Endocrine https://doi.org/10.1007/s12020-020-02294-5 VIEW POINT COVID-19 and endocrine diseases. A statement from the European Society of Endocrinology M. Puig-Domingo1 M. Marazuela2 A. Giustina3,4 ● ● Keywords Covid-19 Diabetes mellitus Obesity Malnourishment Hypoadrenalism ● ● ● ● © Springer Science+Business Media, LLC, part of Springer Nature 2020 Introduction self-protect from this viral disease, which is demonstrating to have a very high disseminating and devastating capacity. Coronavirus disease 2019 (COVID-19) outbreak requires We urge Health Authorities to provide adequate protection that endocrinologists from all over Europe move on, even to the whole workforce of health professionals and to 1234567890();,: 1234567890();,: more, to the first line of care of our patients, also in colla- consistently test for COVID-19 the exposed personnel. A boration with other physicians such as those in internal decrease in the number of healthcare professionals available medicine and emergency units. This will preserve the health for active medical practice in case they contract the disease status and prevent the adverse COVID-19-related outcomes as it is happening in certain countries, is itself, a threat for in people affected by different endocrine diseases. People the healthcare system and the well-being of our patients. with diabetes in particular are among those in high-risk The virus seems to have spread from infected animals categories who can have serious illness if they get the virus, and human-to-human transmission is now more than evi- according to the data published so far from the Chinese dent, with a high suspicion that non-symptomatic indivi- researchers, but other endocrine diseases such as obesity, duals act as the major vectors. It spreads like any other malnutrition, and adrenal insufficiency may also be respiratory infectious disease, through contaminated air- impacted by COVID-19. Therefore, since the responsi- droplets that come out of the mouth of infected persons bilities of endocrinologists worldwide due to the current when talking, coughing, or sneezing. The virus can survive COVID-19 outbreak are not minor we have been appointed in the environment from a few hours to a few days, by the European Society of Endocrinology (ESE) to write depending on surfaces and environmental conditions, and the current statement in order to support the ESE members touching affected surfaces. The mouth, nose, and ocular and the whole endocrine community in this critical mucosa appears to be the major way of transmission. situation. In addition, endocrinologists, as any other healthcare worker under the current COVID-19 outbreak, will need to Symptoms of COVID-19 infection General symptoms are relatively nonspecific and similar to * A. Giustina other common viral infections targeting the respiratory giustina.andrea@hsr.it system, and include fever, cough, myalgia, and shortness of 1 breath. The clinical spectrum of the virus ranges from mild Endocrinology and Nutrition Service, Department of Medicine, disease with nonspecific signs and symptoms of acute Germans Trias i Pujol Health Science Research Institute and Hospital, Universitat Autònoma de Barcelona, Badalona, Spain respiratory illness, to severe pneumonia with respiratory 2 failure and septic shock. Possibly, an overreaction of the Department of Endocrinology and Nutrition, Hospital Universitario de la Princesa, Instituto de Investigación Princesa, immune system leading to an autoimmune aggression of the Universidad Autónoma de Madrid, Madrid, Spain lungs could be involved in the most severe cases of acute 3 Chair of Endocrinology, Vita-Salute San Raffaele University, distress respiratory syndrome. There have also been reports Milan, Italy of asymptomatic infection and research in this matter is 4 Division of Endocrinology, IRCCS San Raffaele Hospital, currently ongoing worldwide to elucidate the real pre- Milan, Italy valence of the disease and the true relative mortality ratio. Endocrine COVID-19 infection and diabetes mellitus Europe and worldwide as measures hopefully effective in contrast to the spread of infection. We recommend that due to Increased risk of morbidity and mortality in patients the increased dangers of developing COVID-19, persons with with diabetes regarding COVID-19 infection diabetes should strictly adhere to these preventive measures and adopt them also within their homes in order to avoid Older adults and those with serious chronic medical con- being in contact with their relatives. Therefore, under these ditions like heart disease, lung disease, and diabetes are at circumstances, it is recommended that people with diabetes the highest risk for complications from COVID-19 infec- try to plan ahead of time what to do in case they get ill. It is tion. Chronic hyperglycemia negatively affects immune important to maintain a good glycemic control, because it function and increases the risk of morbidity and mortality might help reduce the risk of infection itself and may also due to any infection and is associated to organic compli- modulate the severity of the clinical expression of the disease. cations. This is also