Do adipocytes serve as a reservoir for severe acute respiratory symptom coronavirus-2?

Obesity is associated with a higher risk of severe coronavirus disease 2019 (COVID-19) and increased mortality. In the current study, we have investigated the expression of ACE2, NRP1, and HMGB1, known to facilitate severe acute respiratory symptom coronavirus-2 (SARS-CoV-2) cell entry, in adipose tissue from non-COVID-19 control patients with normal weight, overweight, and obesity. All factors were expressed, but no significant differences between the groups were observed. Furthermore, diabetes status and medications did not affect the expression of ACE2. Only in obese men, the expression of ACE2 in adipose tissue was higher than in obese women. In the adipose tissue from patients who died from COVID-19, SARS-CoV-2 was detected in the adipocytes even though the patients died more than 3 weeks after the acute infection. This suggests that adipocytes may act as reservoirs for the virus. In COVID-19 patients, the expression of NRP1 was increased in COVID-19 patients with overweight and obesity. Furthermore, we observed an increased infiltration with macrophages in the COVID-19 adipose tissues compared to control adipose tissue. In addition, crown-like structures of dying adipocytes surrounded by macrophages were observed in the adipose tissue from COVID-19 patients. These data suggest that in obese individuals, in addition to an increased mass of adipose tissue that could potentially be infected, increased macrophage infiltration due to direct infection with SARS-CoV-2 and sustained viral shedding, rather than preinfection ACE2 receptor expression, may be responsible for the increased severity and mortality of COVID-19 in patients with obesity.

The interface of COVID-19, diabetes, and depression.

Comorbid diabetes with depression is a challenging and often under-recognized clinical problem. During the current COVID-19 pandemic, a communicable disease is thriving on the increasing incidences of these non-communicable diseases. These three different health problems are bidirectionally connected forming a vicious cycle. Firstly, depressed individuals show a higher risk of developing diabetes and patients with diabetes have a higher risk of developing symptoms of depression. Secondly, patients with diabetes have a higher risk of developing severe COVID-19 as well as of experiencing breakthrough infections. Thirdly, in both patients with type 2 diabetes and in COVID-19 survivors the prevalence of depression seems to be increased. Fourthly, lockdown and quarantine measurements during the COVID-19 pandemic has led to an increase in depression. Therefore, it is of importance to increase the awareness of this interface between depression, diabetes and COVID-19. Finally, as symptoms of post-COVID, diabetes and depression may be overlapping, there is a need for educating skilled personnel in the management of these comorbidities.

Clinical improvement of Long-COVID is associated with reduction in autoantibodies, lipids, and inflammation following therapeutic apheresis.

In the aftermath of the COVID-19 pandemic, we are witnessing an unprecedented wave of post-infectious complications. Most prominently, millions of patients with Long-Covid complain about chronic fatigue and severe post-exertional malaise. Therapeutic apheresis has been suggested as an efficient treatment option for alleviating and mitigating symptoms in this desperate group of patients. However, little is known about the mechanisms and biomarkers correlating with treatment outcomes. Here, we have analyzed in different cohorts of Long-Covid patients specific biomarkers before and after therapeutic apheresis. In patients that reported a significant improvement following two cycles of therapeutic apheresis, there was a significant reduction in neurotransmitter autoantibodies, lipids, and inflammatory markers. Furthermore, we observed a 70% reduction in fibrinogen, and following apheresis, erythrocyte rouleaux formation and fibrin fibers largely disappeared as demonstrated by dark field microscopy. This is the first study demonstrating a pattern of specific biomarkers with clinical symptoms in this patient group. It may therefore form the basis for a more objective monitoring and a clinical score for the treatment of Long-Covid and other postinfectious syndromes.

SARS-CoV-2 infection and its effects on the endocrine system

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease 2019 (COVID-19) can infect multiple tissues, including endocrine organs, such as the pancreas, adrenal, thyroid, and adipose tissue. The main receptor for SARS-CoV-2, ACE2, is ubiquitously expressed in the cells of the endocrine organs and accordingly, the virus has been detected in various amounts in all endocrine tissues in post-mortem samples from COVID-19 patients. The infection with SARS-CoV-2 may directly lead to organ damage or dysfunction, such as hyperglycaemia or in rare cases, new-onset diabetes. Furthermore, an infection with SARS-CoV-2 may have indirect effects affecting the endocrine system. The exact mechanisms are not yet completely understood and have to be further investigated. Conversely, endocrine diseases may affect the severity of COVID-19 and emphasis has to be laid on reducing the prevalence, or enhance the treatment, of these often non-communicable diseases in the future.

