Diabetes and COVID-19
DEFINITION
- SARS-COV-2 is a novel, positive-sense, single-stranded RNA virus belonging to the Coronaviridae family.[31]
- The virus was first isolated from throat swabs of patients in Wuhan, Hubei Province, China in late-2019.
- The disease caused by SARS-COV-2 was named COVID-19 by the World Health Organization in January 2020.
- COVID-19 causes symptoms ranging from mild, flu-like illness to acute respiratory distress syndrome (ARDS) and severe end-organ damage.[7]
- For more information regarding microbiology, please refer to the Johns Hopkins Antibiotic Guide
EPIDEMIOLOGY
- Real-time global reports available through Coronavirus COVID-19 Global Cases Dashboard by Johns Hopkins CSSE.
- The CDC cites multiple risk factors for severe COVID-19 infection, including:
- T2DM
- Serious cardiovascular disease
- COPD
- CKD
- Active malignancy
- Obesity
- History of solid organ transplant
- There are also several factors associated with possible increased risk for severe COVID-19 infection, including:
- T1DM
- Asthma
- CVA or other neurological condition
- Cystic fibrosis
- Pulmonary fibrosis
- Current tobacco use
- Hypertension
- Immunocompromised state
- Liver disease
- Pregnancy
- The mechanism by which diabetes increases risk for severe COVID-19 infection may be a dysregulated inflammatory response caused by chronic, low-grade inflammation.[44]
- COVID-19 admission rates are higher among patients with diabetes.
- In an American study, the COVID-19 admission rate for patients with diabetes was 34.7% compared to 9.7% in those without.[4]
- DKA occurs frequently among individuals with diabetes and COVID-19 infection.
DIAGNOSIS
- COVID-19 infection should be considered in all patients with concerning symptoms, labs or imaging findings or who have had close contact with a suspected or confirmed case.
- For coronavirus COVID-19 (SARS-CoV-2) testing information, see the Johns Hopkins Antibiotic Guide
SIGNS AND SYMPTOMS
COVID-19 infection in the adult population
COVID-19 infection in the adult population
- A large percentage of patients with positive COVID-19 throat swabs are asymptomatic.
- The most common symptoms of COVID-19 include:[22]
- Fever (44-98%)
- Cough (69-82%)
- Dyspnea (19-64%)
- Sputum production (14-34%)
- Myalgias (11-15%)
- Less common symptoms of COVID-19 include:
- Rhinorrhea (4-24%)
- Sore throat (5-14%)
- Headache (5-14%)
- Diarrhea (2-5%)
- Nausea/vomiting (1-10%)
- Loss of taste/smell
- Characteristic laboratory findings in COVID-19 infection:
- CBC: Lymphopenia, leukopenia, thrombocytopenia
- Chemistry: Elevated AST/ALT
- Inflammatory markers: Elevated CRP, elevated ESR, elevated D-dimer, elevated LDH, elevated serum ferritin, elevated IL-6
- Characteristic imaging findings in COVID-19 infection:
- CT chest: ground-glass opacities, bilateral patchy shadows, subsegmental areas of consolidation
COVID-19 infection in the pediatric population
COVID-19 infection in the pediatric population
- Symptoms are similar to those reported in adults.
- A small subset of the pediatric population develops multisystem inflammatory syndrome (MIS-C), leading to multiple organ system dysfunction.[3]
- In a limited cohort study conducted at a New York hospital, 30% of children with MIS-C developed cardiomegaly, 69% developed decreased EF and 18% developed bilateral pulmonary opacities. One patient was sick enough to require ECMO, and another needed an intra-aortic balloon pump.
Concerning symptoms in patients with preexisting diabetes
Concerning symptoms in patients with preexisting diabetes
- Any infection can increase the risk for severe hyperglycemia, DKA and HHS in patients with preexisting diabetes.[43]
- Patients with preexisting diabetes who contract the novel coronavirus need be educated about possible symptoms of severe hyperglycemia, DKA and HHS, and may need to monitor glucose levels at home more frequently.
- Concerning symptoms: polyuria/polydipsia, nausea/vomiting, abdominal pain, fruity odor on the breath, difficulty breathing or rapid breathing, altered level of consciousness
CLINICAL TREATMENT
Outpatient diabetes management in patients with COVID-19
Outpatient diabetes management in patients with COVID-19
- Previous oral regimen can be continued provided patient is tolerating PO and completes more frequent blood glucose checks.
