Search Results (3,967)

SARS-CoV-2, first identified in December 2019, caused a global pandemic, resulting in over 6.8 million deaths by March 2023. The elderly, or individuals over 65, accounted for the majority of COVID-19 deaths, with 81% of fatalities in the US in 2020 occurring in this group. Beyond mortality, aging populations are also at higher risk of long-term cardiovascular complications and acute respiratory distress syndrome (ARDS). Although these outcomes may be influenced by comorbidities common in the elderly, age has been found to be a standalone risk factor for severe COVID-19 infection. Therefore, investigating age-related factors in COVID-19 outcomes is crucial in protecting this vulnerable group. Of particular interest is the cytokine storm phenomenon, an excessive inflammatory response that contributes to severe COVID-19 symptoms, including ARDS and cardiovascular damage. Elevated levels of multiple cytokines are common in severe cases of COVID-19. We propose that changes that occur to cytokine profiles as we age may contribute to these aberrant inflammatory responses. This review specifically explored the interleukin class cytokines IL-1, IL-6, IL-17, and IL-23 and considered the potential of biologics targeting these cytokines to alleviate severe outcomes in both COVID-19 and aging individuals. Full article

Background/Objectives: The coronavirus disease (COVID-19) pandemic was associated with an intense impact on health worldwide. Among the sequelae, it became necessary to clarify respiratory impairment related to lung function and aerobic capacity, as well as the treatment of curative and preventive measures of pulmonary involvement. In this context, this study aimed to compare vital signs, the sensation of dyspnea (Borg scale), lung function, and exercise tolerance before and after the use of non-invasive mechanical ventilation (NIV) in adults of both sexes after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: A cross-sectional analytical clinical study was performed with the inclusion of individuals who had been diagnosed with COVID-19 at least three months before data collection. Individuals were evaluated for vital signs (heart rate and peripheral oxygen saturation), Borg scale, spirometry, and submaximal exercise protocol of two minutes of the step test before and after receiving NIV in ventilation mode by continuous positive airway pressure of 6 cm H₂O for 30 min. Results: A total of 50 participants were enrolled and grouped as a mild (N = 25) or severe (N = 25) clinical phenotype during SARS-CoV-2 infection according to the criteria of the World Health Organization. In our data, the forced vital capacity (p < 0.001), the ratio between the forced expiratory volume in the first one second to the forced vital capacity and the forced vital capacity (p = 0.020), and the two-minute submaximal step exercise protocol (number of steps—p = 0.001) showed a statistical improvement in the severe clinical phenotype group after NIV. In addition, forced expiratory volume in the first one second to the forced vital capacity (p = 0.032) and the two-minute submaximal step exercise protocol (number of steps—p < 0.001) showed a statistical improvement in the mild clinical phenotype group after NIV. No changes were described for vital signs and the Borg scale. Conclusions: This study allowed us to identify that NIV is a tool that promotes better exercise capacity by increasing the number of steps achieved in both clinical phenotype groups and improving lung function observed in the spirometry markers. Full article

The entry and infection of the Severe Acute Respiratory Syndrome Coronavirus 2 virus (SARS-CoV-2) involve recognition and binding of the receptor-binding domain (RBD) of the virus surface spike protein to the peptidase domain (PD) of the host cellular Angiotensin-Converting Enzyme-2 (ACE2) receptor. ACE2 is also involved in normal blood pressure control. An association between hypertension and COVID-19 severity and fatality is evident, but how hypertension predisposes patients diagnosed with COVID-19 to unfavorable outcomes remains unclear. High temperature early during SARS-CoV-2 infection impairs binding to human cells and retards viral progression. Low body temperature can prelude poor prognosis. In this study, all-atom molecular dynamics simulations were performed to examine the effects of high pressure and temperature on RBD/PD binding. A high blood pressure of 940 mmHg enhanced RBD/PD binding. A high temperature above 315 K significantly weakened RBD/PD binding, while a low temperature of 305 K enhanced binding. The curvature of the PD α1-helix and proximity of the PD β3β4-hairpin tip to the RBM motif affected the compactness of the binding interface and, hence, binding affinity. These findings provide novel insights into the underlying mechanisms by which hypertension predisposes patients to unfavorable outcomes in COVID-19 and how an initial high temperature retards viral progression. Full article

