer is closely related to a variety of thrombotic diseases, including myocardial infarction, cerebral infraction, pulmonary embolism, and venous thrombosis.
In our study, we found that the concentration of serum D-dimer of diabetic patients was significantly higher than that of non-diabetic patients, indicating that COVID-19 patients with diabetes are more likely to develop a hypercoagulable pro-thrombotic state.
It is reported that ACE2 is widely expressed in multiple organs, including heart, respiratory tract, liver, kidney, pancreas, and intestine,
which might provide an explanation for why some COVID-19 patients have multiple organ dysfunctions. In our study, we observed that the incidence of respiratory failure and acute cardiac injury in diabetes group were significantly higher than those in non-diabetes group. These results suggest that more attention should be paid to respiratory support and heart protection in COVID-19 patients with diabetes.
So far, there is no clear evidence to indicate that antiviral treatment can significantly improve the prognosis of COVID-19 patients. The majority of the patients only received treatments such as oxygen therapy, fluid management, and respiratory support. Some received antibiotics, corticosteroids and intravenous immunoglobin. Critical ill patients required ICU monitoring and mechanical ventilation. In our study, the diabetic patients were more likely to receive corticosteroids, intravenous immunoglobin and mechanical ventilation than non-diabetic patients, which indicated that the diabetic patients had a more severe disease progression and needed more advanced therapy.
Diabetes patients with uncontrollable plasma glucose levels may have more complications and a worse prognosis, usually requiring insulin therapy. We divided diabetic patients into insulin required and non-insulin required groups according to whether they needed insulin. We found that the incidence of respiratory failure, acute cardiac injury, acute kidney injury, and death in the insulin required group was significantly higher than that in non-insulin required group. Kaplan-Meier survival curve showed that the insulin required diabetic patients had a shorter overall survival time. These results indicate that diabetic patients requiring insulin have a higher risk of disease progression and worse prognosis after the infection of SARS-CoV-2.
Our study has several limitations. First, a selection bias exits in this retrospective cohort study, and more prospective studies are needed. Second, our research is only based on a single center study, and more large-scale multi-center researches need to be performed to validate our conclusions.
In conclusion, diabetes is an independent risk factor for the prognosis of COVID-19. Diabetic patients should be intensely monitored during treatment, especially those who require insulin therapy.
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Declarations of interest: none.
Authorship: All authors had access to the data and participated in writing the manuscript.
Funding: This study is supported by research grants from the National Major Scientific and Technological Special Project for Significant New Drugs Development (No. 2020ZX09201007) and National Natural Science Foundation of China (No. 81800494).
© 2020 Published by Elsevier Inc.