- Consider holding SGLT-2 inhibitors as these may precipitate euglycemic DKA in acute illness.[29][35][33]
- Any patient prescribed insulin should be counseled about inappropriate dose reduction and omission.
- Potential symptoms of DKA (including impaired consciousness, nausea/vomiting and abdominal pain) should prompt further evaluation for blood ketones (even if the blood glucose is normal).
- It is still possible for SGLT-2 inhibitors to precipitate DKA in patients not prescribed insulin. We are most concerned about individuals who are insulin-deficient and/or have severe elevated HbA1c. There is also increased risk to persons who follow ketogenic (carbohydrate-restricted) diets or drink alcohol to excess. Most other patients treated with oral diabetes medications can be considered very low risk for DKA.
- CGM users can review the effects of the virus on blood glucose values in real-time.
- It may be necessary to adjust home insulin dosing based on sick-day protocols.
- Empiric dexamethasone may not be appropriate in all inpatients with diabetes.
- Oral diabetes medications may interact with those used to treat COVID-19.[18]
- Hydroxychloroquine interacts with sulfonylureas and causes hypoglycemia.
- Protease inhibitors interact with most classes of non-insulin diabetes medication and may cause hyperglycemia.
- Some oral diabetes medications have antiviral properties and decrease lung inflammation in animal models.[29][5][42][34][36][30][38]
- There was no evidence of clinical improvement starting a DPP-4 inhibitor in patients with SARS or MERS.
Inpatient diabetes management in patients with COVID-19
Inpatient diabetes management in patients with COVID-19
- Good outpatient glycemic control is important for survival.[49]
- T2DM OR for death from COVID-19 at HbA1c > 10% = 1.62
- T1DM OR for death from COVID-19 at HbA1c > 10% = 2.19
- Inpatient hyperglycemia in COVID-19 increases the risk of death independent of diabetes.[8]
- No current COVID-specific inpatient blood glucose targets
- Italian study published in Lancet showed reduced inflammatory markers at mean inpatient blood glucose 115 mg/dL compared to 135 mg/dL.[18]
- Recent American study showed that 45.5% of T1DM patients admitted with COVID-19 had DKA, and 11% of admitted T2DM patients with COVID-19 had DKA or HHS[20]
- Some patients may not even have a preexisting diabetes diagnosis, and COVID-19 infection with hyperglycemia and/or DKA could be the initial presentation.[11][26][2]
- Subcutaneous protocols to treat DKA available from numerous academic centers designed to limit nursing exposure[21][17]
- There is a sample protocol (Mt. Sinai) available at: https://professional.diabetes.org/sites/professional.diabetes.org/files/me...
- Any patient who has a new diagnosis of diabetes or preexisting T2DM and develops DKA/HHS should have islet antibody and c-peptide screening.
- SARS-COV2 binds to the ACE-2 receptor on beta cells leading to impaired insulin secretion and/or destruction.[8]
- Previous research on the HHV-8 virus showed increased ketosis in patients with T2DM.[39]
- Continuous glucose monitoring (CGM) offers promise as an effective tool for monitoring hospitalized patients. During the COVID-19 pandemic, this technology can be implemented to address emergent needs when there is increased demand for both nursing staff and PPE.[9]
- In April 2020, the FDA allowed use of inpatient CGM to monitor coronavirus patients.[10]
- Abbott and Dexcom offered to supply hospitals with CGM systems and help clients learn to use these devices effectively.[47][45]
- The newest generation of CGM devices have alarms that can alert clinicians (and patients) to abnormal blood glucose values.
- A few of the newer systems are FDA approved for nonadjunctive use to dose insulin (i.e. confirmatory fingerstick not required).
- CGM accuracy is no longer impacted by use of acetaminophen.
- More data are needed to assess performance of CGM in mainstream hospital practice:
- The current EHR must be modified to accept blood glucose data from the sensor.
- Hospitalist physicians and staff need to be trained to interpret CGM trends.
- CGM may not be feasible for patients who require frequent imaging (must be removed prior to CT and MRI).
FOLLOW UP
- There are no published guidelines on appropriate follow-up for patients with diabetes who contract COVID-19.
- An elevated HbA1c during hospitalization argues against hyperglycemia due to acute illness..
- Any new outpatient insulin requirement following COVID-19 infection should be referred to primary care or Endocrinology at discharge.
