Increased Angio-Derived Index of Microcirculatory Resistance Within a Timeframe of 30-60 days After COVID-19 Infection.

BACKGROUND AND OBJECTIVES: Chest pain is a relatively long-term symptom that commonly occurs in patients who have contracted COVID-19. The reasons for these symptoms remain unclear, with coronary microvascular dysfunction (CMD) emerging as a potential factor. This study aimed to assess the presence of CMD in these patients by measuring the angio-derived index of microcirculatory resistance (AMR). METHODS: In this cross-sectional case-control study, patients who had chest pain and a history of COVID-19 infection within the preceding 30 to 60 days were included. The control subjects were patients without COVID-19. Demographic, clinical, and echocardiographic data were recorded. Angiographic images were collected for AMR analysis through an angioplus quantitative flow ratio measurement system. Propensity score matching (PSM) was performed to match the two groups. Multivariate logistic regression was used to examine the association between COVID-19 incidence and the increase in AMR (AMR > 285 mmHg*s/m) after correction for other confounders. RESULTS: After PSM, there were 58 patients in each group (the mean age was 66.3 ± 9.04 years, and 55.2% were men). The average time between the onset of COVID-19 infection and patient presentation at the hospital for coronary angiography was 41 ± 9.5 days. Moreover, there was no significant difference in the quantitative flow ratio between the two groups. Patients with COVID-19 had a greater mean AMR (295 vs. 266, p = 0.002). Multivariate logistic regression analysis revealed that COVID-19 (OR = 3.32, 95% CI = 1.50-7.60, p = 0.004) was significantly associated with an increase in AMR. CONCLUSIONS: Long-term COVID-19 patients who experience chest pain without evidence of myocardial ischemia exhibit an increase in AMR, and CMD may be one of the reasons for this increase. COVID-19 is an independent risk factor for an increase in AMR.

[Lung pathology in children with a long-term novel coronavirus infection COVID-19]. / Patologiya legkikh u detei pri dlitel'no tekushchei novoi koronavirusnoi infektsii COVID-19.

New coronavirus infection is registered less frequently in children than in adults. Among all patients with COVID-19, the share of children is 8.6%. Clinical practice shows that in children, COVID-19 can be severe and even fatal. Articles have been published reflecting the clinical manifestations of Long Covid in children, while data on pathomorphological examination of the lungs during long-term COVID-19 in children are not available in the literature. On the basis of the Department of Pathological Anatomy with a course of Forensic Medicine and the Pathological-Anatomical Department of the Clinic of St. Petersburg State Pediatric Medical University, an analysis of medical documentation was carried out, autopsy materials were selected from 3 observations of the death of children from COVID-19. The selection criterion was the duration of the disease. A histological examination using standard methods and IHC analysis using antibodies to the nucleocapsid of SARS-Cov-2, CD95, CD31 were carried out on the lung tissue of 3 children aged 2 months to 2 years who died from a new coronavirus infection. Microscopically, all three patients showed microvessels damage, their thrombosis, angiogenesis, as well as signs of diffuse alveolar damage The combination of expression of the SARS-CoV-2 nucleocapsid and the apoptosis marker on the vascular endothelium of the MCR is of interest. CONCLUSION: The data obtained indicate infection with coronavirus and death of endothelial cells due to apoptosis. Endothelial damage in the microvessels of the lungs is the initiating factor in the development of capillary-alveolar block, tissue hypoxia, and disseminated intravascular coagulation syndrome, leading in some cases to respiratory/multiple organ failure and death.

Leveraging Serologic Testing to Identify Children at Risk For Post-Acute Sequelae of SARS-CoV-2 Infection: An Electronic Health Record-Based Cohort Study from the RECOVER Program.