The global impact of the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), persists in part due to the emergence of new variants. Understanding variant-specific infection dynamics and pathogenesis in murine models is crucial for identifying phenotypic changes and guiding the development of countermeasures. To address the limitations of earlier studies that investigated only a few variants or used small sample sizes, we evaluated clinical disease, infection kinetics, viral titers, cellular localization, and histopathologic changes in the lungs and brains of transgenic B6.Cg-Tg(K18-ACE2)2Prlmn/J (“K18”) and corresponding genetic control (C57BL/6J) mice expressing human angiotensin-converting enzyme 2 (hACE2). Six SARS-CoV-2 variants were assessed: B.1 (WA1-like), alpha, beta, delta, omicron, and omicron XBB.1.5, using cohorts of ≥18 mice. Following intranasal inoculation with B.1, alpha, beta, or delta variants, K18 mice experienced rapid weight loss and reached euthanasia criteria by 5–6 days post-inoculation (dpi). In contrast, K18 mice inoculated with both omicron variants recovered to their starting weight within 4–6 dpi. Infectious SARS-CoV-2 was detected in the oropharynx at 1 and2 dpi, in the lungs at 2, 4, and 6 dpi, and in the brain at 4 and 6 dpi for all variants except omicron. SARS-CoV-2 nucleoprotein was detected, and interstitial pneumonia of varying severity was observed in K18 mice infected with all variants. Brain lesions were identified in mice infected with the B.1, beta, and delta variants 6 dpi. As K18 mice express hACE2 in the brain—a feature not present in humans—we also compared infection dynamics of three variants to those of a mouse-adapted WA1 strain in C57BL/6J mice lacking the human ACE2 gene. C57BL/6J mice did not experience lethal disease, exhibited milder pneumonia, and had no evidence of neuroinvasion despite similar infection kinetics to K18 mice. These findings demonstrate contrasting phenotypes across the two models and reduced tropism and pathology of omicron compared to earlier variants in both models. This comprehensive analysis of SARS-CoV-2 variants in two mouse models provides valuable insights for model and variant selection for future studies. Full article

Neurological symptoms such as impaired smell and taste have been recognized as hallmark manifestations of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. This study investigates and quantifies microstructural changes in the white matter of the olfactory bulb and taste-related brain regions (frontal operculum, insular cortex and parietal operculum) using diffusion-weighted magnetic resonance imaging (DW-MRI). Apparent diffusion coefficient (ADC) values were measured in patients with confirmed coronavirus disease of 2019 (COVID-19) at the onset of anosmia and ageusia (24 patients, scanned between March and December 2020), 1 month post-infection (20 subjects) and 36 months post-infection (20 participants). ADC values were analyzed over time and compared to normal white matter ADC ranges (calculated retrospectively from 979 pre-pandemic patients) and to those from patients infected with the 2024 strain of SARS-CoV-2 (27 patients). The results revealed significantly elevated ADC values in the white matter of the targeted brain regions, with a peak at the time of infection, followed by a decline 1 month post-infection, and a return to near-normal levels 3 years later. In contrast, the 2024 COVID-19 variant demonstrated reduced virus-related alterations in brain microstructure compared to the 2020 strain. These findings highlight the potential of DWI as a non-invasive tool for elucidating the molecular mechanisms underlying olfactory and taste dysfunction in COVID-19 patients. Full article

Inflammatory cardiomyopathy is a condition that is characterised by the presence of inflammatory cells in the myocardium, which can lead to a significant deterioration in cardiac function. The etiology of this condition involves multiple factors, both infectious and non-infectious causes. While it is primarily associated with viral infections, other potential causes include bacterial, protozoal, or fungal infections, as well as a wide variety of toxic substances and drugs, and systemic immune-mediated pathological conditions. In spite of comprehensive investigation, the presence of inflammatory cardiomyopathy accompanied by left ventricular dysfunction, heart failure or arrhythmia is indicative of an unfavourable outcome. The reasons for the occurrence of either favourable outcomes, characterised by the absence of residual myocardial injury, or unfavourable outcomes, marked by the development of dilated cardiomyopathy, in patients afflicted by the condition remain to be elucidated. The relative contributions of pathogenic agents, genomic profiles of the host, and environmental factors in disease progression and resolution remain subjects of ongoing discourse. This includes the determination of which viruses function as active inducers and which merely play a bystander role. It remains unknown which changes in the host immune profile are critical in determining the outcome of myocarditis caused by various viruses, including coxsackievirus B3 (CVB3), adenoviruses, parvoviruses B19 and SARS-CoV-2. The objective of this review is unambiguous: to provide a concise summary and comprehensive assessment of the extant evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy. Its focus is exclusively on virus-induced and virus-associated myocarditis. In addition, the extant lacunae of knowledge in this field are identified and the extant experimental models are evaluated, with the aim of proposing future directions for the research domain. This includes differential gene expression that regulates iron and lipid and metabolic remodelling. Furthermore, the current state of knowledge regarding the cardiovascular implications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is also discussed, along with the open questions that remain to be addressed. Full article

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underwent significant mutations, resulting in the Omicron variant. Methods: In this study, we analyzed blood samples from 98 patients with acute coronavirus disease 19 (COVID-19) hospitalized during the initial SARS-CoV-2 wave and the onset of Omicron in 2021. High-resolution melting (HRM) analysis of PCR products was used to analyze RNA extracted from clinical samples collected in July and November 2021 from patients infected with SARS-CoV-2. Results: HRM analysis revealed a characteristic deletion in the N protein RNA of the virus isolated in November 2021, associated with the Omicron variant. Elevated levels of inflammatory markers and interleukin-6 (IL-6) were observed in both waves of COVID-19. Complement levels and IgG and IgM antibodies to SARS-CoV-2 were detected more often during the second wave. An increase in hemagglutinin-inhibiting (HI) antibodies against influenza viruses was observed in paired blood specimens from moderate to severe COVID-19 patients during both outbreaks. Conclusions: Patients admitted during both waves of COVID-19 showed a significant rise in inflammatory markers, suggesting that Omicron triggers inflammatory responses. The rapid formation of IgM and IgG in Omicron may indicate a faster immune response. Seasonal flu may negatively impact the clinical course of coronavirus infections. Full article

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) can damage the endothelium and increase arterial stiffness, potentially leading to adverse cardiovascular events. In parallel, systemic inflammation in COVID-19 also impacts endothelial function. Angiotensin-converting enzyme 2 (ACE2) promotes vasodilation and anti-inflammatory effects, but also facilitates SARS-CoV-2 entry into human cells. Thus, concerns have been raised about the use of RAAS inhibitors (RAASi) in COVID-19 patients due to potential ACE2 upregulation. However, the clinical significance of increased plasma ACE2 (sACE2) in RAASi-treated COVID-19 patients remains unclear. Methods: This prospective, single-centre study evaluated RAASi, sACE2, and vascular function in acutely ill patients with COVID-19 in comparison with acutely ill patients without COVID-19. Adult emergency department patients with confirmed or suspected COVID-19 were enrolled and underwent pulse wave velocity, ankle brachial index, and sACE2 measurements. Results: In the 152 included patients (50% female, median age 62 years, 68% COVID-19 positive), the sACE2 values were slightly higher in the COVID-19 (0.485 [0.364–1.329]) than in the non-COVID-19 subgroup (0.458 [0.356–1.138]; p = 0.70). No significant differences in sACE2 were observed between patients with and without RAASi, regardless of COVID-19 status. Pulse wave velocity values differed significantly between groups (p = 0.015). Conclusions: In emergency department patients, sACE2 was upregulated in COVID-19 patients, probably due to oxidative stress and inflammation. RAASi did not increase sACE2, but may have protective effects against inflammation. Elevated sACE2 appeared to have a beneficial effect on arterial stiffness in all patients. These findings support continued RAASi therapy in COVID-19 patients to protect against chronic inflammation and apoptosis. Full article

The peptide TAT-I24, a fusion of the TAT peptide (amino acids 48–60) and the 9-mer peptide I24, has been previously shown to neutralize several double-stranded (ds) DNA viruses in vitro. We have now extended the testing to potentially sensitive RNA viruses and analyzed the antiviral effect of the peptide against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). In Vero E6 cells, TAT-I24 neutralized the human 2019-nCoV isolate (Wuhan variant) in a dose-dependent manner, while it was unable to neutralize two SARS-CoV-2 variants of concern, Delta and Omicron. Moreover, TAT-I24 could not significantly neutralize any of the SARS-CoV-2 variants in the human lung carcinoma cell line Calu-3, which provides an alternative entry route for SARS-CoV-2 by direct membrane fusion. Therefore, a possible dependence on virus uptake by endocytosis was investigated by exposing Vero E6 cells to chloroquine (CQ), an inhibitor of endosomal acidification. The Wuhan variant was highly sensitive to inhibition by CQ, an effect which was further enhanced by TAT-I24, while the Delta variant was less sensitive to inhibition by higher concentrations of CQ compared to the Wuhan variant. The microscopic analysis of COS-7 cells using a rhodamine-labeled TAT-I24 (Rho-TAT-I24) showed the endosomal localization of fluorescent TAT-I24 and co-localization with transfected GFP-Rab14 but not GFP-Rab5. As these proteins are found in distinct endosomal pathways, our results indicate that the virus entry pathway determines sensitivity to the peptide. Full article

