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      (Our response to) COVID-19: In science we trust

      editorial
      Endocrine
      Springer US

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          Abstract

          To the readers of Endocrine, 2020 has drawn to a close, and an end to the pandemic that has made this year so disastrous is now in sight, thanks to an unprecedented scientific achievement: in the 10 months that have passed since the first cases of “atypical pneumonia” were reported in China, the molecular structure of the virus that causes COVID-19 has been identified, and vaccines capable of defending us against that virus have already been produced, and are now being administered throughout the world. The possibility that we will soon be able to recover some sense of normalcy is exhilarating, the desire to put this annus horribilis behind us overwhelming. But before we race ahead, it is imperative that we look back and reflect on what exactly has happened. During the final months of 2019, yet another zoonotic virus was making the leap from animals to human hosts. Unlike many of its predecessors, this one spread like wildfire and quickly began to cause suffering with almost 2 million deaths, leaving in its wake grieving disoriented communities, shattered economies, healthcare systems on the verge of collapse, and a pervasive sense of uncertainty. And yet, 2020 also brought with it hard but invaluable lessons that we can not afford to forget: First, our planet is crisscrossed with essential networks that ensure almost real-time global distribution and redistribution of food, livestock, raw materials, manufactured goods, and last but not least human beings. Science has shown us unequivocally how these networks distribute viruses and other pathogens as well. It is thus essential that our concept of “health” and “healthcare” needs to be broadened, made more global. It would be short-sited [myopic] for any country to believe that health can be achieved or maintained in national terms alone. Second, the lockdowns imposed on societies to slow the alarming spread of this previously unknown disease have had equally disruptive effects. The restrictions have had a dismaying impact on virtually all the activities of our daily life: shopping, working, learning, teaching, socializing, commuting, traveling, healthcare activities (from routine prevention to urgent diagnostic procedures and treatment), etc. have all been appreciably restricted [o disrupted]. And yet, remote alternatives and work-arounds are being discovered, distributed, improved, mastered, and updated with remarkable speed, and once again, these solutions have been provided by the fields of science and technology. The world’s remarkable response to the COVID-19 pandemic is rooted in active and often innovative forms of collaboration and exchange, among scientists across the world, and in the combined power of public and private investments. The field of endocrinology, like other disciplines, has been strongly impacted by this pandemic. Patients with acute and chronic endocrine disease have suddenly been faced with delays or suspension of care and medical advice (sometimes self-imposed for fear of contagion) they once considered essential (e.g., routine follow-up visits, treatments, surgery, diagnostic procedures). But COVID-19 also has numerous direct effects on the endocrine system that have been and continue to be described [1]. Endocrine has been at the forefront in documenting and promoting awareness of these aspects of the disease, as reflected by our publication of the ESE statement outlining the effect of COVID-19 on the endocrine system [1] and editorials calling attention to the evolving changes, the emerging challenges, and new scenarios introduced by COVID-19 [2, 3]. Since the April 2020 issue, Endocrine has published 29 articles dealing with the endocrine effects and implications of infection with SARS-CoV-2. Springer has already collected these papers and published them on the Endocrine web site as a single open-access portfolio readily available to all readers. The year 2020 has witnessed a 45% increase in submissions compared to 2019, and Endocrine’s impact is steadily growing, with roughly one-third of the readers who access the journal hailing from North or South America (31%), Asia and the Pacific (32%), or Europe (28%). We look forward to increasing our visibility in the Middle East and Africa in 2021. The growing number of papers submitted for publication has put an undeniable strain on our review process. We have made every attempt to expedite the publication of COVID-19-related papers without sacrificing the quality standards that are our hallmark. Despite these efforts, delays in some of our responses to authors have occurred. What are our plans for the next 12 months? First and foremost, an expanded editorial board that can accelerate and improve our ability to provide readers with high-quality, original, and innovative contents dealing with the