Using an electronic health record-based algorithm, we identified children with Coronavirus disease 2019 (COVID-19) based exclusively on serologic testing between March 2020 and April 2022. Compared with the 131 537 polymerase chain reaction-positive children, the 2714 serology-positive children were more likely to be inpatients (24% vs 2%), to have a chronic condition (37% vs 24%), and to have a diagnosis of multisystem inflammatory syndrome in children (23% vs <1%). Identification of children who could have been asymptomatic or paucisymptomatic and not tested is critical to define the burden of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection in children.

Diabetes mellitus and the risk of post-acute COVID-19 hospitalizations-a nationwide cohort study.

AIMS: This cohort study, based on Danish health registers, examined the post-acute consequences of hospitalization for COVID-19 in patients with diabetes. METHODS: The study population comprised all Danish citizens (≥18 years old) who had diabetes when the pandemic started. A patient was exposed if he/she had a hospitalization with COVID-19 after 1 March 2020. A patient was unexposed when he/she was not hospitalized with COVID-19 between 1 March 2020 and the end of follow-up (4 January 2022), or the first registered event of interest. The outcomes included post-COVID-19 hospitalizations and death. We used a Cox proportional hazards model with time varying exposure estimating the hazards ratio (HR) to analyze if the hazard for an outcome of interest was impacted by being hospitalized with COVID-19. RESULTS: In patients with type 1 diabetes, 101 were hospitalized with COVID-19, and 25,459 were not. We did not have sufficient statistical power to identify differences in risk for those with type 1 diabetes. In type 2 diabetes, 1515 were hospitalized with COVID-19, and 95,887 were not. The adjusted HRs of post-acute hospitalization for respiratory diseases and infections were 1.71 (95% CI 1.45-2.03) and 1.87 (95% CI 1.61-2.18), respectively. The HR of death was 2.05 (95% CI 1.73-2.43). Patients with uncertain type had results similar to those with type 2 diabetes. CONCLUSIONS/INTERPRETATION: In type 2 diabetes and diabetes of uncertain type, hospitalization with COVID-19 was associated with an increased risk of post-acute hospitalization for respiratory diseases, infections and death.

The Thai version of the COVID-19 Yorkshire Rehabilitation Scale: a valid instrument for the psychometric assessment of the community members in Bangkok, Thailand.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can develop into a long-term COVID in some cases, which can have a major impact on various health systems requiring appropriate treatment involving multi-disciplinary healthcare. The COVID-19 Yorkshire Rehabilitation Scale (C19-YRS) is a standardized tool widely used for screening the symptoms and severity of long-term COVID. Translation of the English version of the C19-YRS into the Thai language and testing it is essential for the psychometric evaluation of the severity of the long-term COVID syndrome prior to providing rehabilitation care for community members. METHODS: Forward-and back-translations including cross-cultural aspects were conducted in order to develop a preliminary Thai version of that tool. Five experts evaluated the content validity of the tool and produced a highly valid index. A cross-sectional study was then conducted on a sample of 337 Thai community members recovering from COVID-19. Assessment of internal consistency and individual item analyses were also performed. RESULTS: The content validity resulted in valid indices. The analyses showed that 14 items had acceptable internal consistency, based on the corrected item correlations. However, five symptom severity items and two functional ability items were deleted. The Cronbach's alpha coefficient of the final C19-YRS was 0.723, indicating acceptable internal consistency and reliability of the survey instrument. CONCLUSIONS: This study indicated that the Thai C19-YRS tool had acceptable validity and reliability for the evaluation and testing of the psychometric variables in a Thai community population. The survey instrument also had acceptable validity and reliability for screening the symptoms and severity of long-term COVID. Further studies are warranted in order to standardize the various applications of this tool.

[COVID-19 as a trigger for the onset and progression of neurodegenerative pathology predominantly in elderly and senile population.]

A brief literature review on the association of COVID-19 and the manifestation or progression of neurodegenerative pathology is presented. The etiopathogenetic mechanisms of central nervous system damage are shown. The evidence base of the effect of SARS-CoV-2 on the central nervous system, which leads to the development of long-term neurological diseases, including neurodegeneration, is analyzed. It is concluded that it is necessary to develop official criteria and methodological recommendations for monitoring especially elderly and senile patients for possible onset or progression of neurodegenerative pathology.

