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Probiotics in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects.
Kurian, SJ, Unnikrishnan, MK, Miraj, SS, Bagchi, D, Banerjee, M, Reddy, BS, Rodrigues, GS, Manu, MK, Saravu, K, Mukhopadhyay, C, et al
Archives of medical research. 2021;52(6):582-594
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The novel coronavirus pandemic of 2019 (COVID-19), an emerging infectious disease, is caused by multiple strains of Severe Acute Respiratory Syndrome Coronavirus-2. The main aim of this study was to outline the potential role of probiotics in fighting the COVID-19. This study focuses on recent evidence on the association between microbiota, probiotics, and COVID-19, the role of probiotics as an immune-modulator and antiviral agent. Findings support probiotics’ role in regulating the immune system, suggesting a definitive role for probiotics in viral infections. Thus, probiotics supplementation could reduce the severity of COVID-19 morbidity and mortality. Authors conclude that supplementation of probiotics in high risk and severely ill patients, and frontline health workers, may help to limit the infection and flatten the COVID-19 curve. However, further studies should be conducted for more conclusive evidence.
Abstract
Saving lives and flattening the curve are the foremost priorities during the ongoing pandemic spread of SARS-CoV-2. Developing cutting-edge technology and collating available evidence would support frontline health teams. Nutritional adequacy improves general health and immunity to prevent and assuage infections. This review aims to outline the potential role of probiotics in fighting the COVID-19 by covering recent evidence on the association between microbiota, probiotics, and COVID-19, the role of probiotics as an immune-modulator and antiviral agent. The high basic reproduction number (R0) of SARS-CoV-2, absence of conclusive remedies, and the pleiotropic effect of probiotics in fighting influenza and other coronaviruses together favour probiotics supplements. However, further support from preclinical and clinical studies and reviews outlining the role of probiotics in COVID-19 are critical. Results are awaited from many ongoing clinical trials investigating the benefits of probiotics in COVID-19.
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Cinnamon and its possible impact on COVID-19: The viewpoint of traditional and conventional medicine.
Yakhchali, M, Taghipour, Z, Mirabzadeh Ardakani, M, Alizadeh Vaghasloo, M, Vazirian, M, Sadrai, S
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021;143:112221
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COVID-19 is a disease that is associated with extremely high inflammation within the body, because of the body’s immune system trying to fight the infection. Conventional treatments focus on decreasing the immune response and controlling the disease; however, no treatment strategy has been shown to be effective. Traditional Persian Medicine (TPM) focuses on a holistic approach to the prevention and treatment of disease. Cinnamon has been thought as a TPM, which may be effective in the treatment of COVID-19 and this systematic review aimed to analyse the data behind these claims. Cinnamon was found to have anti-viral, anti-inflammatory, and antioxidant effects. Anti-viral effects were shown in cells against several viruses including the virus responsible for COVID-19. Cinnamon was shown to have extensive anti-inflammatory and antioxidant effects in various cells, however no specific research was found on COVID-19. It was concluded that as cinnamon has the potential to target different aspects of COVID-19 it could be used as an effective therapy. This study could be used by healthcare professionals to understand that cinnamon may have therapeutic effects in COVID-19, however clinical trials need to be performed before specific recommendations are made.
Abstract
The COVID-19 global epidemic caused by coronavirus has affected the health and other aspects of life for more than one year. Despite the current pharmacotherapies, there is still no specific treatment, and studies are in progress to find a proper therapy with high efficacy and low side effects. In this way, Traditional Persian Medicine (TPM), due to its holistic view, can provide recommendations for the prevention and treatment of new diseases such as COVID-19. The muco-obstruction of the airway, which occurs in SARS-CoV-2, has similar features in TPM textbooks that can lead us to new treatment approaches. Based on TPM and pharmacological studies, Cinnamomum verum (Darchini)'s potential effective functions can contribute to SARS-CoV-2 infection treatment and has been known to be effective in corona disease in Public beliefs. From the viewpoint of TPM theories, Cinnamon can be effective in SARS-CoV-2 improvement and treatment through its anti-obstructive, diuretic, tonic and antidote effects. In addition, there is pharmacological evidence on anti-viral, anti-inflammatory, antioxidant, organ-o-protective and anti-depression effects of Cinnamon that are in line with the therapeutic functions mentioned in TPM.Overall, Cinnamon and its ingredients can be recommended for SARS-CoV2 management due to multi-targeting therapies. This review provides basic information for future studies on this drug's effectiveness in preventing and treating COVID-19 and similar diseases.
