CC BY
3FEATURES OF LONG COVID IN PEOPLE WITH DIABETES
Pavlovych L.,
Candidate of medical sciences, associate professor of the department of clinical immunology, allergology and endocrinology.
Yuzvyk I., 6th year medical student №1 Vyhnanchuk V., Lishchuk K., Oshchepkov M., 4th year medical student №1 Babloniuk A. Bukovinian State Medical University Chernivtsi, Ukraine DOI: 10.5281/zenodo.7347317
ABSTRACT
Today, the attention of many scientists is focused on studying the features of the pathogenesis, course and persistent manifestations of infection caused by the SARS CoV-2 virus in patients with existing chronic diseases. It is known that in such cases this disease has a more severe course and is often associated with the development of complications. This article examines the problem of the long-term course of COVID-19 in patients with type 2 diabetes.
Keywords: COVID-19, SARS CoV-2, type 2 diabetes, long COVID.
Introduction. Long-COVID is a new syndrome characterized by manifestations of functional, metabolic, coagulation or inflammatory dysfunctions after COVID-19 [1, p. 2].
Prolonged COVID is usually defined as sequelae lasting more than 4 weeks after initial infection and may include a range of symptoms affecting multiple organs [14, p. 2].
The most common manifestations of post-exposure syndrome are: fatigue, shortness of breath, dizziness, changes in taste and smell, as well as musculo-skeletal and arthritic pains. Sometimes the picture of Long-COVID can resemble chronic fatigue syndrome [1, p. 2].
The risk of post-covid syndrome increases in people with more than 5 symptoms during the acute course of COVID-19 and is more common in women, the elderly, obese people, and patients with diabetes [2, p. 1].
The mechanisms underlying the association between COVID-19 and diabetes risk are not fully understood. Several types of pancreatic cells secrete three proteins - angiotensin-converting enzyme receptor protein 2, TMPRSS2 enzyme protein, and neuropilin 1. The SARS-CoV-2 virus interacts with some of these proteins to enter human cells [4, p. 6].
Studies have shown that SARS-CoV-2 can infect and multiply in insulin-producing beta cells of the pancreas. Over time, this leads to impaired insulin production and secretion. However, human pancreatic islets infected in vitro with SARS-CoV-2 show mainly non-cytopathic mild cellular disturbances and inflammatory reactions. In turn, this suggests that direct infection of pancreatic cells alone is unlikely to fully explain exacerbations of existing or new diabetes in people with COVID-19 [4, p. 8].
Other studies are working to assess the impact of autonomic dysfunction, hyperactivated immune re-
sponse or autoimmunity, and persistent low-grade inflammation that ultimately leads to insulin resistance [4, p. 10].
Type 2 diabetes has a bidirectional relationship with COVID-19. Poorly controlled diabetes increases the risk of severe COVID-19 and is associated with increased morbidity and mortality. On the other hand, COVID-19 has led to poor control of diabetes, its progression, and an increase in the number of new cases (especially corticosteroid-induced diabetes) [2, p. 1].
COVID-19 may add to or exacerbate tachycardia, sarcopenia (and muscle fatigue), and microvascular dysfunction (and organ damage) in patients with diabetes [2, p. 3].
When considering the course of post-convulsive syndrome in diabetes, one of the most common complaints is muscle weakness. In diabetes, neuropathy and myopathy lead to muscle atrophy and sarcopenia. Protein deficiency and corticosteroid therapy often cause rapid onset of sarcopenia in severe COVID-19 [4, p. 1].
The SARS-CoV-2 virus directly attacks the endocrine pancreas and its beta cells, which leads to damage and subsequent disruption of insulin secretion. [4, p. 1]
The presumed anti-inflammatory effect of diabetic drugs such as metformin, pioglitazone, incretin-based therapies, etc. should not be overlooked when diagnosing hyperglycemia as a result of COVID-19. Some reports suggest that the dipeptidyl peptidase 4 receptor may act as a binding target, possibly in conjunction with ACE2 receptors [3, p. 2].
Rehabilitation of patients with post-covid syndrome proceeds slowly and requires the efforts of various specialists. Patients with a history of diabetes should strictly adhere to the basic principles of treatment. Strict glycemic control and control of comorbidities during the acute course of COVID-19 reduce the development of post-covid syndrome. Steroids are used only under strict indications, for the shortest period,
while it is necessary to strictly control the level of sugar in the blood [6, p. 4].
