JOURNAL/nrgr/04.03/01300535-202510000-00030/figure1/v/2024-11-26T163120Z/r/image-tiff Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 infections. Previous studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019 (COVID-19). However, neuroimaging studies on sleep disturbances caused by COVID-19 are scarce, and existing studies have primarily focused on the long-term effects of the virus, with minimal acute phase data. As a result, little is known about the pathophysiology of sleep disturbances in the acute phase of COVID-19. To address this issue, we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection, and verified the results using 3-month follow-up data. A total of 26 COVID-19 patients with sleep disturbances (aged 51.5 ± 13.57 years, 8 women and 18 men), 27 COVID-19 patients without sleep disturbances (aged 47.33 ± 15.98 years, 9 women and 18 men), and 31 age- and gender-matched healthy controls (aged 49.19 ± 17.51 years, 9 women and 22 men) were included in this study. Eleven COVID-19 patients with sleep disturbances were included in a longitudinal analysis. We found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain lobes. The cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index scores. Additionally, we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy controls. The 3-month follow-up data revealed indices of altered cerebral structure (cortical thickness, cortical grey matter volume, and cortical surface area) in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep disturbances. Our findings indicate that the sleep disturbances patients had altered morphology in the cortical and hippocampal structures during the acute phase of infection and persistent changes in cortical regions at 3 months post-infection. These data improve our understanding of the pathophysiology of sleep disturbances caused by COVID-19.

Significance: Damage after stroke is not only limited to the brain but also often occurs in remote organs, including the heart, lung, liver, kidney, digestive tract, and spleen, which are frequently affected by complex pathophysiological changes. The organs in the human body are closely connected, and signals transmitted through various molecular substances could regulate the pathophysiological changes of remote organs. Recent Advances: The latest studies have shown that inflammatory response plays an important role in remote organ damage after stroke, and can aggravate remote organ damage by activating oxidative stress, sympathetic axis, and hypothalamic axis, and disturbing immunological homeostasis. Remote organ damage can also cause damage to the brain, aggravating inflammatory response and oxidative damage. Critical Issues: Therefore, an in-depth exploration of inflammatory and oxidative mechanisms and adopting corresponding comprehensive intervention strategies have become necessary to reduce damage to remote organs and promote brain protection. Future Directions: The comprehensive intervention strategy involves multifaceted treatment methods such as inflammation regulation, antioxidants, and neural stem cell differentiation. It provides a promising treatment alternative for the comprehensive recovery of stroke patients and an inspiration for future research and treatment. The various organs of the human body are interconnected at the molecular level. Only through comprehensive intervention at the molecular and organ levels can we save remote organ damage and protect the brain after stroke to the greatest extent. Antioxid. Redox Signal. 00, 000-000.

Atrial fibrillation (AF) is associated with a high burden of cardiovascular disease, which has been worsened during the coronavirus disease 2019 (COVID-19) pandemic. The purpose of this study was to assess the association between clinical markers, especially interleukin-6 (IL-6) and other inflammatory biomarkers, and the severity of COVID-19 in patients with AF.

This retrospective cohort study categorized patients based on clinical presentations and laboratory results to investigate the prognostic significance of inflammatory markers in COVID-19 outcomes among those with AF. The study included 100 hospitalized COVID-19 patients aged between 40 to 80 years and was conducted at the Chapidze Hospital in Tbilisi, Georgia. Patients were then grouped by disease severity according to computed tomography (CT) scores, clinical symptoms, respiratory rate and oxygen saturation. Levels of IL-6 were obtained at three time points during hospitalization. A broad range of laboratory tests, including C-reactive protein (CRP), ferritin, and D-dimer, were also conducted.

Patients with AF demonstrated significantly elevated levels of IL-6 (P = 0.024), CRP (P = 0.001), and ferritin (P < 0.001), suggesting a severe inflammatory response. D-dimer levels were also notably higher in the AF group (P < 0.005), indicating an increased risk of thrombotic complications. Oxygen saturation levels were significantly lower (P = 0.004) and CT scores higher in patients with AF. Furthermore, the length of hospitalization was longer among patients with AF (median duration significantly higher, P = 0.032), indicating a more severe disease course.

The proinflammatory markers such as IL-6 are independent predictive markers of COVID-19 severity in AF patients. Overall, it highlights urgent treatment approaches, such as available anti-inflammatory drugs, for COVID-19 patients with arrhythmias. Combining these biomarkers into clinical routines helps us better identify patients at risk and how to treat them.

Long COVID describes long-term health sequelae after a SARS-CoV-2 infection. Despite various theoretical approaches, the pathogenesis of long COVID is not yet fully understood and the diagnostic criteria are vague. This makes the development of targeted, cause-specific therapies challenging. In addition to the symptoms, many patients suffer from various psychosocial burdens and a significantly reduced quality of life. In order to address this, psychosomatic or psychotherapeutic interventions should be used in addition to symptom-oriented treatment. Within the PsyLoCo project, a psychotherapeutic treatment manual was developed that is tailored to the specific needs of long COVID patients. In four modules, it addresses (1) coping and distress management, (2) physical complaints and pain, (3) chronic fatigue and affective symptoms and (4) social and working life. The manual was tested for feasibility and effectiveness in a multicentre, randomized controlled pilot study. The contents of this treatment manual are presented below.

The impacts of COVID-19 on acute myocardial infarction (AMI) care were heterogeneous. The study aims to analyze the clinical characteristics and outcomes of AMI patients in China during different stages of the COVID-19 pandemic.