Myopathy as a cause of fatigue in long-term post-COVID-19 symptoms: Evidence of skeletal muscle histopathology.

BACKGROUND AND PURPOSE: Among post-COVID-19 symptoms, fatigue is reported as one of the most common, even after mild acute infection, and as the cause of fatigue, myopathy diagnosed by electromyography has been proposed in previous reports. This study aimed to explore the histopathological changes in patients with post-COVID-19 fatigue. METHODS: Sixteen patients (mean age = 46 years) with post-COVID-19 complaints of fatigue, myalgia, or weakness persisting for up to 14 months were included. In all patients, quantitative electromyography and muscle biopsies analyzed with light and electron microscopy were taken. RESULTS: Muscle weakness was present in 50% and myopathic electromyography in 75%, and in all patients there were histological changes. Muscle fiber atrophy was found in 38%, and 56% showed indications of fiber regeneration. Mitochondrial changes, comprising loss of cytochrome c oxidase activity, subsarcollemmal accumulation, and/or abnormal cristae, were present in 62%. Inflammation was found in 62%, seen as T lymphocytes and/or muscle fiber human leukocyte antigen ABC expression. In 75%, capillaries were affected, involving basal lamina and cells. In two patients, uncommon amounts of basal lamina were found, not only surrounding muscle fibers but also around nerves and capillaries. CONCLUSIONS: The wide variety of histological changes in this study suggests that skeletal muscles may be a major target of SARS-CoV-2, causing muscular post-COVID-19 symptoms. The mitochondrial changes, inflammation, and capillary injury in muscle biopsies can cause fatigue in part due to reduced energy supply. Because most patients had mild-moderate acute affection, the new variants that might cause less severe acute disease could still have the ability to cause long-term myopathy.

Return to work after COVID-19 infection - A Danish nationwide registry study.

OBJECTIVES: This study aimed to explore return to work after COVID-19 and how disease severity affects this. STUDY DESIGN: This is a Nationwide Danish registry-based cohort study using a retrospective follow-up design. METHODS: Patients with a first-time positive SARS-CoV-2 polymerase chain reaction test between 1 January 2020 and 30 May 2020, including 18-64 years old, 30-day survivors, and available to the workforce at the time of the first positive test were included. Admission types (i.e. no admission, admission to non-intensive care unit [ICU] department and admission to ICU) and return to work was investigated using Cox regression standardised to the age, sex, comorbidity and education-level distribution of all included subjects with estimates at 3 months from positive test displayed. RESULTS: Among the 7466 patients included in the study, 81.9% (6119/7466) and 98.4% (7344/7466) returned to work within 4 weeks and 6 months, respectively, with 1.5% (109/7466) not returning. Of the patients admitted, 72.1% (627/870) and 92.6% (805/870) returned 1 month and 6 months after admission to the hospital, with 6.6% (58/870) not returning within 6 months. Of patients admitted to the ICU, 36% (9/25) did not return within 6 months. Patients with an admission had a lower chance of return to work 3 months from positive test (relative risk [RR] 0.95, 95% confidence interval [CI] 0.94-0.96), with the lowest chance in patients admitted to an ICU department (RR 0.54, 95% CI 0.35-0.72). Female sex, older age, and comorbidity were associated with a lower chance of returning to work. CONCLUSION: Hospitalised patients with COVID-19 infection have a lower chance of returning to work with potential implications for postinfection follow-up and rehabilitation.

Post COVID-19 hospitalizations in patients with chronic inflammatory diseases - A nationwide cohort study.

