Serum levels of TNF alpha as diabetics prognostic marker in nondiabetic patients during coronavirus 19  infection. a prospective longitudinal  study

doi:10.21203/rs.3.rs-1555674/v1

PDF

Research Article

Serum levels of TNF alpha as diabetics prognostic marker in nondiabetic patients during coronavirus 19 infection. a prospective longitudinal study

https://doi.org/10.21203/rs.3.rs-1555674/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted 02 May, 2022

You are reading this latest preprint version

Coronavirus person with diabetes mellitus, old age and other comorbidities are considered predictors of higher morbidity and mortality. Also, blood glucose levels are independent predictors of morbidity and mortality in patients with COVID19. Diabetes Mellitus can effects immune response, whether up or down, according to control levels of glucose in circulation,

Materials and methods: A prospective longitudinal study was carried out from January 2021 till January 2022 at Murjan hospital; in Babil, Iraq; blood samples were obtained from 150 COVID 19 patients, divided into 50 patients in three groups. The first group had uncontrolled diabetes, the second group with controlled diabetes and the last group none diabetic patients developed hyperglycemia during COVID19 infection. An ELISA technique was done for the TNF alpha detection in serum and Hba1c by chromatographic and fasting blood sugar for all cases and other medical data taken from patients' files.

Results: ANOVA shows a significant high p-value of 0.0005,0.005&0.006 for ( TNF, CRP, Hba1c and fasting blood sugar, respectively ) correlated with hyperglycemia in none diabetic patients during COVID19 infection; meanwhile, the elevated levels of TNF correlated with sever cases development in diabetic groups, also TNF alpha elevated with Hba1c and fasting blood sugar test and CRP the study also used Kaplen Meier test where high levels of Hba1c, fasting blood sugar and TNF alpha correlated with an increased mortality rate (P < 0.002, 0.001 and 0.oo1 respectively). Although TNF alpha can be an excellent predictive test for the development of diabetes mellitus in none diabetic COVID 19 patients and predicts severe stages of COVID19 infection, also Hba1c considered an excellent test. In contrast, fasting sugars test outstanding in prognosis hyperglycemic and severity cases in three groups of COVID 19 patients.

Conclusion: From these findings, we can conclude that high TNF alpha proteins are considered good prognosis factors for the development of hyperglycemia in none diabetic COVID 19 patients and predict the severity of infection and mortality rate among patients with COVID19.

Coronavirus

COVID-19

hyperglycemia

TNF alpha

Hba1c and Diabetes mellitus.

COVID-19 is a respiratory illness caused by a new coronavirus SARS-Cov-2 also known as COVID-19. It was first described in December 2019 in Wuhan, China, and has since spread globally (1–3). Since Iraq's first COVID-19 case was reported on February 24 2020, the COVID-19 pandemic has become very alarming in Iraq, with the country currently reporting new cases every day (4, 5).

A relationship between diabetes and infection has long been clinically recognized by different studies(6–9). Wang et al. study reported 138 patients, 72% of them with COVID-19 with comorbidities including diabetes, required admission to ICU, compared to 37% of patients without comorbidities(7). In an analysis of 201 patients with COVID-19, Wu et al. found that diabetic patients had a hazard ratio (HR) of 2.34 (95% CI, 1.35 to 4.05; p = 0.002) for the acute respiratory syndrome (ARDS)(6).

Infections, particularly influenza and pneumonia, are common and more severe in older people with type 2 diabetes mellitus (T2DM) (10). Diabetes and uncontrolled glycemia have been reported as significant predictors of severity, and deaths in patients infected with various viruses showed that elderly patients with chronic diseases, including diabetes, are at higher risk of severe COVID-19 and mortality(8, 9, 11)