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Protective Effect of Epigallocatechin-3-Gallate (EGCG) in Diseases with Uncontrolled Immune Activation: Could Such a Scenario Be Helpful to Counteract COVID-19?
Menegazzi, M, Campagnari, R, Bertoldi, M, Crupi, R, Di Paola, R, Cuzzocrea, S
International journal of molecular sciences. 2020;21(14)
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Some individuals who have contracted Covid-19 experience an extreme inflammatory reaction known as cytokine storm syndrome. This review paper of 129 studies aimed to review the use of epigallocatechin 3-gallate (EGCG), a green tea derived chemical reported to reduce inflammation with a view to be used in individuals with Covid-19. Conventional therapies used in diseases known to induce extreme inflammation were discussed focusing on steroid based drugs. However, results in Covid-19 patients have shown increased mortality and decreased viral clearance. Several other drugs are being trialled in Covid-19. The use of EGCG and green tea extract (GTE) in several diseases such as rheumatoid arthritis, Sjogrens syndrome, multiple sclerosis, human immunodeficiency virus, dengue virus and inflammatory bowel disease was discussed and beneficial effects such as being anti-inflammatory, antiviral, antimicrobial, and having anti-cancer properties were outlined. The possible mechanisms involved were extensively discussed. The use of EGCG and GTE in a clinical setting was reported to have favourable outcomes and be a potentially safe natural supplement. It was concluded that given the safety and many benefits shown by EGCG in viruses and inflammatory diseases, EGCG/GTE may be effective in Covid-19, and clinical trials are needed. This study could be used by healthcare professionals to justify the recommendation of EGCG/GTE in individuals with Covid-19 and many other inflammatory and viral diseases.
Abstract
Some coronavirus disease 2019 (COVID-19) patients develop acute pneumonia which can result in a cytokine storm syndrome in response to Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection. The most effective anti-inflammatory drugs employed so far in severe COVID-19 belong to the cytokine-directed biological agents, widely used in the management of many autoimmune diseases. In this paper we analyze the efficacy of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea leaves and a well-known antioxidant, in counteracting autoimmune diseases, which are dominated by a massive cytokines production. Indeed, many studies registered that EGCG inhibits signal transducer and activator of transcription (STAT)1/3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factors, whose activities are crucial in a multiplicity of downstream pro-inflammatory signaling pathways. Importantly, the safety of EGCG/green tea extract supplementation is well documented in many clinical trials, as discussed in this review. Since EGCG can restore the natural immunological homeostasis in many different autoimmune diseases, we propose here a supplementation therapy with EGCG in COVID-19 patients. Besides some antiviral and anti-sepsis actions, the major EGCG benefits lie in its anti-fibrotic effect and in the ability to simultaneously downregulate expression and signaling of many inflammatory mediators. In conclusion, EGCG can be considered a potential safe natural supplement to counteract hyper-inflammation growing in COVID-19.
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Can Natural Polyphenols Help in Reducing Cytokine Storm in COVID-19 Patients?
Giovinazzo, G, Gerardi, C, Uberti-Foppa, C, Lopalco, L
Molecules (Basel, Switzerland). 2020;25(24)
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During covid-19 infection the body experiences a hyper-immune reaction resulting in an extreme inflammatory response known as cytokine release syndrome (CRS), which correlates with poor prognosis and severe illness. There are no effective treatments for CRS, although there are ongoing trials. The use of natural plant chemicals known as polyphenols have been shown in previous trials to improve inflammation This review of over 90 studies aimed to summarise the use of polyphenols to fight severe covid-19 infection. The paper began by reviewing current drug therapies, which have been shown in studies to be of benefit to inflammation, with tocilizumab being heavily reviewed. The authors then reviewed several plant polyphenols and reviewed how they can modulate inflammation through inhibiting inflammatory molecules and viral activity. It was concluded that human studies are lacking data and so phytochemicals may be promising for the treatment of covid-19. This study could be used by health care professionals to understand the importance of recommending a whole food, plant rich diet with many different coloured foods for individuals who are suffering from covid-19.
