Gender-dependent impact of COVID-19 lockdown on metabolic and psychological aspects.

The first COVID-19 lockdown resulted in enforced quarantine of heavily affected areas with social isolation and related measures by several governments to slow the spread of the disease. The general population experienced several mental and lifestyle changes. Herein, we aimed to evaluate the metabolic and psychological effects induced by lifestyle changes during COVID-19 self-isolation among an Apulian overweight/obese cohort with metabolic disturbances. The study assessed anthropometric data (weight, abdominal circumferences), dietary habits (adherence to the Mediterranean diet, junk food score), lifestyle habits (i.e., smoking, and physical activity), levels of stress and anxiety, and depression. Subjects underwent bioumoral exams before and after self-isolation to monitor glycemic and lipid profiles. A total of 245 subjects (M:F = 118:127) have been included in the study. After lockdown, the number of obese subjects significantly increased in both sexes, and was higher in females than in males (P < 0.0001). Glycemic and lipid profiles worsened, with higher levels of insulinemia, lower levels of HDL cholesterol, and higher levels of triglycerides in females than in males. Adherence to the Mediterranean diet and consumption of junk foods were altered in both groups, especially in females. Psychological aspects were significantly higher in females than in males. Finally, work activities and familial status strongly affected the metabolic and psychological profile. In conclusion, COVID-19 self-isolation induced changes in lifestyle and dietary habits with psychological distress and detrimental effects on metabolic patterns, which were more pronounced in female gender.

Application of a Decision Tree Model to Predict the Outcome of Non-Intensive Inpatients Hospitalized for COVID-19.

Many studies have identified predictors of outcomes for inpatients with coronavirus disease 2019 (COVID-19), especially in intensive care units. However, most retrospective studies applied regression methods to evaluate the risk of death or worsening health. Recently, new studies have based their conclusions on retrospective studies by applying machine learning methods. This study applied a machine learning method based on decision tree methods to define predictors of outcomes in an internal medicine unit with a prospective study design. The main result was that the first variable to evaluate prediction was the international normalized ratio, a measure related to prothrombin time, followed by immunoglobulin M response. The model allowed the threshold determination for each continuous blood or haematological parameter and drew a path toward the outcome. The model's performance (accuracy, 75.93%; sensitivity, 99.61%; and specificity, 23.43%) was validated with a k-fold repeated cross-validation. The results suggest that a machine learning approach could help clinicians to obtain information that could be useful as an alert for disease progression in patients with COVID-19. Further research should explore the acceptability of these results to physicians in current practice and analyze the impact of machine learning-guided decisions on patient outcomes.

Environmental health, COVID-19, and the syndemic: internal medicine facing the challenge.

Internists are experts in complexity, and the COVID-19 pandemic is disclosing complex and unexpected interactions between communicable and non-communicable diseases, environmental factors, and socio-economic disparities. The medicine of complexity cannot be limited to facing comorbidities and to the clinical management of multifaceted diseases. Evidence indicates how climate change, pollution, demographic unbalance, and inequalities can affect the spreading and outcomes of COVID-19 in vulnerable communities. These elements cannot be neglected, and a wide view of public health aspects by a "one-health" approach is strongly and urgently recommended. According to World Health Organization, 35% of infectious diseases involving the lower respiratory tract depend on environmental factors, and infections from SARS-Cov-2 is not an exception. Furthermore, environmental pollution generates a large burden of non-communicable diseases and disabilities, increasing the individual vulnerability to COVID-19 and the chance for the resilience of large communities worldwide. In this field, the awareness of internists must increase, as privileged healthcare providers. They need to gain a comprehensive knowledge of elements characterizing COVID-19 as part of a syndemic. This is the case when pandemic events hit vulnerable populations suffering from the increasing burden of chronic diseases, disabilities, and social and economic inequalities. Mastering the interplay of such events requires a change in overall strategy, to adequately manage not only the SARS-CoV-2 infection but also the growing burden of non-communicable diseases by a "one health" approach. In this context, experts in internal medicine have the knowledge and skills to drive this change.

Different Variation of Intra-familial Body Mass Index subjected to Covid-19 Lockdown.

