COVID-19 and DIABETES

I have Diabetes, should I go for COVID-19 vaccination?

Covid-19 and Diabetes – In December 2019, a novel coronavirus, SARS-CoV-2, was identified as the pathogen  causing coronavirus disease (COVID-19) in Wuhan, China (11, 51, 55). On March 11, 2020, COVID-19 was declared a pandemic  by the World Health Organization. As of March 27, 2020, there have been a total of 103,942 confirmed cases with 1689 deaths in the United States. Globally, 27,324 deaths have been reported among 595,800 confirmed cases.

On 21^st January 2021 there have been 95,612,831 confirmed cases of COVID-19, including 2,066,176 deaths, reported to WHO. As of January 2021, there have been 24.037.236 confirmed cases in the United States, 3.505.758 confirmed cases in the United Kingdom, 951.651 confirmed cases in Indonesia.

In 2019, approximately 463 million adults (20-79 years) were living with diabetes; by 2045 this will rise to 700 million. The proportion of people with type 2 diabetes is increasing in most countries 79% of adults with diabetes were living in low- and middle-income countries. 1 in 5 of the people who are above 65 years old have diabetes. 1 in 2 (232 million) people with diabetes were undiagnosed. Diabetes caused 4.2 million deaths. Diabetes caused at least USD 760 billion dollars in health expenditure in 2019 – 10% of total spending on adults. More than 1.1 million children and adolescents are living with type 1 diabetes. More than 20 million live births (1 in 6 live births) are affected by diabetes during pregnancy, 374 million people are at increased risk of developing type 2 diabetes.

Also Read Things People With Diabetes Must Know About the COVID-19 Vaccines

Diabetes is a serious threat to global health that respects neither socioeconomic status nor national boundaries. People living with diabetes are at risk of developing a number of serious and life-threatening complications, leading to an increased need for medical care, a reduced quality of life, and undue stress on families. Diabetes and its complications, if not well managed, can lead to frequent hospital admissions and premature death. Globally, diabetes is among the top 10 causes of death.

•  The pathophysiology of SARS-CoV-2 and Potential mechanisms that increase the risk of COVID-19 in Diabetes

The genetic sequence of SARS-CoV-2 showed more than 80% shared identity to SARS-CoV and 50% to the MERS-CoV, and both SARS-CoV and MERS-CoV originate in bats and infect humans and wild animals. CoV is made up of four structural proteins: spike (S), membrane (M), nucleocapsid (N), and envelope (E) proteins. The S protein mediates receptor binding on the host cell membrane through the receptor-binding domain (RBD) in the S1 domain and membrane fusion through the S2 subunit. Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV and SARSCoV-2, in contrast to MERS-CoV, which utilizes dipeptidyl peptidase 4 (DPP4) as its cellular receptor. This interaction thus determines host tropism and ultimately clearance of the virus. ACE2 is expressed in the upper respiratory system, type I and II alveolar epithelial cells in the lungs, the heart, endothelial cells, kidney tubular epithelium, enterocytes, and the pancreas. After binding to ACE2, proximal serine proteases such as TMPRSS2 are involved in S protein priming and cleavage of the spike. Proteases such as Furin subsequently release the spike fusion peptide, and the cellular virus enters through an endosomal pathway . The low pH and presence of proteases such as cathepsin-L  characteristic of the endosomal micro environment favor the delivery of SARS-CoV-2 genome into the cytosol  where further viral replication leads to the formation of mature virions and subsequent spread. Infected cells undergo apoptosis  or necrosis  and trigger inflammatory responses marked by the activation of proinflammatory cytokines or chemokines, which leads to the recruitment of inflammatory cells. CD4+ T helper (Th1) cells regulate antigen presentation and immunity against intracellular pathogens such as CoV through interferon gamma (IFN-ℽ) production. Th17 cells induce the recruitment of neutrophils and macrophages by producing interleukin-17 (IL-17), IL-21, and IL-22. SARS-CoV-2 infects circulating immune cells and increases apoptosis of lymphocytes (CD3, CD4, and CD8 T cells), leading to lymphocytopenia. Indeed, the degree of lymphocytopenia is associated with the severity of SARS CoV-2 infection. Lower T cell function relieves the inhibition on innate immune system leading to secretion of high amounts of inflammatory cytokines in what is known as a “cytokine storm”. In fact, circulating levels of cytokines/chemokines [IL-6, tumor necrosis factor-α (TNF)] and chemokines [CXC-chemokine ligand 10 (CXCL10) and CC-chemokine ligand 2 (CCL2)] involved in the cytokine storm syndrome are elevated and may play a role in SARSCoV-2-driven hyperinflammation leading to multiorgan failure.

Potential mechanisms that increase the risk of COVID-19 in diabetes. It is now well recognized that older age and the presence of diabetes, hypertension, and severe obesity (BMI =40 kg/m2 ) increase morbidity and mortality in patients with COVID-19. Considering the high prevalence of cardiovascular disease (CVD), obesity, and hypertension in patients with diabetes, it is unknown whether diabetes independently contributes to this increased risk. However, plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Potential mechanisms that may increase the susceptibility forCOVID-19 in patients with diabetes include: 1) higher affinity cellular binding and efficient virus entry, 2) decreased viral clearance, 3) diminished T cell function, 4) increased susceptibility to hyperinflammation and cytokine storm syndrome, and 5) presence of CVD. Augmented ACE2 expression in alveolar AT2 cells, muscle of the heart, kidney, and pancreas may favor increased cellular binding of SARS-CoV-2. Increased expression of ACE2 has been demonstrated in the lung, kidney, heart, and pancreas in rodent models of diabetes. Insulin  administration attenuates ACE2 expression, while hypoglycemic agents such as glucagon-like peptide-1 (GLP-1) agonists (liraglutide) and thiazolidinediones (TZDs; pioglitazone), antihypertensives such as ACE inhibitors, and statins upregulate ACE2. Until recently, whether diabetes was causally linked to ACE2 expression levels in the lung in humans was unknown.

Fig. 3. Cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The initial step in cellular entry of the virus is the binding of SARS-CoV-2 spike protein to cell surface angiotensin converting enzyme 2 (ACE2). Cellular proteases such as TMPRSS2 and furin are involved in priming of the S protein, which involves cleavage at the S1/S2 domains. This allows the fusion of the virus to the cell surface. Virions are taken up into endosomes, where SARS-CoV-2-S is cleaved and possibly activated by the pH-dependent cysteine protease cathepsin L. Once inside the cell, SARS-CoV-2 uses the endogenous cellular machinery to replicate itself. ACE catalyzes the conversion of angiotensin(Ang)ItotheoctapeptideAngII,whereasACE2 converts Ang II to Ang1–7. AngII through the activation of Ang II type 1a receptors induces vasoconstriction and proliferation,whereasAng1–7 stimulates vasodilatation and suppresses cell growth.

Fig. 4. Putative mechanisms contributing to increased susceptibility for coronavirus disease (COVID-19) in patients with diabetes mellitus (DM). Following aerosolized uptake of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), invasion of the respiratory epithelium and other target cells by SARS-CoV-2 involves binding to cell surface angiotensin converting enzyme 2 (ACE2). Increased expression of ACE2 may favor more efficient cell binding and entry into cells. Early recruitment and function of neutrophils and macrophages are impaired in DM. Delay in the initiation of adaptive immunity and dysregulation of the cytokine response in DM may lead to the initiation of cytokine storm.

            There is a paucity of data in the world (including Indonesia) regarding comorbidities and COVID-19 outcomes and mechanism that modulate viral pathogenesis. But here is our mainly concern that people with comorbidities likely have chance to get COVID-19, so its mainly our concern that people with Diabetes should get vaccinated.

•  COVID-19 vaccine prioritization for type 1 and type 2 diabetes

Several clinical reports have described greater morbidity and mortality from COVID-19 in people with diabetes, often accompanied by obesity. Most of this information is from individuals with type 2 diabetes, with less known about the risk in type 1 diabetes, a phenotypically distinct disorder. Experts have cautioned against extrapolating from studies of type 2 diabetes to individuals with type 1 diabetes. In the USA, the Centers for Disease Control and Prevention (CDC) currently categorize type 1 and type 2 diabetes differently in terms of risk for severe illness from COVID-19, with people with type 2 diabetes considered “at increased risk for severe illness” and those with type 1 diabetes categorized as “might be at increased risk”. Importantly, several recent studies have shown that both people with type 2 diabetes and those with type 1 diabetes have an increased vulnerability to serious illness from SARS-CoV-2 compared with people without diabetes. In relative terms, patients with type 1 diabetes and those with type 2 diabetes had similar adjusted odds ratios (ORs) for hospitalization (3·90 for type 1 diabetes vs 3·36 for type 2 diabetes), severity of illness (3·35 vs 3·42), and in-hospital mortality (3·51 vs 2·02). In a population-based study in Scotland, the risk of fatal or critical care unit treated COVID-19 was increased for both diabetes types (OR 2·4 with type 1 diabetes vs 1·4 with type 2 diabetes).

Abbreviation: COVID-19 = coronavirus disease 2019.

* Data sources for each group: health care personnel (American Community Survey, 2019; ); long-term care facility residents (Minimum Data Set. Centers for Medicare & Medicaid Services; ); frontline and other essential workers (American Community Survey, 2019; ); age-specific groups (U.S. Census; ); high-risk medical conditions (Behavioral Risk Factors Surveillance System, 2018; ).

† Excludes persons who were recommended to receive vaccine in an earlier phase (e.g., persons aged 65–74 years who are living in long-term care facilities or who are health care personnel, who would have been included in Phase 1a) and accounting for overlap between groups within the same phase (e.g., essential workers with high risk medical conditions).

§ Estimates for frontline and other essential workers are approximate and derived from prepandemic survey data; relative proportions will vary by state.

¶ As of December 18, only the Pfizer-BioNTech COVID-19 vaccine is authorized for use in persons aged 16–17 years.

            Based on ongoing review of the literature, CDC has identified medical conditions or risk behavior that are associated with increased risk for severe COVID-19. The risk for COVID-19 associated hospitalization increases with the number of high-risk medical conditions, from 2,5 times the risk for hospitalization for person with one condition to 5 times the risk for those with three or more conditions.

            As we can see from the table above that Person aged 65-74years and Person aged 16-64years with high-risk medical conditions are included in Phase 1c to receive COVID-19 vaccine. So we conclude that person with diabetes are included in Phase 1c.

Indonesian Society of Internal Medicine(PAPDI) made the recommendations regarding COVID-19 vaccination (Sinovac) in patients with concomitant disease/comorbidities. People with diabetes are included to get vaccination which they described it all patient with controlled type 2 diabetes and HbA1C below 58 mmol/mol or 7,5%, vaccine can be given.

REFERENCES

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