- Some patients may require insulin for an extended duration following hospitalization due to insulin resistance (from counter-regulatory hormones) and glucose toxicity.
- These patients should receive instruction on blood glucose monitoring and nutrition inpatient if possible.
- These patients must be given a prescription for a glucagon emergency kit if intending to continue insulin.
- Any patient who develops DKA or HHS in the setting of COVID-19 should be referred to Endocrinology at discharge.
- There is no literature on what percentage of patients recover previous beta cell function.
EXPERT COMMENTS
- There is no direct evidence that diabetes increases the risk of contracting COVID-19, but we know that hyperglycemia impairs leukocyte function in vitro.[37][41][40]
- In a Chinese meta-analysis, the prevalence of diabetes in COVID-19 patients was similar to that in the general population.[28]
- In an Italian study, the prevalence of diabetes in patients admitted for COVID-19 infection was lower than that in the same region.[27]
- In an American study, T1DM patients who contracted COVID-19 had similar clinical characteristics and outpatient glycemic control compared to those not infected.[15]
- It is clear that diabetes increases the risk of complications and death from COVID-19.
- In an Italian study, 31.1% of hospitalized patients who died from COVID-19 had diabetes.[46]
- In a French study, 43% of hospitalized patients who died from COVID-19 had diabetes.[19]
- In an English study, 31.4% of hospitalized patients who died from COVID-19 had T2DM (adjusted OR = 1.8) and 1.5% had T1DM (adjusted OR = 2.86).[14]
- We use a glycemic target of 140-180 mg/dL for hospitalized COVID-19 patients similar to other patients with diabetes.
- There is increased incidence of DKA and HHS in COVID-19 infection[12][20], including among patients with no previous known history of diabetes.
- We do not yet know whether this is due to increased insulin resistance/glucose toxicity, beta cell destruction or induction of autoimmunity.
- There are no published data on the post-discharge clinical course of patients with new insulin requirement following COVID-19 infection.
- Where appropriate, some institutions have implemented scheduled subcutaneous insulin protocols adapted from previous studies versus intravenous insulin to help reduce nursing exposure.[17]
- As diabetes providers, we need to be advocating for influenza vaccination and COVID-19 vaccination once it becomes available.
References
- Waterer GW, Rello J. Steroids and COVID-19: We Need a Precision Approach, Not One Size Fits All. Infect Dis Ther. 2020. [PMID:32953385]
- Rabizadeh S, Hajmiri M, Rajab A, et al. Severe diabetic ketoacidosis and coronavirus disease 2019 (COVID-19) infection in a teenage patient with newly diagnosed diabetes. J Pediatr Endocrinol Metab. 2020;33(9):1241-1243. [PMID:32809963]
- Kaushik S, Aydin SI, Derespina KR, et al. Multisystem Inflammatory Syndrome in Children Associated with Severe Acute Respiratory Syndrome Coronavirus 2 Infection (MIS-C): A Multi-institutional Study from New York City. J Pediatr. 2020;224:24-29. [PMID:32553861]
- Petrilli CM, Jones SA, Yang J, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020;369:m1966. [PMID:32444366]
- Sharma S, Ray A, Sadasivam B. Metformin in COVID-19: A possible role beyond diabetes. Diabetes Res Clin Pract. 2020;164:108183. [PMID:32360697]
- Deng F, Gao D, Ma X, et al. Corticosteroids in diabetes patients infected with COVID-19. Ir J Med Sci. 2020. [PMID:32588377]
- Ge H, Wang X, Yuan X, et al. The epidemiology and clinical information about COVID-19. Eur J Clin Microbiol Infect Dis. 2020;39(6):1011-1019. [PMID:32291542]
- Bode B, Garrett V, Messler J, et al. Glycemic Characteristics and Clinical Outcomes of COVID-19 Patients Hospitalized in the United States. J Diabetes Sci Technol. 2020;14(4):813-821. [PMID:32389027]