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) lockdown has represented an inedited model of increased metabolic risk in all age groups, due to negative changes in dietary habits, physical activity, lifestyle. These effects have been generally explored at a population level in distinct age groups. Potential intra-familial, specific effects in adults and children sharing the same socio-economic, cultural level and living habits have been scarcely explored. We aimed to characterize changes of anthropometric indices in parents and in their children during COVID-19 lockdown. METHODS: A cohort of 149 couple parent/children were prospectively enrolled. By a validated questionnaire we explored changes of body mass index (BMI) and individual lifestyle during a 2-month lockdown (May- July 2020). RESULTS: BMI increased in 70.5% of parents and in 67.8% of their children, with a Δ-BMI of 1.44+0.09 kg/ m 2 and 0.36+0.02 Kg/m 2 , respectively. BMI increments, however, were only significant in adults and did not correlate in the couple parents/children. Most adults (80.5%) and children (71.4%) did not perform regular physical activity during the lockdown. Direct correlations between dietary changes and BMI variations became evident in children, mainly in terms of a decreased consumption of fresh fruit, pulses, fish, and an increased consumption of cereals, carbohydrates, dairy products, olive oil. In normal weight, overweight and obese children, but not in adults, the increase in sleep hours increased with BMI. CONCLUSIONS: Despite marked lifestyle changes imposed by the COVID-19 lockdown, BMI variations in parents were independent from those observed in their children, pointing to different outcomes in response to the same external, critical event. Thus, primary prevention measures aimed at maintaining a healthy lifestyle require different approaches according to age.

COVID-19: Specific and Non-Specific Clinical Manifestations and Symptoms: The Current State of Knowledge.

Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become an epidemiological threat and a worldwide concern. SARS-CoV-2 has spread to 210 countries worldwide and more than 6,500,000 confirmed cases and 384,643 deaths have been reported, while the number of both confirmed and fatal cases is continually increasing. COVID-19 is a viral disease that can affect every age group-from infants to the elderly-resulting in a wide spectrum of various clinical manifestations. COVID-19 might present different degrees of severity-from mild or even asymptomatic carriers, even to fatal cases. The most common complications include pneumonia and acute respiratory distress syndrome. Fever, dry cough, muscle weakness, and chest pain are the most prevalent and typical symptoms of COVID-19. However, patients might also present atypical symptoms that can occur alone, which might indicate the possible SARS-CoV-2 infection. The aim of this paper is to review and summarize all of the findings regarding clinical manifestations of COVID-19 patients, which include respiratory, neurological, olfactory and gustatory, gastrointestinal, ophthalmic, dermatological, cardiac, and rheumatologic manifestations, as well as specific symptoms in pediatric patients.

Reduced COVID-19 mortality linked with early antibodies against SARS-CoV-2, irrespective of age.

BACKGROUND: COVID-19 pandemic has generated a million deaths worldwide. The efficiency of the immune system can modulate individual vulnerability with variable outcomes. However, the relationships between disease severity and the titer of antibodies produced against SARS-CoV-2 in non-vaccinated, recently infected subjects need to be fully elucidated. METHODS: A total of 99 patients admitted to a COVID-unit underwent clinical assessment and measurement of serum levels of anti-spike protein (S1) IgM, and anti-nucleocapsid protein IgG. Patients were stratified according to the clinical outcome (i.e., discharged at home or in-hospital death). RESULTS: Following hospitalization, 18 died during the hospital stay. They were older, had lymphopenia, a higher co-morbidity rate, and longer hospital stay than 81 patients who were discharged after healing. Patients in this latter group had, at hospital admittance, 7.9-fold higher serum concentration of IgM, and 2.4-fold higher IgG levels. Multivariate Cox regression models indicated age and anti-nucleocapsid protein IgG concentration at admission as independently associated with the risk of in-hospital death. CONCLUSIONS: An efficient immunological response during the early phase of COVID-19 protects from mortality, irrespective of age. Advanced age is a critical risk factor for poor outcome in infected subjects. Further studies must explore potential therapeutic strategies able to restore a valid functional humoral immunity in elderly patients with poor antibody response during the early stage of COVID-19 infection.

Nitrogen dioxide pollution increases vulnerability to COVID-19 through altered immune function.

Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To explore the relationships between previous exposure to particulate matter < 10 µm (PM10) and nitrogen dioxide (NO2), the clinical outcome following hospital admittance, and lymphocyte subsets in COVID-19 patients with pneumonia. In 147 geocoded patients, we assessed the individual exposure to PM10 and NO2 in the 2 weeks before hospital admittance. We divided subjects according to the clinical outcome (i.e., discharge at home vs in-hospital death), and explored the lymphocyte-related immune function as an index possibly affecting individual vulnerability to the infection. As compared with discharged subjects, patients who underwent in-hospital death presented neutrophilia, lymphopenia, lower number of T CD45, CD3, CD4, CD16/56 + CD3 + , and B CD19 + cells, and higher previous exposure to NO2, but not PM10. Age and previous NO2 exposure were independent predictors for mortality. NO2 concentrations were also negatively related with the number of CD45, CD3, and CD4 cells. Previous NO2 exposure is a co-factor independently affecting the mortality risk in infected individuals, through negative immune effects. Lymphopenia and altered lymphocyte subsets might precede viral infection due to nonmodifiable (i.e., age) and external (i.e., air pollution) factors. Thus, decreasing the burden of air pollutants should be a valuable primary prevention measure to reduce individual susceptibility to SARS-CoV-2 infection and mortality.

Noncommunicable diseases, climate change and iniquities: What COVID-19 has taught us about syndemic.

BACKGROUND: COVID-19 is generating clinical challenges, lifestyle changes, economic consequences. The pandemic imposes to familiarize with concepts as prevention, vulnerability and resilience. METHODS: We analysed and reviewed the most relevant papers in the MEDLINE database on syndemic, noncommunicable diseases, pandemic, climate changes, pollution, resilience, vulnerability, health costs, COVID-19. RESULTS: We discuss that comprehensive strategies must face multifactorial consequences since the pandemic becomes syndemic due to interactions with noncommunicable diseases, climate changes and iniquities. The lockdown experience, on the other hand, demonstrates that it is rapidly possible to reverse epidemiologic trends and to reduce pollution. The worst outcome is evident in eight highly industrialized nations, where 12% of the world population experienced about one-third of all COVID-19-deaths worldwide. Thus, a great economic power has not been fully protective, and a change of policy is obviously needed to avoid irreversible consequences. CONCLUSIONS: We are accumulating unhealthy populations living in unhealthy environments and generating unhealthy offspring. The winning policy should tackle structural inequities through a syndemic approach, to protect vulnerable populations from present and future harms.

Multiplying effects of COVID-19 lockdown on metabolic risk and fatty liver.

BACKGROUND: Social containment measures imposed in Europe during the lockdown to face COVID-19 pandemic can generate long-term potential threats for metabolic health. METHODS: A cohort of 494 non-COVID-19 subjects living in 21 EU countries were interviewed by an anonymous questionnaire exploring anthropometric and lifestyle changes during 1-month lockdown. A subgroup of 41 overweight/obese Italian subjects with previously diagnosed nonalcoholic fatty liver (NAFLD) joined the study following a 12-month follow-up period promoting weight loss by healthy lifestyle. RESULTS: During the lockdown, body weight increased in 55% of subjects (average 2.4 ± 0.9 kg). Weight change increased with age, but not baseline body mass index. Subjects living in Italy had greater weight gain than those living in other European Countries. Weight gain during the lockdown was highest in subjects reporting no physical activity, and low adherence to Mediterranean diet. In the NAFLD group, weight gain occurred in 70% of cases. Subjects reporting weight loss during lockdown had decreased fatty liver score at 3 months before the lockdown, as compared with 1 year before. CONCLUSIONS: Strict measures of social containment-even short-term-pave the way to the increased risk of metabolic abnormalities in the medium-long term. In this context, adherence to Mediterranean diet and regular physical activity play a protective role both in terms of weight gain and fatty liver development/progression, with implication for primary and secondary prevention. When adopting measures imposing social containment, intensive educational campaigns must increase public awareness about beneficial effects of healthy lifestyles.

Pulmonary Artery Filling Defects in COVID-19 Patients Revealed Using CT Pulmonary Angiography: A Predictable Complication?

