Sarcopenia, sarcopenic obesity and the clinical outcome of the older inpatients with COVID-19 infection: a prospective observational study.

OBJECTIVE: We aimed to investigate the impact of sarcopenia and sarcopenic obesity (SO) on the clinical outcome in older patients with COVID-19 infection and chronic disease. METHODS: We prospectively collected data from patients admitted to Huadong Hospital for COVID-19 infection between November 1, 2022, and January 31, 2023. These patients were included from a previously established comprehensive geriatric assessment (CGA) cohort. We collected information on their pre-admission condition regarding sarcopenia, SO, and malnutrition, as well as their medical treatment. The primary endpoint was the incidence of intubation, while secondary endpoints included in-hospital mortality rates. We then utilized Kaplan-Meier (K-M) survival curves and the log-rank tests to compare the clinical outcomes related to intubation or death, assessing the impact of sarcopenia and SO on patient clinical outcomes. RESULTS: A total of 113 patients (age 89.6 ± 7.0 years) were included in the study. Among them, 51 patients had sarcopenia and 39 had SO prior to hospitalization. Intubation was required for 6 patients without sarcopenia (9.7%) and for 18 sarcopenia patients (35.3%), with 16 of these being SO patients (41%). Mortality occurred in 2 patients without sarcopenia (3.3%) and in 13 sarcopenia patients (25.5%), of which 11 were SO patients (28%). Upon further analysis, patients with SO exhibited significantly elevated risks for both intubation (Hazard Ratio [HR] 7.43, 95% Confidence Interval [CI] 1.26-43.90, P < 0.001) and mortality (HR 6.54, 95% CI 1.09-39.38, P < 0.001) after adjusting for confounding factors. CONCLUSIONS: The prevalence of sarcopenia or SO was high among senior inpatients, and both conditions were found to have a significant negative impact on the clinical outcomes of COVID-19 infection. Therefore, it is essential to regularly assess and intervene in these conditions at the earliest stage possible.

Exosome for mRNA delivery: strategies and therapeutic applications.

Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity. Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism. Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs. However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed. This article outlines current breakthroughs in cell-derived vesicle-mediated mRNA delivery and its biomedical applications.

Hospital services utilisation and cost before and after COVID-19 hospital treatment: Evidence from Indonesia.

OBJECTIVE: To estimate hospital services utilisation and cost among the Indonesian population enrolled in the National Health Insurance (NHI) program before and after COVID-19 hospital treatment. METHODS: 28,159 Indonesian NHI enrolees treated with laboratory-confirmed COVID-19 in hospitals between May and August 2020 were compared to 8,995 individuals never diagnosed with COVID-19 in 2020. A difference-in-difference approach is used to contrast the monthly all-cause utilisation rate and total claims of hospital services between these two groups. A period of nine months before and three to six months after hospital treatment were included in the analysis. RESULTS: A substantial short-term increase in hospital services utilisation and cost before and after COVID-19 treatment was observed. Using the fifth month before treatment as the reference period, we observed an increased outpatient visits rate in 1-3 calendar months before and up to 2-4 months after treatment (p<0.001) among the COVID-19 group compared to the comparison group. We also found a higher admissions rate in 1-2 months before and one month after treatment (p<0.001). Consequently, increased hospital costs were observed in 1-3 calendar months before and 1-4 calendar months after the treatment (p<0.001). The elevated hospital resource utilisation was more prominent among individuals older than 40. Overall, no substantial increase in hospital outpatient visits, admissions, and costs beyond four months after and five months before COVID-19 treatment. CONCLUSION: Individuals with COVID-19 who required hospital treatment had considerably higher healthcare resource utilisation in the short-term, before and after the treatment. These findings indicated that the total cost of treating COVID-19 patients might include the pre- and post-acute period.

Palliative Care for SARS-CoV-2 Patients in the Intensive Care Unit: A Comprehensive Study.

OBJECTIVE: To comprehend the multiprofessional actions regarding palliative care for patients in the Intensive Care Unit affected by SARS-CoV-2. METHODS: A comprehensive qualitative study conducted with 31 professionals from the Intensive Care Units of a university hospital, based on the Theory of Peaceful End of Life. RESULTS: The analysis of the discourse led to the identification of two categories: "Multidisciplinary actions to promote comfort at the end of life" and "Palliative care during the pandemic period and the promotion of emotional and spiritual comfort." FINAL CONSIDERATIONS: It became evident that local administration needs to invest in measures that reduce barriers to the implementation of palliative care during times of crisis. Understanding the discourse highlighted that non-specialized professionals can provide basic palliative care appropriately, without diminishing the importance and necessity of the presence of palliative care specialists in various hospital areas.

