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PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.
Navarese, EP, Podhajski, P, Gurbel, PA, Grzelakowska, K, Ruscio, E, Tantry, U, Magielski, P, Kubica, A, Niezgoda, P, Adamski, P, et al
Journal of the American College of Cardiology. 2023;(3):224-234
Abstract
BACKGROUND The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. OBJECTIVES The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. METHODS In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. RESULTS Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%). CONCLUSIONS PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).
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Short-term complications and post-acute sequelae in hospitalized paediatric patients with COVID-19 and obesity: A multicenter cohort study.
Valenzuela, G, Alarcón-Andrade, G, Schulze-Schiapacasse, C, Rodríguez, R, García-Salum, T, Pardo-Roa, C, Levican, J, Serrano, E, Avendaño, MJ, Gutiérrez, M, et al
Pediatric obesity. 2023;(2):e12980
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Abstract
BACKGROUND Obesity increases the severity of coronavirus disease 2019 illness in adults. The role of obesity in short-term complications and post-acute sequelae in children is not well defined. OBJECTIVE To evaluate the relationship between obesity and short-term complications and post-acute sequelae of SARS-CoV-2 infection in hospitalized paediatric patients. METHODS An observational study was conducted in three tertiary hospitals, including paediatric hospitalized patients with a confirmatory SARS-CoV-2 RT-PCR from March 2020 to December 2021. Obesity was defined according to WHO 2006 (0-2 years) and CDC 2000 (2-20 years) growth references. Short-term outcomes were intensive care unit admission, ventilatory support, superinfections, acute kidney injury, and mortality. Neurological, respiratory, and cardiological symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms were considered as post-acute sequalae. Adjusted linear, logistic regression and generalized estimating equations models were performed. RESULTS A total of 216 individuals were included, and 67 (31.02%) of them had obesity. Obesity was associated with intensive care unit admission (aOR = 5.63, CI95% 2.90-10.94), oxygen requirement (aOR = 2.77, CI95% 1.36-5.63), non-invasive ventilatory support (aOR = 6.81, CI95% 2.11-22.04), overall superinfections (aOR = 3.02 CI95% 1.45-6.31), and suspected bacterial pneumonia (aOR = 3.00 CI95% 1.44-6.23). For post-acute sequalae, obesity was associated with dyspnea (aOR = 9.91 CI95% 1.92-51.10) and muscle weakness (aOR = 20.04 CI95% 2.50-160.65). CONCLUSIONS In paediatric hospitalized patients with COVID-19, severe short-term outcomes and post-acute sequelae are associated with obesity. Recognizing obesity as a key comorbidity is essential to develop targeted strategies for prevention of COVID-19 complications in children.
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Long-term outcomes in critically ill patients who survived COVID-19: The NUTRICOVID observational cohort study.
Álvarez-Hernández, J, Matía-Martín, P, Cáncer-Minchot, E, Cuerda, C, ,
Clinical nutrition (Edinburgh, Scotland). 2023;(10):2029-2035
Abstract
BACKGROUND & AIMS Malnutrition and sarcopenia may last beyond hospital discharge, especially in patients admitted to intensive care units (ICU), having a negative impact on patient recovery and leading to disability, poor quality of life, and additional morbidity. No prior evidence is available for post-ICU management and follow-up of coronavirus disease 2019 (COVID-19) patients and their long-term evolution. This study reports on the one-year-long evolution of a cohort of COVID-19 survivors after ICU discharge, in terms of nutritional and functional status as well as health-related quality of life (HRQoL). METHODS A multicenter, ambispective, observational cohort study (NUTRICOVID study) was conducted in 16 public hospitals located in the Community of Madrid with COVID-19 survivors who were admitted to ICU during the first outbreak. Retrospective and prospective data were collected from hospital admission to one year after discharge. At hospital discharge and at 3, 6 and 12 months post-discharge, the following outcomes were recorded: weight, risk of malnutrition (MUST) and sarcopenia (SARC-F), medical nutrition therapy (MNT), functional status (Barthel index), and HRQoL (EQ-5D-5L). RESULTS A total of 199 patients (70.4% male, mean age [SD] of 60.7 [10.1]) were included in the study. At hospital discharge, mean weight loss was 16.4% (8.0%), whereas most patients gained weight after discharge with an increase of 16.5% (14.0%) at 12 months. The proportion of patients at high risk of malnutrition decreased from 83.2% at hospital discharge to 2.1% at 12 months. The proportion at risk of sarcopenia decreased from 86.9% at hospital discharge to 13.4% at 12 months. At hospital discharge, 69 patients received MNT by means of oral nutritional supplements (ONS) while two patients required enteral nutrition (EN). At 12 months, only 12 patients continued taking ONS, with no patients taking EN. Regarding functional status, 72.9% of patients were moderately or severely dependent at hospital discharge, whereas 87.2% showed low dependency or independency after 12 months. The EQ-VAS values increased from hospital discharge (39 [21.2]) to 6 months post-discharge and remained steady up to 12 months (72.7 [19.0]). The mean health value improved from hospital discharge (0.25 [0.41]) to 6 months post-discharge (0.80 [0.24]) and was maintained thereafter. CONCLUSIONS Patients' nutritional and functional impairment at hospital discharge was high, with high dependency status and low HRQoL; however, their situation improved progressively during the 12 months following hospital discharge. Nevertheless, there is a need to define early strategies to optimize the nutritional and functional recovery of COVID-19 patients.