- Galindo RJ, Aleppo G, Klonoff DC, et al. Implementation of Continuous Glucose Monitoring in the Hospital: Emergent Considerations for Remote Glucose Monitoring During the COVID-19 Pandemic. J Diabetes Sci Technol. 2020;14(4):822-832. [PMID:32536205]
- Pasquel FJ, Umpierrez GE. Individualizing Inpatient Diabetes Management During the Coronavirus Disease 2019 Pandemic. J Diabetes Sci Technol. 2020;14(4):705-707. [PMID:32370606]
- Suwanwongse K, Shabarek N. Newly diagnosed diabetes mellitus, DKA, and COVID-19: Causality or coincidence? A report of three cases. J Med Virol. 2020. [PMID:32706395]
- Goldman N, Fink D, Cai J, et al. High prevalence of COVID-19-associated diabetic ketoacidosis in UK secondary care. Diabetes Res Clin Pract. 2020;166:108291. [PMID:32615280]
- Rayman G, Lumb AN, Kennon B, et al. Dexamethasone therapy in COVID-19 patients: implications and guidance for the management of blood glucose in people with and without diabetes. Diabet Med. 2020. [PMID:32740972]
- Barron E, Bakhai C, Kar P, et al. Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study. Lancet Diabetes Endocrinol. 2020;8(10):813-822. [PMID:32798472]
- Vamvini M, Lioutas VA, Middelbeek RJW. Characteristics and Diabetes Control in Adults With Type 1 Diabetes Admitted With COVID-19 Infection. Diabetes Care. 2020;43(10):e120-e122. [PMID:32769127]
- Mittal S, Madan K, Mohan A. COVID-19 and steroid therapy: Impact on diabetes. Prim Care Diabetes. 2020;14(5):568. [PMID:32778507]
- Korytkowski M, Antinori-Lent K, Drincic A, et al. A Pragmatic Approach to Inpatient Diabetes Management during the COVID-19 Pandemic. J Clin Endocrinol Metab. 2020;105(9). [PMID:32498085]
- Apicella M, Campopiano MC, Mantuano M, et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol. 2020;8(9):782-792. [PMID:32687793]
- Cariou B, Hadjadj S, Wargny M, et al. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. Diabetologia. 2020;63(8):1500-1515. [PMID:32472191]
- Ebekozien OA, Noor N, Gallagher MP, et al. Type 1 Diabetes and COVID-19: Preliminary Findings From a Multicenter Surveillance Study in the U.S. Diabetes Care. 2020;43(8):e83-e85. [PMID:32503837]
- Palermo NE, Sadhu AR, McDonnell ME. Diabetic Ketoacidosis in COVID-19: Unique Concerns and Considerations. J Clin Endocrinol Metab. 2020;105(8). [PMID:32556147]
- Pascarella G, Strumia A, Piliego C, et al. COVID-19 diagnosis and management: a comprehensive review. J Intern Med. 2020;288(2):192-206. [PMID:32348588]
- Ai T, Yang Z, Hou H, et al. Correlation of Chest CT and RT-PCR Testing for Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases. Radiology. 2020;296(2):E32-E40. [PMID:32101510]
- Scohy A, Anantharajah A, Bodéus M, et al. Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis. J Clin Virol. 2020;129:104455. [PMID:32485618]
- Long QX, Tang XJ, Shi QL, et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med. 2020;26(8):1200-1204. [PMID:32555424]
- Soliman AT, Al-Amri M, Alleethy K, et al. Newly-onset type 1 diabetes mellitus precipitated by COVID-19 in an 8-month-old infant. Acta Biomed. 2020;91(3):ahead of print. [PMID:32921748]
- Fadini GP, Morieri ML, Longato E, et al. Prevalence and impact of diabetes among people infected with SARS-CoV-2. J Endocrinol Invest. 2020;43(6):867-869. [PMID:32222956]
- Guan WJ, Liang WH, Zhao Y, et al. Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis. Eur Respir J. 2020;55(5). [PMID:32217650]
- Mirabelli M, Chiefari E, Puccio L, et al. Potential Benefits and Harms of Novel Antidiabetic Drugs During COVID-19 Crisis. Int J Environ Res Public Health. 2020;17(10). [PMID:32456064]
- Iacobellis G. COVID-19 and diabetes: Can DPP4 inhibition play a role? Diabetes Res Clin Pract. 2020;162:108125. [PMID:32224164]
- Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. [PMID:31986264]
- Alessi J, de Oliveira GB, Schaan BD, et al. Dexamethasone in the era of COVID-19: friend or foe? An essay on the effects of dexamethasone and the potential risks of its inadvertent use in patients with diabetes. Diabetol Metab Syndr. 2020;12:80. [PMID:32922517]