hyperglycemia and insulin resistance promote the increased synthesis of glycosylation end products (AGEs) and pro-inflammatory cytokines, oxidative stress, and stimulating the production of adhesion molecules that mediate tissue inflammation (12). This inflammatory process could be the underlying mechanism that contributes to increased infection susceptibility and poorer outcomes in diabetic patients(12). Although diabetes is related to decreased glucose availability in tissues that depend on insulin for glucose absorption, prolonged or random rises in blood glucose levels cause damage and dysfunction in tissues that do not rely on insulin for glucose uptake. In terms of clinical manifestations, this injury causes neuropathy, nephropathy, cataractogenesis, retinopathy, and an elevated risk of cardiovascular disease, notably atherosclerosis. (1ñ3). The mechanisms of the secondary complications of diabetes are not well understood, but metabolic abnormalities such as increased levels of inflammatory cytokines, osmotic and oxidative stress, altered protein kinase C (PKC) activity, and nonenzymatic glycation of proteins are considered important causative factors are contributing to tissue injury and dysfunction associated with long-term diabetes (1ñ4). Collectively, these changes result in dysregulated cell growth and apoptosis(13).

Recently several nondiabetic patients developed hyperglycemia during covid19 infection and correlated with the severity of covid 19 infection in diabetic patients; whether controlled or uncontrolled blood sugar, COVID 19 patients with hyperglycemia suffer from pneumonia, severe respiratory tract infection and may develop cytokine storm that increases the mortality rate, so we need to a prognostic immunological marker that helps to indicate the severity of COVID 19 infection and monitor the survival rate study aims to investigate the TNF-alpha levels as prognosis factors in circulations of diabetes mellitus patients with COVID19 and predisposing patients with severe infection.

2.1.Study Design

A prospective study conducted in Al-Sadeq hospital, Hilla /Babil/Iraq, in the period between July 13, 2020, until July 20, 2021, the study included 200 COVID-19 patients divided into three groups

The first group (50): cases who are free from diabetes mellitus with early infection phase with mild symptoms of upper respiratory tract infection
A second group(50): patients with hyperglycemia (control blood sugar) in the pulmonary phase with all signs and symptoms of pneumonia
The third group(50) has uncontrolled blood sugar, is infected with COVID-19 in the hyperinflammatory phase, and developed acute respiratory distress syndrome in intense care units with sepsis, kidney, and other organ failures.

The present study included age groups (18-38 years old), body mass index (BMI), smoking and both genders. The haematological markers (CBC, D-Dimmer, Ferritin and CRP and fasting blood sugar and Hba1c) chek for all patients as a general blood test. The nasopharyngeal swab was taken for all of them and proved positive for COVID-19 by PCR(14,15). According to WHO criteria, a physician diagnoses all cases diagnosed with COVID19 (16,17). And diabetic Mellitus. According to Standards of Medical Care in Diabetes(18), a Chest X-ray and CT scan is done for all patients to prove infection; the medical history data is taken from patients' files.

The study has excluded 50 covid 19 patients from Design whom with other illnesses than diabetes

2.3. Hypothesis

The study included the following hypothesis:

There is no correlation between diabetes mellitus development in COVID 19 patients and tumor necrosis factors-alpha. (H₀: p = p₀),
There is no correlation between diabetes mellitus and levels of TNF-alpha on survival rate. (H₀: p ≠ p₀) p₀is the null hypothesis, and p is the sample proportion

2.4.Materials and methods

A (5 millilitre) of blood samples were taken from patients, and the serum was obtained; then the ELISA technique was used, quantitative TNF-alpha human ELISA kit by Thermo Fisher Scientific/Frederick/USA, in serum with 96 well plates and assay range about (15.6-1000 pg/Ml).

2.5.Statistical analysis:

Data collected then transformed into computers for assistance using SPSS and Graph pad prism. Horizontal bars indicate the means. For multiple comparisons, p values will be calculated by a one-way ANOVA. Also, R for correlation coefficient between variables is used. The Kaplan-Meier method with the log-rank test was used to calculate survival rates; the receiver operating characteristic (ROC) was also used to measure the strongest of the test and sensitivity and specificity. The significant p-value <0.005

2.6. Ethics approval

This study has an ethical clearance certificate from the research ethics committee protocol/ by the Al-farahidi university faculty of medical techniques.