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The three facets of the SARS-CoV-2 pandemic during the first two waves in the northern, central, and southern Italy.
Buscemi, S, Davoli, C, Trecarichi, EM, Morrone, HL, Tassone, B, Buscemi, C, Randazzo, C, Barile, AM, Colombrita, P, Soresi, M, et al
Journal of infection and public health. 2023;(4):520-525
Abstract
BACKGROUND There is a scarcity of information in literature regarding the clinical differences and comorbidities of patients affected by Coronavirus disease 2019 (COVID-19), which could clarify the different prevalence of the outcomes (composite and only death) between several Italian regions. OBJECTIVE This study aimed to assess the heterogeneity of clinical features of patients with COVID-19 upon hospital admission and disease outcomes in the northern, central, and southern Italian regions. METHODS An observational cohort multicenter retrospective study including 1210 patients who were admitted for COVID-19 in Infectious diseases, Pulmonology, Endocrinology, Geriatrics and Internal Medicine Units in Italian cities stratified between north (263 patients); center (320 patients); and south (627 patients), during the first and second pandemic waves of SARS-CoV-2 (from February 1, 2020 to January 31, 2021). The data, obtained from clinical charts and collected in a single database, comprehended demographic characteristics, comorbidities, hospital and home pharmacological therapies, oxygen therapy, laboratory values, discharge, death and Intensive care Unit (ICU) transfer. Death or ICU transfer were defined as composite outcomes. RESULTS Male patients were more frequent in the northern Italian region than in the central and southern regions. Diabetes mellitus, arterial hypertension, chronic pulmonary and chronic kidney diseases were the comorbidities more frequent in the southern region; cancer, heart failure, stroke and atrial fibrillation were more frequent in the central region. The prevalence of the composite outcome was recorded more frequently in the southern region. Multivariable analysis showed a direct association between the combined event and age, ischemic cardiac disease, and chronic kidney disease, in addition to the geographical area. CONCLUSIONS Statistically significant heterogeneity was observed in patients with COVID-19 characteristics at admission and outcomes from northern to southern Italy. The higher frequency of ICU transfer and death in the southern region may depend on the wider hospital admission of frail patients for the availability of more beds since the burden of COVID-19 on the healthcare system was less intense in southern region. In any case, predictive analysis of clinical outcomes should consider that the geographical differences that may reflect clinical differences in patient characteristics, are also related to access to health-care facilities and care modalities. Overall, the present results caution against generalizability of prognostic scores in COVID-19 patients derived from hospital cohorts in different settings.
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Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China.