Timely treatment of the infection and its complications is important. It is necessary to ensure proper nutrition, in particular, increasing the consumption of proteins and correcting the deficiency of vitamins and microelements [5, p. 1].
Physiotherapy and exercise should be given after a sufficient period of recovery from the illness, but should not be delayed for long. Exercise can have a positive effect on sarcopenia, mental health disorders, lung function, immunity, glycemia, and elevated blood pressure levels. It is advisable to start the patient on supervised individual training, including aerobic and resistance exercises, as well as physical therapy [5, p. 2; 6, p. 4].
The purpose of the research: to evaluate the influence of clinical and demographic parameters (age, sex, body mass index (BMI), glycemic control (HbAlc)), as well as antidiabetic drugs on clinical outcomes in patients with type 2 diabetes (T2DM) after experiencing COVID- 19.
Materials and methods. In the course of this study, the materials of a cohort study of observation of patients from a special ward for patients with COVID-19 at the Hospital of the Faculty of Medicine of the University of Sao Paulo (Brazil) were used.
Inclusion criteria: detection of SARS-CoV-2 RNA by polymerase chain reaction.
The first group consisted of patients diagnosed with type 2 DM diagnosed before infection with COVID-19. The second group consisted of patients without a diagnosis of DM before SARS-CoV-2 infection (practically healthy) [12, p. 2].
Exclusion criteria: presence of neoplasia, immunodeficiency or other concomitant infections.
Ninety-six patients with a positive diagnosis of COVID-19 were studied. Only 50 people met the inclusion criteria considering the exclusion criteria.
All data for this study were collected from medical records.
All 50 patients underwent 3- and 6-month follow-up: 20 patients without diabetes (type 2 diabetes) and 30 patients with diabetes.
Laboratory analysis included: complete blood count (CBC), coagulogram, liver enzymes (alanine aminotransferase—ALAT and aspartate aminotransferase—ASAT), C-reactive protein, activated partial thromboplastin time, platelets, gamma-glutamyltrans-ferase, glucose, glycated hemoglobin, and C-peptide.
The results.
20 non-DM patients (12 men and 8 women) with a mean age of 62 years and 30 diabetic patients (18 men and 12 women) with a mean age of 60.5 years were hospitalized with COVID-19, in the first wave of COVID-19 and returned for laboratory evaluation 90 and 180 days after hospital discharge.
No difference was observed in inflammatory markers of infection in relation to the period of SARS-CoV-2 disease at hospitalization, hospital discharge and after hospitalization (90 and 180 days), such as neutrophil-to-lymphocyte ratio, lymphocyte, neutrophil, monocyte count, aspartate aminotransferase
(ASAT), alanine aminotransferase (ALAT), C-reactive protein and coagulation biomarkers between patients with and without diabetes.
Gammaglutamyltransferase levels were similar between patients with and without DM at admission, immediately after discharge, and at 180 days, but values in DM patients were increased compared to non-DM patients at the 90-day time point.
Urea was similar between groups at all time points, and creatinine (at 90 days) was significantly increased only in patients with DM compared to non-DM patients.
Next, we take into account the results after 180 days to determine the long-term effects of COVID-19.
Both groups had similar levels of anti-SARS-CoV-2-specific IgG.
As expected, an increase in fasting blood glucose was observed in the group of patients with diabetes compared to patients without diabetes. But in more than 20% (3 patients) without diabetes, reference fasting blood glucose levels were detected.
Further, the increase in glycated hemoglobin was verified in the group of patients with diabetes compared to the group of healthy people (without diabetes). However, 20% (5 patients) of the group without diabetes had elevated reference values for glycated hemoglobin.
In addition, C-peptide levels were similar between the group with and without diabetes. In both groups, C-peptide was within or above reference values.
Also, in parallel during this study, a survey was conducted on the main complaints. The survey data is provided below. Fatigue, musculoskeletal pain, and dyspnea on exertion were the most common long-term symptoms of Long COVID-19 in patients with diabetes, with a prevalence of 70.5%, 42.3%, and 55%, respectively. Symptoms such as loss of concentration (27.5%), anxiety (depression) (22.2%), sleep disorders (40.5%), memory loss (19.4%) and hair loss ( 31.4%) [8,p. 5].
Discussion. The study did not examine long-term inflammatory changes in patients with and without DM after experiencing COVID-19. However, changes in glucose metabolism were detected in patients from both groups, but C-peptide levels were the same (within the presence of inflammation) [12, p. 2].
