COVID-19 and its long-term sequelae: what do we know in 2023?

Post­viral syndrome is a well­known medical condition characterized by different levels of physical, cognitive, and emotional impairment that may persist with fluctuating severity after recovering from an acute viral infection. Unsurprisingly, COVID­19 may also be accompanied by medium- and long­term clinical sequelae after recovering from a SARS­CoV­2 infection. Although many clinical definitions have been provided, "long­COVID" can be defined as a condition occurring in patients with a history of SARS­CoV­2 infection, developing 3 months from the symptoms onset, persisting for at least 2 months, and not explained by alternative diagnoses. According to recent global analyses, the cumulative prevalence of long­COVID seems to range between 9% and 63%, and is up to 6­fold higher than that of similar postviral infection conditions. Long­COVID primarily encompasses the presence of at least 1 symptom, such as fatigue, dyspnea, cognitive impairment / brain fog, postexertional malaise, memory issues, musculoskeletal pain / spasms, cough, sleep disturbances, tachycardia / palpitations, altered smell / taste perception, headache, chest pain, and depression. The most important demographic and clinical predictors to date are female sex, older age, cigarette smoking, pre­existing medical conditions, lack of COVID­19 vaccination, infection with pre­Omicron SARS­CoV­2 variants, number of acute phase symptoms, viral load, severe / critical COVID­19 illness, as well as invasive mechanical ventilation. Concerning the care for long­COVID patients, the greatest challenge is the fact that this syndrome cannot be considered a single clinical entity, and thus it needs an integrated multidisciplinary management, specifically tailored to the type and severity of symptoms.

Exercise effects on cardiovascular disease: from basic aspects to clinical evidence.

Cardiovascular (CV) disease (CVD) remains the leading cause of major morbidity and CVD- and all-cause mortality in most of the world. It is now clear that regular physical activity (PA) and exercise training (ET) induces a wide range of direct and indirect physiologic adaptations and pleiotropic benefits for human general and CV health. Generally, higher levels of PA, ET, and cardiorespiratory fitness (CRF) are correlated with reduced risk of CVD, including myocardial infarction, CVD-related death, and all-cause mortality. Although exact details regarding the ideal doses of ET, including resistance and, especially, aerobic ET, as well as the potential adverse effects of extreme levels of ET, continue to be investigated, there is no question that most of the world's population have insufficient levels of PA/ET, and many also have lower than ideal levels of CRF. Therefore, assessment and promotion of PA, ET, and efforts to improve levels of CRF should be integrated into all health professionals' practices worldwide. In this state-of-the-art review, we discuss the exercise effects on many areas related to CVD, from basic aspects to clinical practice.

Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm.

The "novel" coronavirus disease 2019 (abbreviated "COVID-19") is the third coronavirus outbreak emerging during the past two decades. This infectious disease, sustained by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has been recently declared a global pandemic by the World Health Organization. Despite the concerning epidemiological burden, many people, including some policymakers, are underestimating this pandemic and are remaining enigmatically inactive against a human pathology which, for a combination of reasons, can be reasonably defined as a perfect storm (i.e., the "wrong virus" at the "wrong time"). These many paradigmatic aspects include SARS-CoV-2 structure and peculiar biology of infection, high risk of inter-human transmission, long incubation time combined with early and sustained viral load, existence of asymptomatic or mildly-symptomatic carriers, viral shedding for days after symptom relief, unfavorable progression towards respiratory distress and death in up to 5-10% of patients thus causing dramatic healthcare challenges, as well as environmental contamination. Last but not least, the combination of the current case fatality rate with the extraordinary number of people that could be potentially infected by SARS-CoV-2 would permit to estimate that the worldwide deaths for COVID-19 may even approximate those recorded during World War II if appropriate restrictive measures for preventing human-to-human transmission are not readily undertaken. Everybody should be inexcusably aware that this is not a drill, and that the consequences of inadequate action will be tragedy.

Coronavirus disease 2019, hypertension, and renin-angiotensin-aldosterone system inhibitors.

PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mostly uses the angiotensin-converting enzyme 2 (ACE-2) as cellular receptor for entering the host cells. Some, but not all, animal studies have shown that renin-angiotensin-aldosterone system (RAAS) inhibitors can increase ACE-2 expression. On that premise, it was hypothesized that these agents could make it more likely to develop coronavirus disease 2019 (COVID-19). On the other hand, there was also evidence that being on these agents could lessen the severity of the lung injury in patients with severe SARS-CoV-2 infection. Herein, we review the available evidence on the role of RAAS inhibitors on SARS-CoV-2 and COVID-19 development. RECENT FINDINGS: Recent randomized controlled trials demonstrate that RAAS blockade or withdrawal does not influence the severity of COVID-19 in patients who are already on these medications. Currently, there is no evidence to support stopping RAAS inhibitors in patients hospitalized for COVID-19. Several questions still need to be addressed. Ongoing studies are currently evaluating the de novo use of RAAS inhibitors in patients with COVID-19. Another area that needs to be investigated is whether or not using these medications increase the risk of infection. SUMMARY: The wealth of evidence indicates that ACE inhibitors and angiotensin-receptor blocker administration has no harmful effects on hospitalizations and severity of COVID-19 in patients already on these medications and might even reduce mortality among hypertensive patients diagnosed with COVID-19. More evidence and data need to be collected, and at this time, these agents should not be discontinued.

Metabolic Impacts of Confinement during the COVID-19 Pandemic Due to Modified Diet and Physical Activity Habits.

