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Recent Advances in Psoriasis Research; the Clue to Mysterious Relation to Gut Microbiome.
Komine, M
International journal of molecular sciences. 2020;21(7)
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Psoriasis is a chronic inflammatory disease where the skin forms bumpy red patches covered with white scales. There is no cure, but medications have focused on supressing the immune response. There is a link between the gut microbiome and psoriasis but it is poorly understood. This review includes the current understanding of how psoriasis develops and discusses the recent findings to support further research in this area. The composition of the gut microbiome affects inflammation in the whole body. This inflammation is associated with cardiovascular disease, diabetes mellitus and other inflammatory disorders. Recent studies have linked cardiovascular disease, insulin resistance, and metabolic syndrome to an imbalance in the gut microbiome. Psoriasis is often found alongside these conditions with similar abnormalities in gut bacteria. An imbalance in gut microbiome could cause certain people to develop psoriasis. The role of the gut microbiome needs to be further clarified but mounting evidence for this gut/skin link means that other therapeutic options may be available for treatment in the future.
Abstract
Psoriasis is a chronic inflammatory cutaneous disease, characterized by activated plasmacytoid dendritic cells, myeloid dendritic cells, Th17 cells, and hyperproliferating keratinocytes. Recent studies revealed skin-resident cells have pivotal roles in developing psoriatic skin lesions. The balance in effector T cells and regulatory T cells is disturbed, leading Foxp3-positive regulatory T cells to produce proinflammatory IL-17. Not only acquired but also innate immunity is important in psoriasis pathogenesis, especially in triggering the disease. Group 3 innate lymphoid cell are considered one of IL-17-producing cells in psoriasis. Short chain fatty acids produced by gut microbiota stabilize expression of Foxp3 in regulatory T cells, thereby stabilizing their function. The composition of gut microbiota influences the systemic inflammatory status, and associations been shown with diabetes mellitus, cardiovascular diseases, psychomotor diseases, and other systemic inflammatory disorders. Psoriasis has been shown to frequently comorbid with diabetes mellitus, cardiovascular diseases, psychomotor disease and obesity, and recent report suggested the similar abnormality in gut microbiota as the above comorbid diseases. However, the precise mechanism and relation between psoriasis pathogenesis and gut microbiota needs further investigation. This review introduces the recent advances in psoriasis research and tries to provide clues to solve the mysterious relation of psoriasis and gut microbiota.
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The Role of Lung and Gut Microbiota in the Pathology of Asthma.
Barcik, W, Boutin, RCT, Sokolowska, M, Finlay, BB
Immunity. 2020;52(2):241-255
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Over 300 million people suffer with asthma worldwide and it has emerged that microbiome analysis of the lung and gut bacteria, fungi, viruses, and archaea may help with disease management. This microbiome plays an important role in immune response. Disturbances to these microbes, known as dysbiosis, may influence onset of disease and the body’s ability to respond naturally, and/or to pharmaceutical treatments. Asthma is not a singular disease and there are great variations in symptom severity and underlying immune mechanisms. Patients are typically classified as type 2 or non-type 2. Type 2 patients tend to be allergic to common air-born allergens which can trigger an attack. Treatment usually consists of glucocorticosteroids or novel biologicals. Non type-2 asthma is associated with obesity-related asthma and typically responds poorly to steroid treatment. For a long time, researchers believed the human lungs to be sterile, so they were initially not included in the 2007 Human Microbiome Project. It has since been shown that, like the gut, the lungs and respiratory tract also host various microbes, and this healthy-airway microbiota influence innate and adaptive immune processes. The Gut-Lung axis also confers additional microbial benefits from the intestines. In asthma patients, there is often an over-dominance of pathogenic bacteria. Fungal dysbiosis is associated with high-risk asthma phenotypes in childhood. Viral infections have been shown as a primary cause of asthmatic episodes. Future diagnosis and treatment of patients with asthma should be assisted by analysis of the composition and metabolic activity of an individual’s microbiome.
Abstract
Asthma is a common chronic respiratory disease affecting more than 300 million people worldwide. Clinical features of asthma and its immunological and molecular etiology vary significantly among patients. An understanding of the complexities of asthma has evolved to the point where precision medicine approaches, including microbiome analysis, are being increasingly recognized as an important part of disease management. Lung and gut microbiota play several important roles in the development, regulation, and maintenance of healthy immune responses. Dysbiosis and subsequent dysregulation of microbiota-related immunological processes affect the onset of the disease, its clinical characteristics, and responses to treatment. Bacteria and viruses are the most extensively studied microorganisms relating to asthma pathogenesis, but other microbes, including fungi and even archaea, can potently influence airway inflammation. This review focuses on recently discovered connections between lung and gut microbiota, including bacteria, fungi, viruses, and archaea, and their influence on asthma.