management of endocrine diseases in the COVID-19 and post-COVID-19 era. We intend to focus on novel, less frequently examined topics such as Information Technology applications in the field of endocrinology (IT), Patient-Centered Outcomes Research, and the effects of environmental and climate changes on endocrine diseases. I am also excited to announce that in March, Endocrine will publish an entire issue devoted specifically to rare endocrine conditions, with the collaboration of numerous Endo-ERN (European Reference Network on Rare Endocrine Conditions) experts and co-edited by Alberto Pereira and Olaf Hiort. With this initiative, we hope to draw attention to the need for concrete actions to support patients with these diseases, whose suffering has been markedly exacerbated by the pandemic. Before I close, let me also thank my colleagues on the Editorial Board for the heavy workload they have shouldered over the past year, Bex Chang, the journal’s Publishing Editor, and Aiswarya Satheesan and Prathap Panneerselvam, the journal’s editorial assistant and production editor, respectively. Their commitment and generosity over the past 12 months have been extraordinary and remarkable. And last but not least, you, our readers and contributors: your manuscripts are the beating heart of the journal, and we are counting on you to help us provide the international community of endocrinologic researchers and clinicians with reliable, thought-provoking guidance for 2021—the science in which all of us must continue to place our trust. Best wishes to all. Sebastiano Filetti, MD

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          COVID-19 and endocrine diseases. A statement from the European Society of Endocrinology

          Introduction Coronavirus disease 2019 (COVID-19) outbreak requires that endocrinologists from all over Europe move on, even more, to the first line of care of our patients, also in collaboration with other physicians such as those in internal medicine and emergency units. This will preserve the health status and prevent the adverse COVID-19-related outcomes in people affected by different endocrine diseases. People with diabetes in particular are among those in high-risk categories who can have serious illness if they get the virus, according to the data published so far from the Chinese researchers, but other endocrine diseases such as obesity, malnutrition, and adrenal insufficiency may also be impacted by COVID-19. Therefore, since the responsibilities of endocrinologists worldwide due to the current COVID-19 outbreak are not minor we have been appointed by the European Society of Endocrinology (ESE) to write the current statement in order to support the ESE members and the whole endocrine community in this critical situation. In addition, endocrinologists, as any other healthcare worker under the current COVID-19 outbreak, will need to self-protect from this viral disease, which is demonstrating to have a very high disseminating and devastating capacity. We urge Health Authorities to provide adequate protection to the whole workforce of health professionals and to consistently test for COVID-19 the exposed personnel. A decrease in the number of healthcare professionals available for active medical practice in case they contract the disease as it is happening in certain countries, is itself, a threat for the healthcare system and the well-being of our patients. The virus seems to have spread from infected animals and human-to-human transmission is now more than evident, with a high suspicion that non-symptomatic individuals act as the major vectors. It spreads like any other respiratory infectious disease, through contaminated air-droplets that come out of the mouth of infected persons when talking, coughing, or sneezing. The virus can survive in the environment from a few hours to a few days, depending on surfaces and environmental conditions, and touching affected surfaces. The mouth, nose, and ocular mucosa appears to be the major way of transmission. Symptoms of COVID-19 infection General symptoms are relatively nonspecific and similar to other common viral infections targeting the respiratory system, and include fever, cough, myalgia, and shortness of breath. The clinical spectrum of the virus ranges from mild disease with nonspecific signs and symptoms of acute respiratory illness, to severe pneumonia with respiratory failure and septic shock. Possibly, an overreaction of the immune system leading to an autoimmune aggression of the lungs could be involved in the most severe cases of acute distress respiratory syndrome. There have also been reports of asymptomatic infection and research in this matter is currently ongoing worldwide to elucidate the real prevalence of the disease and the true relative mortality ratio. COVID-19 infection and diabetes mellitus Increased risk of morbidity and mortality in patients with diabetes regarding COVID-19 infection Older adults and those with serious chronic medical conditions like heart disease, lung