This is a multicenter retrospective cohort study in Shanxi Province of northern China. Patients diagnosed with AMI during the zero-case, lockdown, and outbreak periods were included. Characteristics and outcomes were analyzed according to time periods and COVID-19 infection. The primary outcome was in-hospital mortality. Additional outcomes included reperfusion times, coronary angiographic measures, procedure or AMI-associated complications, arrhythmia, other adverse events, and left ventricular systolic dysfunction (LVSD).

The study included 1021 AMI patients, with 393, 250, and 378 from the zero-case, lockdown, and outbreak periods. No differences in in-hospital mortality or other adverse events were found by time periods. By infection status, 264 patients were COVID-positive, and 706 were COVID-negative. The COVID-positive ST-elevation myocardial infarction population had longer symptom-to-first medical contact (3.07 vs. 2.31, p = 0.026), pre-hospital time (4.58 vs. 3.67, p = 0.032), door-to-balloon (1.20 vs. 1.08, p = 0.046), and total ischemic time (5.80 vs. 4.70, p = 0.011). No differences in other in-hospital outcomes were found, except that multivariate logistic regression analysis demonstrated COVID-19 infection was correlated with increased risks of LVSD (OR 1.73, 95% CI 1.11-2.69, p = 0.015).

In-hospital mortality did not differ by time period or COVID-19 infection status. The COVID-positive AMI patients had longer reperfusion times and higher risks of LVSD. AMI treatments were impacted during the pandemic, and measures are warranted to minimize the reperfusion time.

While ambient air pollution has been associated with COVID-19 outcomes, the role of early-life exposure in childhood COVID-19 infection and sequelae remains unexplored.

To assess the associations between early-life exposure to ambient air pollutants during and childhood COVID-19 infection and sequelae.

This cross-sectional retrospective cohort study surveyed families with children aged 3-6 years in families across nine Chinese cities between December 2019 and May 2023. The primary outcomes were doctor-diagnosed childhood COVID-19 infection and sequelae. Individual exposure to PM2.5, PM2.5-10, PM10, SO2, NO2, CO, O3, and temperature were estimated.

Among 20,012 children from 60,036 participants, 5.81 % were diagnosed with COVID-19 infection, and 1.72 % had sequelae. Prenatal CO exposure was associated with higher infection risk (OR: 1.33; 95 % CI: 1.05-1.69 per IQR increase). SO2 exposure during the first trimester (OR: 3.02; 95 % CI: 1.20-7.61), second trimester (OR: 4.00; 95 % CI: 1.56-10.27) and third trimester (OR: 3.84; 95 % CI: 1.69-8.76) of pregnancy and the first year of life (OR: 8.43; 95 % CI: 1.80-39.48) was strongly associated with sequelae. Pre-existing allergies and coarser particulate matter (PM2.5-10 and PM10) amplified these associations. High relative humidity significantly increased the effect of exposure to NO2 during four-six months before pregnancy and the second trimester of pregnancy, as well as O3 exposure during the first year on childhood COVID-19 infection.

Early-life exposure to air pollutants and interactions with allergic conditions and coarser particles influence childhood COVID-19 risks.

Although some reports suggest that COVID-19 vaccination may exacerbate existing autoimmune diseases or trigger new-onset cases, a definitive causal relationship between the vaccines and these conditions has not been established. Several potential mechanisms have been proposed to explain this association, including: (i) molecular mimicry, which refers to a structural similarity between SARS-CoV-2 and human antigens; (ii) bystander activation, involving both B and T lymphocytes; and (iii) the effects of adjuvants. In this study, we investigated whether two doses of the mRNA COVID-19 vaccine influenced blood cytokine levels associated with major T helper cell populations, which are known to play a significant role in autoimmunity and revisited the role of the humoral autoimmune response directed against heat shock proteins (Hsps) in individuals with no history of COVID-19. While no significant differences were found in the levels of IFN-γ, IL-6, IL-22, IL-4, IL-8, IL-10, and IL-17A, between vaccinated and unvaccinated people, several positive correlations were observed between serum cytokine levels and circulating autoantibodies directed against self-Hsps exclusively in vaccinated individuals. These findings suggest that the mRNA COVID-19 vaccine does not impact cytokines involved in the pathogenesis of autoimmune diseases. Further research is required to evaluate the safety of COVID-19 vaccination in patients with autoimmune conditions, particularly those in whom anti-Hsps autoantibodies are suspected to contribute to disease development.

Background/Objectives: Current studies on adverse events related to the COVID-19 vaccine have predominantly focused on severe, life-threatening side effects. However, numerous less severe but common adverse events (AEs) remain underreported and insufficiently investigated despite their potential impact. Methods: This population-based cohort study investigated the cumulative incidence rate (cIR) and risk of the broad-spectrum AEs of special interests (AESIs) based on immune response, including gynecological, dermatological, ophthalmological, otologic, and dental problems, following COVID-19 vaccination. Results: Among 4,203,887 individuals in Seoul, South Korea, the final analysis included 1,458,557 vaccinated subjects and 289,579 non-vaccinated subjects after the exclusion of underlying diseases. The cIR of AESIs for three months was significantly higher in vaccinated subjects than in non-vaccinated subjects, except for endometriosis. The vaccination significantly increased the risks of all the AESIs except for visual impairment. The risk of alopecia showed the highest HRs (HR [95% CI] = 2.40 [1.90-3.03]) among the AESIs following COVID-19 vaccination. Among the vaccinated subjects, heterologous vaccination was associated with the increased risk of most of the AESIs. Conclusions: Our findings suggest that clinicians should closely recognize and follow up on various COVID-19 vaccine-related AEs due to their unknown impact, even if they may not be serious at present.