The study included tested TNF-α among COVID19 patients, divided into three groups mentioned previously in the study design to investigate the levels among these groups. Hence, the results were first tested using an ANOVA table for all variables among three groups to see the effects on glucose levels in the blood. The table (1) shows elevated mean of CRP (55.46–47.66 mg/L), Hba1c(10.5600-4.7400pg/ml) and TNF-alpha(528.78-122.06 pg/ml) in uncontrolled blood sugar group compared with non-diabetics patients p-value (0.006,0.005&0.005)respectively, while none significant with other demographic markers like BMI, D-dimmer, ferritin,age, gender & smoking so excluded from statistical.

To measure the effects and correlation between TNF-α on CRP, fasting blood sugar, Hba1cand COVID19 infection stages, the study used one-way ANOVA, and the analysis shows there are significant p-value (< 0.0001) difference between means of the first tercile TNF-α (lowest) < 250 pg/ml means and trecile (highest) > 450 pg/ml among blood sugar test with positive correlation (r = 0.7766) between two of them Fig. 1-A. among severity and stages of COVID19 infections the analysis shows there is a strong positive correlation (r = 0.7669) between high levels of TNF-α and third stage (sever cases) also a significant difference between means of TNF-α in the third stage and first stage of COVID19 infections (505.9–110 pg/ml p < 0.0001). Figure (1-B) the TNF-α correlated positive correlation and very good positive correlation between high levels of CRP, Hba1c and third tercile levels > 450 pg/ml and a significant difference between increased in levels of CRP AND Hba1c among third tercile levels > 450 pg/ml (p < 0.0001 ).figure(1-C&D).

To measure the importance of TNF-α as prognostic factors to predict severe stages of COVID19 infections, the study used Kaplan mieir test to explain that patients with third tercile levels > 450 pg/ml have a high probability of developing the third stage of COVID 19 infections (p < 0.001).figure 2

The validity of the test was done by using the ROC curve in figure (3-A), were used three two standard markers (fasting sugar test and Hba1c) besides TNF-α to predict severe cases (third stage )where the area under the test shows that (AUC = 0.897 and 0.878 p < 0.0001) for TNF-α & HbA1C respectively both of the test considered a good test to predict cases that developed sever sign and symptoms of COVID19 infections while fasting blood sugar a very good test (AUC = 0.984, p < 0.0001). The cutoff value predicts cases with the third stage COVID19 infection for TNF-α 454.5 PG/ML with 82% sensitivity and 95% specificity, Hba1c: 7.5%, with sensitivity:94% specificity:62% and fasting blood sugar cutoff value 261 with 98%and99% sensitivity and specificity respectively. Table 2& Fig. 3-a

And the TNF-α is a very good test ( AUC = 0.839, p < 0.0001) as a prognostic test for hyperglycemia with a Cutoff value for TNF-α among hyperglycemia 454.50 PG/ML with 80% sensitivity and 87% specificity. Table 2& Fig. 3-b

Diabetes is one of the first diseased linked with other diseased like heart, kidney, nerve and liver disease, and diabetics complication can increase the mortality rate (12)

Coronavirus infection in diabetic patients can increase blood glucose, and also infections with the virus can cause hyperglycemia in nondiabetic patients during the infection course Infection of SARS-CoV-2 in those with diabetes possibly triggers higher stress conditions, with the greater release of hyperglycemic hormones, e.g., glucocorticoids and catecholamines, leading to increased blood glucose levels and abnormal glucose variability (19)

Yet so far, the inflammatory and immunological process in patients with diabetes mellitus infected with COVID19 does not fully understand how exactly the mechanisms occur in these patients, viruses may alter the SARS-CoV-2 virulence, or the virus itself interferes with insulin secretion or glycemic control or immune response pathway interacts with insulin and glucose metabolisms lead to hyperglycemia.