OBJECTIVE: To study long term consequences of hospitalization for COVID-19 in patients with chronic inflammatory diseases. We studied the risk of subsequent hospitalizations in patients with chronic inflammatory diseases, who survived a hospitalization for COVID-19, compared to other patients who had been hospitalized for COVID-19. DESIGN AND SETTING: Population based cohort study based on Danish nationwide health registers. The study population included all adult patients in Denmark who had been discharged alive after a hospitalization with COVID-19 from March 1, 2020 to July 31, 2021. POPULATION: From the study population, the exposed cohort constituted patients who had inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathy (SpA), or psoriatic arthritis (PsA) prior to hospitalization for COVID-19, and the unexposed cohort constituted those without these diseases. MAIN OUTCOME MEASURES: We estimated the adjusted Hazard Rate (aHR) for the following outcomes: overall risk of hospitalization, cardiovascular diseases, respiratory diseases, blood and blood-forming organs, nervous system diseases, infections, sequelae of COVID-19, and death. RESULTS: A total of 417 patients with IBD/RA/SpA/PsA were discharged alive after COVID-19, and 9,248 patients without these diseases. Across the different outcomes examined, the median length of follow up was 6.50 months in the exposed cohort (25-75% percentiles: 4.38-8.12), and among the unexposed the median time of follow up was 6.59 months (25-75% percentiles: 4.17-8.49). Across different analyses, we consistently found a significantly increased risk of hospitalizations due to respiratory diseases (aHR 1.27 (95% CI 1.02-1.58)) and infections (aHR 1.55 (95% CI 1.26-1.92)). In sensitivity analyses, the overall risk of hospitalization was aHR 1.15 (95% CI 0.96-1.38) and the risk of hospitalization due to cardiovascular diagnoses was aHR 1.14 (95% CI 0.91-1.42). During the time of follow up, the risk of nervous system diagnoses or death was not increased in patients with IBD/RA/SpA/PsA. CONCLUSIONS: After hospitalization with COVID-19, patients with IBD/RA/SpA/PsA had an increased risk of subsequent hospitalizations for a number of categories of diseases, compared to other patients who have been hospitalized with COVID-19. These results are disturbing and need to be examined further. The implication of our results is that clinicians should be particularly alert for post COVID-19 symptoms from several organ systems in patients with IBD/RA/SpA/PsA.

A Critical Review on the Long-Term COVID-19 Impacts on Patients With Diabetes.

BACKGROUND: The world is currently grappling with the potentially life-threatening coronavirus disease 2019 (COVID-19), marking it as the most severe health crisis in the modern era. COVID-19 has led to a pandemic, with the World Health Organization (WHO) predicting that individuals with diabetes are at a higher risk of contracting the virus compared to the general population. This review aims to provide a practical summary of the long-term impacts of COVID-19 on patients with diabetes. Specifically, it focuses on the effects of SARS-CoV-2 on different types of diabetic patients, the associated mortality rate, the underlying mechanisms, related complications, and the role of vitamin D and zinc in therapeutic and preventive approaches. METHODS: Relevant literature was identified through searches on PubMed, Web of Science, and Science Direct in English, up to April 2023. RESULTS: COVID-19 can lead to distressing symptoms and pose a significant challenge for individuals living with diabetes. Older individuals and those with pre-existing conditions such as diabetes, coronary illness, and asthma are more susceptible to COVID-19 infection. Managing COVID-19 in individuals with diabetes presents challenges, as it not only complicates the fight against the infection but also potentially prolongs the recovery time. Moreover, the virus may thrive in individuals with high blood glucose levels. Various therapeutic approaches, including antidiabetic drugs, are available to help prevent COVID-19 in diabetic patients. CONCLUSIONS: Diabetes increases the morbidity and mortality risk for patients with COVID-19. Efforts are globally underway to explore therapeutic interventions aimed at reducing the impact of diabetes on COVID-19.

Elevated Troponins after COVID-19 Hospitalization and Long-Term COVID-19 Symptoms: Incidence, Prognosis, and Clinical Outcomes-Results from a Multi-Center International Prospective Registry (HOPE-2).

Background: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits.

Clinical manifestations and long-term symptoms associated with SARS-CoV-2 omicron infection in children aged 0-17 years in Beijing: a single-center study.