Background: Patients with liver cirrhosis are at an increased risk of mortality from coronavirus disease 2019 (COVID-19). Remdesivir, an adenosine analog, exhibits activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is thus recommended for inpatients with COVID-19. This study evaluated the effectiveness and safety of remdesivir in patients with COVID-19 and liver cirrhosis. Methods: This retrospective study was conducted using data from Taiwan’s largest healthcare system. The study cohort comprised adult patients with COVID-19 and liver cirrhosis who visited our emergency department between April 2021 and September 2022. Remdesivir’s adverse effects, including bradycardia, anemia, unstable glucose levels, and abnormal liver function test results, were recorded. Treatment outcomes were assessed in terms of hospitalization duration, mortality, intubation, and intensive care unit admission. Results: This study included 1368 patients with COVID-19 and liver cirrhosis, of whom 46 received remdesivir. Remdesivir recipients were older (66.5 vs. 62 years; p = 0.042) and had a higher rate of oxygen therapy use (56.52% vs. 32.22%; p = 0.001) than nonrecipients. Common adverse effects of remdesivir included lower heart rates (83 vs. 96 bpm; p < 0.001) and decreased hemoglobin levels (9.5 vs. 10.2 g/dL; p = 0.003) without fatal consequences. No statistically significant difference between remdesivir recipients and nonrecipients in hospitalization duration, intubation rates, or mortality rates was found. Conclusions: Remdesivir is safe for treating COVID-19 in patients with liver cirrhosis. Although remdesivir recipients exhibited trends toward improved outcomes in our study, large-scale studies are required to confirm its efficacy in this population. Full article

The global outbreak of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the strategies adopted by different nations have affected and altered the transmission of different respiratory pathogens around the world. We examined the impact of SARS-CoV-2 on the spread of respiratory viruses in the period between 2021 and 2024 in patients with severe influenza-like symptoms in the Lazio region using multiplex PCR tests for the identification of common seasonal respiratory viruses. Our data reveal a change in the transmission of respiratory viruses from 2021 to 2024, with a sharp decline in the transmission of SARS-CoV-2 and a rise in the transmission of other respiratory viruses, especially influenza viruses, and human rhinovirus/enterovirus in 2024. Moreover, viral co-infections, both those involving two viruses and those involving three viruses, have also increased. This work shows how the spread of SARS-CoV-2 influenced the spread of other respiratory viruses over four years in patients with severe influenza-like symptoms in the Lazio region. In conclusion, the resurgence and fluctuation of various respiratory viruses emphasize the dynamic nature of viral epidemiology in the post-pandemic context and highlight the ongoing need for vigilant public health monitoring and intervention strategies. Full article

Background: The clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is broad; it can range from asymptomatic cases to mild upper respiratory tract illness, respiratory failure, and severe multiorgan failure resulting in death. Therefore, it is important to identify the clinical course of the disease and the factors associated with mortality. Objective: The aim of this study is to identify the risk factors associated with the severity of the disease, intensive care unit admission, and mortality in COVID-19 patients. Methods: A total of 1075 patients with clinical and radiological findings compatible with COVID-19 pneumonia and positive SARS-CoV-2 PCR were selected and retrospectively screened. All included patients were classified according to the 7th edition of the 2019 Coronavirus Disease Guidelines published by the National Health Commission of China. Results: It was observed that elevated white blood count (WBC) increased the severity of COVID-19 by 3.26 times and the risk of intensive care unit (ICU) admission by 3.47 times. Patients with high D-dimer levels had a 91% increased risk, and those with high fibrinogen levels had a 2.08 times higher risk of severe disease. High C-reactive protein (CRP) values were found to increase disease severity by 6.89 times, mortality by 12.84 times, and ICU admission by 3.37 times. Conclusions: Identifying the factors associated with disease severity, ICU admission, and mortality in COVID-19 patients could help reduce disability and mortality rates in pandemics. Full article