The present study shows that patients with uncontrolled diabetes correlated with severe COVID 19 infection. The study is based on testing fasting blood sugar and Hba1c as the gold standard to indicate diabetes mellitus status and TNF-α as new prognostic factors to predict both cases of developed hyperglycemia during COVID19 infection and severity of infections besides other general haematological markers like (d-dimmer,ferritine&CRP) and demographic markers; the results show that people with poorly controlled diabetes have been linked with sever stages of COVID19 infections, the results corresponding with the study of Hussain A et al. (2020) (20), increased levels in glucose can lead to decreased in lymphocytes especially monocyte/macrophage and neutrophil functions meanwhile insulin resistance can enhance advanced glycation end products (AGEs) formation, oxidative stress, increased expression of adhesion molecules that play a role in inflammation also activate the secretion of pro-inflammatory cytokines (21–23).

The results also show CRP levels elevated during COVID 19 infection in uncontrolled diabetes and suffer from severe covid19 infection; this marker is used as a general and non-specific indicator for infection and can be elevated in all infections and inflammations (24)

Also, the statistical result explains that CRP and Hba1c are significantly elevated in patients with diabetes groups, whether controlled or uncontrolled glucose levels, and can be rises in first groups who are none diabetic but suffer from hyperglycemia during COVID19 patients. The result is constant with the study of Stringer et al. 2021(25) and Sachdeva S et al. (2020), who conclude that's elevated glucose levels in nondiabetic patients linked with the severity of the infection and increased mortality rate compared with those with normal values of blood glucose (26). Coronavirus can stimulate the expression of ACE2 receptors in the pancreas leading to interaction with the glucose metabolism pathway(27, 28), and also some study shows that elevated glucose may persist for 3 years after recovery from SARS, indicating transient damage to beta cells (29)

Although all mention previously the diabetic status was used as an independent mark, so the present study spotlight on a new inflammatory marker to choose patients with a high chance of developing diabetes mellitus during COVID19 infection, which also may be correlated with the severity of the disease, so study levels of TNF- α in three groups and the results show increased significantly with COVID 19 sever stages patients the results agree with results of Mortaz E et al. (2019) (30).

Also, statistically, the analysis explains that TNF-alpha significantly correlated with high Hba1c percentage and high fasting blood sugar and CRP while none significant with other haematological markers like D-Dimmer, ferritin, this results consistent with Kroder G et al. (1996) study(31) and results of Kirwan J et al. (2001)(32) because when inflammatory cytokines increased in serum may link with downregulation insulin receptor tyrosine kinase activity in the adipose tissue and skeletal muscle and may inhibition insulin-dependent tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) and the insulin receptor in adipocytes and myeloid 32D cells leading to elevated in glucose level and insulin resistance (33)

Over time, the survival rate decreases with a high concentration of (Hba1c, fasting blood glucose and TNF-alpha) compared with a mean of low concentration. This result agrees with Karki R et al. (2021), who concluded that treatment of COVID 19 infected with the anti-TNF-α increased surviving rate(34) and study Yuan S et al. (2021) and study of Liu Y et al. (2021), whose results shows that hyperglycemia correlated with the increased mortality rate in diabetics patients with COVID19 infection (35, 36)

The statistical results appear by ROC curved that TNF-α, Hba1C and fasting blood sugar can help in diagnosis and selected patients with a high risk of severe cases of COVID 19 results appropriate with Karki R et al. (2020), Yuan S et al. (2021) and Liu Y et al. (2021)(35–37)

Moreover, TNF-α can be used as a test to predict hyperglycemia in nondiabetic patients during COVID19 infection; the results agree with Bilen A et al. (2021), who showed that increased correlated with harm effect of hyperglycemia on the kidney(38)

Thompson RN. Novel coronavirus outbreak in Wuhan, China, 2020: Intense surveillance is vital for preventing sustained transmission in new locations. Journal of Clinical Medicine. 2020;9(2).
Wang W, Tang J, Wei F. Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China. Journal of Medical Virology. 2020;92(4).
Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, et al. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health — The latest 2019 novel coronavirus outbreak in Wuhan, China. Vol. 91, International Journal of Infectious Diseases. 2020.
Darweesh O, Abdulrazzaq GM, Al-Zidan RN, Bebane P, Merkhan M, Aldabbagh R, et al. Evaluation of the Pharmacologic Treatment of COVID-19 Pandemic in Iraq. Vol. 7, Current Pharmacology Reports. 2021.
Aziz PY, Hadi JM, Sha AM, Aziz SB, Rahman HS, Ahmed HA, et al. The strategy for controlling COVID-19 in Kurdistan Regional Government (KRG)/Iraq: Identification, epidemiology, transmission, treatment, and recovery. International Journal of Surgery Open. 2020;25.
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Internal Medicine. 2020;180(7).
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA - Journal of the American Medical Association. 2020;323(11).
Singh AK, Gupta R, Ghosh A, Misra A. Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020 July 1;14(4):303–10.
Singh AK, Gupta R, Ghosh A, Misra A. Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020 July 1;14(4):303–10.
Cuschieri S, Grech S. COVID-19 and diabetes: The why, the what and the how. Journal of Diabetes and its Complications. 2020;34(9).
Muniyappa R, Gubbi S. COVID-19 pandemic, coronaviruses, and diabetes mellitus. Vol. 318, American Journal of Physiology - Endocrinology and Metabolism. 2020.
Hussain A, Bhowmik B, do Vale Moreira NC. COVID-19 and diabetes: Knowledge in progress. Vol. 162, Diabetes Research and Clinical Practice. 2020.
Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Vol. 414, Nature. 2001.
Laboratory diagnosis of COVID-19 | Elsevier Enhanced Reader [Internet]. [cited 2022 Apr 7]. Available from: https://reader.elsevier.com/reader/sd/pii/S0021755720301996?token=245F9A0F555BBB1843EA5EE86A57763CADEB988DB7DE90461C5BA78558F4149872C7D18E8F8F79F8DC59077BC6609E9C&originRegion=eu-west-1&originCreation=20220406222106
Goudouris ES. Laboratory diagnosis of COVID-19. Jornal de Pediatria [Internet]. 2021 January 1 [cited 2022 April 7];97(1):7–12. Available from: www.jped.com.br
Zhai P, Ding Y, Wu X, Long J, Zhong Y, Li Y. The epidemiology, diagnosis and treatment of COVID-19. International Journal of Antimicrobial Agents. 2020 May 1;55(5):105955.
Wang Y-Y, Jin Y-H, Ren X-Q, Li Y-R, Zhang X-C, Zeng X-T, et al. Updating the diagnostic criteria of COVID-19 "suspected case" and "confirmed case" is necessary. Mil Med Res [Internet]. 2020;7(17). Available from:
https://doi.org/10.1186/
2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2019. Diabetes Care [Internet]. 2019 January 1 [cited 2022 April 7];42(Suppl 1):S13–28. Available from: https://pubmed.ncbi.nlm.nih.gov/30559228/
Videa EO, Murillo NGR, Alvarenga PC, Ochoa VLB. Characterization of Patients With Type 2 Diabetes Mellitus and COVID-19. J Endocr Soc. 2021;5(Supplement_1).
Hussain A, Bhowmik B, do Vale Moreira NC. COVID-19 and diabetes: Knowledge in progress. Diabetes Research and Clinical Practice. 2020 April 1;162:108142.
Knapp S. Diabetes and Infection: Is There a Link? - A Mini-Review. Gerontology [Internet]. 2013 Feb [cited 2022 Apr 9];59(2):99–104. Available from: https://www.karger.com/Article/FullText/345107
Petrie JR, Guzik TJ, Touyz RM. Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. Canadian Journal of Cardiology [Internet]. 2018 May 1 [cited 2022 Apr 9];34(5):575–84. Available from: http://creativecommons.org/licenses/by/4.0/
Hussain A, Bhowmik B, do Vale Moreira NC. COVID-19 and diabetes: Knowledge in progress. Diabetes Research and Clinical Practice. 2020 April 1;162:108142.