Abstract
SARS-CoV-2 first emerged in China during late 2019 and rapidly spread all over the world. Alterations in the inflammatory cytokines pathway represent a strong signature during SARS-COV-2 infection and correlate with poor prognosis and severity of the illness. The hyper-activation of the immune system results in an acute severe systemic inflammatory response named cytokine release syndrome (CRS). No effective prophylactic or post-exposure treatments are available, although some anti-inflammatory compounds are currently in clinical trials. Studies of plant extracts and natural compounds show that polyphenols can play a beneficial role in the prevention and the progress of chronic diseases related to inflammation. The aim of this manuscript is to review the published background on the possible effectiveness of polyphenols to fight SARS-COV-2 infection, contributing to the reduction of inflammation. Here, some of the anti-inflammatory therapies are discussed and although great progress has been made though this year, there is no proven cytokine blocking agents for COVID currently used in clinical practice. In this regard, bioactive phytochemicals such as polyphenols may become promising tools to be used as adjuvants in the treatment of SARS-CoV-2 infection. Such nutrients, with anti-inflammatory and antioxidant properties, associated to classical anti-inflammatory drugs, could help in reducing the inflammation in patients with COVID-19.
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Liver injury is associated with severe coronavirus disease 2019 (COVID-19) infection: A systematic review and meta-analysis of retrospective studies.
Parohan, M, Yaghoubi, S, Seraji, A
Hepatology research : the official journal of the Japan Society of Hepatology. 2020;50(8):924-935
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Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and Coronavirus disease 2019 (COVID-19) can cause intestinal, respiratory, neuronal and hepatic diseases, and may lead to respiratory distress syndrome, organ failure, and even death in severe cases. The aim of this study was to assess the association between serum levels of Aspartate aminotransferase [enzyme], Alanine aminotransferase [enzyme], total Bilirubin [yellowish blood pigment] and Albumin [protein] with severity of COVID-19 infection. This study is a systemic review and meta-analysis of 20 retrospective studies conducted in China. The sample size of studies ranged from 21 to 651 patients (mean age, 53.3 years). Results indicate that high serum levels of aspartate aminotransferase, alanine aminotransferase, total bilirubin and lower serum levels of albumin are associated with a significant increase in the severity of COVID-19 infection. Authors conclude that attention should be paid to monitor the occurrence of liver dysfunction in patients with COVID-19 infection.
Abstract
The coronavirus disease 2019 (COVID-19) outbreak is a major threat to human beings. Lung injury has been reported as the major outcome of COVID-19 infection. However, liver damage has also been considered to occur in severe cases. The current meta-analysis of retrospective studies was carried out to summarize available findings on the association between liver injury and severity of COVID-19 infection. Online databases including PubMed, Scopus, Web of Science, and Cochrane Library were searched to detect relevant publications up to 1 April 2020, using relevant keywords. To pool data, a fixed- or random-effects model was used depending on the heterogeneity between studies. Furthermore, publication bias test and sensitivity analysis were also applied. In total, 20 retrospective studies with 3428 COVID-19 infected patients (severe cases, n = 1455; mild cases, n = 1973), were included in this meta-analysis. Higher serum levels of aspartate aminotransferase (weighted mean difference, 8.84 U/L; 95% confidence interval [CI] 5.97 to 11.71; P < 0.001), alanine aminotransferase (weighted mean difference, 7.35 U/L; 95% CI, 4.77 to 9.93; P < 0.001), total bilirubin (weighted mean difference, 2.30 mmol/L; 95% CI, 1.24 to 3.36; P < 0.001), and lower serum levels of albumin (weighted mean difference, -4.24 g/L; 95% CI, -6.20 to -2.28; P < 0.001) were associated with a significant increase in the severity of COVID-19 infection. The incidence of liver injury, as assessed by serum analysis (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and albumin levels), seems to be higher in patients with severe COVID-19 infection.
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The Functional Medicine Approach to COVID-19: Nutrition and Lifestyle Practices for Strengthening Host Defense.
Minich, DM, Hanaway, PJ
Integrative medicine (Encinitas, Calif.). 2020;19(Suppl 1):54-62
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Lifestyle interventions can be an effective means to help patients regain their locus of control during times of uncertainty like those experienced in a pandemic. The study is a review about emerging research focusing on nutrition and lifestyle practices for strengthening host defense. Research indicates that there are three mechanisms that may be involved in the ability of food-derived compounds to reduce viral infection and severity: a. balancing inflammatory pathways, b. reducing oxidative stress and increasing antioxidant levels, and c. harmonizing the gut microbiome. Clinical recommendations focus mainly on nutrition, stress reduction/management, sleep quality and quantity, physical activity programme and social factors/connections. Authors conclude by emphasising that the findings of this study are only intended to identify lifestyle practices that may boost the immune system as they have not been proven effective against COVID-19.