disease, and diabetes are at the highest risk for complications from COVID-19 infection. Chronic hyperglycemia negatively affects immune function and increases the risk of morbidity and mortality due to any infection and is associated to organic complications. This is also the case for COVID-19 infection [1]. During the Influenza A (H1N1) pandemic, the presence of diabetes tripled the risk of hospitalization and quadrupled the risk of ICU admission once hospitalized. Among COVID-19 mortality cases in Wuhan, China, major associated comorbidities included hypertension (53.8%), diabetes (42.3%), previous heart disease (19.2%), and cerebral infarction (15.4%) [2]. In addition, as for seasonal influenza, new data regarding COVID-19 indicate that the infection potentiates myocardial damage and identifies underlying heart disorders as a new risk factor for severe complications and worsening of prognosis [3]. Among the confirmed COVID-19 cases in China by Feb 11, 2020, the overall mortality reported is 2.3% [4]. This data refers mostly to hospitalized patients [4, 5]. Among persons with no underlying medical conditions, the reported mortality in China is 0.9%. There is a lack of data regarding the number of non-symptomatic cases, as in most countries universal microbiological screening has not been performed. It is presumed that the prevalence of the infection is probably high or very high in the community, thus leading to an overestimation of the prevalence of case fatality. However, mortality is strongly increased with the presence of comorbid diseases, including previous cardiovascular disease (10.5%), diabetes (7.3%), chronic respiratory disease, hypertension, and cancer, each at 6%. Among 60-year-old people and older, mortality has been reported to be 14.8% in those >80 years, 8% for those between 70 and 79 years and 3.6% in the 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]. Worldwide mortality rates may vary by region, but this information is not yet consistently available and comparable, as public health policies applied and health registers used in every region of the world are not homogeneous. What people with diabetes should do to prevent infection by COVID-19 Social distancing as well as home confinement of the whole population are now widely adopted in many countries in Europe and worldwide as measures hopefully effective in contrast to the spread of infection. We recommend that due to the increased dangers of developing COVID-19, persons with diabetes should strictly adhere to these preventive measures and adopt them also within their homes in order to avoid being in contact with their relatives. Therefore, under these circumstances, it is recommended that people with diabetes try to plan ahead of time what to do in case they get ill. It is important to maintain a good glycemic control, because it might help reduce the risk of infection itself and may also modulate the severity of the clinical expression of the disease. Contact with healthcare providers, such as endocrinologists in the case of type 1 diabetes, and including also internal medicine specialists and general practitioners for type 2 diabetes patients may be advisable. However, routine appointments in person are not recommended for people with diabetes, as they should avoid crowds (waiting rooms). Therefore, we recommend phone calls, video calls, and emails as the main way for patients to keep in touch with their healthcare provider team, in order to guarantee an optimal control of the disease. Moreover, it is advised to ensure adequate stock of medications and supplies for monitoring blood glucose during the period of home confinement. What people with diabetes should do if they are infected by COVID-19 People with diabetes who are infected with COVID-19 may experience a deterioration of glycemic control during the illness, like in any other infectious episodes. Implementation of “Sick day rules” is therefore mandatory to overcome potential diabetes decompensation. Contacting the healthcare provider team by telephone, email, or videoconference is also mandatory in case of possible symptoms of COVID-19 infection in order to seek advice concerning the measures to avoid risk of deterioration of diabetes control or the possibility to be referred to another specialist (pneumologist or infectious disease doctor) or in the Emergency Services of the referral hospital to avoid the most serious systemic complication of the viral infection itself. COVID-19 and other endocrine and metabolic disorders Obesity There is a general lack of data regarding the impact of COVID -19 in people suffering from obesity. However, as for what is currently being the experience in some hospitals in Spain, cases of young people in which severe obesity is present may evolve toward destructive alveolitis with respiratory failure and death (Puig-Domingo M, personal experience). There is no current explanation for this clinical presentation, although it is well known that severe obesity is associated to sleep-apnea syndrome, as well as to surfactant dysfunction, which may contribute to a worse scenario in the case of COVID-19 infection. Also, deterioration of glycemic control is associated with an impairment of ventilatory function and thus may contribute to a worse prognosis in these patients. In addition, type 2 diabetes and obesity may concur in a given patient, which typically is also frequently accompanied by an age >65. In summary, these patients may be at a higher risk of impaired outcomes in the case of COVID-19 infection. Undernourishment Regarding undernourished subjects, COVID-19 infection is 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 also a hyporexic state, thus contributing to a negative nutritional balance. Estimated nutritional requirements are 25–30 kcal/kg of weight and 1.5 g protein/kg/day [7]. A nutrient dense diet is recommended in hospitalized cases including high protein supplements (2–3 intakes per day) containing at least 18 g of protein per intake. Adequate supplementation of vitamin D is recommended particularly in areas with large known prevalence of hypovitaminosis D and due to the decreased sun exposure [8, 9]. If nutritional requirements are not met, complementary or complete enteral feeding may be required, and in case that enteral feeding may not be possible due to inadequate gastrointestinal tolerance, the patient should be put on parenteral nutrition. COVID-19 patients’ outcome is expected to improve with nutritional support [10]. Adrenal insufficiency Adrenal insufficiency is a chronic condition of lack of cortisol production. Live-long replacement treatment aiming to mimic physiologic plasma cortisol concentrations is not easy for these patients. Based on current data, there is no evidence that patients with adrenal insufficiency are at increased risk of contracting COVID-19. However, it is known that patients with Addison’s disease (primary adrenal insufficiency) and congenital adrenal hyperplasia have a slightly increased overall risk of catching infections. Moreover, primary adrenal insufficiency is associated to an impaired natural immunity function with a defective action of neutrophils and natural killer cells [11]. This may explain, in part, this slightly increased rate of infectious diseases in these patients, as well as an overall increased mortality. This latter could also be accounted by an insufficient compensatory increase of the hydrocortisone dosage at the time of the beginning of an episode of infection. For all these reasons, patients with adrenal insufficiency may be at higher risk of medical complications and eventually at increased mortality risk in the case of COVID-19 infection. So far, there are no reported data on the outcomes of COVID-19 infection in adrenal insufficient subjects. In the case of suspicion of COVID-19, a prompt modification of the replacement treatment as indicated for the “Sick days” should be established when minor symptoms appear. This means in the first instance to at least double the usual doses of glucocorticoid replacement, to avoid adrenal crisis. In addition, patients are also recommended to have sufficient stock at home of steroid pills and injections in order to maintain the social confinement that is required in most of the countries for impeding the COVID-19 outbreak spread. Actions to be taken if infection by COVID-19 is suspected If a person with endocrine and metabolic diseases has fever with cough or trouble breathing and may have been exposed to COVID-19 (if living in or visited a country affected in the 14 days before getting sick, or if having been around a person who may have had the virus), a call to the physician or nurse for advice should be made. Some countries have set up COVID-19 phone lines for the public. The personnel in charge of these phone lines will prioritize arrangements, if needed, regarding what should be the next step in the healthcare protocol. If the person is advised to go to the hospital, it is recommended to put on a face mask. In countries with explosive outbreak, most of the people have already bought a face mask by their own initiative. Fluid samples taken from the nose or throat will be used for microbiologic diagnosis. There is currently no specific treatment for COVID-19, but since the majority of cases are mild, only a limited amount of people will require hospitalization for supportive care. However, in most of the countries in which the outbreak has been declared and recognized, particularly in China, the Northern regions of Italy, Iran, and Spain, the situation has been very challenging and the requirement of hospitalization has led national health systems to the limit of their capacities [12]. What to do in case of confinement at home? Individuals and families affected or suspected to be affected by COVID-19 that stay at home should follow proper measures for infection prevention and control. Management should focus on prevention of transmission to others and monitoring for clinical deterioration, which may prompt hospitalization. Affected