Stringer D, Braude P, Myint PK, Evans L, Collins JT, Verduri A, et al. The role of C-reactive protein as a prognostic marker in COVID-19. International Journal of Epidemiology [Internet]. 2021 May 17 [cited 2022 Apr 9];50(2):420. Available from: /pmc/articles/PMC7989395/
Stringer D, Braude P, Myint PK, Evans L, Collins JT, Verduri A, et al. The role of C-reactive protein as a prognostic marker in COVID-19. International Journal of Epidemiology [Internet]. 2021 May 17 [cited 2022 Apr 9];50(2):420. Available from: /pmc/articles/PMC7989395/
Sachdeva S, Desai R, Gupta U, Prakash A, Jain A, Aggarwal A. Admission Hyperglycemia in Non-diabetics Predicts Mortality and Disease Severity in COVID-19: a Pooled Analysis and Meta-summary of Literature. SN Comprehensive Clinical Medicine. 2020 Nov;2(11):2161–6.
Yang Shan-Shan Lin AE Xiu-Juan Ji AE Li-Min Guo J-KA. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010;27:193–9.
Lepper PM, Ott S, Nüesch E, von Eynatten M, Schumann C, Pletz MW, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ [Internet]. 2012 June 16 [cited 2022 April 9];344(7861). Available from: https://pubmed.ncbi.nlm.nih.gov/22645184/
Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetologica. 2010;47(3).
Mortaz E, Tabarsi P, Jamaati H, Roofchayee ND, Dezfuli NK, Hashemian SM, et al. Increased Serum Levels of Soluble TNF-a Receptor Is Associated With ICU Mortality in COVID-19 Patients. 2019;12:1. Available from: www.frontiersin.org
Kroder G, Bossenmaier B, Kellerer M, Capp E, Stoyanov B, Mühlhöfer A, et al. TNF-and Hyperglycemia-induced Insulin Resistance Tumor Necrosis Factor-and Hyperglycemia-induced Insulin Resistance Evidence for Different Mechanisms and Different Effects on Insulin Signaling Key words: non-insulin-dependent di-abetes mellitus • obesity • insulin receptor • protein kinase C • phosphotyrosine phosphatase. Vol. 97, J. Clin. Invest. 1996.
Kirwan JP, Krishnan RK, Weaver JA, del Aguila LF, Evans WJ. Human aging is associated with altered TNF-alpha production during hyperglycemia and hyperinsulinemia. Am J Physiol Endocrinol Metab [Internet]. 2001 [cited 2022 Apr 9];281(6). Available from: https://pubmed.ncbi.nlm.nih.gov/11701426/
Liu Y, Wang X, Zhao Y, Zhao P, Wang L, Zhai Q, et al. Upregulation of Tumor Necrosis Factor-α-Induced Protein 8-Like 2 mRNA Is Negatively Correlated with Serum Concentrations of Tumor Necrosis Factor-α and Interleukin 6 in Type 2 Diabetes Mellitus. Journal of Diabetes Research [Internet]. 2017 [cited 2022 Apr 9];2017. Available from: /pmc/articles/PMC5463106/
Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, Samir P, et al. Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes. Cell [Internet]. 2021 Jan 7 [cited 2022 Apr 13];184(1):149–168.e17. Available from: https://pubmed.ncbi.nlm.nih.gov/33278357/
Liu Y, Lu R, Wang J, Cheng Q, Zhang R, Zhang S, et al. Diabetes, even newly defined by HbA1c testing, is associated with an increased risk of in-hospital death in adults with COVID-19. BMC Endocr Disord [Internet]. 2021 Dec 1 [cited 2022 Apr 13];21(1). Available from: https://pubmed.ncbi.nlm.nih.gov/33771154/
Yuan S, Li H, Chen C, Wang F, Wang DW. Association of glycosylated haemoglobin HbA1c levels with outcome in patients with COVID-19: A Retrospective Study. Journal of Cellular and Molecular Medicine. 2021 April 1;25(7):3484–97.
Karki R, Sharma BR, Tuladhar S, Williams EP, Zalduondo L, Samir P, et al. COVID-19 cytokines and the hyperactive immune response: Synergism of TNF-α and IFN-γ in triggering inflammation, tissue damage, and death. bioRxiv [Internet]. 2020 Oct 29 [cited 2022 Apr 13]; Available from: http://www.ncbi.nlm.nih.gov/pubmed/33140051
Bilen A, Calik I, Yayla M, Dincer B, Tavaci T, Cinar I, et al. Does daily fasting shielding kidney on hyperglycemia-related inflammatory cytokine via TNF-α, NLRP3, TGF-β1 and VCAM-1 mRNA expression. Int J Biol Macromol [Internet]. 2021 Nov 1 [cited 2022 Apr 13];190:911–8. Available from: https://pubmed.ncbi.nlm.nih.gov/34492249/