While the detrimental effects of a chronic positive energy balance due to a sedentary lifestyle have been well established, the impacts of a short period of abruptly reduced physical activity and overeating arising from strict confinement due to the COVID-19 pandemic will soon start to emerge. To reasonably anticipate major consequences according to the available evidence, we hereby review the literature for studies that have explored the health impacts of several weeks of a reduction in physical activity and daily step-count combined with modified eating habits. These studies identify as main metabolic consequences increases in insulin resistance, total body fat, abdominal fat and inflammatory cytokines. All these factors have been strongly associated with the development of metabolic syndrome, which in turn increases the risk of multiple chronic diseases. A plausible mechanism involved in these impacts could be a positive energy balance promoted by maintaining usual dietary intake while reducing energy expenditure. This means that just as calorie intake restriction could help mitigate the deleterious impacts of a bout of physical inactivity, overeating under conditions of home confinement is very likely to exacerbate these consequences. Moreover, hypertension, diabetes, and cardiovascular disease have been identified as potential risk factors for more severely ill patients with COVID-19. Thus, adequate control of metabolic disorders could be important to reduce the risk of severe COVID-19.

Cardiac magnetic resonance in the diagnosis of the unusually detected acute myocarditis in the young people: a case report.

Myocarditis is among the causes of arrhythmic sudden cardiac death (SCD) in young athletes, with viral infection being the most common cause worldwide. Myocarditis recently has been reported as one of the cardiac complications of coronavirus disease 2019 (COVID-19) in athletes. Here we present a case of a 20-year-old male recreational soccer player with an episode of loss of consciousness in the context of respiratory infection. The patient reports having woken up with symptoms of an upper respiratory tract infection, and after playing a soccer match, he developed dizziness and a headache. He then suffered vasovagal syncope without loss of sphincter control. Physical examination, heart auscultation, peripheral and carotid pulses, and blood, microbiological/serological tests result on admission were normal. Moreover, no jugular engorgement at 45º, malleolar edema, or other heart failure signs were found. The 12-lead electrocardiogram (ECG), echocardiogram, 24-hour Holter-ECG did not reveal any significant finding. A cardiac magnetic resonance (CMR) was finally performed, revealing an abnormal signal increase was observed at the apical level in the short-tau inversion-recovery (STIR) and 4-chamber sequences. In addition, a pattern of apical fibrosis was observed in 4- and 2-chamber and short-axis late enhancement sequences for assessment of myocardial viability confirming the diagnosis of myocarditis. In athletes with suspected myocarditis, CMR seems to be a useful diagnostic tool, with excellent sensitivity for detecting inflammation, myocardial edema, and/or focal scarring.

Physical Activity, Screen Time, Sedentary and Sleeping Habits of Polish Preschoolers during the COVID-19 Pandemic and WHO's Recommendations: An Observational Cohort Study.

BACKGROUND: Restrictions related to the COVID-19 pandemic may lead to a significant decrease in physical activity, an increase in sedentary behavior, and thus also such things as screen time or a change in health behavior patterns. The survey aimed to compare levels of physical activity, screen time, hours spent sitting and sleeping time among Polish children aged 3-5 years of age before and during the COVID-19 pandemic. METHODS: We identified 3000 respondents under five years of age, at Polish kindergartens. The questionnaire consists of 62 questions according to the recommendations of health behavior in school-aged children. The questionnaire was completed by the parents of these children. RESULTS: Only 30.77% of children complied with WHO criteria before the pandemic. During the pandemic, the percentage of children meeting the recommendations for physical activity decreased even more. Children spent much more time in a sitting position before the restrictions. The children slept as recommended 10-13 h a day, and the pandemic caused an increase in sleep duration of 10-18%. Most children had a limited time allowed for the use of electronic devices already before the pandemic, but during the pandemic the results negatively decreased by 71.54%. CONCLUSIONS: The results clearly indicate decreased physical activity and increased screen time. It is also crucial to develop recommendations for prevention management strategies of sedentary lifestyles in the youngest group.

Cytokeratin 18 cell death assays as biomarkers for quantification of apoptosis and necrosis in COVID-19: a prospective, observational study.

BACKGROUND: The mechanism by which SARS-CoV-2 triggers cell damage and necrosis are yet to be fully elucidated. We sought to quantify epithelial cell death in patients with COVID-19, with an estimation of relative contributions of apoptosis and necrosis. METHODS: Blood samples were collected prospectively from adult patients presenting to the emergency department. Circulating levels of caspase-cleaved (apoptosis) and total cytokeratin 18 (CK-18) (total cell death) were determined using M30 and M65 enzyme assays, respectively. Intact CK-18 (necrosis) was estimated by subtracting M30 levels from M65. RESULTS: A total of 52 COVID-19 patients and 27 matched sick controls (with respiratory symptoms not due to COVID-19) were enrolled. Compared with sick controls, COVID-19 patients had higher levels of M65 (p = 0.046, total cell death) and M30 (p = 0.0079, apoptosis). Hospitalised COVID-19 patients had higher levels of M65 (p= 0.014) and intact CK-18 (p= 0.004, necrosis) than discharged patients. Intensive care unit (ICU)-admitted COVID-19 patients had higher levels of M65 (p= 0.004), M30 (p= 0.004) and intact CK-18 (p= 0.033) than hospitalised non-ICU admitted patients. In multivariable logistic regression, elevated levels of M65, M30 and intact CK-18 were associated with increased odds of ICU admission (OR=22.05, p=0.014, OR=19.71, p=0.012 and OR=14.12, p=0.016, respectively). CONCLUSION: Necrosis appears to be the main driver of hospitalisation, whereas apoptosis and necrosis appear to drive ICU admission. Elevated levels CK-18 levels are independent predictors of severe disease, and could be useful for risk stratification of COVID-19 patients and in assessment of therapeutic efficacy in early-phase COVID-19 clinical trials.