Abstract
The developing symptoms of COVID-19, as well as the progression of illness and fatality, are a clearly a function of the overall health status of the individual. Complex, chronic diseases such as obesity, hypertension, and diabetes are directly correlated with risk of disease severity and mortality. We explore lifestyle interventions that have specifically been demonstrated to strengthen host defense, reduce the probability and mitigate the severity of viral infection. Lifestyle interventions, from a Functional Medicine perspective, include nutrition, sleep, exercise, stress reduction, and connection. These factors, when in balance, provide a foundation for optimal health and immune function.
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Nutrition, the digestive system and immunity in COVID-19 infection.
Bold, J, Harris, M, Fellows, L, Chouchane, M
Gastroenterology and hepatology from bed to bench. 2020;13(4):331-340
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Covid-19 needs both prevention and recovery strategies to reduce complications. This review study aimed to discuss the associations between nutrition, obesity, and the impact these have on stomach symptoms associated with Covid-19. Obesity has been identified as a risk factor for Covid-19 and this could be due to several factors such as impaired immune function, increased inflammation, increased susceptibility to infection and the high number of cells on fat tissue, which express the receptor known to allow Covid-19 into cells. The involvement of the gut microbiota of obese individuals was extensively reviewed and gut dysbiosis has been associated with many diseases, thus improving gut microbiota may go some way to improving Covid-19 outcomes. Nutritional interventions to reduce obesity need to be part of a multi-pronged strategy and the possible introduction of vitamin D supplements and probiotics. The paper did not draw any conclusions; however this paper could be used by healthcare professionals to understand the role of obesity in increasing the risk of Covid-19 infection, complications that may arise upon and after infection and nutritional strategies as part of a management plan.
Abstract
The current review aimed to synthesize the literature on the complex relationship between food consumption and nutritional status as well as the digestive system in order to examine the relationship between immunity and potential responses to COVID-19 infection. The goal is to help inform the many healthcare professionals working with COVID-19 patients. A literature search was performed on PubMed, Scopus, and EMBASE databases. Hand searches were also undertaken using Google and reference lists to identify recent evidence. Studies were critically appraised, and the findings were analyzed by narrative synthesis. Nutritional status can impact immunity in several ways, including affecting susceptibility to infection, severity of disease, and recovery time, and is therefore a significant consideration in the management of COVID-19. COVID-19 can also impact digestive function, which can further impact nutritional status. The role of Vitamin D deficiency in vulnerability to severe respiratory infections, including COVID-19, has been recognized, and it may have a role in treatment where deficiency is indicated. Healthcare professionals should be aware that obesity may be accompanied by micronutrient malnutrition including vitamin D deficiency and alterations in the microbiome and inflammatory responses, which can further impact immunity and disease severity. Multidisciplinary team-work is recommended in the management of patients with COVID-19, and approaches should include a consideration of nutritional status (both macronutrients and micronutrients), body weight, and gastrointestinal signs and symptom.
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The Functional Medicine Approach to COVID-19: Virus-Specific Nutraceutical and Botanical Agents.
Evans, JM, Luby, R, Lukaczer, D, Rountree, R, Stone, PM, Guilliams, TG, Yanuck, S, Messier, H, Ramsdell, K, Hanaway, PJ
Integrative medicine (Encinitas, Calif.). 2020;19(Suppl 1):34-42
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The practice of Functional Medicine, with respect to interventions, emphasizes the primacy of safety, validity, and effectiveness. Data for the effectiveness of interventions targeting the viral mechanisms of Covid-19 are nascent and rapidly emerging. The aim of this review was to assess the scientific plausibility of promising prevention approaches and therapeutic (nutraceutical and botanical) interventions and suggest clinical recommendations. A coronavirus such as SARS-CoV-2 can be deadly because of its ability to stimulate a part of the innate immune response called the inflammasome. This can cause uncontrolled release of pro-inflammatory cytokines, leading to cytokine storm and severe, sometimes irreversible, damage to respiratory epithelium. In order to prevent the activation of a particular inflammasome the following compounds are being recommended; quercetin, curcumin, epigallocatechin gallate, n-acetylcysteine, resveratrol, vitamin D, vitamin A, vitamin C, elderberry, melatonin, zinc and palmitoylethanolamide. Authors emphasise that the recommendations are meant to identify botanical and nutraceutical agents that may boost the immune system and not as a means of treatment.