SARS-CoV-2 infection and its effects on the endocrine system.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease 2019 (COVID-19) can infect multiple tissues, including endocrine organs, such as the pancreas, adrenal, thyroid, and adipose tissue. The main receptor for SARS-CoV-2, ACE2, is ubiquitously expressed in the cells of the endocrine organs and accordingly, the virus has been detected in various amounts in all endocrine tissues in post-mortem samples from COVID-19 patients. The infection with SARS-CoV-2 may directly lead to organ damage or dysfunction, such as hyperglycaemia or in rare cases, new-onset diabetes. Furthermore, an infection with SARS-CoV-2 may have indirect effects affecting the endocrine system. The exact mechanisms are not yet completely understood and have to be further investigated. Conversely, endocrine diseases may affect the severity of COVID-19 and emphasis has to be laid on reducing the prevalence, or enhance the treatment, of these often non-communicable diseases in the future.

The Impact of Information About COVID-19 on the Endocrine Stress System and Cognitive Distortions.

The coronavirus disease 2019 (COVID-19) pandemic is one of the major health concerns worldwide affecting not only human physical health but also contributing to the development of many mental disorders including impairment of the cognitive function. It is highly conceivable that elevation of the stress hormones, i.e., glucocorticoids and catecholamines, due to the infection, as well as the presence of psychosocial stressors, such as COVID-19 information, play a critical role in the development of these disorders. In the present study, the potential impact of exposure to COVID-19 information on the cognitive distortion and stress levels was analyzed in a population of 32 first-year medical sciences students using the stress assessment questionnaire (SAQ) and the posttraumatic cognitions inventory (PTCI) surveys. Both surveys demonstrated no acute change in the stress and post-traumatic cognition levels between medical sciences students who were either exposed or not to information about COVID-19. Interestingly, analysis of the stress and cognition points across the first and second measurements of the SAQ categories revealed a significant change in the control group but not in the experimental group. In addition, there was no significant difference among groups when considering the time*group factor. To conclude, we found that exposure to information about COVID-19 did not contribute acutely to cognitive distortion and stress levels among participating students. The previous exposure to COVID-19-related information from media and living during the COVID-19 pandemic era might have enhanced the awareness of the students to the situation.

Post COVID and Apheresis - Where are we Standing?

A continual increase in cases of Long/Post COVID constitutes a medical and socioeconomic challenge to health systems around the globe. While the true extent of this problem cannot yet be fully evaluated, recent data suggest that up to 20% of people with confirmed SARS-CoV-2 suffer from clinically relevant symptoms of Long/Post COVID several weeks to months after the acute phase. The clinical presentation is highly variable with the main symptoms being chronic fatigue, dyspnea, and cognitive symptoms. Extracorporeal apheresis has been suggested to alleviate symptoms of Post/COVID. Thus, numerous patients are currently treated with apheresis. However, at present there is no data from randomized controlled trials available to confirm the efficacy. Therefore, physicians rely on the experience of practitioners and centers performing this treatment. Here, we summarize clinical experience on extracorporeal apheresis in patients with Post/COVID from centers across Germany.

Diabetes and COVID-19: Short- and Long-Term Consequences.

When the corona pandemic commenced more than two years ago, it was quickly recognized that people with metabolic diseases show an augmented risk of severe COVID-19 and an increased mortality compared to people without these comorbidities. Furthermore, an infection with SARS-CoV-2 has been shown to lead to an aggravation of metabolic diseases and in single cases to new-onset metabolic disorders. In addition to the increased risk for people with diabetes in the acute phase of COVID-19, this patient group also seems to be more often affected by long-COVID and to experience more long-term consequences than people without diabetes. The mechanisms behind these discrepancies between people with and without diabetes in relation to COVID-19 are not completely understood yet and will require further research and follow-up studies during the following years. In the current review, we discuss why patients with diabetes have this higher risk of developing severe COVID-19 symptoms not only in the acute phase of the disease but also in relation to long-COVID, vaccine breakthrough infections and re-infections. Furthermore, we discuss the effects of lockdown on glycemic control.

Long-COVID, Metabolic and Endocrine Disease.