- Fitchett D. A safety update on sodium glucose co-transporter 2 inhibitors. Diabetes Obes Metab. 2019;21 Suppl 2:34-42. [PMID:31081590]
- Mazidi M, Karimi E, Rezaie P, et al. Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. J Diabetes Complications. 2017;31(7):1237-1242. [PMID:28479155]
- Goldenberg RM, Berard LD, Cheng AYY, et al. SGLT2 Inhibitor-associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis. Clin Ther. 2016;38(12):2654-2664.e1. [PMID:28003053]
- Viby NE, Isidor MS, Buggeskov KB, et al. Glucagon-like peptide-1 (GLP-1) reduces mortality and improves lung function in a model of experimental obstructive lung disease in female mice. Endocrinology. 2013;154(12):4503-11. [PMID:24092637]
- de Souza Ferreira C, Araújo TH, Ângelo ML, et al. Neutrophil dysfunction induced by hyperglycemia: modulation of myeloperoxidase activity. Cell Biochem Funct. 2012;30(7):604-10. [PMID:22610543]
- Aoki Y, Maeno T, Aoyagi K, et al. Pioglitazone, a peroxisome proliferator-activated receptor gamma ligand, suppresses bleomycin-induced acute lung injury and fibrosis. Respiration. 2009;77(3):311-9. [PMID:18974632]
- Sobngwi E, Choukem SP, Agbalika F, et al. Ketosis-prone type 2 diabetes mellitus and human herpesvirus 8 infection in sub-saharan africans. JAMA. 2008;299(23):2770-6. [PMID:18560004]
- Gupta S, Koirala J, Khardori R, et al. Infections in diabetes mellitus and hyperglycemia. Infect Dis Clin North Am. 2007;21(3):617-38, vii. [PMID:17826615]
- Bagdade JD, Root RK, Bulger RJ. Impaired leukocyte function in patients with poorly controlled diabetes. Diabetes. 1974;23(1):9-15. [PMID:4809622]
- Cure E, Cumhur Cure M. Can dapagliflozin have a protective effect against COVID-19 infection? A hypothesis. Diabetes Metab Syndr. 2020;14(4):405-406. [PMID:32335366]
- Stratigou T, Vallianou N, Vlassopoulou B, et al. DKA cases over the last three years: has anything changed? Diabetes Metab Syndr. 2019;13(2):1639-1641. [PMID:31336534]
- Marhl M, Grubelnik V, Magdič M, et al. Diabetes and metabolic syndrome as risk factors for COVID-19. Diabetes Metab Syndr. 2020;14(4):671-677. [PMID:32438331]
- Dexcom. Press release. https://www.dexcom.com/hospitalfacts. Accessed September 29, 2020.
- EpiCentro. Portale di epidemiologia per gli operatori sanitari. https://www.epicentro.iss.it/ (accessed September 29, 2020).
Comment:
- Abbott .Press release. https://abbott.mediaroom.com/2020-04-08-Abbotts-FreeStyle-R-Libre-14-Day-S.... Accessed September 29, 2020.
- Johns Hopkins University & Medicine. Coronavirus Resource Center. https://coronavirus.jhu.edu/map.html(accessed 10/2/2020)
Comment:
- Holman N, Knighton P, Kar P, et al. Type 1 and type 2 diabetes and COVID-19 related mortality in England: a cohort study in people with diabetes. https://www.bapo.com/wp-content/uploads/2020/05/Valabhji-COVID-19-and-Diabetes-Paper-2-Full-Manuscript.pdf (accessed September 29, 2020).
Last updated: November 16, 2020
Citation
Chae, Kacey, et al. "Diabetes and COVID-19." Johns Hopkins Diabetes Guide, 2020. Johns Hopkins Guides, www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Diabetes_Guide/547212/all/Diabetes_and_COVID_19.
Chae K, Perlman J, Rastogi Kalyani R. Diabetes and COVID-19. Johns Hopkins Diabetes Guide. 2020. https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Diabetes_Guide/547212/all/Diabetes_and_COVID_19. Accessed December 1, 2023.
Chae, K., Perlman, J., & Rastogi Kalyani, R. (2020). Diabetes and COVID-19. In Johns Hopkins Diabetes Guide https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Diabetes_Guide/547212/all/Diabetes_and_COVID_19
Chae K, Perlman J, Rastogi Kalyani R. Diabetes and COVID-19 [Internet]. In: Johns Hopkins Diabetes Guide. ; 2020. [cited 2023 December 01]. Available from: https://www.hopkinsguides.com/hopkins/view/Johns_Hopkins_Diabetes_Guide/547212/all/Diabetes_and_COVID_19.
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