Quality of Care Transition for COVID-19 Patients in a University Hospital in Southern Brazil.

OBJECTIVE: To assess the quality of care transition from hospital to home for COVID-19 patients. METHOD: A cross-sectional study conducted at a University Hospital in Southern Brazil, involving 78 patients discharged after COVID-19 hospitalization. Data collection was performed via telephone using the Brazilian version of the Care Transitions Measure (CTM-15). Data were analyzed using descriptive and analytical statistics. RESULTS: The mean quality of care transition was 70.8 on a scale ranging from zero to 100, indicating moderate quality of care transition. The highest score was attributed to factor 1, "Preparation for self-management," and the lowest to factor 4, "Care Plan." CONCLUSIONS: It is important to enhance communication and support provided to patients during the transition process, especially regarding understanding prescribed medications and the development of clear care plans.

The respiratory oxygenation index for identifying the risk of orotracheal intubation in COVID-19 patients receiving high-flow nasal cannula oxygen.

OBJECTIVE: To assess whether the respiratory oxygenation index (ROX index) measured after the start of high-flow nasal cannula oxygen therapy can help identify the need for intubation in patients with acute respiratory failure due to coronavirus disease 2019. METHODS: This retrospective, observational, multicenter study was conducted at the intensive care units of six Brazilian hospitals from March to December 2020. The primary outcome was the need for intubation up to 7 days after starting the high-flow nasal cannula. RESULTS: A total of 444 patients were included in the study, and 261 (58.7%) were subjected to intubation. An analysis of the area under the receiver operating characteristic curve (AUROC) showed that the ability to discriminate between successful and failed high-flow nasal cannula oxygen therapy within 7 days was greater for the ROX index measured at 24 hours (AUROC 0.80; 95%CI 0.76 - 0.84). The median interval between high-flow nasal cannula initiation and intubation was 24 hours (24 - 72), and the most accurate predictor of intubation obtained before 24 hours was the ROX index measured at 12 hours (AUROC 0.75; 95%CI 0.70 - 0.79). Kaplan-Meier curves revealed a greater probability of intubation within 7 days in patients with a ROX index ≤ 5.54 at 12 hours (hazard ratio 3.07; 95%CI 2.24 - 4.20) and ≤ 5.96 at 24 hours (hazard ratio 5.15; 95%CI 3.65 - 7.27). CONCLUSION: The ROX index can aid in the early identification of patients with acute respiratory failure due to COVID-19 who will progress to the failure of high-flow nasal cannula supportive therapy and the need for intubation.

A comparison study of temporal trends of SARS-CoV2 RNAemia and biomarkers to predict success and failure of high flow oxygen therapy among patients with moderate to severe COVID-19.

Optimal timing for intubating patients with coronavirus disease 2019 (COVID-19) has been debated throughout the pandemic. Early use of high-flow nasal cannula (HFNC) can help reduce the need for intubation, but delay can result in poorer outcomes. This study examines trends in laboratory parameters and serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA levels of patients with COVID-19 in relation to HFNC failure. Patients requiring HFNC within three days of hospitalization between July 1 and September 30, 2021 were enrolled. The primary outcome was HFNC failure (early failure ≤Day 3; late failure ≥Day 4), defined as transfer to intensive care just before/after intubation or in-hospital death. We examined changes in laboratory markers and SARS-CoV2-RNAemia on Days 1, 4, and 7, together with demographic data, oxygenation status, and therapeutic agents. We conducted a univariate logistic regression with the explanatory variables defined as 10% change rate in each laboratory marker from Day 1 to 4. We utilized the log-rank test to assess the differences in HFNC failure rates, stratified based on the presence of SARS-CoV2 RNAemia. Among 122 patients, 17 (13.9%) experienced HFNC failure (early: n = 6, late: n = 11). Seventy-five patients (61.5%) showed an initial SpO2/FiO2 ratio ≤243, equivalent to PaO2/FiO2 ratio ≤200, and the initial SpO2/FiO2 ratio was significantly lower in the failure group (184 vs. 218, p = 0.018). Among the laboratory markers, a 10% increase from Day 1 to 4 of lactate dehydrogenase (LDH) and interleukin (IL)-6 was associated with late failure (Odds ratio [OR]: 1.42, 95% confidence interval [CI]: 1.09-1.89 and OR: 1.04, 95%CI: 1.00-1.19, respectively). Furthermore, in patients with persistent RNAemia on Day 4 or 7, the risk of late HFNC failure was significantly higher (Log-rank test, p<0.01). In conclusion, upward trends in LDH and IL-6 levels and the persistent RNAemia even after treatment were associated with HFNC failure.

[Value of modified ROX index in predicting the outcome of patients with acute respiratory distress syndrome due to SARS-CoV-2 infection treated with high-flow nasal cannula oxygen therapy].

OBJECTIVE: To investigate the value of the modified ROX (mROX) index in predicting the outcome of patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection treated with high-flow nasal cannula oxygen therapy (HFNC). METHODS: A retrospective observational study was conducted, including 57 patients with ARDS caused by SARS-CoV-2 infection who required HFNC treatment in the intensive care unit (ICU) of the Lanzhou University Second Hospital from December 2022 to June 2023. The patients were divided into HFNC failure group and HFNC success group according to whether they were successfully weaned from HFNC. Laboratory tests, acute physiology and chronic health evaluation II (APACHE II), and sequential organ failure assessment (SOFA) in the first 24 hours of ICU admission were recorded in both groups, vital signs and arterial blood gas analysis immediately and after 6 hours of HFNC treatment, treatment regimen, length of ICU stay, and total length of hospital stay were recorded in both groups, and patients' outcomes at 28 days and 90 days were followed up by telephone. Univariate analysis was used to analyze the above indexes, and the significant indexes were included in the binary multivariate Logistic regression analysis to analyze the influencing factors of HFNC failure in patients. Kaplan-Meier survival curves were plotted to analyze the 28-day and 90-day outcomes of patients in both groups. Receiver operator characteristic curve (ROC curve) was plotted to analyze the value of treatment 6-hour mROX index and 6-hour ROX index in predicting the success of HFNC. RESULTS: A total of 57 patients with ARDS due to SARS-CoV-2 infection were enrolled, including 34 patients in the HFNC success group and 23 patients in the HFNC failure group. Procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), lactic acid (Lac) and the proportion of vasopressors, the proportion of continuous renal replacement therapy (CRRT), the APACHE II score and the SOFA score, the respiratory rate (RR) immediately and 6 hours after treatment were significantly higher in the HFNC failure group compared with the HFNC success group. The length of ICU stay was significantly longer, and oxygenation index (PaO2/FiO2) at the time of treatment, and pulse oxygen saturation (SpO2), arterial partial pressure of oxygen (PaO2), ROX index, and mROX index at the time of treatment and at 6 hours after treatment were significantly lower in the HFNC failure group compared with the HFNC success group (all P < 0.05). Kaplan-Meier survival curves showed that the 28-day cumulative survival rates (100% vs. 26.1%) and 90-day cumulative survival rates (85.3% vs. 21.7%) of patients in the HFNC success group were significantly higher than those in the HFNC failure group (both P < 0.001). On binary multivariate Logistic regression analysis, Lac [odds ratio (OR) = 0.129, 95% confidence interval (95%CI) was 0.020-0.824], SOFA score (OR = 0.382, 95%CI was 0.158-0.925), 6-hour ROX index (OR = 0.099, 95%CI was 0.011-0.920), and 6-hour mROX index (OR = 23.703, 95%CI was 1.415-396.947) were associated with HFNC treatment outcome (all P < 0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of the 6-hour mROX index and the 6-hour ROX index for predicting the success of HFNC were both higher (0.809 and 0.714, respectively), and the AUC of 6-hour mROX index was significantly higher than that of 6-hour ROX index (P < 0.01), and the sensitivity was 88.2% and the specificity was 52.2% when the cut-off value of 6-hour mROX index was 4.5. CONCLUSIONS: The predictive value of the 6-hour mROX index in the treatment of patients with ARDS caused by SARS-CoV-2 infection is higher than that of the 6-hour ROX index, and the 6-hour mROX index is greater than 4.5, which is more likely to predict the success of HFNC treatment.

Impact of the SARS-CoV-2 pandemic on acute coronary syndrome patients admitted to an urban academic hospital in Soweto, South Africa.