In the aftermath of the corona pandemic, long-COVID or post-acute COVID-19 syndrome still represents a great challenge, and this topic will continue to represent a significant health problem in the coming years. At present, the impact of long-COVID on our health system cannot be fully assessed but according to current studies, up to 40% of people who have been infected with SARS-CoV-2 suffer from clinically relevant symptoms of long-COVID syndrome several weeks to months after the acute phase. The main symptoms are chronic fatigue, dyspnea, and various cognitive symptoms. Initial studies have shown that people with overweight and diabetes mellitus have a higher risk of developing long-COVID associated symptoms. Furthermore, repeated treatment of acute COVID-19 and long-COVID with steroids can contribute to long-term metabolic and endocrine disorders. Therefore, a structured program with rehabilitation and physical activity as well as optimal dietary management is of utmost importance, especially for patients with metabolic diseases and/or long-COVID. Furthermore, the removal of autoantibodies and specific therapeutic apheresis procedures could lead to a significant improvement in the symptoms of long-COVID in individual patients.

Obesity and COVID-19: What are the Consequences?

Obesity is an increasing health problem all over the world. In combination with the current COVID-19 pandemic, this has turned into a massive challenge as individuals with overweight and obesity at all ages show a significant increase in their risk of getting severe COVID-19. Around 20% of all patients that were hospitalized for COVID-19 suffered from obesity alone, whereas obesity in combination with other metabolic comorbidities, such as type 2 diabetes and hypertension, account for up to 60% of all hospitalizations in relation to COVID-19. Therefore, it is of immense importance to put the spotlight on the high incidence of obesity present already in childhood both by changing the individual minds and by encouraging politicians and the whole society to commence preventive interventions for achieving a better nutrition for all social classes all over the world. In the current review, we aim to explain the different pathways and mechanisms that are responsible for the increased risk of severe COVID-19 in people with overweight and obesity. Furthermore, we discuss how the pandemic has led to weight gains in many people during lockdown. At the end, we discuss the importance of preventing such an interface between a non-communicable disease like obesity and a communicable disease like COVID-19 in the future.

COVID-19 and metabolic disease: mechanisms and clinical management.

Up to 50% of the people who have died from COVID-19 had metabolic and vascular disorders. Notably, there are many direct links between COVID-19 and the metabolic and endocrine systems. Thus, not only are patients with metabolic dysfunction (eg, obesity, hypertension, non-alcoholic fatty liver disease, and diabetes) at an increased risk of developing severe COVID-19 but also infection with SARS-CoV-2 might lead to new-onset diabetes or aggravation of pre-existing metabolic disorders. In this Review, we provide an update on the mechanisms of how metabolic and endocrine disorders might predispose patients to develop severe COVID-19. Additionally, we update the practical recommendations and management of patients with COVID-19 and post-pandemic. Furthermore, we summarise new treatment options for patients with both COVID-19 and diabetes, and highlight current challenges in clinical management.

Stillborn child with diffuse SARS-CoV-2 viral infection of multiple organs.

In May 2020, a pregnant woman in her 37th pregnancy week was diagnosed with COVID-19 in St. Petersburg in Russia. All treatments failed and the patient died after 11 days due to acute respiratory distress syndrome. A stillborn child was removed by caesarian section. Pathological investigations showed that the child died due to antenatal asphyxia with aspiration pneumonia. The child was positive for SARS-CoV-2 and immunohistochemical investigations showed viral infection and cellular changes in several organs such as pancreas, brain, spleen, and adrenals. These results emphasize the importance of vaccinating pregnant women against SARS-CoV-2.

Viral infiltration of pancreatic islets in patients with COVID-19.

Metabolic diseases are associated with an increased risk of severe COVID-19 and conversely, new-onset hyperglycemia and complications of preexisting diabetes have been observed in COVID-19 patients. Here, we performed a comprehensive analysis of pancreatic autopsy tissue from COVID-19 patients using immunofluorescence, immunohistochemistry, RNA scope and electron microscopy and detected SARS-CoV-2 viral infiltration of beta-cells in all patients. Using SARS-CoV-2 pseudoviruses, we confirmed that isolated human islet cells are permissive to infection. In eleven COVID-19 patients, we examined the expression of ACE2, TMPRSS and other receptors and factors, such as DPP4, HMBG1 and NRP1, that might facilitate virus entry. Whereas 70% of the COVID-19 patients expressed ACE2 in the vasculature, only 30% displayed ACE2-expression in beta-cells. Even in the absence of manifest new-onset diabetes, necroptotic cell death, immune cell infiltration and SARS-CoV-2 viral infection of pancreatic beta-cells may contribute to varying degrees of metabolic dysregulation in patients with COVID-19.