Long-COVID is a new syndrome characterized by manifestations of functional, metabolic, coagulation or inflammatory dysfunctions after COVID-19 [9, p. 5].
SARS-CoV-2 infection can lead to a decrease in the function of pancreatic beta cells or even their destruction, which can lead to an exacerbation of diabetes, its onset or long-term metabolic changes [13, p. 8].
In the cohort, more than 20% of patients without diabetes and more than 85% of patients with diabetes had values above the reference range for fasting blood glucose. To confirm a long-term increase in blood glucose, a glycated hemoglobin test was performed and its changes were detected in the entire group of patients with diabetes and in more than 20% without diabetes [16, p. 3].
References
1. Berboudi A, Rahmadika N, Tyakhjadi AI, Rus-lami R. Type 2 diabetes and its impact on the immune system. (2019) 16:442-449. doi: 10.2174/1573399815666191024085838
2. Lopez-Leon S, Wegman-Ostrosky T, Perelman S, Sepulveda R, Rebolledo PA, Quapio A, et al. Over 50 long-term consequences of COVID-19: a systematic review and meta-analysis. (2021) doi: 10.1038/s41598-021-95565-8
3. Davies H.E., Assaf G.S., McCorkell L. and others. Characterization of persistent COVID in an international cohort: 7 months of symptoms and their impact. 2021.
4. Han Q, Zheng B, Daines L, Sheikh A. Long-term consequences of COVID-19: a systematic review and meta-analysis of one-year follow-up studies on post-Covid symptoms. 2022; 11:269.
5. Michalakis K., Ilias I. COVID-19 and hypergly-cemia/diabetes. J. 2021; 12:642-650.
6. COVID-19 Quick Guide: Managing the Long-Term Consequences of COVID-19. National Institute for Health and Healthcare Excellence (Great Britain); London: 2020 December 18.
7. Fernandez de Las Peñas C., Florencio LL., Gómez-Mayordomo V., Cuadrado ML., Palacios-Siña D., Ravendran A.V. 2021; 15(4):102159. doi: 10.1016/j.dsx.2021.05.032.
8. Proal A.D., VanElzakker M.B. Long COVID or post-acute consequences of COVID-19 (PASC): a review of biological factors that may contribute to persistent symptoms. doi: 10.3389/fmicb.2021.698169.
9. Anagnostis P., Gkekas N.K., Achilla S., Pananastasiou G., Touxidou P., Mitsiu M., Kenanidis
E., Potupnis M., Tsiridis E., Goulis D.G. Type 2 diabetes mellitus is associated with an increased risk of sar-copenia: a systematic review and meta-analysis. doi: 10.1007/s00223-020-00742-y.
10. Blomberg B., Mohn K.G.I., Brokstad K.A. Long-term COVID in a prospective cohort of home-isolated patients. 2021 doi: 10.1038/s41591-021-01433-3.
11. Proal A.D., VanElzakker M.B. Long COVID or post-acute consequences of COVID-19 (PASC): a review of biological factors that may contribute to persistent symptoms. 2021 doi: 10.3389/fmicb.2021.698169.
12. Jimeno-Almazan A., Pallares J.G., Buendia-Romero A., Martinez-Cava A., Franco-Lopez F., Sanchez-Alcaraz Martinez B.Y., Bernal-Morel E., Cu-rel-Ibanez J. Post-COVID-19 syndrome and the potential benefits of exercise. 2021 doi: 10.3390/ijerph18105329. PMID: 34067776.
13. Quraishi H.M., Al-Garib A.I., Alblihead M., Guerreiro S.G., Cruz-Martins N., Batiha G.E. COVID-19 in relation to hyperglycemia and diabetes. 2021;
14. Michalakis K., Ilias I. COVID-19 and hyper-glycemia/diabetes. 2021; 12:642-650.
15. Akter F, Mannan A, Mehedi HMH, Rob MA, Ahmed S, Salauddin A, et al. Clinical characteristics and short-term outcomes after recovery from COVID-19 in patients with and without diabetes in Bangladesh. (2020) 14:2031-8. doi: 10.1016/j.dsx.2020.10.016
16. Kamal M, Abo Omira M, Hussein A, Saeed H. Assessment and characterization of post-COVID-19 manifestations. doi: 10.1111/ijcp.13746