Table (1): the means of Demographic, haematological and immunological markers among diabetes mellitus patients with COCID19

DM Groups		age	Gender	BMI kg	smoking	CRP mg/L	D-Dimmer pg/ml	ferritin pg/ml	Hba1c	TNF pg/ml
uncontrolled blood sugar	Mean	49.50	1.44	33.96	17.32	55.46	1594.56	1718.16	10.5600	528.78
	N	50	50	50	50	50	50	50	50	50
	Std. Deviation	13.798	.501	3.849	12.280	14.927	650.765	728.375	2.28714	161.734
Controlled blood sugar	Mean	50.96	1.46	33.36	21.92	48.66	1371.62	1836.64	8.5800	330.54
	N	50	50	50	50	50	50	50	50	50
	Std. Deviation	14.868	.503	3.451	10.832	15.900	572.819	718.717	1.48585	104.369
Non-diabetic	Mean	52.50	1.60	33.72	18.10	47.66	1659.38	1679.92	4.7400	122.06
	N	50	50	50	50	50	50	50	50	50
	Std. Deviation	15.526	.495	3.742	11.236	14.723	537.032	668.459	.77749	116.738
P-value		0.374	0.084	0.925	0.450	0.006	0.089	0.426	0.0005	0.0005

DM: Diabetes melitus groups, Body mass index, CRP:c-reactive protein,Hba1c:,TNF-α:tumor necrosis factors-alpha ,p-value significant <0.05

Mg/L: Miligram Per Liter, pg/ml:picogram per milliliters; Kg: kilogram

Table (2): The Area Under ROC Curve For TNF-α, Hba1c & fasting blood sugar When Used as a Test to Predict Cases with a risk of severe cases COVID19 & TNF-α for development hyperglycemia in nondiabetics COVID-19 patients

Variables among COVID19 severity	Area	P-value	Asymptotic 95% Confidence Interval
Variables among COVID19 severity	Area	P-value	Lower Bound	Upper Bound
TNF pg/ml	0.897	<0.0001	.838	.957
Hba1c %	0.878	<0.0001	.826	.931
Fasting blood sugar	0.984	<0.0001	.951	1.000
TNF-α among hyperglycemia	0.839	<0.0001	0.757	0.920

AUC: Area Under the Curve, P-value:<0.05

The cutoff value for TNF-α 454.5 PG/ML with 82 % sensitivity and 95% specificity, Hba1c: 7.5%,with sensitivity :94 % and specificity:62% and fasting blood sugar cutoff value 261 with 98%and99% sensitivity and specificity respectively
The cutoff value for TNF-α among hyperglycemia is 454.50 PG/ML with 80% sensitivity and 87% specificity

No competing interests reported.

PDF

Version 1

posted 02 May, 2022

You are reading this latest preprint version

Serum levels of TNF alpha as diabetics prognostic marker in nondiabetic patients during coronavirus 19 infection. a prospective longitudinal study

Status:

Version 1

Abstract

Figures

1. Introduction

2. Material & Methods

3. Results

4. Discussion

References

Tables

Competing Interests

Status:

Version 1