Introduction: recent worldwide data has shown a concerning decline in the number of acute coronary syndrome (ACS) related admissions and percutaneous coronary intervention (PCI) procedures during the coronavirus disease 2019 (COVID-19) pandemic. We suspected a similar trend at Chris Hani Baragwanath Hospital (CHBAH). Methods: a retrospective descriptive study was conducted to evaluate and compare all ACS-related admissions to the cardiac care unit (CCU) at CHBAH in the pre-COVID-19 (November 2019 to March 2020) and during COVID-19 periods (April 2020 to August 2020). Results: the study comprised 182 patients with a mean age of 57.9 ±10.9 years (22.5% females). Of these, 108 (59.32%) patients were admitted in the pre-COVID-19 period and 74 (40.66%) during COVID-19 (p=0.0109). During the pre-COVID-19 period, 42.9% of patients had ST-segment-elevation myocardial infarction (STEMI), 39.2% with non-ST-segment -elevation myocardial infarction (NSTEMI) and unstable angina (UA) was noted in 18.52%. In contrast, STEMI was noted in 50%, NSTEMI in 43.24% and UA in 6.76% of patients during the COVID-19 period. A statistically significant difference in STEMI and NSTEMI-related admissions was not noted, however, there was a greater number of admissions for UA during the pre-COVID-19 period (18.52% vs 6.76%, P =0.013). Only a third of the patients with STEMI received thrombolysis during the pre-and COVID-19 periods (30.4% vs 37.8%, P=0.47). No difference in the number of PCI procedures was noted between the pre-and during the COVID-19 periods (78.7% vs 72.9%, P=0.37). Conclusion: there was a difference in overall ACS admissions to the CCU between pre-and during COVID-19 periods, however no difference between STEMI and NSTEMI in both periods. A higher number of UA admissions was noted during the pre-COVID-19 period. During both periods, the use of thrombolysis was low for STEMI and no difference in PCI was noted.

Racial Differences in Accuracy of Predictive Models for High-Flow Nasal Cannula Failure in COVID-19.

OBJECTIVES: To develop and validate machine learning (ML) models to predict high-flow nasal cannula (HFNC) failure in COVID-19, compare their performance to the respiratory rate-oxygenation (ROX) index, and evaluate model accuracy by self-reported race. DESIGN: Retrospective cohort study. SETTING: Four Emory University Hospitals in Atlanta, GA. PATIENTS: Adult patients hospitalized with COVID-19 between March 2020 and April 2022 who received HFNC therapy within 24 hours of ICU admission were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four types of supervised ML models were developed for predicting HFNC failure (defined as intubation or death within 7 d of HFNC initiation), using routine clinical variables from the first 24 hours of ICU admission. Models were trained on the first 60% (n = 594) of admissions and validated on the latter 40% (n = 390) of admissions to simulate prospective implementation. Among 984 patients included, 317 patients (32.2%) developed HFNC failure. eXtreme Gradient Boosting (XGB) model had the highest area under the receiver-operator characteristic curve (AUROC) for predicting HFNC failure (0.707), and was the only model with significantly better performance than the ROX index (AUROC 0.616). XGB model had significantly worse performance in Black patients compared with White patients (AUROC 0.663 vs. 0.808, p = 0.02). Racial differences in the XGB model were reduced and no longer statistically significant when restricted to patients with nonmissing arterial blood gas data, and when XGB model was developed to predict mortality (rather than the composite outcome of failure, which could be influenced by biased clinical decisions for intubation). CONCLUSIONS: Our XGB model had better discrimination for predicting HFNC failure in COVID-19 than the ROX index, but had racial differences in accuracy of predictions. Further studies are needed to understand and mitigate potential sources of biases in clinical ML models and to improve their equitability.

Monoclonal Antibody Generation Using Single B Cell Screening for Treating Infectious Diseases.

The screening of antigen-specific B cells has been pivotal for biotherapeutic development for over four decades. Conventional antibody discovery strategies, including hybridoma technology and single B cell screening, remain widely used based on their simplicity, accessibility, and proven track record. Technological advances and the urgent demand for infectious disease applications have shifted paradigms in single B cell screening, resulting in increased throughput and decreased time and labor, ultimately enabling the rapid identification of monoclonal antibodies with desired biological and biophysical properties. Herein, we provide an overview of conventional and emergent single B cell screening approaches and highlight their potential strengths and weaknesses. We also detail the impact of innovative technologies-including miniaturization, microfluidics, multiplexing, and deep sequencing-on the recent identification of broadly neutralizing antibodies for infectious disease applications. Overall, the coronavirus disease 2019 (COVID-19) pandemic has reinvigorated efforts to improve the efficiency of monoclonal antibody discovery, resulting in the broad application of innovative antibody discovery methodologies for treating a myriad of infectious diseases and pathological conditions.