Objective: The study aims to analyze the clinical characteristics of acute phase of SARS-CoV-2 infection in children aged 0-17 years with the Omicron variant, and summarize the persistent symptoms or new-onset clinical manifestations from 4 to 12 weeks after acute COVID. Explore the association between the vaccination status and SARS-CoV-2 neutralizing antibody levels post infection among preschool-aged children. The comprehensive study systematically describes the clinical characteristics of children infected with SARS-CoV-2, providing a foundation for diagnosis and evaluating long-term COVID in pediatric populations. Methods: The study enrolled children who were referred to the Children's Hospital, Capital Institute of Pediatrics, (Beijing, China) from January 10, 2023 to March 31, 2023. Participants were classified as infant and toddlers, preschool, school-age, and adolescent groups. Children or their legal guardians completed survey questionnaires to provide information of previous SARS-CoV-2 infection history, as well as clinical presentation during the acute phase and long-term symptoms from 4 to 12 weeks following infection. Furthermore, serum samples were collected from children with confirmed history of SARS-CoV-2 infection for serological testing of neutralizing antibodies. Results: The study recruited a total of 2,001 children aged 0-17 years who had previously tested positive for SARS-CoV-2 through nucleic acid or antigen testing. Fever emerged as the predominant clinical manifestation in 1,902 (95.1%) individuals with body temperature ranging from 37.3 to 40.0°C. Respiratory symptoms were identified as secondary clinical manifestations, with cough being the most common symptom in 777 (38.8%) children, followed by sore throat (22.1%), nasal congestion (17.8%), and runnning nose (17.2%). Fatigue (21.6%), headache (19.8%) and muscle-joint pain (13.5%) were frequently reported systemic symptoms in children. The proportion of children with symptoms of SARS-CoV-2 infection varied across age groups. 1,100 (55.0%) children experienced persistent symptoms from 4 to 12 weeks post the acute phase of infection. Trouble concentrating (22.1%), cough (22.1%), and fatigue (12.1%) were frequently reported across age groups in the extended period. A limited number of children exhibited cardiovascular symptoms with chest tightness, tachycardia, and chest pain reported by 3.5%, 2.5%, and 1.8% of children, respectively. Among 472 children aged 3-5 years, 208 children had received two doses of SARS-CoV-2 vaccine at least 6 months prior to infection, and no association was found between the incidence of long-term COVID and pre-infection vaccination statuses among the 3-5 years age groups (χ2 = 1.136, P = 0.286). Conclusions: In children aged 0-17 years infected with SARS-CoV-2 Omicron variant, fever was the primary clinical manifestation in the acute phase, followed by respiratory symptoms, systemic non-specific and digestive presentations. In particular, respiratory and digestive system symptoms were more frequent in children aged above 6 years. Regarding the long-term symptoms from 4 to 12 weeks post-infection, the most common presentations were concentrating difficulty, cough, and fatigue. The incidence of persistent symptoms of SARS-CoV-2 did not exhibit a significant correlation with vaccination status, which was attributed to the waning efficacy of the vaccine-induced humoral immune response after 6 months.

Patients recovering from COVID-19 who presented with anosmia during their acute episode have behavioral, functional, and structural brain alterations.

Patients recovering from COVID-19 commonly exhibit cognitive and brain alterations, yet the specific neuropathological mechanisms and risk factors underlying these alterations remain elusive. Given the significant global incidence of COVID-19, identifying factors that can distinguish individuals at risk of developing brain alterations is crucial for prioritizing follow-up care. Here, we report findings from a sample of patients consisting of 73 adults with a mild to moderate SARS-CoV-2 infection without signs of respiratory failure and 27 with infections attributed to other agents and no history of COVID-19. The participants underwent cognitive screening, a decision-making task, and MRI evaluations. We assessed for the presence of anosmia and the requirement for hospitalization. Groups did not differ in age or cognitive performance. Patients who presented with anosmia exhibited more impulsive alternative changes after a shift in probabilities (r = - 0.26, p = 0.001), while patients who required hospitalization showed more perseverative choices (r = 0.25, p = 0.003). Anosmia correlated with brain measures, including decreased functional activity during the decision-making task, thinning of cortical thickness in parietal regions, and loss of white matter integrity. Hence, anosmia could be a factor to be considered when identifying at-risk populations for follow-up.

