Search Results (740)

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: Growing interest in post-viral conditions following COVID-19 infection has led researchers and clinicians to develop several definitions of post-COVID-19 syndrome. This study aimed to understand the meaning given to post-COVID-19 syndrome by individuals who survived the first wave of the pandemic two years after its onset. Methods: A descriptive qualitative study was performed according to the Standards for Reporting Qualitative Research guidelines. An inductive and content analysis were adopted on narratives collected via the interview of patients who had been infected with SARS-CoV-2 during the first pandemic wave in the Friuli Venezia Giulia Region (Italy). Results: This study included 230 patients, of whom 158 experienced post-COVID-19 syndrome, and 46 (29.1%) reported suffering from this condition 24 months after the infection. On average, patients experienced three symptoms, with most of them experiencing at least one. Seventy-five patients reported being familiar with the definition of the post-COVID-19 syndrome, mainly through media and the internet (28.9% and 28.2%, respectively). The post-COVID-19 syndrome was described as characterized by two themes: (a) the experience of interrelated physical and psychological symptoms and (b) the experience of fighting like warriors for a long time. Conclusions: The post-COVID-19 syndrome is highly prevalent but poorly understood. Patients rely on low-quality information rather than that offered by clinicians. The post-COVID-19 syndrome appears to be a complex syndrome encompassing physical and mental symptoms, as well as those disabling the person with an unclear trajectory. There is a need to focus on the long-term consequences of COVID-19, incorporating insights from individuals’ lived experiences. Full article

Introduction: Desirable outcome after venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome (ARDS) is frequently defined by survival. However, quality of life (QoL) and mental health status may take precedence over mere survival, from a patient-centered perspective. We aimed to evaluate QoL and mental health status in survivors after V-V ECMO for coronavirus disease 2019 (COVID-19)-related ARDS, hypothesizing a similar QoL comparable to the general population. Methods: All patients supported with venovenous ECMO for COVID-19-related ARDS between 01/2020 and 03/2022 in our center were included. Survivors were invited to participate in a follow-up interview assessing QoL, anxiety, and depression one year after hospital discharge. Primary endpoint was the quality of life, measured by the SF-36 questionnaire, with results compared to data from the DEGS1 study (German normative population). Results: During the study period, 97 patients received venovenous ECMO for COVID-19 ARDS at our ICU. Overall, 43/97 (44.3%) survived, and 21/97 (21.6%) completed the SF-36 questionnaire. The median follow-up duration was 1.7 years. Patients who completed the SF-36 were significantly younger than those who did not (48.7 vs. 55.6 years, p = 0.012); other patient characteristics and ECMO parameters were similar between those with and without questionnaire. Anxiety, depression, and post-traumatic stress disorder were detected in 33%, 14%, and 29% of patients, respectively. Compared to the German normative population, ECMO survivors had significantly lower QoL (mean 77.2 vs. 61.0, p < 0.001). Conclusions: QoL and mental health status after venovenous ECMO for ARDS was significantly lower compared to the normative population. These findings highlight the importance of further research and comprehensive follow-up care for ECMO survivors. Full article

Increasing long-term observations suggest that coronavirus disease 2019 (COVID-19) vasculopathy may persist even 1.5 years after the acute phase, potentially accelerating the development of atherosclerotic cardiovascular diseases. This study systematically reviewed the variability of brachial flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (cfPWV) from the acute phase of COVID-19 through 16 months of follow-up (F/U). Databases including PubMed, Web of Science, MEDLINE, and Embase were screened for a meta-analysis without language or date restrictions (PROSPERO reference CRD42025642888, last search conducted on 1 February 2025). The quality of the included studies was assessed using the Newcastle–Ottawa Quality Scale. We considered all studies (interventional pre-post studies, prospective observational studies, prospective randomized, and non-randomized trials) that assessed FMD or cfPWV in adults (aged ≥ 18 years) with or after laboratory-confirmed COVID-19 compared with non-COVID-19 controls or that assessed changes in these parameters during the F/U. Twenty-one studies reported differences in FMD, and 18 studies examined cfPWV between COVID-19 patients and control groups during various stages: acute/subacute COVID-19 (≤30 days from disease onset), early (>30–90 days), mid-term (>90–180 days), late (>180–270 days), and very late (>270 days) post-COVID-19 recovery. Six studies assessed variability in FMD, while nine did so for cfPWV during the F/U. Data from 14 FMD studies (627 cases and 694 controls) and 15 cfPWV studies (578 cases and 703 controls) were included in our meta-analysis. FMD showed a significant decrease compared to controls during the acute/subacute phase (standardized mean difference [SMD]= −2.02, p < 0.001), with partial improvements noted from the acute/subacute phase to early recovery (SMD = 0.95, p < 0.001) and from early to mid-term recovery (SMD = 0.92, p = 0.006). Normalization compared to controls was observed in late recovery (SMD = 0.12, p = 0.69). In contrast, cfPWV values, which were higher than controls in the acute/subacute phase (SMD = 1.27, p < 0.001), remained elevated throughout the F/U, with no significant changes except for a decrease from mid-term to very late recovery (SMD= −0.39, p < 0.001). In the very late recovery, cfPWV values remained higher than those of controls (SMD = 0.45, p = 0.010). In the manuscript, we discuss how various factors, including the severity of acute COVID-19, the persistence of long-term COVID-19 syndrome, and the patient’s initial vascular age, depending on metrics age and cardiovascular risk factors, influenced the time and degree of FMD and cfPWV improvement. Full article

Long COVID following SARS-CoV-2 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) following infectious mononucleosis (IM) are two examples of post-viral syndromes. The identification of risk factors predisposing patients to developing and maintaining post-infectious syndromes may help uncover their underlying mechanisms. The majority of patients with ME/CFS report infectious illnesses before the onset of ME/CFS, with 30% of cases of ME/CFS due to IM caused by the Epstein–Barr virus. After developing IM, one study found 11% of adults had ME/CFS at 6 months and 9% had ME/CFS at 1 year. Another study of adolescents found 13% and 7% with ME/CFS at 6 and 12 months following IM, respectively. However, it is unclear which variables are potential risk factors contributing to the development and maintenance of ME/CFS following IM, because few prospective studies have collected baseline data before the onset of the triggering illness. The current article provides an overview of a study that included pre-illness predictors of ME/CFS development following IM in a diverse group of college students who were enrolled before the onset of IM. Our data set included an ethnically and sociodemographically diverse group of young adult students, and we were able to longitudinally follow these youths over time to better understand the risk factors associated with the pathophysiology of ME/CFS. General screens of health and psychological well-being, as well as blood samples, were obtained at three stages of the study (Stage 1—Baseline—when the students were well, at least 6 weeks before the student developed IM; Stage 2—within 6 weeks following the diagnosis of IM, and Stage 3—six months after IM, when they had either developed ME/CFS or recovered). We focused on the risk factors for new cases of ME/CFS following IM and found factors both at baseline (Stage 1) and at the time of IM (Stage 2) that predicted nonrecovery. We are now collecting seven-year follow-up data on this sample, as well as including cases of long COVID. The lessons learned in this prospective study are reviewed. 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

An exhausted antiviral immune response is observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-SARS-CoV-2 syndrome, also termed long COVID. In this study, potential mechanisms behind this exhaustion were investigated. First, the viral load of Epstein–Barr virus (EBV), human adenovirus (HAdV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV6), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was determined in sputum samples (n = 29) derived from ME/CFS patients (n = 13), healthy controls (n = 10), elderly healthy controls (n = 4), and immunosuppressed controls (n = 2). Secondly, autoantibodies (autoAbs) to type I interferon (IFN-I) in sputum were analyzed to possibly explain impaired viral immunity. We found that ME/CFS patients released EBV at a significantly higher level compared to controls (p = 0.0256). HHV6 was present in ~50% of all participants at the same level. HAdV was detected in two cases with immunosuppression and severe ME/CFS, respectively. HCMV and SARS-CoV-2 were found only in immunosuppressed controls. Notably, anti-IFN-I autoAbs in ME/CFS and controls did not differ, except in a severe ME/CFS case showing an increased level. We conclude that ME/CFS patients, compared to controls, have a significantly higher load of EBV. IFN-I autoAbs cannot explain IFN-I dysfunction, with the possible exception of severe cases, also reported in severe SARS-CoV-2. We forward that additional mechanisms, such as the viral evasion of IFN-I effect via the degradation of IFN-receptors, may be present in ME/CFS, which demands further studies. Full article

On 11 March 2020, the World Health Organization (WHO) declared a pandemic caused by SARS-CoV-2, raising global health concerns. Reports of persistent and new symptoms following the acute phase of infection highlighted the complexities of recovery and prompted the investigation of what is now termed long COVID. Officially recognized by the WHO in October 2021, long COVID presents various health implications, though the terminology—such as post-COVID syndrome and post-acute sequelae of COVID-19 (PASC)—remains inconsistent, complicating diagnostic standardization. Long COVID affects an estimated 10% to 30% of SARS-CoV-2-infected individuals, with common symptoms including fatigue, dyspnea, cognitive dysfunction, and joint pain, all of which significantly impair quality of life. Public perception is influenced by factors like education and health history, while misinformation and stigma hinder accurate diagnosis and treatment. The absence of biomarkers and overlap with other post-viral syndromes further complicate clinical recognition. Experts emphasize the need for refined diagnostic criteria and integrated strategies combining biomedical research, public policy, and educational initiatives to improve clinical management, address healthcare inequalities, and mitigate the impacts of long COVID. This review unveils the state of the art and knowledge gaps to encourage discussion, with the aim of achieving better clinical decision-making and public awareness related to long COVID. Full article

Objectives: To compare the health status, exercise capacity, and health-related quality of life (HRQoL) in survivors of COVID-19-associated acute respiratory distress syndrome (ARDS) at 8, 12, and 24 months post-diagnosis. Methods: We conducted a prospective, single-center follow-up study embedded within a larger multicenter cohort of adults with COVID-19 who required hospital admission. Eligible participants underwent clinical interviews, physical examinations, chest radiography, and the 6-min walk test (6MWT). Standardized scales were used to assess post-traumatic stress disorder (PTSD), anxiety, depression, and HRQoL. Results: Out of 1295 patients with COVID-19, 365 developed ARDS, of whom 166 survived. After excluding deaths and loss to follow-up, 95 patients were monitored for 24 months. Over 60% of patients had persistent symptoms, though significant improvements were recorded in quality of life and physical recovery. More than 70% recovered their previous physical capacity, but 15% did not return to their usual lifestyle habits. Symptoms such as arthralgia and fatigue decreased, but cognitive issues, such as memory loss and insomnia, persisted. Radiological improvements were noted, although pulmonary function remained impaired. The prevalence of PTSD and anxiety decreased, while depression remained stable at around 30%. Conclusions: Long COVID continues to impose significant physical, mental, and social challenges. Symptoms like fatigue and anxiety have a profound impact on daily life. Strategies are urgently needed to help patients regain health and resume their normal lives. Full article

Background: Long-COVID is characterized by the persistency of COVID-19 symptoms beyond 12 weeks, and it is probably consequent to immune dysregulation induced by SARS-CoV-2 infection. Immune dysregulation is associated with and probably involved in the pathogenesis of chronic gynecological conditions like endometriosis and adenomyosis. This study evaluated whether the presence of endometriosis or adenomyosis increases the risk of long-COVID, i.e., the persistence of COVID-19 symptoms beyond 12 weeks since infection. Methods: This retrospective observational study was performed at the outpatient service for endometriosis and chronic pelvic pain, at a university hospital. The diagnosis of endometriosis/adenomyosis was primarily based on clinical symptoms and ultrasonography assessment. Data regarding infection, vaccination, symptoms associated with SARS-CoV-2 infection, and their persistence for a minimum of 12 weeks were collected. Results: This study included 247 women, 149 controls without and 98 cases with endometriosis/adenomyosis. Among these, 194 (116 controls and 78 cases) had suffered from SARS-CoV-2 infection. Rates of infection and vaccination were similar in the two groups. The distribution of the SARS-CoV-2 vaccine was uniform across the two cohorts. COVID-19 patients with endometriosis or adenomyosis exhibited a higher prevalence (p < 0.001) of dyspnea and chest pain. The prevalence of long-COVID beyond 12 weeks was higher in cases than controls (42% vs. 12%; p < 0.001) with chest pain (p < 0.001) and ageusia (p < 0.05), forming the most representative symptoms. Conclusions: Symptoms of long-COVID are more frequent in women with than without endometriosis/adenomyosis. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused post-acute sequelae, especially for people with pre-existing conditions, including chronic kidney disease (CKD), which may impact the cardiovascular system. Yet, despite the preliminary description of the general population’s long-COVID-19 consequences, data on CKD patients is scarce. The aim of this study was to investigate the longitudinal effects of COVID-19 on echocardiographic parameters of cardiac function and on cardiac biomarkers in patients with CKD. Methods: A total of 163 patients were included in this observational prospective trial (listed under NCT05125913 code): 88 in the COVID-19 group and 75 in the control group. The serial echocardiographic characteristics in patients who survived beyond one year, focused on left and right ventricular systolic function, together with cardiac biomarkers evolution, were compared between the two groups. Results: At baseline, there were no significant differences in left ventricular (LV) function parameters, except for a higher Tei Index in the COVID-19 group (p < 0.01). Right ventricular (RV) systolic dysfunction was more frequent in the COVID-19 group, with worse fractional area change (FAC) (p = 0.01), RV free wall longitudinal strain (RVFWLS) (p = 0.01), and RV Tei Index (p = 0.01). Over time, the control group showed a decline in LV ejection fraction (EF), while the COVID-19 group slightly improved. RV global systolic function was better preserved in the COVID-19 group. To the best of our knowledge, this is the first study that demonstrates a statistically significant increase in LAVi in patients with COVID-19. Conclusions: Prior COVID-19 infection influenced the trajectory of LV and RV function in CKD patients over 12 months, suggesting potential transient myocardial adaptations. While overall cardiac function did not differ significantly between groups, COVID-19 survivors exhibited better preservation of some ventricular function parameters. Full article

Background/Objectives: Before the Coronavirus disease 2019 (COVID-19) era, the global prevalence of pulmonary arterial hypertension (PAH) was between 0.4 and 1.4 per 100,000 people. The long-term effects of protracted COVID-19 associated with pulmonary vascular disease (PVD) risk factors may increase this prevalence. According to preliminary data, the exact prevalence of early estimates places the prevalence of PVD in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 22%, although its predictive value remains unknown. PVD caused by COVID-19 co-infections is understudied and underreported, and its future impact is unclear. However, due to COVID-19/co-infection pathophysiological effects on pulmonary vascularization, PVD mortality and morbidity may impose a genuine concern—both now and in the near future. Based on reported studies, this literature review focused on the potential link between COVID-19, parasitic co-infection, and PVD. This review article also highlights hypothetical pathophysiological mechanisms between COVID-19 and parasitic co-infection that could trigger PVD. Methods: We conducted a systematic literature review (SLR) searching peer-reviewed articles, including link between COVID-19, parasitic co-infection, and PVD. Results: This review hypothesized that multiple pathways associated with pathogens such as underlying schistosomiasis, human immunodeficiency virus (HIV), pulmonary tuberculosis (PTB), pulmonary aspergillosis, Wuchereria bancrofti, Clonorchis sinensis, paracoccidioidomycosis, human herpesvirus 8, and scrub typhus coupled with acute or long COVID-19, may increase the burden of PVD and worsen its mortality in the future. Conclusions: Further experimental studies are also needed to determine pathophysiological pathways between PVD and a history of COVID-19/co-infections. Full article

Background/Objectives: Post-COVID-19 condition (PCC), also known as long COVID, has emerged as a recognized syndrome affecting millions of people worldwide, significantly impairing their quality of life. Currently, no effective therapeutic options are available to manage this condition. The objective of the present study was to evaluate the long-term effects of personalized, algorithm-based intermittent hypoxia–hyperoxia conditioning (IHHC) on quality of life and pain in patients with PCC. Methods: This open-label cohort study included 199 PCC patients, aged 11–87 years (female-to-male ratio: 67:33) and experiencing moderate-to-severe fatigue, between 1 January 2020 and 31 December 2023. Each patient received an algorithm-based treatment plan tailored to their demographics, symptom duration, and baseline pain (NRS) and quality of life (SF-36) scores. Patients received an average of six treatment sessions (range: 2–21), each consisting of intermittent hypoxic–hyperoxic cycles, with hypoxia (9–13% O₂) lasting 3–8 min and hyperoxia (34–36% O₂) lasting 1–3 min. The primary outcomes were changes in the NRS and SF-36 scores at the 6-week and 6-month follow-ups. Results: At the 6-week follow-up after treatment initiation, the SF-36 scores increased by 102 points (p < 0.001, 95% CI: 78.4–127), and this improvement persisted at the 6-month follow-up (Δ106, p < 0.001, 95% CI: 57.0–154). Pain was reduced by 28–32% at both follow-up time points, exceeding the clinically relevant threshold. Health transition scores indicated a patient-perceived improvement in health status. Conclusions: In this study, a personalized, algorithm-based IHHC alleviated pain and improved quality of life in patients suffering from persistent long-term sequelae after COVID-19 infection. The effects were sustained for up to six months. Further research is warranted to elucidate the mechanisms underlying IHHC’s therapeutic effects in this patient population. Full article