PURPOSE: This study is aimed at assessing the prevalence of pulmonary artery filling defects (PAFDs) consistent with pulmonary artery embolism (PAE) in patients with SARS-CoV-2 infection and at investigating possible radiological or clinical predictors. MATERIALS AND METHODS: Computed Tomography Pulmonary Angiographies (CTPAs) from 43 consecutive patients with a confirmed COVID-19 infection were retrospectively reviewed, taking into consideration the revised Geneva score and the D-dimer value for each patient. Filling defects within the pulmonary arteries were recorded along with pleural and parenchymal findings such as ground glass opacities, consolidation, crazy paving, linear consolidation, and pleural effusion. All these variables were compared between patients with and without PAFD. The predictive performance of statistically different parameters was investigated using the receiver operating characteristics (ROC). RESULTS: Pulmonary embolism was diagnosed in 15/43 patients (35%), whereas CTPA and parenchymal changes related to pulmonary COVID-19 disease were evident in 39/43 patients (91%). The revised Geneva score and the mean D-dimer value obtained using two consecutive measurements were significantly higher in patients with PAFD. The ROC analysis demonstrated that a mean D-dimer value is the parameter with the higher predictivity (AUC 0.831) that is a cut-off value > 1800 µg/l which predicts the probability of PAFD with a sensitivity and specificity of 70% and 78%, respectively. CONCLUSIONS: This single centre retrospective report shows a high prevalence of pulmonary artery filling defects revealed using CTPA in COVID-19 patients and demonstrates that the mean value of multiple D-dimer measurements may represent a predicting factor of this complication.

Familial Mediterranean Fever and COVID-19: Friends or Foes?

Familial Mediterranean Fever (FMF) and COVID-19 show a remarkable overlap of clinical symptoms and similar laboratory findings. Both are characterized by fever, abdominal/chest pain, elevation of C-reactive protein, and leukocytosis. In addition, colchicine and IL-1 inhibitors treatments that are effective in controlling inflammation in FMF patients have recently been proposed for off-label use in COVID-19 patients. Thus, FMF may resemble a milder recapitulation of the cytokine storm that is a hallmark of COVID-19 patients progressing to severe disease. We analyzed the sequence of the MEFV-encoded Pyrin protein - whose mutations cause FMF- in mammals, bats and pangolin. Intriguingly, although Pyrin is extremely conserved in species that are considered either a reservoir or intermediate hosts for SARS-CoV-2, some of the most common FMF-causing variants in humans are present as wildtype residues in these species. We propose that in humans, Pyrin may have evolved to fight highly pathogenic infections.

Gaining Back What Is Lost: Recovering the Sense of Smell in Mild to Moderate Patients After COVID-19.

The purpose of our cohort study was to quantify olfactory deficits in Coronavirus disease 2019 (COVID-19) patients using Sniffin' Sticks and a pre-post design to evaluate olfactory recovery. Thirty adult patients with laboratory-confirmed mild to moderate forms of COVID-19 underwent a quantitative olfactory test performed with the Sniffin' Sticks test (SST; Burghardt, Wedel, Germany), considering olfactory threshold (T), odor discrimination (D), and odor identification (I). Results were presented as a composite TDI score (range 1-48) that used to define functional anosmia (TDI ≤ 16.5), hyposmia (16.5 < TDI < 30.5), or functionally normal ability to smell (TDI ≥ 30.5). Patients also self-evaluated their olfactory function by rating their ability to smell on a visual analogue scale (Visual Analog Scale rating) and answering a validated Italian questionnaire (Hyposmia Rating Scale). Patients were tested during hospitalization and about 2 months after symptoms onset. During the hospitalization, the overall TDI score indicated that our cohort had impairments in their olfactory ability (10% was diagnosed with anosmia and more than 50% were hyposmic). Almost all patients showed a significant improvement at around 1 month following the first test and for all the parts of the SST except for odor identification. None of the subjects at 1 month was still diagnosed with anosmia. We also quantified the improvement in the TDI score based on initial diagnosis. Anosmic subjects showed a greater improvement than hyposmic and normosmic subjects. In conclusion, within a month time window and 2 months after symptoms' onset, in our cohort of patients we observed a substantial improvement in the olfactory abilities.

COVID-19 and non-alcoholic fatty liver disease: Two intersecting pandemics.