Clinical outcomes of immunomodulation therapy in immunocompromised patients with severe Covid-19 and high oxygen requirement.

Covid-19 disease is implicated in increased mortality among immunocompromised patients. The JAK inhibitor, baricitinib (bar), or the IL-6 inhibitor, tocilizumab (toc), demonstrated a survival benefit in patients with severe disease.However, evidence supporting their use in immunocompromised patients with severe Covid-19 is scarce.We aimed to assess clinical outcomes of bar/toc treatment in immunocompromised patients. A multi-center registry of consecutive immunocompromised patients hospitalized due to severe Covid-19 during the Omicron variant dominance period. After excluding patients who did not require high oxygen supply, patients treated with bar/toc were compared to patients treated by standard of care (SOC). Primary outcome was in hospital mortality. Secondary outcomes were 30 and 60 day mortality, super-infection and thromboembolic events. Among an overall 228 immunocompromised patients hospitalized in six Israeli hospitals with severe Covid-19, 112 patients required high oxygen support, of whom 48 (43%) were treated with bar/toc. In-hospital mortality rates were exceptionally high and did not significantly differ between bar/toc and SOC treated patients (62.5% vs. 64.1%, p = 1.0). A logistic regression analysis revealed that advanced age and incomplete vaccination were predictors of in-hospital mortality. Patients treated with bar/toc had no excess of suspected super-infection (62.8% vs. 60.7%, p = 0.84) or thromboembolic events (8.3% vs 3.1%, p = 0.39). In immunocompromised patients with severe Covid-19 and a high oxygen demand, bar/toc therapy was not associated with reduced mortality or with a higher rate of associated complications, compared to SOC. Larger prospective studies should better address efficacy and safety.

Long-term oxygen therapy to reduce length of hospital stay in COVID-19.

OBJECTIVE: The aim of this study was to evaluate the efficacy of long-term oxygen therapy as a strategy to reduce hospitalization time in patients affected by COVID-19. METHODS: Between April and December 2021, COVID-19 patients with stable clinical conditions needing supplementary oxygen therapy during hospitalization were oriented to have hospital discharge with long-term oxygen therapy and reassessment after 15 days. RESULTS: A total of 62 patients were evaluated and, 15 days after discharge, 69% of patients had suspended long-term oxygen therapy, with no difference between the groups admitted to the intensive care unit or the ward (p=0.319). Among the individuals who needed to maintain long-term oxygen therapy, in addition to worse P/F ratio (265±57 vs. 345±51; p<0.001) and lower partial pressure of oxygen (55±12 vs. 72±11 mmHg; p<0.001), were those more obese (37±8 vs. 30±6 kg/m2; p=0.032), needed more time for invasive mechanical ventilation (46±27 vs. 20±16 days; p=0.029), had greater persistence of symptoms (p<0.001), and shorter time between the onset of symptoms and the need for hospitalization (7 [2-9] vs. 10 [6-12] days; p=0.039). CONCLUSION: Long-term oxygen therapy is an effective strategy for reducing hospitalization time in COVID-19 patients, regardless of gravity. Additionally, more obese patients with persistence of respiratory symptoms, faster disease evolution, and more days of invasive mechanical ventilation needed to maintain the long-term oxygen therapy longer.

Using a static magnetic field to attenuate the severity in COVID-19-invaded lungs.

Two important factors affecting the progress of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the S-protein binding function of ACE2 receptors and the membrane fluidity of host cells. This study aimed to evaluate the effect of static magnetic field (SMF) on S-protein/ACE2 binding and cellular membrane fluidity of lung cells, and was performed in vitro using a Calu-3 cell model and in vivo using an animal model. The ability of ACE2 receptors to bind to SARS-CoV-2 spike protein on host cell surfaces under SMF stimulation was evaluated using fluorescence images. Host lung cell membrane fluidity was tested using fluorescence polarization to determine the effects of SMF. Our results indicate that 0.4 T SMF can affect binding between S-protein and ACE2 receptors and increase Calu-3 cell membrane fluidity, and that SMF exposure attenuates LPS-induced alveolar wall thickening in mice. These results may be of value for developing future non-contact, non-invasive, and low side-effect treatments to reduce disease severity in COVID-19-invaded lungs.

Evaluating the delivery of care by telemedicine for incarcerated people living with HIV: a cohort study.