A Case of Anti-Synthetase Syndrome With Anti-Glycyl tRNA Synthetases Antibody Developed After COVID-19.

Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory disease characterized by severe acute infection. In some cases, COVID-19 symptoms may persist for a long term, posing a significant social problem. Long-term COVID-19 symptoms resemble those observed in various autoimmune diseases, such as dermatomyositis and polymyositis. In this report, we present the case of a 55-year-old woman who had been experiencing persistent dyspnea on exertion since contracting COVID-19 a month ago and was subsequently diagnosed with anti-synthetase syndrome (ASS). The patient presented with fever, dyspnea, rash, mechanic's hands, and arthritis. Computed tomography imaging revealed findings indicative of interstitial pneumonia. Immunological test results were positive for anti-EJ antibody, leading to a diagnosis of ASS based on Solomon's established criteria. The patient's condition improved following treatment with prednisolone, tacrolimus, and intravenous cyclophosphamide. Pathological findings of transbronchial biopsy revealed nonspecific interstitial pneumonia with organizing pneumonia, leading to speculation that ASS had developed after COVID-19. Given the scarcity of reports on ASS development post COVID-19, we conducted a literature review and compared our present case to previous ones. This report highlights the importance of considering ASS in the differential diagnosis of patients with long-term COVID-19 symptoms.

Prevalence and determinants of post-COVID-19 syndrome among patients 6 months post-discharge from a teaching hospital in South India.

Background: The coronavirus disease 2019 (COVID-19) infection has affected millions of people worldwide in the last 4 years. Among those infected, the long-term COVID-19 syndrome, in which symptoms of COVID-19 persist for a variable period, is posing new challenges to the health system, but few studies are available in India that examine the post-COVID-19 syndrome, that is, 6 months and beyond COVID-19 infection. This study aimed to find the prevalence and determinants of post-COVID-19 syndrome among patients 6 months and beyond their infection. Methodology: This cross-sectional study was conducted among 300 patients who were admitted and discharged from Government Medical College, Thrissur, at least 6 months before with a diagnosis of COVID-19 infection. The data collection was performed using a semi-structured interview schedule through a telephonic interview. The analysis was performed using the Statistical Package for the Social Sciences (SPSS) software. Results: 21% of the patients studied had at least one persistent symptom at the end of 6 months, and 4.1% had more than one symptom. Among the symptoms persisting most commonly were fatigue (11%) and dyspnea (7.7%). Other than persisting symptoms, 21% of patients developed exertional dyspnea and 19% developed sleep disturbances during the 6 months after discharge. The factors that were associated with persistent symptoms in univariate analysis were increasing age, presence of chronic obstructive pulmonary disease (COPD), presence of chronic kidney disease (CKD), and admission to the intensive care unit (ICU). Conclusion: The study concludes that one-fifth of the patients still suffer from post-COVID-19 syndrome even 6 months after the COVID-19 infection. Our health systems should be prepared for the long-term management of COVID-19-infected people and prepare policies for the same.

A case of Hemophagocytic syndrome due to reactivation of Epstein-Barr virus after novel coronavirus infection.

Background: Reactivation of EBV after novel coronavirus infection is common, and co-infection with EBV in patients with novel coronavirus pneumonia may lead to more severe clinical manifestations, prolong the duration of the underlying disease, or precipitate the progression of post novel coronavirus syndrome. EBV-induced hemophagocytic syndrome is a rare and life-threatening condition, and there are no reports of EBV reactivation leading to hemophagocytic syndrome after novel coronavirus infection. Case presentation: Here, we report a case of a 73-year-old man with EBV reactivation after novel coronavirus infection, who was diagnosed with hemophagocytic syndrome after bone marrow aspiration and died after being treated with acyclovir, dexamethasone. Conclusions: the aim of this report is to increase clinical awareness of this type of disease for early recognition and treatment.