the case for COVID-19 infection [1]. Contact with healthcare providers, such as endocrinologists During the Influenza A (H1N1) pandemic, the presence of in the case of type 1 diabetes, and including also internal diabetes tripled the risk of hospitalization and quadrupled medicine specialists and general practitioners for type 2 dia- the risk of ICU admission once hospitalized. Among betes patients may be advisable. However, routine appoint- COVID-19 mortality cases in Wuhan, China, major asso- ments in person are not recommended for people with ciated comorbidities included hypertension (53.8%), dia- diabetes, as they should avoid crowds (waiting rooms). betes (42.3%), previous heart disease (19.2%), and cerebral Therefore, we recommend phone calls, video calls, and emails infarction (15.4%) [2]. In addition, as for seasonal influenza, as the main way for patients to keep in touch with their new data regarding COVID-19 indicate that the infection healthcare provider team, in order to guarantee an optimal potentiates myocardial damage and identifies underlying control of the disease. Moreover, it is advised to ensure heart disorders as a new risk factor for severe complications adequate stock of medications and supplies for monitoring and worsening of prognosis [3]. blood glucose during the period of home confinement. Among the confirmed COVID-19 cases in China by Feb 11, 2020, the overall mortality reported is 2.3% [4]. This What people with diabetes should do if they are data refers mostly to hospitalized patients [4, 5]. Among infected by COVID-19 persons with no underlying medical conditions, the reported mortality in China is 0.9%. People with diabetes who are infected with COVID-19 may There is a lack of data regarding the number of non- experience a deterioration of glycemic control during the symptomatic cases, as in most countries universal micro- illness, like in any other infectious episodes. Implementa- biological screening has not been performed. It is presumed tion of “Sick day rules” is therefore mandatory to overcome that the prevalence of the infection is probably high or very potential diabetes decompensation. Contacting the health- high in the community, thus leading to an overestimation of care provider team by telephone, email, or videoconference the prevalence of case fatality. However, mortality is is also mandatory in case of possible symptoms of COVID- strongly increased with the presence of comorbid diseases, 19 infection in order to seek advice concerning the mea- including previous cardiovascular disease (10.5%), diabetes sures to avoid risk of deterioration of diabetes control or the (7.3%), chronic respiratory disease, hypertension, and can- possibility to be referred to another specialist (pneumologist cer, each at 6%. Among 60-year-old people and older, or infectious disease doctor) or in the Emergency Services mortality has been reported to be 14.8% in those >80 years, of the referral hospital to avoid the most serious systemic 8% for those between 70 and 79 years and 3.6% in the complication of the viral infection itself. group of 60–69 years. Compared with non-ICU patients, critically ill patients are older (median age 66 vs. 51 years) and have more previous comorbidities (72% vs. 37%) [6]. COVID-19 and other endocrine and Worldwide mortality rates may vary by region, but this metabolic disorders information is not yet consistently available and compar- able, as public health policies applied and health registers Obesity used in every region of the world are not homogeneous. There is a general lack of data regarding the impact of What people with diabetes should do to prevent COVID -19 in people suffering from obesity. However, as infection by COVID-19 for what is currently being the experience in some hospitals in Spain, cases of young people in which severe obesity is Social distancing as well as home confinement of the whole present may evolve toward destructive alveolitis with population are now widely adopted in many countries in respiratory failure and death (Puig-Domingo M, personal Endocrine experience). There is no current explanation for this clinical increase of the hydrocortisone dosage at the time of the presentation, although it is well known that severe obesity is beginning of an episode of infection. For all these reasons, associated to sleep-apnea syndrome, as well as to surfactant patients with adrenal insufficiency may be at higher risk of dysfunction, which may contribute to a worse scenario in medical complications and eventually at increased mortality the case of COVID-19 infection. Also, deterioration of risk in the case of COVID-19 infection. So far, there are no glycemic control is associated with an impairment of ven- reported data on the outcomes of COVID-19 infection in tilatory function and thus may contribute to a worse prog- adrenal insufficient subjects. nosis in these patients. In addition, type 2 diabetes and In the case of suspicion of COVID-19, a prompt mod- obesity may concur in a given patient, which typically is ification of the replacement treatment as indicated for the also frequently accompanied by an age >65. In summary, “Sick days” should be established when minor symptoms these patients may be at a higher risk of impaired outcomes appear. This means in the first instance to at least double the in the case of COVID-19 infection. usual doses of glucocorticoid replacement, to avoid adrenal crisis. In addition, patients are also recommended to have Undernourishment sufficient stock at home of steroid pills and injections in order to maintain the social confinement that is required in most of Regarding undernourished subjects, COVID-19 infection is the countries for impeding the COVID-19 outbreak spread. associated to a high risk of malnutrition development, mostly related to increased requirements and the presence of a severe acute inflammatory status. These patients show Actions to be taken if infection by COVID-19 also a hyporexic state, thus contributing to a negative is suspected nutritional balance. Estimated nutritional requirements are 25–30 kcal/kg of weight and 1.5 g protein/kg/day [7]. A If a person with endocrine and metabolic diseases has fever nutrient dense diet is recommended in hospitalized cases with cough or trouble breathing and may have been exposed including high protein supplements (2–3 intakes per day) to COVID-19 (if living in or visited a country affected in containing at least 18 g of protein per intake. Adequate the 14 days before getting sick, or if having been around a supplementation of vitamin D is recommended particularly person who may have had the virus), a call to the physician in areas with large known prevalence of hypovitaminosis D or nurse for advice should be made. Some countries have and due to the decreased sun exposure [8, 9]. If nutritional set up COVID-19 phone lines for the public. The personnel requirements are not met, complementary or complete ent- in charge of these phone lines will prioritize arrangements, eral feeding may be required, and in case that enteral if needed, regarding what should be the next step in the feeding may not be possible due to inadequate gastro- healthcare protocol. If the person is advised to go to the intestinal tolerance, the patient should be put on parenteral hospital, it is recommended to put on a face mask. In nutrition. COVID-19 patients’ outcome is expected to countries with explosive outbreak, most of the people have improve with nutritional support [10]. already bought a face mask by their own initiative. Fluid samples taken from the nose or throat will be used for Adrenal insufficiency microbiologic diagnosis. There is currently no specific treatment for COVID-19, but since the majority of cases are Adrenal insufficiency is a chronic condition of lack of mild, only a limited amount of people will require hospi- cortisol production. Live-long replacement treatment aim- talization for supportive care. However, in most of the ing to mimic physiologic plasma cortisol concentrations is countries in which the outbreak has been declared and not easy for these patients. recognized, particularly in China, the Northern regions of Based on current data, there is no evidence that patients Italy, Iran, and Spain, the situation has been very challen- with adrenal insufficiency are at increased risk of con- ging and the requirement of hospitalization has led national tracting COVID-19. However, it is known that patients with health systems to the limit of their capacities [12]. Addison’s disease (primary adrenal insufficiency) and congenital adrenal hyperplasia have a slightly increased overall risk of catching infections. Moreover, primary What to do in case of confinement at home? adrenal insufficiency is associated to an impaired natural immunity function with a defective action of neutrophils Individuals and families affected or suspected to be affected and natural killer cells [11]. This may explain, in part, this by COVID-19 that stay at home should follow proper slightly increased rate of infectious diseases in these measures for infection prevention and control. Management patients, as well as an overall increased mortality. This latter should focus on prevention of transmission to others and could also be accounted by an insufficient compensatory monitoring for clinical deterioration, which may prompt Endocrine hospitalization. Affected persons should be placed in a well- Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. ventilated single room, while household members should stay in a different room or, if that is not possible, maintain a distance of at least one meter from the person affected (e.g., sleep in a separate bed) and perform hand hygiene (washing References hands with soap and water) after any type of contact with the affected person or their immediate environment. When 1. J. Casqueiro, J. Casqueiro, C. Alves, Infections in patients with diabetes mellitus: a review of pathogenesis. Indian J. Endocrinol. washing hands, it is preferable to use disposable paper Metab. 16(Suppl 1), S27–S36 (2012). https://doi.org/10.4103/ towels to dry them. If these are not available, clean cloth 2230-8210.94253 towels should be used and replaced when wet. To contain 2. S.-Q. Deng, H.-J. 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