BACKGROUND: Initial evidence from China suggests that most vulnerable subjects to COVID-19 infection suffer from pre-existing illness, including metabolic abnormalities. The pandemic characteristics and high-lethality rate of COVID-19 infection have raised concerns about interactions between virus pathobiology and components of the metabolic syndrome. METHODS: We harmonized the information from the recent existing literature on COVID-19 acute pandemic and mechanisms of damage in non-alcoholic fatty liver disease (NAFLD), as an example of chronic (non-communicable) metabolic pandemic. RESULTS: COVID-19-infected patients are more fragile with underlying metabolic illness, including hypertension, cardiovascular disease, type 2 diabetes, chronic lung diseases (e.g. asthma, chronic obstructive pulmonary disease and emphysema) and metabolic syndrome. During metabolic abnormalities, expansion of metabolically active fat ('overfat condition') parallels chronic inflammatory changes, development of insulin resistance and accumulation of fat in configuring NAFLD. The deleterious interplay of inflammatory pathways chronically active in NAFLD and acutely in COVID-19-infected patients, can explain liver damage in a subgroup of patients and might condition a worse outcome in metabolically compromised NAFLD patients. In a subgroup of patients with NAFLD, the underlying liver fibrosis might represent an additional and independent risk factor for severe COVID-19 illness, irrespective of metabolic comorbidities. CONCLUSIONS: NAFLD can play a role in the outcome of COVID-19 illness due to frequent association with comorbidities. Initial evidences suggest that increased liver fibrosis in NAFLD might affect COVID-19 outcome. In addition, long-term monitoring of post-COVID-19 NAFLD patients is advisable, to document further deterioration of liver damage. Further studies are required in this field.

Covid-19 and ex-smokers: an underestimated prognostic factor?

Dear Editor, The recent and explosive worldwide outbreak of Covid-19 leads many scientists and clinicians to identify the most responsible triggering risk factors in individuals without comorbidities, as well as potential prognostic factors. A notable field of research has been conducted on the role of smoking, which has been initially hypothesized as being a protective factor for Covid-19....

Hepatic consequences of COVID-19 infection. Lapping or biting?

The outbreak of coronavirus disease 2019 (COVID-19) starting last December in China placed emphasis on liver involvement during infection. This review discusses the underlying mechanisms linking COVID-19 to liver dysfunction, according to recent available information, while waiting further studies. The manifestations of liver damage are usually mild (moderately elevated serum aspartate aminotransferase activities), and generally asymptomatic. Few patients can still develop severe liver problems, and therapeutic options can be limited. Liver dysfunction may affect about one-third of the patients, with prevalence greater in men than women, and in elderly. Mechanisms of damage are complex and include direct cholangiocyte damage and other coexisting conditions such as the use of antiviral drugs, systemic inflammatory response, respiratory distress syndrome-induced hypoxia, sepsis, and multiple organ dysfunction. During new COVID-19 infections, liver injury may be observed. If liver involvement appears during COVID-19 infection, however, attention is required. This is particularly true if patients are older or have a pre-existing history of liver diseases. During COVID-19 infection, the onset of liver damage impairs the prognosis, and hospital stay is longer.

COVID-19: Focus on the lungs but do not forget the gastrointestinal tract.

The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared in the last weeks as global pandemic. Currently affecting more than 5 000 000 individuals worldwide, COVID-19 is most commonly associated with symptoms caused by the acute respiratory distress syndrome (ARDS). As the number of infected individuals increases, we are learning that not only lungs, but also other organs can be affected by the virus. The gastrointestinal symptoms, for example diarrhoea, vomiting, nausea or abdominal pain, are frequent in patients with COVID-19. Moreover, alimentary tract symptoms may precede the respiratory presentation of SARS-CoV-2 infection. This can lead to delayed diagnosis and inappropriate management of infected patients. In addition, SARS-CoV-2 nucleic acid can be detected in faeces of infected patients and rectal swabs are even reported to remain positive for a longer period of time than nasopharyngeal swabs. Here, we aim to provide an update on the gastrointestinal involvement of COVID-19 presenting the symptoms that can be encountered in infected patients. We address the role of angiotensin-converting enzyme 2 (ACE2), as a functional receptor for SARS-CoV-2, which also was found in the gastrointestinal tract. Finally, we briefly discuss faecal shedding of SARS-CoV-2 and its potential role in the pathogenesis of the disease.