persons should be placed in a well-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 hands with soap and water) after any type of contact with the affected person or their immediate environment. When washing hands, it is preferable to use disposable paper towels to dry them. If these are not available, clean cloth towels should be used and replaced when wet. To contain respiratory secretions, a medical mask should be provided to the person affected and worn as much as possible. Individuals who cannot tolerate a medical mask should use rigorous respiratory hygiene—i.e., the mouth and nose should be covered with a disposable paper tissue when coughing or sneezing. Caregivers should also wear a tightly fitted medical mask that cover their mouth and nose when in the same room is present the person affected. Conclusions An ESE “decalog” for endocrinologists in the COVID-19 pandemic Adequately protect yourself and ask for COVID-19 testing if exposed. Avoid unnecessary routine appointments in person. Put in place online/email/phone consultation services. Closely monitor glycemic control in patients with diabetes. Recommend to persons with diabetes a strict adherence to general preventive measures. Counsel persons with diabetes about specific measures related to their disease management (sick day rules) in case of infection by COVID-19. Counsel persons with diabetes particularly if aged over 65 and obese about referrals for management in case of suspected infection by COVID-19. Avoid undernourishment with dietary or adjunctive measures if clinically indicated. Closely monitor clinical conditions of patients with adrenal insufficiency. Adapt increased replacement treatment if clinically indicated in patients with adrenal insufficiency.
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            The COVID-19 pandemic requires a unified global response

            The ongoing spread of the COVID-19 pandemic is having profound effects on our private and professional lives, the world economy, and the social organization of the communities we live in. This moment in history is so dramatic as to seem incomprehensible to some, to others a scene straight out of a disaster movie. Those of us who have devoted our lives to understanding and combatting illness know that science is the key to halting this disaster, but we are also aware of the fact that the shape of the world we live will be strikingly altered by this pandemic. Today, our tasks are embodied by the roles we have in society: to be present, to be committed, and to participate wholeheartedly in the fight against the coronavirus outbreak. Foremost in my mind, therefore, is a sense of gratitude and pride when I think of the health professionals on the front lines of the war against this new viral disease, dedicated doctors, nurses, and other paramedicals—our friends and colleagues—working tirelessly and risking their lives to save patients and find the answers we need. The world of endocrinology and metabolism is also immersed in the pandemic, in hospital wards and outpatient clinics, where endocrinologists are supporting high-risk COVID-19 patients, elderly individuals with diabetes or endocrine cancers, and providing ongoing care for the vulnerable patient population with chronic endocrine diseases. With this in mind, I would like to personally thank Prof. Andrea Giustina, former editor-in-chief of Endocrine and current President of the European Society of Endocrinology, for asking us to publish the Society’s statement on the COVID-19 pandemic. The statement appears in this issue of Endocrine [1], and we are convinced it will be of service to our community of readers. It offers a broad range of expert advice on counseling, monitoring, and treating patients with diabetes and endocrine disorders during this difficult time, regardless of whether or not they have COVID-19. I am sure that it will prove to be a valuable resource for all of you. In the meantime, all of us here at Endocrine are committed to remaining fully operational, ensuring timely completion of constructive, objective peer reviews, and minimizing publication delays. We encourage COVID-19-related research submissions regarding research on the relationship between COVID-19 and endocrine disorders as well as on the experience of diabetic and endocrine patients subject to lockdown and social distancing guidelines (https://www.springer.com/journal/12020/updates/17856320). I would like to take this opportunity to thank the journal’s associate editors, who continue to carry out their responsibilities with dedication and punctuality despite significant demands from their own institutions and daily routines. And our efforts would be in vain without the support of the dedicated staff at Springer Nature and the experience and ability of Lisa Hussey, the journal’s Publishing Editor. As always, they are attentive to our requests and quick to find solutions, even in this critical period. With the sincere hope that this crisis will soon be over, I remain.