This study aimed to assess the impact of SARS-CoV-2 therapies on the risk of venous thromboembolism (VTE) and other cardiovascular events. A retrospective, multicenter, observational study included hospitalized patients in Spain due to acute SARS-CoV-2 infection from March 2020 to March 2022. A total of 184,324 hospitalized COVID-19 patients were included, with a mean age of 67.5 (± 16) years of whom 58.4% were male. Among the comorbidities, arterial hypertension was the most common, affecting 52.5% (9618 patients), followed by dyslipidemia in 39.5% (7237 patients), diabetes mellitus in 23.7% (1748 patients), and atrial fibrillation in 10.6% (1948 patients). The overall mortality rate was 17.4% (3183 patients) and 9.9% (1819 patients) required admission to an intensive care unit. Cardiovascular events occurred in 4.08% (748 patients), with VTE occurring in 2.78% (510 patients), myocardial infarction in 0.75% (137 patients), and ischemic stroke in 0.55% (101 patients). Among therapies, beta-lactams were used in 66.7% (12,228 patients), systemic corticosteroids in 56.9% (10,424 patients), and tocilizumab in 11.6% (2128 patients). Multivariate analysis revealed an independent association between VTE and the use of tocilizumab (adjusted OR 2.07; p < 0.01), corticosteroids (adjusted OR 1.44; p = 0.02), and macrolides (adjusted OR 0.58; p < 0.01). None of the therapies were associated with the risk of myocardial infarction or ischemic stroke. In this large national cohort, tocilizumab and corticosteroids exhibited an independent association for the risk of VTE, but not for myocardial infarction or ischemic stroke.

Background: Heart rate turbulence (HRT) is a non-invasive technique that can be used to evaluate autonomic nervous system (ANS) function and cardiac arrhythmia. The objective of this study is to investigate whether COVID-19 can lead to long-term blunted HRT following recovery. Methods: This retrospective cohort study included 253 individuals with a confirmed history of COVID-19, referred to as the recovered COVID-19 group, along with 315 healthy participants who had no history of the virus. The recovered COVID-19 group was categorized into three subgroups based on their chest CT severity scores. The HRT analyses were obtained from a 24-h electrocardiography-Holter recording. Results: This study revealed that the HRT onset value was elevated in the recovered COVID-19 group, while the HRT slope value showed a significant decrease when compared to the control group. Correlation analyses indicated a positive relationship between the chest CT severity score and HRT onset, whereas a negative correlation was observed between the chest CT severity score and HRT slope. Regression analyses identified recovery from severe COVID-19, chest CT severity score, hypertension (HT), and smoking as independent predictors of both abnormal HRT onset and the existence of an abnormal HRT slope. Conclusions: Individuals who have recovered from severe COVID-19 are expected to encounter a permanent blunting of HRT, which is regarded as a significant indicator of an increased risk of ventricular arrhythmias and impaired autonomic nervous system (ANS) function. Recovered severe COVID-19 individuals should be carefully evaluated for HRT with 24-h ECG-Holter.

This study investigates the perceived accessibility of healthcare services among older adults in Lithuania during the COVID-19 pandemic. The study is significant as it sheds light on geographical, organizational, and financial healthcare access issues encountered by the older population.

Conducted in January 2024, the study involved an anonymous questionnaire survey of 1,503 Lithuanian residents aged 65 and older.

The most frequently utilized healthcare services were consultations with a general practitioner (75.4%) 22.0% of respondents reported not receiving any healthcare services. 53.5% respondents were satisfied with travel time to specialists. Common challenges included difficulties in getting appointments with specialists (53.9%) and dentists (36.2%). Financial barriers led to unmet healthcare needs: 12.6% of the respondents did not receive needed services, 12.8% did not undergo recommended tests, and 14.2% did not purchase prescribed medications. Healthcare services were less accessible to elders with lower education, lower incomes, and those who self-rated health poorly (p < 0.05).

Most respondents received the healthcare they needed during the pandemic and rated geographical access positively. However, some problems in organizational and financial access were disclosed. The observed social gradient indicates that socioeconomic factors significantly influence healthcare access, potentially increasing vulnerability among certain groups.

Ferroptosis is a new type of cell death, which is mainly dependent on the formation and accumulation of reactive oxygen species and lipid peroxides mediated by iron. It is distinct from other forms of regulation of cell death in morphology, immunology, biochemistry, and molecular biology. Various cell death mechanisms have been observed in many viral infections, and virus-induced cell death has long been considered as a double-edged sword that can inhibit or aggravate viral infections. However, understanding of the role of ferroptosis in various viral infections is limited. Special attention will be paid to the mechanisms of ferroptosis in mediating viral infection and antiviral treatment associated with ferroptosis. In this paper, we outlined the mechanism of ferroptosis. Additionally, this paper also review research on ferroptosis from the perspective of the virus, discussed the research status of ferroptosis in virus infection and classified and summarized research on the interaction between viral infections and ferroptosis.

The lung microbiome has recently gained attention for potentially affecting respiratory viral infections, including influenza A virus, respiratory syncytial virus (RSV) and SARS-CoV-2. We will discuss the complexities of the lung microenvironment in the context of viral infections and the use of organ-on-chip (OoC) models in replicating the respiratory tract milieu to aid in understanding the role of temporary microbial colonization. Leveraging the innovative capabilities of OoC, particularly through integrating gut and lung models, opens new avenues to understand the mechanisms linking inter-organ crosstalk and respiratory infections. We will discuss technical aspects of OoC lung models, ranging from the selection of cell substrates for extracellular matrix mimicry, mechanical strain, breathing mechanisms and air-liquid interface to the integration of immune cells and use of microscopy tools for algorithm-based image analysis and systems biology to study viral infection in vitro. OoC offers exciting new options to study viral infections across host species and to investigate human cellular physiology at a personalized level. This review bridges the gap between complex biological phenomena and the technical prowess of OoC models, providing a comprehensive roadmap for researchers in the field.

COVID-19 is associated with increased risk of post-acute cardiovascular outcomes. Population-based evidence for long periods of observation is still limited.

This population-based cohort study was conducted using data (2020-2021) from the British Columbia COVID-19 Cohort. The exposure of interest was severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, identified through reverse transcription-polymerase chain reaction (RT-PCR) assay. Individuals who tested positive (exposed) on RT-PCR were matched to negative controls (unexposed) on sex, age, and RT-PCR collection date in a 1:4 ratio. Outcomes of interest were incident major adverse cardiovascular events and acute myocardial infarction, identified more than 30 days after RT-PCR collection date. The association between SARS-CoV-2 infection and cardiovascular risk was assessed through multivariable survival models. Population attributable fractions were computed from Cox models.

We included 649,320 individuals: 129,864 exposed and 519,456 unexposed. The median duration of follow-up was 260 days; 1,786 events (0.34%) took place among the unexposed, and 702 (0.54%) in the exposed. The risk of major adverse cardiovascular events was higher in the exposed (adjusted hazard ratio [aHR] 1.34; 95% confidence interval [CI], 1.22-1.46), with greater risk observed in those who were hospitalized (aHR 3.81; 95% CI, 3.12-4.65) or required intensive care unit admission (aHR 6.25; 95% CI, 4.59-8.52) compared with the unexposed group. The fraction of cardiovascular events attributable to SARS-CoV-2 was 7.04% (95% CI, 4.67-9.41%). Comparable results were observed for acute myocardial infarction.

SARS-CoV-2 infection was associated with higher cardiovascular risk, with graded increase across the acute COVID-19 severity, contributing to 7% of incident major adverse cardiovascular events. These findings suggest that long-term monitoring of cardiovascular risk is required in COVID-19 survivors.

Despite data supporting the safety of SARS-CoV-2 vaccination, concerns regarding the receipt of blood products from donors previously infected or vaccinated against SARS-CoV-2 persist. We assessed whether transfusions of plasma or platelet products from donors with prior SARS-CoV-2 infection or vaccination were associated with adverse outcomes in patients without COVID-19.

We linked donor SARS-CoV-2 spike and nucleocapsid antibody data and vaccination history to blood products transfused between June 1, 2020 and March 31, 2022. We used logistic regression, adjusting for demographics and comorbidities, to calculate odds ratios and 95% confidence intervals (CI) for posttransfusion thrombosis, increased respiratory requirement, and hospital mortality. Outcomes were assessed as per transfused unit from previously infected or vaccinated donors compared to units from uninfected or unvaccinated donors.

Among 8715 hospitalizations of 7773 transfusion recipients linked to donor SARS-CoV-2 antibody data, there were 251 thromboses, 700 hospitalizations with increased respiratory requirements, and 1443 deaths. Among 15,167 transfused plasma units, 4993 and 1106 were from vaccinated donors and previously infected donors, respectively. Among 19,295 transfused platelet units, 8530 and 1368 were from vaccinated and previously infected donors, respectively. There were no associations between the transfusion of blood products from vaccinated or previously infected donors and thrombosis, increased respiratory requirements, or hospital mortality (all CI including 1). Nor were there associations between the receipt of blood products from recently infected or vaccinated donors or high SARS-CoV-2 antibody titers and adverse outcomes.

Donor SARS-Cov-2 infection and vaccination were not associated with adverse patient outcomes and do not need to be considered in blood allocation.

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection is not limited to the respiratory tract as receptors, including the angiotensin-converting enzyme 2 (ACE2), are expressed across many tissues. This study employed a new conditional mouse model, Rosa26creERT2/chACE2, which expresses human ACE2 (hACE2) across multiple organs, to investigate the effects of SARS-CoV-2 infection beyond the respiratory system. This strain demonstrated susceptibility to SARS-CoV-2 infection in a dose and sex-dependent manner, showing that infected male mice exhibited more severe disease outcomes, including significant weight loss, pronounced lung pathology and dysfunction, and increased mortality, compared to females. In contrast to intratracheal infection, intranasal virus administration facilitated viral spread to the brain, thereby underscoring the nasal route's role in the pathogenesis of neurological manifestations. Intranasal infection also led to increased innate immune system activation as compared to intratracheal virus administration, even though both routes activated the adaptive immune response. This model provides a valuable tool to study SARS-CoV-2 in individual tissues or use a multisystemic approach, and it also advances possibilities for preclinical evaluation of antiviral therapies and vaccine strategies.

To evaluate the effects of blood flow restriction (BFR) combined with endurance training on aerobic capacity, lower limb muscle strength, anaerobic power, and sports performance to supply effective scientific guidance for training. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. We searched PubMed, Medline, Cochrane, SPORTDiscus and Web of Science databases up to 28 October 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. We calculated the effect size using standardized mean difference values and the random effects model. The results showed a medium effect size on maximal oxygen uptake (V̇O2max), a large effect size on lower limb muscle strength, a small effect size on anaerobic power and sports performance. In conclusion, while BFR training during endurance training had a significant positive effect on lower limb muscle strength and moderate improvement in V̇O2max, its impact on anaerobic power and sports performance was relatively small. These findings suggest that BFR training may be effective for enhancing muscle strength and aerobic capacity, but its benefits on anaerobic power and sport-specific performance may be limited. Therefore, it is important to carefully design BFR training programs to target specific outcomes.

Background and Objectives: Long-term sequalae of viral diseases, especially after infections with SARS-CoV-2 (COVID-19), can induce multi-organ involvement, as around 65 million people worldwide report persistent symptoms that go far beyond the acute course. Studies indicate that early virus variants pose a higher risk of developing post-COVID-19 conditions. The primary aim of this study was to investigate the possible long-term effects based on the hospitalization rates and associated clinical events in patients infected with SARS-CoV-2 over an observational period of three years after the initial infection. Secondarily, an investigation of health-related quality of life and functional status was performed. Methods and Materials: The study presented was designed as a prospective, controlled cohort study to follow up on COVID-19 cases in the district of Konstanz, Germany (FSC19-KN). The positive group included subjects who had a primary infection with SARS-CoV-2 between March and December 2020. The control group included subjects who did not have a SARS-CoV-2 infection, as evidenced by a negative antibody test. As the primary endpoint, hospitalization rates and respective related admission diagnosis during the observational period of three years from January 2021 until July 2024 were analyzed. The health-related quality of life and functional outcomes were measured by the SF-36 questionnaire and Post-COVID-19 Functional Status (PCFS) as the secondary endpoint. Results: During the three years of observation after inclusion in the study, the hospitalization rate did not differ significantly between the two groups of initially infected and non-infected subjects (cumulative events, verum group 57 to control group 45, OR 1.24, CI 0.83; 1.85, p = 0.30). However, the health-related quality of life, measured by SF-36 sub scores of the SARS-CoV-2-positive subjects, achieved significantly lower results, except for the dimension 'energy and fatigue', in which subjects of the verum group still achieved significantly lower scores. Conclusions: Mild COVID-19 cases have no significant impact on hospitalization rates during an observational period of three years after initial infection. Yet, SARS-CoV-2-positive subjects reported a reduced health-related quality of life and functional outcomes. Ultimately, only the sub score quality 'energy and fatigue' still registered significant differences between both cohorts at the end of the three-year observational period.

Background/Objectives: People affected by COVID-19 are exposed to abnormal clotting and endothelial dysfunction, which may trigger thromboembolic events. This study aimed at retrospectively investigating whether oral anticoagulant therapy (OAT), encompassing either direct oral anticoagulants (DOACs), mainly apixaban, or the vitamin K antagonist (VKA) warfarin, could have impacted medium-term mortality in a cohort of SARS-CoV-2 patients. Methods: Among 1238 COVID-19 patients, hospitalized from 17 March 2020 to 15 June 2021, 247 survivors and 247 deceased within 90 days from hospitalization were matched 1:1 based on age, sex, and intensive care unit (ICU) admission within three days. Conditional logistic regression was used to estimate associations by means of odds ratio (OR) with a 95% confidence interval (CI). Results: A univariate regression analysis suggested that OAT, no differently from subcutaneous low-molecular-weight heparins (LMWHs) during hospitalization, has no significant impact (p value > 0.05) on medium-term mortality. A multivariate analysis, limited to baseline variables (i.e., comorbidities and pharmacotherapies at hospital admission) showing significant association (p < 0.05) to mortality in a univariate analysis, revealed that, compared to patients living at 90 days from hospitalization, deceased patients had cancer histories (OR 1.75, CI 1.06-2.90, p = 0.029) or suffered from asthma (OR 2.25, CI 1.13-4.47, p = 0.021). In contrast, heart failure (HF), atrial fibrillation (AF), arteriopathy, chronic obstructive pulmonary disease (COPD), and kidney failure (KF), which, in a univariate analysis, were found to be associated with the endpoint (p < 0.05), lost significance in a multivariate analysis. Therapy at admission with aldosterone antagonists also appeared to be associated with medium-term mortality (OR 2.49, CI 1.52-4.08, p < 0.001); whereas, vitamin D supplementation during hospitalization appeared to be beneficial. Although not conclusive, a search into the Eudravigilance database, combined with consulting a digital predictive platform (PLATO, polypharmacology platform prediction), suggested potential off-target activities, which might contribute to increasing the severity of SARS-CoV-2 infection. Conclusions: This retrospective clinical study furnished evidences of the impact of OAT, comorbidities and other pharmacological treatments on COVID-19 clinical course.

The study aimed to assess the effect of COVID-19 on hepatic lipid (HL) content, fibrosis risk, and adiposity in persons with type 2 diabetes.

Participants with type 2 diabetes with a history of mild COVID-19 (n=15, age 58±12 years, body mass index 30.9±5.2 kg/m2) were examined before (baseline) and 1 year (12±2 months) after (follow-up) recovery from COVID-19. Investigations for changes in metabolic risk comprised clinical examination, fasting blood sampling and MR-based measurements. Potential changes were corrected with the time course of the respective parameters in a group of participants who did not contract COVID-19 over the same time course (n=14, 61±6 years, 30.0±4.6 kg/m2).

COVID-19 resulted in a relative increase in HL content of 56% (95% CI 18%, 106%; p=0.04) measured as proton density fat fraction (HL-PDFF), corrected for the time course in the absence of COVID-19. While no changes in hepatic stiffness and volume, intramyocellular lipids, whole-body, subcutaneous and visceral adipose tissue volumes as well as homeostatic model assessment of insulin resistance and beta-cell function were observed.

History of COVID-19 in persons with type 2 diabetes is associated with higher HL-PDFF after 1 year following recovery from infection.

NCT01055093.