Zhang, SX, Chen, XX, Zheng, Y, Cai, BH, Shi, W, Ru, M, Li, H, Zhang, DD, Tian, Y, Chen, YL
Journal of integrative medicine. 2023;(4):369-376
Abstract
OBJECTIVE Omicron, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, is responsible for numerous infections in China. This study investigates the association between the use of Seven-Flavor Herb Tea (SFHT) and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019 (COVID-19). METHODS This case-control study was conducted at shelter hospitals and quarantine hotels in China. A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31, 2022, while 2190 uninfected individuals served as healthy controls. Structured questionnaires were used to collect data on demographics, underlying diseases, vaccination status, and use of SFHT. Patients were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity score. Subsequently, a conditional logistic regression model was used for data analysis. RESULTS Overall, 7538 eligible subjects were recruited, with an average age of [45.54 ± 16.94] years. The age of COVID-19 patients was significantly higher than that of uninfected individuals ([48.25 ± 17.48] years vs [38.92 ± 13.41] years; t = 22.437, P < 0.001). A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 ratio. The use of SFHT (odds ratio = 0.753, 95% confidence interval: 0.692, 0.820) was associated with a lower risk of SARS-CoV-2 infection compared to untreated individuals. CONCLUSION Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 infection. This is a useful study in the larger picture of COVID-19 management, but data from large-sample multi-center, randomized clinical trial are warranted to confirm the finding. Please cite this article as: Zhang SX, Chen XX, Zheng Y, Cai BH, Shi W, Ru M, Li H, Zhang DD, Tian Y, Chen YL. Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China. J Integr Med. 2023; 21(4):369-376.
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Co-administration of AYUSH 64 as an adjunct to standard of care in mild and moderate COVID-19: A randomized, controlled, multicentric clinical trial.
Chopra, A, Tillu, G, Chuadhary, K, Reddy, G, Srivastava, A, Lakdawala, M, Gode, D, Reddy, H, Tamboli, S, Saluja, M, et al
PloS one. 2023;(3):e0282688
Abstract
OBJECTIVE Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19. METHODS During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched. RESULTS The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student's 't test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome). CONCLUSIONS AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required. TRIAL REGISTRATION CTRI/2020/06/025557.
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Inhaled prostacyclin therapy in the acute respiratory distress syndrome: a randomized controlled multicenter trial.
Haeberle, HA, Calov, S, Martus, P, Serna-Higuita, LM, Koeppen, M, Goll, A, Bernard, A, Zarbock, A, Meersch, M, Weiss, R, et al
Respiratory research. 2023;(1):58
Abstract
BACKGROUND Acute respiratory distress syndrome (ARDS) results in significant hypoxia, and ARDS is the central pathology of COVID-19. Inhaled prostacyclin has been proposed as a therapy for ARDS, but data regarding its role in this syndrome are unavailable. Therefore, we investigated whether inhaled prostacyclin would affect the oxygenation and survival of patients suffering from ARDS. METHODS We performed a prospective randomized controlled single-blind multicenter trial across Germany. The trial was conducted from March 2019 with final follow-up on 12th of August 2021. Patients with moderate to severe ARDS were included and randomized to receive either inhaled prostacyclin (3 times/day for 5 days) or sodium chloride (Placebo). The primary outcome was the oxygenation index in the intervention and control groups on Day 5 of therapy. Secondary outcomes were mortality, secondary organ failure, disease severity and adverse events. RESULTS Of 707 patients approached 150 patients were randomized to receive inhaled prostacyclin (n = 73) or sodium chloride (n = 77). Data from 144 patients were analyzed. The baseline PaO2/FiO2 ratio did not differ between groups. The primary analysis of the study was negative, and prostacyclin improved oxygenation by 20 mmHg more than Placebo (p = 0.17). Secondary analysis showed that the oxygenation was significantly improved in patients with ARDS who were COVID-19-positive (34 mmHg, p = 0.04). Mortality did not differ between groups. Secondary organ failure and adverse events were similar in the intervention and control groups. CONCLUSIONS The primary result of our study was negative. Our data suggest that inhaled prostacyclin might be beneficial treatment in patients with COVID-19 induced ARDS. TRIAL REGISTRATION The study was approved by the Institutional Review Board of the Research Ethics Committee of the University of Tübingen (899/2018AMG1) and the corresponding ethical review boards of all participating centers. The trial was also approved by the Federal Institute for Drugs and Medical Devices (BfArM, EudraCT No. 2016003168-37) and registered at clinicaltrials.gov (NCT03111212) on April 6th 2017.
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Effects of the COVID-19 Pandemic on Patients With NMO Spectrum Disorders and MOG-Antibody-Associated Diseases: COPANMO(G)-Study.