BACKGROUND: The use of telemedicine has grown significantly since the COVID-19 pandemic and has the potential to improve access to specialized care for otherwise underserved populations. Incarcerated people living with HIV (PLWH) could potentially benefit from expanded access to HIV care through telemedicine. METHODS: All PLWH who were incarcerated within the Tennessee Department of Corrections and received care through the HIV telemedicine clinic at Regional One Hospital between 5/1/2019 through 2/28/2022 were identified from the electronic health records (EHR). Demographics, laboratory data, vaccine history, and treatment outcomes were abstracted from the EHR. Retention in care and viral suppression were defined using Centers for Disease Control and Prevention definitions. RESULTS: Of the 283 incarcerated PLWH receiving care from this telemedicine clinic, 78% remained retained in care and 94% achieved or maintaining viral suppression at 12 months. Many preventative care measures remained unperformed or undocumented, including vaccinations and testing for concurrent sexually transmitted infections. There were 56 patients (20%) found to have chronic hepatitis C in this population, with 71% either cured or still on treatment in this study period. CONCLUSIONS: Retention in care and viral suppression rates were excellent among incarcerated PLWH receiving telemedicine care for their HIV. HIV related primary health care screenings and vaccinations, however, were less consistently documented and represent areas for improvement.

Coronavirus disease 2019-related myocarditis genes contribute to ECMO prognosis.

BACKGROUND: Acute myocardial injury, cytokine storms, hypoxemia and pathogen-mediated damage were the major causes responsible for mortality induced by coronavirus disease 2019 (COVID-19)-related myocarditis. These need ECMO treatment. We investigated differentially expressed genes (DEGs) in patients with COVID-19-related myocarditis and ECMO prognosis. METHODS: GSE150392 and GSE93101 were analyzed to identify DEGs. A Venn diagram was used to obtain the same transcripts between myocarditis-related and ECMO-related DEGs. Enrichment pathway analysis was performed and hub genes were identified. Pivotal miRNAs, transcription factors, and chemicals with the screened gene interactions were identified. The GSE167028 dataset and single-cell sequencing data were used to validate the screened genes. RESULTS: Using a Venn diagram, 229 overlapping DEGs were identified between myocarditis-related and ECMO-related DEGs, which were mainly involved in T cell activation, contractile actin filament bundle, actomyosin, cyclic nucleotide phosphodiesterase activity, and cytokine-cytokine receptor interaction. 15 hub genes and 15 neighboring DEGs were screened, which were mainly involved in the positive regulation of T cell activation, integrin complex, integrin binding, the PI3K-Akt signaling pathway, and the TNF signaling pathway. Data in GSE167028 and single-cell sequencing data were used to validate the screened genes, and this demonstrated that the screened genes CCL2, APOE, ITGB8, LAMC2, COL6A3 and TNC were mainly expressed in fibroblast cells; IL6, ITGA1, PTK2, ITGB5, IL15, LAMA4, CAV1, SNCA, BDNF, ACTA2, CD70, MYL9, DPP4, ENO2 and VEGFC were expressed in cardiomyocytes; IL6, PTK2, ITGB5, IL15, APOE, JUN, SNCA, CD83, DPP4 and ENO2 were expressed in macrophages; and IL6, ITGA1, PTK2, ITGB5, IL15, VCAM1, LAMA4, CAV1, ACTA2, MYL9, CD83, DPP4, ENO2, VEGFC and IL32 were expressed in vascular endothelial cells. CONCLUSION: The screened hub genes, IL6, ITGA1, PTK2, ITGB3, ITGB5, CCL2, IL15, VCAM1, GZMB, APOE, ITGB8, LAMA4, LAMC2, COL6A3 and TNFRSF9, were validated using GEO dataset and single-cell sequencing data, which may be therapeutic targets patients with myocarditis to prevent MI progression and adverse cardiovascular events.

Recurrent spontaneous pneumothorax secondary to lung cystic lesions in a case of convalescent COVID-19: a case report and literature review.