Long COVID represents a significant challenge in understanding the prolonged impact of the disease. Despite its increasing recognition, detailed insights into the long-term cardiopulmonary consequences remain sparse. This study aimed to evaluate the functional capacity of individuals with persistent symptoms after severe COVID-19 infection compared to control individuals without symptomatic COVID or mild COVID after 17 months. This is a case-control study assessing 34 individuals divided into two groups regarding functional capacity by distance in a 6-min walk test (D6MWT) associated with gas analysis, spirometry, respiratory muscle strength, and quality of life. During the 6 MWT, an important lower heart rate (HR) was observed for the COVID group (106 ± 10 bpm, difference mean: 21.3; p < 0.001), with greater exertional perception (Borg dyspnea: 4.5 [2.0-9.0], p < 0.001 and Borg fatigue: 4.0 [2.0-7.0], p = 0.01), a significant decrease in the distance covered (416 ± 94 m, difference mean: 107; p = 0.002), and a low value of O2 uptake (V˙O2) (11 ± 5.0 mL/(kg min), difference mean: 8.3; p = 0.005) and minute ventilation (22 ± 8 L/min, difference mean: 18.6; p = 0.002), in addition to very low quality of life scores. Regression analysis showed a significant association between D6MWT and Borg fatigue and Borg dyspnea at rest (p = 0.003; p = 0.009). V˙O2 and HR were also significantly associated with the outcomes of the D6MWT (p = 0.04 and p = 0.004, respectively). In conclusion, individuals who have severe COVID-19 and persist with symptoms have low functional capacity, low V˙O2, low HR behavior, and low quality of life.

Background/Objectives: This study investigated the prevalence of functional impairments and the effects of long COVID on long-term functional impairments in patients with severe COVID-19. Methods: We conducted a nationwide multicenter cohort study in collaboration with nine hospitals, collecting data using self-administered questionnaires from participants aged 20 years or older who were diagnosed with COVID-19, admitted to the intensive care unit (ICU) between April 2021 and September 2021, and discharged alive. Questionnaires regarding daily life, sequela, and functional impairments were mailed to patients in August 2022. The effects of long COVID on functional impairments were examined using a multivariate logistic regression analysis. Results: The survey was completed by 220 patients, with a mean of 416 days after discharge. Among respondents, 20.5% had physical impairments (n = 45), 35.0% had mental disorders (n = 77), and 42.7% had either (n = 94). Furthermore, 77.7% had long COVID (171/220), and the most common symptom was dyspnea (40.0%). The multivariate analysis showed that fatigue/malaise, upper respiratory tract symptoms, myalgia, muscle weakness, decreased concentration, sleep disorder, brain fog, and dizziness were risk factors for functional impairments at one year. Conclusions: Many patients with severe COVID-19 admitted to the ICU still suffered from post-intensive care syndrome even after one year, which manifested in combination with direct symptoms of the original disease, such as long COVID.

The emergence of the COVID-19 pandemic made it critical to understand the immune and inflammatory responses to the SARS-CoV-2 virus. It became increasingly recognized that the immune response was a key mediator of illness severity and that its mechanisms needed to be better understood. Early infection of both tissue and immune cells, such as macrophages, leading to pyroptosis-mediated inflammasome production in an organ system critical for systemic oxygenation likely plays a central role in the morbidity wrought by SARS-CoV-2. Delayed transcription of Type I and Type III interferons by SARS-CoV-2 may lead to early disinhibition of viral replication. Cytokines such as interleukin-1 (IL-1), IL-6, IL-12, and tumor necrosis factor α (TNFα), some of which may be produced through mechanisms involving nuclear factor kappa B (NF-κB), likely contribute to the hyperinflammatory state in patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) cells, CD8+ T-cells, and B-cells, can contribute to disease severity and may reflect direct cytopathic effects of SARS-CoV-2 or end-organ sequestration. Direct infection and immune activation of endothelial cells by SARS-CoV-2 may be a critical mechanism through which end-organ systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation and microthrombi development can be seen in the lungs and other critical organs throughout the body, such as the heart, gut, and brain. The kidney may be among the most impacted extrapulmonary organ by SARS-CoV-2 infection owing to a high concentration of ACE2 and exposure to systemic SARS-CoV-2. In the kidney, acute tubular injury, early myofibroblast activation, and collapsing glomerulopathy in select populations likely account for COVID-19-related AKI and CKD development. The development of COVID-19-associated nephropathy (COVAN), in particular, may be mediated through IL-6 and signal transducer and activator of transcription 3 (STAT3) signaling, suggesting a direct connection between the COVID-19-related immune response and the development of chronic disease. Chronic manifestations of COVID-19 also include systemic conditions like Multisystem Inflammatory Syndrome in Children (MIS-C) and Adults (MIS-A) and post-acute sequelae of COVID-19 (PASC), which may reflect a spectrum of clinical presentations of persistent immune dysregulation. The lessons learned and those undergoing continued study likely have broad implications for understanding viral infections' immunologic and inflammatory consequences beyond coronaviruses.

Robust COVID-19 outcomes classification is important for ongoing epidemiology research on acute and post-acute COVID-19 conditions. Protocolized medical record review is an established method to validate endpoints for clinical trials and cardiovascular epidemiology cohorts; however, a protocol to adjudicate hospitalizations for COVID-19 among epidemiology cohorts was lacking.

We developed a protocol to ascertain and adjudicate hospitalized COVID-19 across a meta-cohort of 14 US prospective cohort studies. This report describes the first three years of protocol implementation (October 1, 2020-October 1, 2023) and evaluates its repeatability and performance compared to classification by administrative codes.