A first-in-kind MAPK13 inhibitor that can correct stem cell reprogramming and post-injury disease.

The stress kinase MAPK13 (aka p38δ-MAPK) is an attractive entry point for therapeutic intervention because it regulates the structural remodeling that can develop after epithelial barrier injury in the lung and likely other tissue sites. However, a selective, safe, and effective MAPK13 inhibitor is not yet available for experimental or clinical application. Here we identify a first-in-kind MAPK13 inhibitor using structure-based drug design combined with a screening funnel for cell safety and molecular specificity. This inhibitor (designated NuP-4) down-regulates basal-epithelial stem cell reprogramming, structural remodeling, and pathophysiology equivalently to Mapk13 gene-knockout in mouse and mouse organoid models of post-viral lung disease. This therapeutic benefit persists after stopping treatment as a sign of disease modification and attenuates key aspects of inflammation and remodeling as an indication of disease reversal. Similarly, NuP-4 treatment can directly control cytokine-stimulated growth, immune activation, and mucinous differentiation in human basal-cell organoids. The data thereby provide a new tool and potential fix for long-term stem cell reprogramming after viral injury and related conditions that require MAPK13 induction-activation.

The impact of long term COVID-19 infection on the patients' erectile function and on anxiety and on depression as well as the impact of daily tadalafil 5 mg supplementation in patients with erectile dysfunction.

OBJECTIVES: The study examined the impact of long term COVID-19 infection on the patients' erectile function and anxiety and depression in the same patients as well as the impact of daily tadalafil 5 mg supplementation on their erectile function. METHODS: Recovered 114 men were evaluated by the validated Arabic version of the international index of erectile function (ArIIEF-5) and the Arabic versions of the patient health questionnaire-9 (PHQ-9) and the generalized anxiety disorder-7 (GAD-7) at time of presentation, at 3 months and at 6 months, respectively. Forty recovered patients who still complained of ED received tadalafil 5 mg daily for 2 months then were evaluated again at 3 and 6 months by penile duplex, the Arabic versions of the patient health questionnaire-9 (PHQ-9) and the generalized anxiety disorder-7 (GAD-7) at the same periods, respectively. RESULTS: At the time of presentation, there was a positive correlation between the severity of COVID-19 infection, ArIIEF-5 and PHQ-9 (r = 0.249, p = 0.008; r = 0.241, p = 0.010, respectively). Most of the patients showed normal penile duplex parameters. There were 40 ED patients at presentation, 5 ED patients at 3 months and 3 ED patients at 6 months, respectively. CONCLUSIONS: ED in COVID-19 patients who were not suffering from chronic illnesses before the affection, is primarily psychological and completely responsive to tadalafil.

The post-viral GPNMB+ immune niche persists in long-term Covid, asthma, and COPD.

Epithelial injury calls for a regenerative response from a coordinated network of epithelial stem cells and immune cells. Defining this network is key to preserving the repair process for acute resolution, but also for preventing a remodeling process with chronic dysfunction. We recently identified an immune niche for basal-epithelial stem cells using mouse models of injury after respiratory viral infection. Niche function depended on an early sentinel population of monocyte-derived dendritic cells (moDCs) that provided ligand GPNMB to basal-ESC receptor CD44 for reprogramming towards chronic lung disease. These same cell and molecular control points worked directly in mouse and human basal-ESC organoids, but the findings were not yet validated in vivo in human disease. Further, persistence of GPNMB expression in moDCs and M2-macrophages in mouse models suggested utility as a long-term disease biomarker in humans. Here we show increased expression of GPNMB localized to moDC-macrophage populations in lung tissue samples from long-term Covid, asthma, and COPD. The findings thereby provide initial evidence of a persistent and correctable pathway from acute injury to chronic disease with implications for cellular reprogramming and inflammatory memory.