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              A journey through and beyond a “perfect storm”: the COVID-19 pandemic

              Dear Readers, Among other things, the COVID-19 pandemic will likely be recalled as the “perfect storm” that exposed countless weaknesses and alarming deficiencies in healthcare systems throughout the world. As we reflect on the present scenario, we should therefore cast an eye towards the future and begin thinking seriously about the way endocrinology and metabolism services should be organized in the post-COVID-19 era. If you have not already done so already, please take a look at the statement published by the European Society of Endocrinology (https://link.springer.com/article/10.1007/s12020-020-02294-5) in our April issue: it provides a detailed picture of the endocrinological/metabolic pathologies being encountered in the context of COVID-19 [1]. In my previous editorial, I encouraged clinicians and researchers to send Endocrine their personal experiences with COVID-19 and endocrine and metabolic diseases [2]. We have already received numerous contributions, and our editors and reviewers are busily reviewing them all. The May issue contains the first two contributions in this section that have already been accepted. As the storm shows at least some signs of abating, the challenges facing us appear increasingly complex and multifaceted. We hope to provide our readers with insights into these complexities, including certain aspects that may well have been overlooked, and if possible to view the challenges facing us through the eyes of our patients. While the storm was raging, most of our outpatient activities had to be discontinued, and many staff endocrinologists were transferred to internal medicine wards so that the internists there could devote their energies and expertise to the care of patients who had contracted COVID-19. As a result, many surgical procedures for thyroid cancer have been postponed, along with biopsies of suspicious nodules and radioiodine therapy, and diabetes and other endocrine or metabolic disorders are being managed without the regular follow-up visits previously considered essential. How are our patients coping with these changes? Has the fear of hospital-related contagion affected their decisions regarding treatment? And what technological resources do we have at our disposal that can provide patients with effective ongoing guidance and support while “social distancing” is still essential? We eagerly await your contributions on these pressing issues. The light at the end of this tunnel is little more than a glimmer, but it’s already time to begin thinking about how to reestablish contact with our endocrine and diabetic patients, to restore the relationships that have been disrupted by this “perfect storm.” Our community has both the strength and experience to act promptly and find innovative, effective solutions for overcoming the challenges of this phase. The strength of our community is rooted in research, and to highlight the importance of these roots, the current issue of Endocrine contains selected manuscripts from talks given at the Festschrift recently held to honor Professor Marian Ludgate and her colleagues at the University of Cardiff. The papers exemplify Marian’s intellectual curiosity, her inspired problem solving skills, and her commitment to advancing our understanding of and ability to effectively treat thyroid disease. We are proud to acknowledge and celebrate Marian’s outstanding contributions to the field of thyroid disease and the work she has done to support and promote the Cardiff Thyroid Research Group. This elite group, one of the U.K.’s oldest centers of tradition and excellence, includes other prestigious figures such as Reginald Hall and John Lazarus, and its major contributions to science go far beyond the UK, reaching all corners of international scientific community. So, in closing then, let me say: Many thanks, Marian! May your career serve as an example of the talent, the strength, and the commitment we will need to meet the many and varied challenges of this perfect storm and resolve them as quickly and effectively as possible.
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                Author and article information

                Contributors
                editor.endocrine@gmail.com
                Journal
                Endocrine
                Endocrine
                Endocrine
                Springer US (New York )
                1355-008X
                1559-0100
                21 January 2021
                : 1-2
                Affiliations
                School of Health, UnitelmaSapienza, Rome, Italy
                Article
                2608
                10.1007/s12020-021-02608-1
                7819140
                33475977
                66abf678-0238-4b7a-aef6-6c56e738ad69
                © The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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