Hümmert, MW, Bütow, F, Tkachenko, D, Ayzenberg, I, Pakeerathan, T, Hellwig, K, Klotz, L, Häußler, V, Stellmann, JP, Warnke, C, et al
Neurology(R) neuroimmunology & neuroinflammation. 2023;(2)
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BACKGROUND AND OBJECTIVES To evaluate the effects of the coronavirus disease 2019 (COVID-19) pandemic on the life of patients with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD). METHODS This multicenter, cross-sectional study included data of 187 patients recruited from 19 different German and Austrian Neuromyelitis Optica Study Group (NEMOS) centers between July 2021 and March 2022. The effects of the pandemic on immunotherapeutic treatment and access to care, the possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the potential effect of vaccination against SARS-CoV-2 on disease incidence and relapse risk were assessed using a patient questionnaire. Health-related quality of life (HRQoL) was measured with the EuroQoL Group 5-Dimension 5-Level Scale (EQ-5D-5L). Demographic and clinical characteristics were retrieved from the NEMOS database. RESULTS One hundred eighty-seven patients (75% women; median age 47 [range 21-86] years; median disease duration 5.5 [range 0-67] years; median Expanded Disability Status Scale 2.0 [range 0-8.0]; 51% aquaporin-4 immunoglobulin G (AQP4-IgG)-positive, 36% myelin oligodendrocyte glycoprotein (MOG)-IgG-positive 13% double-seronegative) were analyzed. Most patients maintained excellent access to healthcare services throughout the pandemic. Immunotherapy was not changed in 88% of patients. Ninety-one percent of all patients were satisfied with medical care during the pandemic. Nearly two-thirds (64%) of patients rated their risk of infection with SARS-CoV-2 as low or moderate. Among this study sample, 23 patients (12%) knowingly acquired an infection with SARS-CoV-2 and predominantly had a nonsevere course of illness (n = 22/23, 96%). The SARS-CoV-2 vaccination rate was 89%, with 4 cases of confirmed attack or first manifestation of NMOSD/MOGAD occurring in temporal association with the vaccination (range 2-9 days). The reported HRQoL did not decline compared with a prepandemic assessment (mean EQ-5D-5L index value 0.76, 95% bootstrap confidence interval [CI] 0.72-0.80; mean EQ-VAS 66.5, 95% bootstrap CI 63.5-69.3). DISCUSSION This study demonstrates that, overall, patients with NMOSD/MOGAD affiliated with specialized centers received ongoing medical care during the pandemic. Patients' satisfaction with medical care and HRQoL did not decrease.
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Clinical outcomes of aspergillosis among paediatric and adult inpatients: A multicentre study in a Brazilian metropolitan area.
Martins, AC, Psaltikidis, EM, Cristiano de Lima, T, Fagnani, R, Gomide, HCAC, Gilli, FH, Schreiber, AZ, de Oliveira Conterno, L, Matsuzawa, T, Watanabe, A, et al
Journal de mycologie medicale. 2023;(4):101435
Abstract
BACKGROUND Invasive Aspergillosis (IA) is a disease of significant clinical relevance, especially among immunosuppressed patients, and is associated with high mortality rates. In this study, we evaluated the epidemiological features and clinical outcomes in children and adults with IA. METHODS This was an observational, multicentre, prospective surveillance study of inpatients with IA at two different hospitals in Campinas, Brazil, between 2018 and 2021. RESULTS A total of 44 patients were identified (54.5% males), with a median age of 42 years (interquartile range (IQR):19.25-59 years, varying between 1 and 89 years). The following baseline conditions were identified: 61.4% were oncohaematological patients and 20.5% were solid organ transplant recipients. Among oncohaematological patients, 77.8% exhibited severe or persistent neutropenia. The median time between the onset of neutropenia and the diagnosis of fungal infection was 20 days (IQR: 10.5-26 days; range, 0-68 days). The interval between neutropenia onset and fungal infection was longer in paediatric than in general hospital (average, 29 vs. 13.4 days; median 26 vs 11 days; p=0.010). After the diagnosis of IA, the survival rates were 44.2% and 30.0% at 180 and 360 days, respectively. Survival was greater in patients aged ≤ 21 years (p = 0.040; log-rank test). They observed no difference in IA mortality related to COVID-19 pandemic. CONCLUSION High mortality associated with IA was observed in both hospitals. Individuals over the age of 21 have a lower survival rate than younger patients.
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The evolving landscape of COVID-19 and post-COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL.
Visentin, A, Chatzikonstantinou, T, Scarfò, L, Kapetanakis, A, Demosthenous, C, Karakatsoulis, G, Minga, E, Chamou, D, Allsup, D, Cabrero, AA, et al
American journal of hematology. 2023;(12):1856-1868
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Abstract
In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations.