Mesenchymal Stem Cells Therapy for COVID-19: From Basic Research to Clinical Trial.

The novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a serious challenge for human health. In severe cases, patients suffer from acute respiratory distress syndrome even organ failure, usually owing to the dysregulated immune response and widespread inflammation. Considering that there is no known cure for COVID-19 despite the increased morbidity and mortality rate of COVID-19, modalities targeting immunity and inflammation may be promising therapeutics against COVID-19. Mesenchymal stem cells (MSCs) possessing immunomodulatory, anti-inflammatory, anti-apoptotic, and antiviral properties, can be of potential benefit to a subset of severe and critically ill patients with COVID-19. In the present study, we described the underlying mechanisms of MSCs therapy and provided a thorough research study on the recent clinical trials of MSCs for SARS-CoV-2 infection.

Effects of adjuvant ozone autohemotherapy combined with routine treatment on clinical and paraclinical features of mechanically ventilated COVID-19 patients in the intensive care unit: a pilot randomized controlled trial.

Until the availability of an effective and practical vaccine, there is a serious need to recognize alternative treatments for coronavirus disease 2019 (COVID-19). This study aimed to determine whether major ozonated autohemotherapy (MOAH) can improve the clinical and paraclinical parameters in critically-ill patients with COVID-19 requiring mechanical ventilation. In this controlled trial, we enrolled 40 critically ill COVID-19 patients receiving invasive mechanical ventilation. The enrolled patients were then randomized into the MOAH and control groups. The patients in the MOAH group received MOAH three times per week (10 times in total) in addition to routine treatment and standard critical supportive care. Patients in the control group were only given regular treatment and standard critical supportive care. The patients in the MOAH group had more days of breathing with no aid than those in the control group. Moreover, the length of stay in the intensive-care unit was significantly lower in the MOAH group than in the control group. MOAH resulted in higher ventilation-free days and less intensive-care unit stay compared with the control treatment. In COVID-19 patients undergoing mechanical ventilation, MOAH with routine treatment resulted in more ventilator-free days and less intensive-care unit stay compared with the standard therapy.

Differences in COVID-19 treatment across Japan: Analysis of the COVID-19 Registry Japan (COVIREGI-JP).

BACKGROUND: This study investigated the differences between metropolitan and non-metropolitan areas in the treatment of hospitalized patients with COVID-19 using data from the nationwide COVID-19 Registry Japan (COVIREGI-JP). METHODS: Data of patients hospitalized for COVID-19 during waves 2-4 (June 1, 2020-June 30, 2021) treated in one of the 800 medical institutions participating in the Registry were extracted. Treatment and treatment outcomes were evaluated in inpatients with moderate 2 and severe disease using propensity score matching performed between metropolitan and non-metropolitan areas. RESULTS: A total of 32797 patients were identified during epidemic waves 2-4. After matching (wave 2, n = 307; wave 3, n = 913; wave 4, n = 479), the population comprised mostly elderly patients with a median age of ≥65 years (IQR: 52-81 years) and median SpO2 of 93/94 (IQR: 91%-96%), and the proportion of patients with moderate 2 (SpO2≤93%/require oxygenation) vs severe disease (ICU admission) ranged from 82.7% to 89.8% vs 10.2% to 17.3% in metropolitan areas vs non-metropolitan areas, respectively, across all epidemic waves. Noninvasive mechanical ventilation was used significantly more in waves 2 and 3 and invasive mechanical ventilation in wave 4 in metropolitan vs non-metropolitan areas, compared with other waves. In wave 2, death as an outcome was significantly higher in metropolitan vs non-metropolitan areas compared with patient discharge to home/transfer. CONCLUSION: During the COVID-19 epidemic, starting from wave 2 up until and through wave 4, no clear differences in mortality rates and no regional differences in treatment provision patterns were observed between metropolitan and non-metropolitan areas in Japan.

Airway Pressure Release Ventilation in COVID-19-Associated Acute Respiratory Distress Syndrome-A Multicenter Propensity Score-Matched Analysis.

Background: There are limited and partially contradictory data on the effects of airway pressure release ventilation (APRV) in COVID-19-associated acute respiratory distress syndrome (CARDS). Therefore, we analyzed the clinical outcome, complications, and longitudinal course of ventilation parameters and laboratory values in patients with CARDS, who were mechanically ventilated using APRV. Methods: Respective data from 4 intensive care units (ICUs) were collected and compared to a matched cohort of patients receiving conventional low tidal volume ventilation (LTV). Propensity score matching was performed based on age, sex, blood gas analysis, and APACHE II score at admission, as well as the implementation of prone positioning. Findings: Forty patients with CARDS, who were mechanically ventilated using APRV, and 40 patients receiving LTV were matched. No significant differences were detected for tidal volumes per predicted body weight, peak pressure values, and blood gas analyses on admission, 6 h post admission as well as on day 3 and day 7. Regarding ICU survival, no significant difference was identified between APRV patients (40%) and LTV patients (42%). Median duration of mechanical ventilation and duration of ICU treatment were comparable in both groups. Similar complication rates with respect to ventilator-associated pneumonia, septic shock, thromboembolic events, barotrauma, as well as the necessity for hemodialysis were detected for both groups. Clinical characteristics that were associated with increased mortality in a Cox proportional hazards regression analysis included age (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.04-1.1; P < .001), severe acute respiratory distress syndrome (HR 2.62, 95% CI 1.02-6.7; P = .046) and the occurrence of septic shock (HR 17.18, 95% CI 2.06-143.2; P = .009), but not the ventilation mode. Interpretation: Intensive care unit survival, duration of mechanical ventilation, and ICU treatment as well as ventilation-associated complication rates were equivalent using APRV compared to conventional LTV in patients with CARDS.

Characteristics and Presentations of Hospitalized Children Due to 3 Predominate COVID-19 Variants Within a Health Care Network.

Objective of this article is to describe differences in the demographic and clinical characteristics, severity of illness, and outcomes in pediatric patients with different SARS-CoV-2 variants. We conducted a retrospective study of pediatric patients admitted with COVID-19 during the 3 large waves of infection within a health network in New Jersey. We included demographic characteristics, clinical features, and outcomes and compared the data with respect to the different variants. Of 351 total patients included in this study, 74 were admitted during wave 1, 94 during wave 2, and 181 during wave 3. The median age of patients decreased from wave 1 (11.5 years) to wave 3 (3 years) (P = .0034). 87.7% of the patients were unvaccinated. The overall incidence of admissions due to pneumonia related to COVID-19 decreased in wave 3. COVID-19 bronchiolitis or croup admissions occurred mostly in wave 3. There was no significant difference in the number of patients requiring intensive care in any particular wave. Length of stay decreased across the waves (P < .0001). Treatments required did not vary between the waves except for a decrease in antibiotic use with each subsequent wave (P < .0001). The impact of COVID-19 on the pediatric population differs from the adult population, and the overall number of hospitalized children has mirrored the peak in cases observed during each infection wave. Our study illustrates the changes in clinical presentation and severity observed with the different coronavirus variants.

Respiratory rate­oxygenation (ROX) index for predicting high-flow nasal cannula failure in patients with and without COVID-19.

BACKGROUND: The predictive value of the respiratory rate­oxygenation (ROX) index for a high-flow nasal cannula (HFNC) in patients with COVID-19 with acute hypoxemic respiratory failure (AHRF) may differ from patients without COVID-19 with AHRF, but these patients have not yet been compared. We compared the diagnostic accuracy of the ROX index for HFNC failure in patients with AHRF with and without COVID-19 during acute emergency department (ED) visits. METHODS: We performed a retrospective analysis of patients with AHRF treated with an HFNC in an ED between October 2020 and April 2022. The ROX index was calculated at 1, 2, 4, 6, 12, and 24 h after HFNC placement. The primary outcome was the failure of the HFNC, which was defined as the need for subsequent intubation or death within 72 h. A receiver operating characteristic (ROC) curve was used to evaluate discriminative power of the ROX index for HFNC failure. RESULTS: Among 448 patients with AHRF treated with an HFNC in an ED, 78 (17.4%) patients were confirmed to have COVID-19. There was no significant difference in the HFNC failure rates between the non-COVID-19 and COVID-19 groups (29.5% vs. 33.3%, p = 0.498). The median ROX index was higher in the non-COVID-19 group than in the COVID-19 group at all time points. The prognostic power of the ROX index for HFNC failure as evaluated by the area under the ROC curve was generally higher in the COVID-19 group (0.73-0.83) than the non-COVID-19 group (0.62-0.75). The timing of the highest prognostic value of the ROX index for HFNC failure was at 4 h for the non-COVID-19 group, whereas in the COVID-19 group, its performance remained consistent from 1 h to 6 h. The optimal cutoff values were 6.48 and 5.79 for the non-COVID-19 and COVID-19 groups, respectively. CONCLUSIONS: The ROX index had an acceptable discriminative power for predicting HFNC failure in patients with AHRF with and without COVID-19 in the ED. However, the higher ROX index thresholds than those in previous publications involving intensive care unit (ICU) patients suggest the need for careful monitoring and establishment of a new threshold for patients admitted outside the ICU.

COVID-19 Admission Rates and Changes in US Hospital Inpatient and Intensive Care Unit Occupancy.

Importance: The COVID-19 pandemic had unprecedented effects on hospital occupancy, with consequences for hospital operations and patient care. Previous studies of occupancy during COVID-19 have been limited to small samples of hospitals. Objective: To measure the association between COVID-19 admission rates and hospital occupancy in different US areas and at different time periods during 2020. Design, Setting, and Participants: This cross-sectional study used data from the Healthcare Cost and Utilization Project State Inpatient Databases (2019-2020) for patients in nonfederal acute care hospitals in 45 US states, including the District of Columbia. Data analysis was performed between September 1, 2022, and April 30, 2023. Exposures: Each hospital and week in 2020 was categorized based on the number of COVID-19 admissions per 100 beds (<1 [low], 1-4.9, 5-9.9, 10-14.9, or ≥15 [high]). Main Outcomes and Measures: The main outcomes were inpatient and intensive care unit (ICU) occupancy. We used regression analysis to estimate the average change in occupancy for each hospital-week in 2020 relative to the same hospital week in 2019. Results: This study included 3960 hospitals and 54 355 916 admissions. Of the admissions in the 40 states used for race and ethnicity analyses, 15.7% were for Black patients, 12.9% were for Hispanic patients, 62.5% were for White patients, and 7.2% were for patients of other race or ethnicity; 1.7% of patients were missing these data. Weekly COVID-19 admission rates in 2020 were less than 4 per 100 beds for 63.9% of hospital-weeks and at least 10 in only 15.9% of hospital-weeks. Inpatient occupancy decreased by 12.7% (95% CI, 12.1% to 13.4%) during weeks with low COVID-19 admission rates and increased by 7.9% (95% CI, 6.8% to 9.0%) during weeks with high COVID-19 admission rates. Intensive care unit occupancy rates increased by 67.8% (95% CI, 60.5% to 75.3%) during weeks with high COVID-19 admissions. Increases in ICU occupancy were greatest when weighted to reflect the experience of Hispanic patients. Changes in occupancy were most pronounced early in the pandemic. During weeks with high COVID-19 admissions, occupancy decreased for many service lines, with occupancy by surgical patients declining by 43.1% (95% CI, 38.6% to 47.2%) early in the pandemic. Conclusions and Relevance: In this cross-sectional study of US hospital discharges in 45 states in 2020, hospital occupancy decreased during weeks with low COVID-19 admissions and increased during weeks with high COVID-19 admissions, with the largest changes occurring early in the pandemic. These findings suggest that surges in COVID-19 strained ICUs and were associated with large decreases in the number of surgical patients. These occupancy fluctuations may have affected quality of care and hospital finances.

COVID-19 outcome is not affected by anti-CD20 or high-titer convalescent plasma in immunosuppressed patients.