BACKGROUND: While spontaneous pneumothorax has been documented in COVID-19 patients, reports on recurrent spontaneous pneumothorax due to cystic lesions in convalescent COVID-19 patients are scarce. The progression of these lung cystic lesions remains inadequately explored. CASE PRESENTATION AND LITERATURE REVIEW: An 81-year-old male, a non-smoker with a history of rheumatoid arthritis, presented with fever, cough, and expectoration for 14 days. Initially diagnosed with moderate COVID-19, he deteriorated to severe COVID-19 despite adherence to local treatment guidelines. Successive identification of three cystic lesions termed "bulla" or "pneumatocele", and one cystic lesion with air-fluid level, referred to as "pneumo-hamatocele" (PHC), occurred in his lungs. Gradual improvement followed anti-inflammatory therapy and optimal supportive care. However, on day 42, sudden worsening dyspnea prompted a computed tomography (CT) scan, confirming a right spontaneous pneumothorax and subcutaneous emphysema, likely due to PHC rupture. Discharge followed chest tube implementation for pneumothorax resolution. On day 116, he returned to the hospital with mild exertional dyspnea. Chest CT revealed recurrent right pneumothorax from a remaining cyst in the right lung. Apart from our patient, literature retrieval identified 22 COVID-19 patients with spontaneous pneumothorax due to cystic lesions, with a male predominance (95.6%; 22/23). Diagnosis of pneumothorax and lung cystic lesions occurred around day 29.5 (range: 18-35) and day 26.4 (± 9.8) since symptom onset, respectively. Except for one patient whose pneumothorax occurred on day seven of illness, all patients eventually recovered. CONCLUSIONS: Recurrent spontaneous pneumothorax secondary to lung cystic lesions may manifest in convalescent COVID-19 patients, particularly males with COVID-19 pneumonia. Chest CT around 2 to 3 weeks post-symptom onset may be prudent to detect cystic lesion development and anticipate spontaneous pneumothorax.

Clinical course, management and outcomes of COVID-19 in HIV-infected renal transplant recipients: A case series.

BACKGROUND: HIV-infected kidney transplant recipients with COVID-19 are at increased risk of acute illness and death owing to their underlying comorbidities and chronic immunosuppression. OBJECTIVES: To describe the incidence, clinical presentation and course of COVID-19, vaccination status, and SARS-CoV-2 antibody positivity rate among HIV-infected-to-HIV-infected kidney transplant recipients in South Africa (SA). METHODS: This retrospective study reports on rates of SARS-CoV-2 infection, COVID-19 and mortality among SA HIV-infected kidney transplant recipients who received organs from HIV-infected donors (HIV positive to HIV positive), before and after vaccination. Patient demographics, clinical presentation, course, management and disease outcomes were analysed. Antibody serology tests were performed between May and September 2022. RESULTS: Among 39 HIV-positive-to-HIV-positive transplant recipients, 11 cases of COVID-19 were diagnosed from March 2020 to September 2022. Six patients (55%) required hospitalisation, of whom 3 were admitted to a high-care unit or intensive care unit. Two patients required mechanical ventilation, and 2 received acute dialysis. One patient was declined access to intensive care. Four patients (10%) died of COVID-19 pneumonia. All the COVID-19-positive patients had at least one comorbidity. Vaccination data were available for 24 patients, of whom 5 had refused SARS-CoV-2 vaccination. SARS-CoV-2 antibody data were available for 20 patients; 4 vaccinated patients had a negative nucleocapsid protein antibody test and a positive spike protein antibody test, suggesting vaccination-acquired immunity. The remaining 16 patients demonstrated immunity that was probably due to COVID infection, and of these, 14 were also vaccinated. Of the 11 COVID-19 cases, only 1 was observed after vaccination. CONCLUSION: In our case series, ~10% of the HIV-positive-to-HIV-positive transplant recipients died of COVID-19 pneumonia. This mortality rate appears higher than figures reported in other transplant cohorts. However, it is likely that the actual number of cases of SARS-CoV-2 infection was much higher, as the study only included polymerase chain reaction-confirmed cases. It remains unclear whether HIV infection, transplant or the combination of the two drives poorer outcomes, and larger studies adjusting for important demographic and biological factors may isolate these effects.

Telehealth Availability for Mental Health Care During and After the COVID-19 Public Health Emergency.