The protocol was adapted from cohort approaches to clinical cardiovascular events ascertainment and adjudication. Potential COVID-19 hospitalizations and deaths were identified by self-/proxy-report and, in some cases, active surveillance. Medical records were requested from hospitals and adjudicated for COVID-19 outcomes by clinically trained personnel according to a standardized rubric. Inter-rater agreement was assessed. The sensitivity and specificity of discharge diagnosis codes was compared to adjudicated diagnoses.

The study obtained medical records for 1,167 potential COVID-19 hospitalizations, which underwent protocolized adjudication. Adjudication confirmed COVID-19 infection was present for 1,030 (88%) events, of which COVID-19 was not the cause of hospitalization for 78 (8%). Of 952 hospitalizations determined by adjudicators to be caused by COVID-19, 319 (34%) participants were critically ill and 210 (22%) died. Pneumonia was confirmed in 822 (86%) and acute kidney injury in 350 (37%); other cardiovascular and thrombotic complications were rare (2-5%). Interrater reliability among adjudicators was high (kappa = 0.85-1.00) except for myocardial infarction (kappa = 0.60). Compared to adjudication, sensitivity of discharge diagnosis codes was higher for pneumonia (84%) and pulmonary embolism (81%) than for other complications (48-70%).

Protocolized adjudication confirmed four out of five COVID-19 hospitalizations in a US meta-cohort and confirmed cases of pneumonia, pulmonary embolism, and other conditions that were not indicated by discharge diagnosis codes. These results highlight the importance of validating health outcomes for use in research on COVID-19 and post-COVID-19 conditions, and some limitations of claims-based data.

COVID-19 skin manifestations are multifaceted, ranging from urticaria, morbilliform or papulovesicular rash, livedoid purpuric lesions, and to pseudochilblains (also called COVID toes). Recent insights into the mechanism of these manifestations have highlighted that morbilliform, papulovesicular, and livedoid/purpuric rashes are related to virus-induced endothelial cell damage and linked to moderate-to-severe disease, whereas pseudochilblains are related to an exaggerated IFN-1 production by plasmacytoid dendritic cells in protected individuals. In this paper, we will review the clinical and physiopathological features of cutaneous COVID-19 manifestations in relation to the direct viral cytopathic effects and dysregulated IFN-1 responses. We will also review the emerging insights into post-COVID conditions (also termed long COVID) and how they may be implicated in the persistence of COVID-19-associated skin diseases.

The coronavirus disease 2019 (COVID-19) interventions in interrupting transmission have paid heavy losses politically and economically. The Chinese government has replaced scaling up testing with monitoring focus groups and randomly supervising sampling, encouraging scientific research on the COVID-19 transmission curve to be confirmed by constructing epidemiological models, which include statistical models, computer simulations, mathematical illustrations of the pathogen and its effects, and several other methodologies. Although predicting and forecasting the propagation of COVID-19 are valuable, they nevertheless present an enormous challenge. This paper emphasis on pandemic simulation models by introduced respiratory-specific transmission to extend and complement the classical Susceptible-Exposed-(Asymptomatic)-Infected-Recovered SE(A)IR model to assess the significance of the COVID-19 transmission control features to provide an explanation of the rationale for the government policy. A novel epidemiological model is developed using mean-field theory. Utilizing the SE(A)IR extended framework, which is a suitable method for describing the progression of epidemics over actual or genuine landscapes, we have developed a novel model named SEIAPUFR. This model effectively detects the connections between various stages of infection. Subsequently, we formulated eight ordinary differential equations that precisely depict the population's temporal development inside each segment. Furthermore, we calibrated the transmission and clearance rates by considering the impact of various control strategies on the epidemiological dynamics, which we used to project the future course of COVID-19. Based on these parameter values, our emphasis was on determining the criteria for stabilizing the disease-free equilibrium (DEF). We also developed model parameters that are appropriate for COVID-19 outbreaks, taking into account varied population sizes. Ultimately, we conducted simulations and predictions for other prominent cities in China, such as Wuhan, Shanghai, Guangzhou, and Shenzhen, that have recently been affected by the COVID-19 outbreak. By integrating different control measures, respiratory-specific modeling, and disease supervision sampling into an expanded SEI (A) R epidemic model, we found that supervision sampling can improve early warning of viral activity levels and superspreading events, and explained the significance of containments in controlling COVID-19 transmission and the rationality of policy by the influence of different containment measures on the transmission rate. These results indicate that the control measures during the pandemic interrupted the transmission chain mainly by inhibiting respiratory transmission, and the proportion of supervision sampling should be proportional to the transmission rate, especially only aimed at preventing a resurgence of SARS-CoV-2 transmission in low-prevalence areas. Furthermore, The incidence hazard of Males and Females was 1.39(1.23-1.58), and 1.43(1.26-1.63), respectively. Our investigation found that the ratio of peak sampling is directly related to the transmission rate, and both decrease when control measures are implemented. Consequently, the control measures during the pandemic interrupted the transmission chain mainly by inhibiting respiratory transmission. Reasonable and effective interventions during the early stage can flatten the transmission curve, which will slow the momentum of the outbreak to reduce medical pressure.

COVID-19 disease, triggered by SARS-CoV-2 virus infection, has led to more than 7.0 million deaths worldwide, with a significant fraction of recovered infected people reporting postviral symptoms. Smart surfaces functionalized with nanoparticles are a powerful tool to inactivate the virus and prevent the further spreading of the disease. Literature reports usually focus on the role of nanomaterial composition and size dispersion in evaluating their efficacy against SARS-CoV-2. Here, the anti-SARS-CoV-2 activity of oleylamine (OAm) used as a capping agent of silver nanoparticles is quantified for the first time. Spherical hydrophobic nanoparticles with 8 ± 2 nm diameter were prepared and characterized by Fourier transform infrared, dynamic light scattering, and transmission electron microscopy techniques. Biological assays showed that microgram amounts of nanoparticles, deposited on nonwoven textile obtained from surgical masks, efficiently inactivated up to 99.6(2)% of the virus with just 2 min of exposure. The virucidal activity of the corresponding amount of free OAm has been determined as well, reaching up to 67(1)% of activity for an exposure time of 10 min. Inductively coupled plasma optical emission spectrometry results pointed out a low leaching out of the nanoparticles in contact with water or culture medium. All in all, these results propose the capping molecules as an important chemical variable to be taken into account in the design of fast, efficient, and long-lasting anti-SARS-CoV-2 coatings.

COVID-19 has been a challenge at the healthcare level not only in the early stages of the pandemic, but also in the subsequent appearance of long-term COVID-19. Several investigations have attempted to identify proteomic biomarkers in an attempt to improve clinical care, guide treatment and predict possible patient outcomes. Proteins such as C-reactive protein (CRP) or interleukin 6 (IL-6) are clear markers of severe disease, but many others have been proposed that could help in risk stratification and in the prediction of specific complications. This review aims to bring together the most relevant studies in this regard, providing information to identify the most notable biomarkers in relation to COVID-19 found to date.

Coronavirus disease 2019 (COVID-19) is characterized by fever, fatigue, dry cough, dyspnea, mild pneumonia and acute lung injury (ALI), which can lead to acute respiratory distress syndrome (ARDS), and SARS-CoV-2 can accelerate tumor progression. However, the molecular mechanism for the increased mortality in cancer patients infected with COVID-19 is unclear.

Colony formation and wound healing assays were performed on Huh-7 cells cocultured with syncytia. Exosomes were purified from the cell supernatant and verified by nanoparticle tracking analysis (NTA), Western blot (WB) analysis and scanning electron microscopy (SEM). Differentially expressed proteins in syncytia-derived exosomes (Syn-Exos) and their functions was analyzed by Proteomic sequencing. Syn-Exo-mediated promotion of hepatocellular carcinoma cells was measured by CCK-8 and Transwell migration assays. The mechanism by which Syn-Exos promote tumor growth was analyzed by Western blotting. A patient-derived xenotransplantation (PDX) mouse model was constructed to evaluate the pathological role of the SARS-CoV-2 spike protein (SARS-2-S). The number of syncytia in the tumor tissue sections was determined by immunofluorescence analysis.

Syncytium formation promoted the proliferation and migration of hepatocellular carcinoma cells. Proteomic sequencing revealed that proteins that regulate cell proliferation and metastasis in Syn-Exos were significantly upregulated. Syn-Exos promote the proliferation and migration of hepatocellular carcinoma cells. Animal experiments showed that a pseudotyped lentivirus bearing SARS-2-S (SARS-2-Spp) promoted tumor development in PDX mice. More syncytia were found in tumor tissue from SARS-2-Spp mice than from VSV-Gpp mice.

Syn-Exos induced by SARS-2-S can promote the proliferation and metastasis of hepatocellular carcinoma cells.

SARS-CoV-2 affects brain, body, and their interchange. We investigated interoceptive mechanisms in COVID-19 survivors focusing on their potential link with psychopathology and inflammatory biomarkers.

We assessed interoceptive accuracy (IAc) and time-perceiving (TA) skills of 57 COVID-19 survivors one month after hospital discharge through, respectively, a heartbeats perception task and a time duration task. Each participant was assessed about his interoceptive awareness (IAw) through Multidimensional Assessment of Interoceptive Awareness questionnaire (MAIA) and then, screened for post-traumatic (Impact of Events Scale - IES-R), anxious (State-Trait Anxiety Inventory - STAI-Y1) and depressive (Zung Self-Rating Depression Scale - ZSDS; Beck Depression Inventory - BDI-13) symptoms. Biomarkers of inflammation (platelet count, PC; mean platelet volume, MPV and systemic immune-inflammation index, SII) were obtained in a subsample of 40 survivors by a blood sampling conducted at admission and discharge time from the hospital. Correlational, GLM, GLMZ, and mediation analyses were performed.

IAc did not correlate with TA confirming the reliability of interoceptive measure. IAc positively predicts MAIA's Trusting subscale and negatively predicts anxious psychopathology which fully mediates the effect of IAc on Trusting.PC at hospital admission predicts anxiety at one month after recovery. Again, a higher decrease of SII during hospitalization predicts higher IAc skill and lower anxiety state at one month. The link between SII change and anxiety is fully mediated by IAc.

Our results unveil a potential key role of interoception and brain-body interchange in the exacerbation and maintenance of anxiety psychopathology in COVID-19 survivors.

In this study, we examined preexisting systemic inflammation before COVID-19 (SIC), as assessed through C-reactive protein (CRP) levels, to gain insights into the origins of acute kidney injury (AKI) in adults with comorbidities affected by COVID-19. Although aging is not categorized as a disease, it is characterized by chronic inflammation, and older individuals typically exhibit higher circulating levels of inflammatory molecules, particularly CRP, compared to younger individuals. Conversely, elevated CRP concentrations in older adults have been linked with the development of comorbidities. Simultaneously, these comorbidities contribute to the production of inflammatory molecules, including CRP. Consequently, older adults with comorbidities have higher CRP concentrations than their counterparts without comorbidities or those with fewer comorbidities. Given that CRP levels are correlated with the development and severity of AKI in non-COVID-19 patients, we hypothesized that individuals with greater SIC are more likely to develop AKI during SARS-CoV-2 infection than those with less SIC.