Background: Although autoimmune complications of COVID-19 have aroused concerns, there is no consensus on its ocular complications. Sjögren’s syndrome is an autoimmune disease accompanied by the ocular abnormality keratoconjunctivitis sicca (SS-KCS), which may be influenced by COVID-19. Thereby, we explored the possible interaction between COVID-19 and SS-KCS, and we aimed to elucidate the potential correlated mechanism. Methods: Differentially expressed genes (DEGs) in COVID-19 and SS-KCS transcriptome data obtained from the gene expression omnibus database were identified, and COVID-19-related genes were screened using weighted gene coexpression network analysis. Common genes were verified using four machine-learning diagnostic predictors. The clinical relationship between the two common hub genes of COVID-19 was analyzed. Finally, the immune cell types infiltrating the microenvironment in the COVID-19 dataset were analyzed using CIBERSORT, and the interrelation between key genes and differentially infiltrating immune cells was verified via Pearson correlation. Results: Ten potential primary hub mRNAs were screened by intersecting the COVID-19 DEGs, SS-KCS DEGs, and WGCNA genes. After a multifaceted evaluation using four mainstream machine-learning diagnostic predictors, the most accurate and sensitive random forest model identified CR1 and TAP2 as the common hub genes of COVID-19 and SS-KCS. Together with the clinical information on COVID-19, the expression of CR1 and TAP2 was significantly correlated with the status and severity of COVID-19. CR1 and TAP2 were significantly positively correlated with M0 and M2 macrophages, neutrophils, and CD4+ memory resting T cells and negatively correlated with activated NK cells, monocytes, and CD8+ T cells. Conclusions: We validated the hub genes associated with both COVID-19 and SS-KCS, and we investigated the immune mechanisms underlying their interaction, which may help in the early prediction, identification, diagnosis, and management of SARS-CoV-2 infection-related SS-KCS syndrome or many other immune-related complications in the long COVID period. Full article

Background: After the start of the COVID-19 pandemic, general fatigue in patients with long COVID and post-COVID-19 conditions (PCC) became a medical issue. Although there is a lack of evidence-based treatments, Kampo medicine (traditional Japanese medicine) has gained attention in Japan. At an outpatient clinic in Japan specializing in long COVID, 24% of all prescriptions were Kampo medicines, and 72% of Kampo medicine prescriptions were hochuekkito. However, there has been no prospective, quantitative study on the course of fatigue in patients with long COVID and PCC who were prescribed hochuekkito. The aim of this study was to clarify the course of fatigue in those patients. Methods: This study included patients aged 18 years or older with general fatigue who visited the long COVID specialized outpatient clinic at Okayama University Hospital and consented to participate after being prescribed hochuekkito. We reviewed the backgrounds of the patients, and we evaluated the patients’ fatigue assessment scale in person or online. Results: Twenty patients were enrolled in this study from September to December in 2023. The average age of the patients was 42.9 years (SD: 15.8 years) and 12 patients (60%) were female. After hochuekkito administration, the fatigue assessment scale score decreased from 35.9 (SD: 5.9) at the initial visit to 31.2 (SD: 9.4) after 8 weeks, indicating a trend for improvement in fatigue (difference: 4.7; 95% CI: 0.5–8.9). Conclusions: A trend for improvement in fatigue was observed in patients with long COVID and PCC who were prescribed hochuekkito, indicating a potential benefit of hochuekkito for general fatigue in such patients. General fatigue in patients with long COVID or PCC can be classified as post-infectious fatigue syndrome and is considered a condition of qi deficiency in Kampo medicine, for which hochuekkito is appropriately indicated. Full article