Importance: Telehealth services expanded rapidly during the COVID-19 public health emergency (PHE). Objective: To evaluate changes in availability of telehealth services at outpatient mental health treatment facilities (MHTFs) throughout the US during and after the COVID-19 PHE. Design, Setting, and Participants: In this cohort study, callers posing as prospective clients contacted a random sample of 1404 MHTFs drawn from the Substance Abuse and Mental Health Services Administration's Behavioral Health Treatment Locator from December 2022 to March 2023 (wave 1 [W1]; during PHE). From September to November 2023 (wave 2 [W2]; after PHE), callers recontacted W1 participants. Analyses were conducted in January 2024. Main Outcomes and Measures: Callers inquired whether MHTFs offered telehealth (yes vs no), and, if yes, whether they offered (1) audio-only telehealth (vs audio and video); (2) telehealth for therapy, medication management, and/or diagnostic services; and (3) telehealth for comorbid alcohol use disorder (AUD). Sustainers (offered telehealth in both waves), late adopters (did not offer telehealth in W1 but did in W2), nonadopters (did not offer telehealth in W1 or W2), and discontinuers (offered telehealth in W1 but not W2) were all compared. Results: During W2, 1001 MHTFs (86.1%) were successfully recontacted. A total of 713 (71.2%) were located in a metropolitan county, 151 (15.1%) were publicly operated, and 935 (93.4%) accepted Medicaid as payment. The percentage offering telehealth declined from 799 (81.6%) to 765 (79.0%) (odds ratio [OR], 0.84; 95% CI, 0.72-1.00; P < .05). Among MHTFs offering telehealth, a smaller percentage in W2 offered audio-only telehealth (369 [49.3%] vs 244 [34.1%]; OR, 0.53; 95% CI, 0.44-0.64; P < .001) and telehealth for comorbid AUD (559 [76.3%] vs 457 [66.5%]; OR, 0.62; 95% CI, 0.50-0.76; P < .001) compared with W1. In W2, MHTFs were more likely to report telehealth was only available under certain conditions for therapy (141 facilities [18.0%] vs 276 [36.4%]; OR, 2.62; 95% CI, 1.10-3.26; P < .001) and medication management (216 facilities [28.0%] vs 304 [41.3%]; OR, 1.81; 95% CI, 1.48-2.21; P < .001). A total of 684 MHTFs (72.0%) constituted sustainers, 94 (9.9%) were discontinuers, 106 (11.2%) were nonadopters, and 66 (7.0%) were late adopters. Compared with sustainers, discontinuers were less likely to be private for-profit (adjusted OR [aOR], 0.28; 95% CI, 0.11-0.68) or private not-for-profit (aOR, 0.26; 95% CI, 0.14-0.48) after adjustment for facility and area characteristics. Conclusions and Relevance: Based on this longitudinal cohort study of 1001 MHTFs, telehealth availability has declined since the PHE end with respect to scope and modality of services, suggesting targeted policies may be necessary to sustain telehealth access.

Development and validation of a model to predict ceiling of care in COVID-19 hospitalized patients.

BACKGROUND: Therapeutic ceiling of care is the maximum level of care deemed appropiate to offer to a patient based on their clinical profile and therefore their potential to derive benefit, within the context of the availability of resources. To our knowledge, there are no models to predict ceiling of care decisions in COVID-19 patients or other acute illnesses. We aimed to develop and validate a clinical prediction model to predict ceiling of care decisions using information readily available at the point of hospital admission. METHODS: We studied a cohort of adult COVID-19 patients who were hospitalized in 5 centres of Catalonia between 2020 and 2021. All patients had microbiologically proven SARS-CoV-2 infection at the time of hospitalization. Their therapeutic ceiling of care was assessed at hospital admission. Comorbidities collected at hospital admission, age and sex were considered as potential factors for predicting ceiling of care. A logistic regression model was used to predict the ceiling of care. The final model was validated internally and externally using a cohort obtained from the Leeds Teaching Hospitals NHS Trust. The TRIPOD Checklist for Prediction Model Development and Validation from the EQUATOR Network has been followed to report the model. RESULTS: A total of 5813 patients were included in the development cohort, of whom 31.5% were assigned a ceiling of care at the point of hospital admission. A model including age, COVID-19 wave, chronic kidney disease, dementia, dyslipidaemia, heart failure, metastasis, peripheral vascular disease, chronic obstructive pulmonary disease, and stroke or transient ischaemic attack had excellent discrimination and calibration. Subgroup analysis by sex, age group, and relevant comorbidities showed excellent figures for calibration and discrimination. External validation on the Leeds Teaching Hospitals cohort also showed good performance. CONCLUSIONS: Ceiling of care can be predicted with great accuracy from a patient's clinical information available at the point of hospital admission. Cohorts without information on ceiling of care could use our model to estimate the probability of ceiling of care. In future pandemics, during emergency situations or when dealing with frail patients, where time-sensitive decisions about the use of life-prolonging treatments are required, this model, combined with clinical expertise, could be valuable. However, future work is needed to evaluate the use of this prediction tool outside COVID-19.