The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma in the treatment of Coronavirus Disease 2019 (COVID-19) in immunosuppressed individuals remains controversial. We describe the course of COVID-19 in patients who had received anti-CD20 therapy within the 3 years prior to infection. We compared outcomes between those treated with and those not treated with high titer SARS-CoV2 convalescent plasma. We identified 144 adults treated at Mayo clinic sites who had received anti-CD20 therapies within a median of 5.9 months prior to the COVID-19 index date. About one-third (34.7%) were hospitalized within 14 days and nearly half (47.9%) within 90 days. COVID-19 directed therapy included anti-spike monoclonal antibodies (n = 30, 20.8%), and, among those hospitalized within 14 days (n = 50), remdesivir (n = 45, 90.0%), glucocorticoids (n = 36, 72.0%) and convalescent plasma (n = 24, 48.0%). The duration from receipt of last dose of anti-CD20 therapy did not correlate with outcomes. The overall 90-day mortality rate was 14.7%. Administration of convalescent plasma within 14 days of the COVID-19 diagnosis was not significantly associated with any study outcome. Further study of COVID-19 in CD20-depleted individuals is needed focusing on the early administration of new and potentially combination antiviral agents, associated or not with vaccine-boosted convalescent plasma.

Epidemiology, clinical characteristics and outcomes of multisystem inflammatory syndrome in children.

BACKGROUND: We describe the epidemiology, clinical characteristics, and outcomes of multisystem inflammatory syndrome in children (MIS-C) among children from Negeri Sembilan, Malaysia. METHODS: A retrospective, multicentre, observational study was performed among children ≤15 years old who were hospitalized for MIS-C between January 18, 2021 and June 30, 2023. The incidence of MIS-C was estimated using reported SARS-CoV-2 cases and census population data. Descriptive analyses were used to summarize the clinical presentation and outcomes. RESULTS: The study included 53 patients with a median age of 5.7 years (IQR 1.8-8.7 years); 75.5% were males. The overall incidence of MIS-C was approximately 5.9 cases per 1,000,000 person-months. Pediatric intensive care unit (PICU) admission was required for 22 (41.5%) patients. No mortalities were recorded. Children aged 6-12 years were more likely to present with cardiac dysfunction/shock (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.67-17.66), whereas children below 6 years were more likely to present with a Kawasaki disease phenotype (OR 5.50, 95% CI 1.33-22.75). Twenty patients (37.7%) presented with involvement of at least four organ systems, but four patients (7.5%) demonstrated single-organ system involvement. CONCLUSION: An age-based variation in the clinical presentation of MIS-C was demonstrated. Our findings suggest MIS-C could manifest in a spectrum, including single-organ involvement. Despite the high requirement for PICU admission, the prognosis of MIS-C was favorable, with no recorded mortalities.

From intensive care to rehabilitation: survey on the satisfaction with care received during prolonged hospitalization for COVID-19 at a northern Italian university hospital.

OBJECTIVE: Investigating the experiences perceived by COVID-19 inpatients is a fundamental research area that is starting to be explored. For this reason, our objective was to provide the first Italian survey on COVID-19 inpatients' satisfaction, obtained through a self-completed questionnaire previously used in a reference study in a UK cohort of COVID-19 patients. SUBJECTS AND METHODS: Hospitalized COVID-19 patients (>20 days) admitted to Ferrara University Hospital who underwent rehabilitation during their hospital stay were invited to complete an anonymous questionnaire. The survey's questions explored the patients' satisfaction with the health services received, and their completion took place approximately one year after hospitalization. Information on sex, number of wards, ICU stays, and hospital discharge dates was collected. RESULTS: Sixty-two completed questionnaires were analyzed. The average overall satisfaction score obtained from the answers indicated by the participants in the tenth question was 4.7 out of 5.0. Very positive responses were observed for information about discharge plans, privacy, management of pain, sleep quality, and feeling of safety. The possibility of being consulted about medications and side effects received a very low satisfaction score. Considering overall satisfaction, no significant differences were noted for sex or ICU stay. The obtained results were almost superimposable to those reported in the cohort of COVID-19 patients of the reference study. CONCLUSIONS: This survey suggested that COVID-19 patients' healthcare satisfaction was high. Nevertheless, some areas must be improved, such as the communication and involvement of the patients in the decision-making of care and the discussion about medications or possible side effects.

Cambio de la atención psicológica presencial a modalidad remota: facilitadores y obstáculos en la pandemia de COVID-19 / Changing face-to-face psychological care to remote mode: facilitators and obstacles in the COVID-19 pandemic / Mudança do atendimento psicológico presencial para modalidade remota: facilitadores e dificultadores na pandemia de COVID-19

Objetivo: verificar asociaciones entre variables sociodemográficas y factores que facilitan y dificultan la transición de la atención psicológica presencial a la modalidad remota en el primer año de la pandemia de COVID-19. Método: se trata de un estudio analítico, cuantitativo y de corte transversal. Después de la aprobación del Comité de Ética en Investigación, la recolección de datos se realizó mediante la aplicación de un formulario en línea que consta de 55 preguntas. Los datos fueron analizados utilizando técnicas de estadística descriptiva e inferencial. Resultados: la muestra de conveniencia estuvo compuesta por 385 psicólogos brasileños, en su mayoría mujeres (67,01%), jóvenes profesionales con hasta cinco años de actuación después de la graduación (44,16%) y predominio de actividades en la clínica privada. Se encontró que el tiempo de formación entre cinco y 10 años se asoció con una mayor percepción de dificultades y que la experiencia previa con la atención a distancia facilitó la adaptación en la transición de una modalidad a otra. Conclusión: considerando que la teleasistencia puede ser una poderosa herramienta en el escenario de la salud, se sugiere que los temas de la teleasistencia sean incluidos en la agenda de investigación y los contenidos programáticos en los currículos de los cursos de formación en salud.

Objective: to verify associations between sociodemographic variables and factors that facilitate and hinder the transition from face-to-face psychological care to remote mode in the first year of the COVID-19 pandemic. Method: this is an analytical, quantitative, cross-sectional study. After approval by the Research Ethics Committee, data collection was performed by applying an online form consisting of 55 questions. Data were analyzed using descriptive and inferential statistics techniques. Results: the intentional sampling consisted of a total of 385 Brazilian psychologists, mostly women (67.01%), young professionals with up to five years of graduation (44.16%) most of activities in the private clinic. It was found that training time between five and 10 years was associated with a greater perception of difficulties and that previous experience with remote care facilitated adaptation in the transition from one modality to another. Conclusion: considering that call center can be a powerful tool in the health scenario, it is suggested the inclusion of remote care issues in the research agenda and syllabus in the curricula of health training courses.

Objetivo: verificar associações entre variáveis sociodemográficas e fatores facilitadores e dificultadores da transição do atendimento psicológico presencial para a modalidade remota no primeiro ano da pandemia de COVID-19. Método: trata-se de um estudo analítico, quantitativo, de corte transversal. Após aprovação do Comitê de Ética em Pesquisa, a coleta foi realizada mediante aplicação de um formulário online composto por 55 questões. Os dados foram analisados por meio de técnicas de estatística descritiva e inferencial. Resultados: a amostra de conveniência foi composta por 385 psicólogos brasileiros, majoritariamente mulheres (67,01%), jovens profissionais com até cinco anos de ofício após a graduação (44,16%) e com predomínio de atividades na clínica privada. Constatou-se que o tempo de formação entre cinco e 10 anos foi associado com uma maior percepção de dificuldades e que a experiência prévia com atendimento remoto foi facilitadora da adaptação na transição de uma modalidade à outra. Conclusão: considerando que o teleatendimento pode ser uma ferramenta potente no cenário da saúde, sugere-se a inclusão das questões do atendimento remoto na agenda de pesquisa e conteúdos programáticos das grades curriculares dos cursos de formação em saúde.

[Characteristics and impact factors of SARS-CoV-2 infection in adult patients with relapsed/refractory B-cell non-Hodgkin lymphoma receiving chimeric antigen receptor T-cell therapy].

Objective: To explore the clinical characteristics and treatment of COVID-19 infection in patients with relapsed/refractory B-cell non-Hodgkin lymphoma before and after receiving chimeric antigen receptor T-cell therapy, and study the influencing factors of severe COVID-19 infection in these patients. Methods: The data of 59 patients with relapsed/refractory B-cell non-Hodgkin lymphoma who received chimeric antigen receptor T-cell therapy at the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology and Department of Hematology, the Second Affiliated Hospital, College of Medicine, Zhejiang University between December 2017 and February 2023, and who were infected with novel coronavirus between December 2022 and February 2023 were retrospectively studied. Patients were divided into light, medium, severe, and critical groups, and the differences between the groups were analyzed using the chi-square test. A univariate logistic regression model was used to evaluate the contribution of each variable and its relationship with severe infection. The chi-square and Fisher's exact tests were used to analyze the differences between the B-cell aplasia and B-cell recovery (BCR) groups. Results: Of the 59 pre- and post-infusion infections, 39 (66.1%) led to mild COVID-19, 9 (15.3%) resulted in moderate COVID-19, 10 (16.9%) resulted in severe COVID-19, and 1 (1.7%) led to critical COVID-19. Moroever, age greater than 55 years, having received autologous hematopoietic stem cell transplantation, progressive disease status, and B-cell aplasia at the time of diagnosis of COVID-19 infection are factors affecting severe infection. Patients with B-cell aplasia had a more severe infection with COVID-19 (P<0.001), a longer duration (P=0.015), a longer antiviral therapy course (P<0.001), and a higher hospitalization rate (P<0.001) than the BCR group. Conclusion: Active prevention and treatment of COVID-19 infection remains a crucial issue requiring urgent attention in managing patients with relapsed/refractory B-cell non-Hodgkin lymphoma treated with chimeric antigen receptor T-cell therapy.

COVID-19: A management update.

The management of COVID-19 has evolved through the course of the pandemic to now include options for outpatients, inpatients with life-threatening critical illness, and everyone in between. The goals of therapy include preventing disease progression and preventing worsening disease in those admitted to the hospital, with the hopes of preserving resources and improving patient outcomes. The Infectious Diseases Society of America and the National Institutes of Health have issued guidelines on treating COVID-19, which the authors review here.

Omicron related COVID-19 prevention and treatment measures for patients with hematological malignancy and strategies for modifying hematologic treatment regimes.

The Omicron variant of SARS-CoV-2 has rapidly become the dominant strain worldwide due to its high transmissibility, although it appears to be less pathogenic than previous strains. However, individuals with hematological malignancy (HM) and COVID-19 remain susceptible to severe infection and mortality, especially those with chronic lymphocytic leukemia (CLL) and those undergoing chimeric antigen receptor T-cell (CAR-T) treatment. Hematologists should thoroughly assess the severity of the patient's hematological disease and the potential risk of SARS-CoV-2 infection before initiating chemotherapy or immunosuppressive treatment. Vaccination and booster doses are strongly recommended and patients with a poor vaccine response may benefit from long-acting COVID-19 neutralizing monoclonal antibodies (such as Evusheld). Early use of small molecule antiviral drugs is recommended for managing mild COVID-19 in HM patients and those with severe immunodeficiency may benefit from SARS-CoV-2 neutralizing monoclonal antibody therapy and high-titer COVID-19 convalescent plasma (CCP). For moderate to severe cases, low-dose glucocorticoids in combination with early antiviral treatment can be administered, with cytokine receptor antagonists or JAK inhibitors added if the condition persists or worsens. In the treatment of hematological malignancies, delaying chemotherapy is preferable for CLL, acute leukemia (AL), and low-risk myelodysplastic syndrome (MDS), but if the disease progresses, appropriate adjustments in dosage and frequency of treatment are required, with the avoidance of anti-CD20 monoclonal antibody, CAR-T and hematopoietic stem cell transplantation (HSCT). Patients with chronic myelocytic leukemia (CML) and myeloproliferative neoplasms (MPNs) can continue current treatment. What's more, non-drug protective measures, the development of new vaccines and antiviral drugs, and monitoring of mutations in immunocompromised populations are particularly important.

Influences of high vs. low-intensity exercises on muscle strength, function, and quality of life in post-COVID-19 patients with sarcopenia: a randomized controlled trial.

OBJECTIVE: The aim of this study was to compare the effectiveness of high vs. low-intensity exercise training on muscle strength, physical function, and quality of life in post-COVID-19 patients with sarcopenia secondary to chronic kidney disease (CKD). PATIENTS AND METHODS: 82 subjects were randomized into 2 groups: high intensity (HIG, n=42), which received high-intensity resistance training, and low intensity (LIG, n=40), which conducted low-intensity aerobic activities. Exercises were performed for 30 min, 3 times per week for 6 weeks. A handheld dynamometer, pinch press, and 1 min sit-to-stand (STS) test were used to assess muscle strength. Modified physical performance test and sarcopenia Quality of Life questionnaire (SAR-QoL) were used to assess function and quality of life, respectively. Measures were collected before and at the end of the treatment program. RESULTS: Participants were similar at baseline. The within-group comparisons demonstrated statistically significant improvement in both HIG and LIG groups in all outcome measures (p<0.001). Between groups, comparisons revealed statistically significant better achievements with high effect size in Modified Physical Performance Test (MMPT) (p<0.001, d=1.28), handgrip (p<0.001, d=3.6), STS (p<0.001, d=2.38), and SAR-QoL (p<0.001, d=3.24) in favor of the HIG. On the other hand, pinch press strength was equally improved in both groups (p=0.09, d=0.36). CONCLUSIONS: High-intensity exercise is better than low-intensity exercises in post-COVID-19 patients with sarcopenia secondary to chronic kidney disease regarding muscle strength, physical function, and quality of life.

Lung mechanics in pediatric acute respiratory distress syndrome associated to acute COVID-19 and MIS-C: implications for therapies and outcomes. / Mecánica pulmonar en el síndrome de distrés respiratorio agudo pediátrico asociado a COVID-19 aguda y MIS-C.

OBJECTIVE: To describe lung mechanics in Pediatric Acute Respiratory Distress Syndrome (PARDS) associated with acute COVID-19 and MIS-C with respiratory failure. METHODS: A concurrent multicenter observational study was performed, analyzing clinical variables and pulmonary mechanics of PARDS associated with COVID-19 in 4 Pediatric intensive care units (PICU) in Peru. The subgroup analysis included PARDS associated with multisystem inflammatory syndrome in children (MIS-C), MIS-PARDS, and PARDS with COVID-19 primary respiratory infection, C-PARDS. In addition, receiver operating characteristic (ROC) curve analysis for mortality and lung mechanics was performed. RESULTS: 30 patients were included. The age was 7.5 (4-11) years, 60% were male, and mortality was 23%. 47% corresponded to MIS-PARDS and 53% to C-PARDS groups. C-PARDS had positive RT-PCR in 67% and MIS-PARDS none (p < 0.001). C-PARDS group had more profound hypoxemia (P/F ratio < 100, 86% vs. 38%, p < 0.01) and higher driving-pressure [14(10-22) vs 10(10-12) cmH2O], and lower compliance of the respiratory system (CRS) [0.5 (0.3-0.6) vs 0.7(0.6-0.8) ml/ kg/cmH2O] compared with MIS-PARDS (all p < 0.05). The ROC analysis for mortality showed that driving pressure had the best performance [AUC 0.91(95%CI0.81-1.00), with the best cut-off point of 15 cmH2O (100% sensitivity and 87% specificity). Mortality in C-PARDS was 38% and 7% in MIS-PARDS (p = 0.09). MV-free days were 12(0-23) in C-PARDS and 23(21-25) in MIS-PARDS (p = 0.02). CONCLUSION: Patients with C-PARDS have lung mechanics characteristics similar to classic moderate to severe PARDS. This was not observed in patients with MIS-C. As seen in other studies, a driving pressure ≥ 15 cmH2O was the best discriminator for mortality. These findings may help guide ventilatory management strategies for these two different presentations.