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Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults.
Ludvigsson, JF
Acta paediatrica (Oslo, Norway : 1992). 2020;109(6):1088-1095
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Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was also previously known as 2019-nCoV. This study is a systematic literature review which summarises the findings on the current knowledge of COVID-19 in children. The review includes 45 scientific papers and letters. Results showed that children have so far accounted for 1%-5% of diagnosed cases. Children often are asymptomatic, have milder disease than adults, and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent. Authors conclude that the disease course in paediatric COVID-19 was milder than in adults, children had a better prognosis and deaths were extremely rare.
Abstract
AIM: The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. METHODS A systematic literature review was carried out to identify papers on COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. RESULTS The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%-5% of diagnosed COVID-19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID-19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. CONCLUSIONS The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.
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COVID-19 infection: the perspectives on immune responses.
Shi, Y, Wang, Y, Shao, C, Huang, J, Gan, J, Huang, X, Bucci, E, Piacentini, M, Ippolito, G, Melino, G
Cell death and differentiation. 2020;27(5):1451-1454
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The SARS-CoV-2 infection triggers an immune response which varies greatly from one person to another. It can be roughly divided into three stages: stage I, an asymptomatic incubation period with or without detectable virus; stage II, non-severe symptomatic period with the presence of virus; stage III, severe respiratory symptomatic stage with high viral load. Currently around 15% of people infected end up in severe stage III. There appears to be a two-phase immune response; an early protective phase and a second inflammation-driven damaging phase. In phase one the adaptive immune system responds to the virus. Being in good general health is important in this phase to limiting the progression of the disease to a more severe stage. In phase two the innate immune system response to tissue damage caused by the virus could lead to widespread inflammation of the lungs and acute respiratory distress syndrome or respiratory failure. Therapeutically this raises the question of whether the immune response should be boosted in phase one and suppressed in phase two. There also appears to be an element of viral relapse in some patients discharged from hospital indicating that a virus-eliminating immune response may be difficult to achieve naturally. These same patients may also not respond to vaccines. Overall, it is still unclear why some people develop severe disease, whilst others do not. Overall immunity alone does not explain the differences in disease presentation.
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The Influence of Small Intestinal Bacterial Overgrowth in Digestive and Extra-Intestinal Disorders.
Losurdo, G, Salvatore D'Abramo, F, Indellicati, G, Lillo, C, Ierardi, E, Di Leo, A
International journal of molecular sciences. 2020;21(10)
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The importance of the gut microbiome in health and disease is a rapidly growing area of research. Small intestinal bacterial overgrowth (SIBO) is a condition in which bacteria that typically exists only in the colon becomes concentrated in the small intestine. SIBO has wide-ranging clinical implications and the aim of this study was to review the current research to assess existing links between SIBO and various diseases. Examining the current literature, the authors found SIBO may be involved in several diseases. SIBO was found to be strongly associated with irritable bowel syndrome (IBS). While the link between SIBO and celiac disease has been studied extensively, findings remain inconsistent. Additionally, SIBO was found to be a potential underlying factor in hepatic encephalopathy. Based on these findings, the authors conclude the scientific hypotheses and the clinical findings are not consistent. While it is widely accepted that alterations in the gut microbiota can influence disease, there is not enough clinical evidence to draw conclusions. The authors conclude the evidence is promising but future research is needed.
Abstract
Small intestinal bacterial overgrowth (SIBO) is a condition hallmarked by an increase in the concentration of colonic-type bacteria in the small bowel. Watery diarrhea, bloating, abdominal pain and distension are the most common clinical manifestations. Additionally, malnutrition and vitamin (B12, D, A, and E) as well as minerals (iron and calcium) deficiency may be present. SIBO may mask or worsen the history of some diseases (celiac disease, irritable bowel disease), may be more common in some extra-intestinal disorders (scleroderma, obesity), or could even represent a pathogenetic link with some diseases, in which a perturbation of intestinal microbiota may be involved. On these bases, we performed a review to explore the multiple links between SIBO and digestive and extra-intestinal diseases.
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Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study.