Background/Objectives: Cancer represents an important risk factor for acquiring severe acute respiratory syndrome by Coronavirus-2 (SARS-CoV-2) and subsequent hospitalization. The utility of early antiviral therapies, including their protective effect on long COVID outcomes, in cancer patients has not yet been clearly demonstrated. We conducted the CO.THER study (COVID-19 THErapies in patients with canceR) to address this knowledge gap. Methods: We designed an ambispective single-center cohort study. We collected clinical and oncological data from the hospital’s electronic patient records at the start of COVID-19 therapy (T0), seven days after T0 (T1), two weeks after T0 (T2), one month after T0 (T3), three months after T0 (T4), six months after T0 (T5), and twelve months after T0 (T6). The primary endpoint of this ambispective single-center cohort study was the rate of hospitalization for COVID-19 disease within 14 days in cancer patients using anti-SARS-CoV-2 early therapies. The proportion of hospitalizations within 14 days (primary endpoint) was computed together with its exact binomial 95% confidence interval (95%CI). Results: 131 patients’ records (53M [40.5%], 78F, [59.5%]; median age 62.45, interquartile range [IQR] 56–71) were enrolled. As shown by the Kaplan–Meier hospitalization-free estimate, only three patients (2.1%) were hospitalized for a COVID-19 related cause within 14 days of starting early treatment (95%CI 0.5–6.6%). The cumulative survival probability beyond 12 months in hospitalization-free patients was 98% (95%CI 93–99%). Twelve patients (9.2%) reported another COVID-19 infection during the follow-up and they were all retreated with Nirmatrelvir–Ritonavir. The cumulative reinfection-free survival was 90% at 12 months (95%CI 83–95%). Further, 15 patients of the 123 evaluable at 3 months (median age 51 years, IQR 40–68) reported long COVID symptoms (12.2%, 95%CI 7.0–19.3%). Conclusions: Our data demonstrate a low rate of hospitalization and reassuring data on safety in this cohort of high-risk subjects. Full article

Patients infected with SARS-CoV-2 may develop mild respiratory symptoms but also Acute Respiratory Distress Syndrome (ARDS). Additionally, severe systemic inflammation contributes to morbidity and mortality. The SARS-CoV-2 virus enters the cell by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, followed by cleavage by transmembrane serine protease 2 (TMPRSS2). Vasoactive intestinal peptide (VIP) is known for its immune-modulating effects by suppressing the release of pro-inflammatory cytokines and enhancing regulatory T-cells. Furthermore, it has been tested in SARS-CoV-2-related clinical trials. We set out to investigate its role in the setting of SARS-CoV-2 infection in vitro. Epithelial cells (CaCo-2) were stimulated with SARS-CoV-2 spike protein, treated with native VIP and analyzed to investigate the mRNA and surface expression of ACE2 and TMPRSS2, the enzyme activity of TMPRSS2 and the infection rate by a SARS-CoV-2 pseudovirus. VIP downregulated ACE2 and TMPRSS2 mRNA and surface expression. Beyond these direct effects, VIP mediates the shedding of surface-expressed ACE2 and TMPRSS2 via upregulation of a sheddase protease (ADAM10). Functionally, these dual mechanisms of VIP-mediated downregulation of proteins involved in SARS-CoV-2 cell entry resulted in a reduced infection rate by the SARS-CoV-2 pseudovirus. These data imply that VIP hampers viral entry mechanisms based on SARS-CoV-2 and the linkage to ADAM10 may stimulate research in other indications beyond SARS-CoV-2. Full article

Nano-luciferase binary technology (NanoBiT)-based pseudoviral sensors are innovative tools for monitoring viral infection dynamics. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells via its trimeric surface spike protein, which binds to the human angiotensin-converting enzyme II (hACE2) receptor. This interaction is crucial for viral entry and serves as a key target for therapeutic interventions against coronavirus disease 2019 (COVID-19). Aptamers, short single-stranded DNA (ssDNA) or RNA molecules, are highly specific, high-affinity biorecognition elements for detecting infective pathogens. Despite their potential, optimizing viral infection assays using traditional protein–protein interaction (PPI) methods often face challenges in optimizing viral infection assays. In this study, we selected and evaluated aptamers for their ability to interact with viral proteins, enabling the dynamic visualization of infection progression. The NanoBiT-based pseudoviral sensor demonstrated a rapid increase in luminescence within 3 h, offering a real-time measure of viral infection. A comparison of detection technologies, including green fluorescent protein (GFP), luciferase, and NanoBiT technologies for detecting PPI between the pseudoviral spike protein and hACE2, highlighted NanoBiT’s superior sensitivity and performance, particularly in aptamer selection. This bioluminescent system provides a robust, sensitive, and early-stage quantitative approach to studying viral infection dynamics. Full article