Ventilatory support and inflammatory peptides in hospitalised patients with COVID-19: A prospective cohort trial.

PURPOSE: Several studies have shown that SARS-CoV-2 can induce a massive release of cytokines which contributes to disease severity and mortality. Therefore, cytokine levels in the serum may help to predict disease severity and survival in COVID-19 patients. METHODS: In this prospective trial, 88 patients who were hospitalised for COVID-19 were enrolled. Blood samples for serum peptide measurements were taken at the time closest to hospitalisation, at day 5, 9 and 13 (±1). The concentrations of cytokines (IL-1α, IL-1ß, IL-1RA, IL-6, L-7, L-10, IFN-γ and TNF-α), chemokines (CCL-3, CCL-4 and CCL-7) and growth factors (G-CSF, GM-CSF and VEGF) were assessed and correlated with the type of ventilation, occurrence of consolidations on imaging and the level of care. RESULTS: COVID-19 patients (median age 68 years, IQR 55-77) stayed in hospital between 5-171 days. Compared to patients in the general care unit, patients in the intermediate care unit (IMCU) and intensive care unit (ICU) presented significantly elevated serum IL-6 (p = 0.004) and lower IFN-γ levels (p = 0.005), respectively. The peak inspiratory pressure in ventilated patients correlated positively with IL-1RA, G-CSF and inversely with IFN-γ serum levels (all p<0.05). VEGF serum levels inversely correlated with the fraction of inspired oxygen in patients receiving high-flow nasal canula oxygen therapy (p = 0.047). No significant correlation between serum concentrations of the measured peptides and the type of ventilation, occurrence of radiological consolidations or in-hospital mortality has been observed. CONCLUSION: IL1-RA, IL-6, IFN-γ, G-CSF, CCL-7 and VEGF serum levels could prove helpful as biomarkers to assess disease severity and the need for intensive care in COVID-19 patients.

Sex differences among children, adolescents and young adults for mental health service use within inpatient and outpatient settings, before and during the COVID-19 pandemic: a population-based study in Ontario, Canada.

OBJECTIVES: The pandemic and public health response to contain the virus had impacts on many aspects of young people's lives including disruptions to daily routines, opportunities for social, academic, recreational engagement and early employment. Consequently, children, adolescents and young adults may have experienced mental health challenges that required use of mental health services. This study compared rates of use for inpatient and outpatient mental health services during the pandemic to pre-pandemic rates. DESIGN: Population-based repeated cross-sectional study. SETTING: Publicly delivered mental healthcare in primary and secondary settings within the province of Ontario, Canada. PARTICIPANTS: All children 6-12 years of age (n=2 043 977), adolescents 13-17 years (n=1 708 754) and young adults 18-24 years (n=2 286 544), living in Ontario and eligible for provincial health insurance between March 2016 and November 2021. PRIMARY OUTCOME MEASURES: Outpatient mental health visits to family physicians and psychiatrists for: mood and anxiety disorders, alcohol and substance abuse disorders, other non-psychotic mental health disorders and social problems. Inpatient mental health visits to emergency departments and hospitalisations for: substance-related and addictive disorders, anxiety disorders, assault-related injuries, deliberate self-harm and eating disorders. All outcomes were analysed by cohort and sex. RESULTS: During the pandemic, observed outpatient visit rates were higher among young adults by 19.01% (95% CI: 15.56% to 22.37%; 209 vs 175 per 1000) and adolescent women 24.17% (95% CI: 18.93% to 29.15%; 131 vs 105 per 1000) for mood and anxiety disorders and remained higher than expected. Female adolescents had higher than expected usage of inpatient care for deliberate self-harm, eating disorders and assault-related injuries. CONCLUSIONS: Study results raise concerns over prolonged high rates of mental health use during the pandemic, particularly in female adolescents and young women, and highlights the need to better monitor and identify mental health outcomes associated with COVID-19 containment measures and to develop policies to address these concerns.