Wang, S, Ma, P, Zhang, S, Song, S, Wang, Z, Ma, Y, Xu, J, Wu, F, Duan, L, Yin, Z, et al
Diabetologia. 2020;63(10):2102-2111
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Hyperglycaemia was a risk factor for mortality from severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and is an independent risk factor for lower respiratory tract infection and poor prognosis. The aim of this retrospective study of 605 patients without previously diagnosed diabetes was to examine the association between fasting blood glucose (FBG) on admission and the 28-day in hospital mortality of COVID-19 patients. Patients with a FBG level of 7.0mmol/l or over had more than double the risk of dying than those with a level of 6.0mmol/l or less. Other risk factors for mortality included age, being male, and severity of pneumonia at admission. Compared with patients whose FBG was 6.0mmol/l or lower at admission, patients with FBG of 7.0 mmol/l and above had a 3.99 times higher risk of in-hospital complications, whilst those with FBG of 6.1–6.9 mmol/l had a 2.61 times higher risk of complications. The authors conclude that glycaemic testing and control are important to all COVID-19 patients even where they have no pre-existing diabetes.
Abstract
AIMS/HYPOTHESIS Hyperglycaemia is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, acute myocardial infarction, trauma and surgery, among other conditions. In this study, we examined the relationship between fasting blood glucose (FBG) and 28-day mortality in coronavirus disease 2019 (COVID-19) patients not previously diagnosed as having diabetes. METHODS We conducted a retrospective study involving all consecutive COVID-19 patients with a definitive 28-day outcome and FBG measurement at admission from 24 January 2020 to 10 February 2020 in two hospitals based in Wuhan, China. Demographic and clinical data, 28-day outcomes, in-hospital complications and CRB-65 scores of COVID-19 patients in the two hospitals were analysed. CRB-65 is an effective measure for assessing the severity of pneumonia and is based on four indicators, i.e. confusion, respiratory rate (>30/min), systolic blood pressure (≤90 mmHg) or diastolic blood pressure (≤60 mmHg), and age (≥65 years). RESULTS Six hundred and five COVID-19 patients were enrolled, including 114 who died in hospital. Multivariable Cox regression analysis showed that age (HR 1.02 [95% CI 1.00, 1.04]), male sex (HR 1.75 [95% CI 1.17, 2.60]), CRB-65 score 1-2 (HR 2.68 [95% CI 1.56, 4.59]), CRB-65 score 3-4 (HR 5.25 [95% CI 2.05, 13.43]) and FBG ≥7.0 mmol/l (HR 2.30 [95% CI 1.49, 3.55]) were independent predictors for 28-day mortality. The OR for 28-day in-hospital complications in those with FBG ≥7.0 mmol/l and 6.1-6.9 mmol/l vs <6.1 mmol/l was 3.99 (95% CI 2.71, 5.88) or 2.61 (95% CI 1.64, 4.41), respectively. CONCLUSIONS/INTERPRETATION FBG ≥7.0 mmol/l at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes. Glycaemic testing and control are important to all COVID-19 patients even where they have no pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders. Graphical abstract.
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Unusual Early Recovery of a Critical COVID-19 Patient After Administration of Intravenous Vitamin C.
Waqas Khan, HM, Parikh, N, Megala, SM, Predeteanu, GS
The American journal of case reports. 2020;21:e925521
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Coronavirus disease (Covid-19) continues to spread globally and to date there are no proven treatments. Current treatment focuses on the management of the associated acute respiratory distress syndrome (ARDS). There are many studies demonstrating that in severe sepsis and ARDS; Vitamin C reduces systemic inflammation, prevents lung damage, reduces the duration of mechanical ventilation (MV) and the length of intensive care unit (ICU) stay in patients. This is a case report where a critically ill patient received high-dose Vitamin C intravenous (IV) infusions and recovered. A 74 year-old woman with Covid-19, developed ARDS and septic shock. Usual medications were given. She needed MV and deteriorated rapidly. On Day 7 she was administered Vitamin C (11g per 24 hours as a continuous IV infusion). Her clinical condition improved slowly after this. In this case, high dose IV Vitamin C was associated with fewer days on mechanical intervention, a shorter ICU stay and earlier recovery. These results show the importance of further investigation of IV Vitamin C to assess its efficacy in critically ill Covid-19 patients requiring mechanical ventilation and ICU care.