Abstract
As the novel infection with SARS-CoV-2 emerges, objective assessment of the scientific plausibility of nutraceutical and botanical interventions for prevention and treatment is important. We evaluate twelve such interventions with mechanisms of action that modulate the immune system, impair viral replication, and/or have been demonstrated to reduce severity of illness. These are examples of interventions that, mechanistically, can help protect patients in the presence of the prevalent and infectious SARS-CoV-2 virus. While there are limited studies to validate these agents to specifically prevent COVID-19, they have been chosen based upon their level of evidence for effectiveness and safety profiles, in the context of other viral infections. These agents are to be used in a patient-specific manner in concert with lifestyle interventions known to strengthen immune response (see related article in this issue of IMCJ).
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COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation.
Zabetakis, I, Lordan, R, Norton, C, Tsoupras, A
Nutrients. 2020;12(5)
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By May 2020, the novel coronoavirus COVID-19 had infected over 4 million people worldwide. Spread through droplet, it gains entry to body cells through ACE2 cell receptors, causing viral infection-related inflammation, and predominantly infects the lower respiratory tract. Those with non-communicable diseases with COVID-19 experience increased inflammation and have a higher risk of adverse outcomes and mortality. This review article gives details of the mechanisms involved in a cytokine storm (an uncontrolled inflammatory response) and current treatment options, before discussing the immune-balancing and anti-inflammatory potential of healthy nutrition in reducing susceptibility to developing infections. Nutrition Practitioners looking to support the immunity and inflammation of their clients will find the summary research presented in relation to dietary strategies, different food groups and nutrients a useful basis for further study.
Abstract
The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has engulfed the world, affecting more than 180 countries. As a result, there has been considerable economic distress globally and a significant loss of life. Sadly, the vulnerable and immunocompromised in our societies seem to be more susceptible to severe COVID-19 complications. Global public health bodies and governments have ignited strategies and issued advisories on various handwashing and hygiene guidelines, social distancing strategies, and, in the most extreme cases, some countries have adopted "stay in place" or lockdown protocols to prevent COVID-19 spread. Notably, there are several significant risk factors for severe COVID-19 infection. These include the presence of poor nutritional status and pre-existing noncommunicable diseases (NCDs) such as diabetes mellitus, chronic lung diseases, cardiovascular diseases (CVD), obesity, and various other diseases that render the patient immunocompromised. These diseases are characterized by systemic inflammation, which may be a common feature of these NCDs, affecting patient outcomes against COVID-19. In this review, we discuss some of the anti-inflammatory therapies that are currently under investigation intended to dampen the cytokine storm of severe COVID-19 infections. Furthermore, nutritional status and the role of diet and lifestyle is considered, as it is known to affect patient outcomes in other severe infections and may play a role in COVID-19 infection. This review speculates the importance of nutrition as a mitigation strategy to support immune function amid the COVID-19 pandemic, identifying food groups and key nutrients of importance that may affect the outcomes of respiratory infections.
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COVID-19 and diabetes: The why, the what and the how.
Cuschieri, S, Grech, S
Journal of diabetes and its complications. 2020;34(9):107637
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Early reports have shown that individuals with diabetes who contract Covid-19 have higher hospital admissions and mortality rates, classing them as a vulnerable group. This review paper aimed to explain why this group of people are vulnerable and what measures could be recommended. The paper outlined that individuals with diabetes have a compromised immune system due to uncontrolled blood sugar levels. In addition to this, individuals with diabetes and Covid-19 may have a higher risk of organ damage due to the effects of the body's immune response combined with the disordered biological processes associated with their pre-existing condition. Conversely, it was discussed that Covid-19 could exacerbate diabetes progression if the Covid-19 virus entered the cells of the pancreas, causing a blood sugar imbalance. As a result, the importance of optimal blood sugar control was outlined. Several medications were addressed and their benefits/disadvantages discussed. Amongst those reviewed were medications such as GLP-1 agonists, which may help with controlling blood sugar levels and may prevent Covid-19 entering the body's own cells, and metformin, which was initially developed as an anti-influenza drug. Finally the paper discussed diabetes specific precautions to avoid contracting Covid-19. Vitamin D supplementation, regular blood sugar checks, lifestyle measures such as exercise and dietary requirements and allowing individuals with diabetes to have large supplies of their medications to avoid leaving the house were discussed. It was concluded that during the Covid-19 pandemic, individuals with diabetes require particular care in order to avoid additional burden on healthcare systems. For those individuals with diabetes who haven’t contracted Covid-19, this paper could be used to recommend any extra precautions to take to avoid contracting this virus.
Abstract
BACKGROUND The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS A search using keywords "COVID-19" and "Diabetes" was performed using different sources, including PubMed and World Health Organization. RESULTS COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute β-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.