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) continues to spread, with confirmed cases now in more than 200 countries. Thus far there are no proven therapeutic options to treat COVID-19. We report a case of COVID-19 with acute respiratory distress syndrome who was treated with high-dose vitamin C infusion and was the first case to have early recovery from the disease at our institute. CASE REPORT A 74-year-old woman with no recent sick contacts or travel history presented with fever, cough, and shortness of breath. Her vital signs were normal except for oxygen saturation of 87% and bilateral rhonchi on lung auscultation. Chest radiography revealed air space opacity in the right upper lobe, suspicious for pneumonia. A nasopharyngeal swab for severe acute respiratory syndrome coronavirus-2 came back positive while the patient was in the airborne-isolation unit. Laboratory data showed lymphopenia and elevated lactate dehydrogenase, ferritin, and interleukin-6. The patient was initially started on oral hydroxychloroquine and azithromycin. On day 6, she developed ARDS and septic shock, for which mechanical ventilation and pressor support were started, along with infusion of high-dose intravenous vitamin C. The patient improved clinically and was able to be taken off mechanical ventilation within 5 days. CONCLUSIONS This report highlights the potential benefits of high-dose intravenous vitamin C in critically ill COVID-19 patients in terms of rapid recovery and shortened length of mechanical ventilation and ICU stay. Further studies will elaborate on the efficacy of intravenous vitamin C in critically ill COVID-19.
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Possible long-term endocrine-metabolic complications in COVID-19: lesson from the SARS model.
Mongioì, LM, Barbagallo, F, Condorelli, RA, Cannarella, R, Aversa, A, La Vignera, S, Calogero, AE
Endocrine. 2020;68(3):467-470
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Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Little is known about how it affects the endocrine system and it is likely that some patients who have recovered may suffer long-term consequences. The severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the SARS outbreak in 2003 has many similarities. This editorial looks at the possible effects on the endocrine system of SARS-CoV-2 by looking at the long-term effects seen in SARS. In the case of SARS-CoV, it was thought that the virus could directly damage pancreatic cells leading to type 2 diabetes. It is hypothesized that Covid-19 patients could develop this condition by the same mechanism. Although no study on SARS reported the link between obesity and higher mortality rate, there is evidence that obese Covid-19 patients have worse clinical outcomes. There is no data yet for Covid-19, but adrenal insufficiency and impaired thyroid function were shown in some cases of SARS. To identify and treat any possible long-term effects of Covid-19, endocrinologists should monitor hormone levels and metabolic functions.
Abstract
The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is centralizing the interest of the scientific world. In the next months, long-term consequences on the endocrine system may arise following COVID-19. In this article, we hypothesized the effects of SARS-CoV-2 taking into account what learned from the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused SARS in 2003.
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Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.
Leung, TYM, Chan, AYL, Chan, EW, Chan, VKY, Chui, CSL, Cowling, BJ, Gao, L, Ge, MQ, Hung, IFN, Ip, MSM, et al
Emerging microbes & infections. 2020;9(1):2190-2199
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The Coronavirus pandemic (Covid-19) has infected millions of people worldwide and there is evidence that it affects many systems in the human body. This rapid review summarises the current evidence on short-term negative health outcomes of Covid-19. It also assesses the risk of potential long-term negative effects by looking at data from the other coronaviruses; Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). The burden for caring for Covid-19 survivors is likely to be huge and so policy makers need suitable data to put the appropriate care strategies in place. The review is divided into sections as per body system affected: Immune, respiratory, cardiovascular, gastrointestinal, hepatic and renal, neurological, dermatological, mental health, pregnancy and prenatal exposure. The evidence (short-term and long-term) is then reviewed by experts in those fields. Further large-scale studies are needed to monitor the adverse effects and to measure the long-term health consequences.
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.
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Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study.
Cariou, B, Hadjadj, S, Wargny, M, Pichelin, M, Al-Salameh, A, Allix, I, Amadou, C, Arnault, G, Baudoux, F, Bauduceau, B, et al
Diabetologia. 2020;63(8):1500-1515
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People with diabetes have an increased risk for infections, especially influenza and pneumonia, and also appear to be particularly vulnerable to develop severe disease or die from Covid-19. The aim of this multicentre observational study from France was to determine clinical and biological features in patients with diabetes and hospitalised for Covid-19. A total of 1317 patients were analysed, with the main outcomes being intubation for mechanical ventilation (reached by 267 patients, 29%) or death (140 patients, 10.6%) within 7 days of being admitted to hospital. HbA1C, as a marker of how well controlled the diabetes was, was not associated with either risk of death or need for mechanical ventilation. When other factors were taken into account, only body mass index was associated with risk of ventilation, whilst age, history of microvascular or macrovascular complications (injury to small or large blood vessels), and treated obstructive sleep apnoea were found to be independently associated with the risk of death. Of clinical and blood test parameters on admission, difficulty breathing, lymphopaenia (low levels of specific white blood cells), and increased AST (marker of liver function) and CRP (marker of inflammation) were independent factors for predicting severity of the course of COVID-19.
Abstract
AIMS/HYPOTHESIS Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION clinicaltrials.gov NCT04324736.