Ordinal Scale For Clinical Improvement Research Articles

Outcomes of corticosteroid treatment in critically ill COVID-19 patients

Objective: This study aims to examine the impact of low-dose and high-dose corticosteroids on the clinical outcomes and mortality of critically ill patients with COVID-19 in intensive care units. Material and Methods: This study was conducted on 197 confirmed COVID-19 patients who received corticosteroid therapy in the intensive care unit (ICU) between June 1st and December 31st, 2020. Patients were divided into two groups for low- and high-dose corticosteroid therapy. Both groups were compared according to demographic features, comorbid conditions, laboratory parameters, as well as the ordinal scale for clinical improvement (OSCI), hospital mortality, and length of stay in the intensive care unit. Results: A total of 140 patients received low-dose corticosteroids, while 57 patients received high-dose corticosteroid therapy. Our findings revealed a significantly higher median length of stay in the ICU and mortality in the group that received high-dose corticosteroid therapy. We observed a significant reduction in ferritin and D-dimer levels in the group receiving high-dose corticosteroid therapy (p < 0.003, p < 0.012, respectively). Furthermore, OSCIs on admission, day 5, and day 10 after corticosteroid therapy were higher in the group receiving high-dose corticosteroids. Conclusion: The results of this study indicate that high-dose corticosteroid therapy in critically ill patients with COVID-19 is associated with high mortality rates and prolonged intensive care stays.

Outcomes Among Patients Hospitalized for COVID-19 Treated with Remdesivir in an Urban Center Pre-COVID-19 Vaccination.

Data on treatment outcomes among minority populations treated with remdesivir are limited. We sought to evaluate outcomes among patients hospitalized with COVID-19 and treated with remdesivir among a predominantly Black and LatinX population. This was a retrospective cohort study of adult patients hospitalized with COVID-19 and treated with remdesivir at an urban hospital in Newark, NJ, between May 1, 2020, and April 30, 2021, prior to widespread COVID-19 vaccination uptake. We describe 28-day mortality by demographic, socio-economic, and clinical factors, including clinical status by World Health Organization's (WHO) 8-point Ordinal Scale for Clinical Improvement. A total of 206 patients met study inclusion criteria (52% were male, 41% non-Hispanic Black and 42% Hispanic). Overall mortality at 28days was 11%. Eighty-one percent of patients with baseline WHO status of 4 or greater recovered by day 14. Mortality was higher among those who were older (p = 0.01), those with underlying diabetes mellitus (p = 0.047), those with more severe illness on admission by WHO Ordinal Scale (WHO status ≥ 4), and those on concomitant tociluzimab or convalescent plasma use. We found that remdesivir was effective in treating most COVID-19 patients in our study. Traditional risk factors, such as advanced age and underlying co-morbidities, were associated with worse clinical outcomes and deaths.

Ozanimod Therapy in Patients With COVID-19 Requiring Oxygen Support: A Randomized Open-Label Pilot Trial

BackgroundSphingosine-1-phosphate receptor ligands (SRLs) dampen immunopathological damages in models of viral pneumonia. Research QuestionIs it feasible to administer an SRL therapy, here ozanimod, to acutely ill SARS-CoV-2-infected patients? Study Design and MethodsThe prospective, randomized, open-label, COVID-19 Ozanimod Intervention (COZI) pilot trial was conducted in three Canadian hospitals. Patients admitted for COVID-19 requiring oxygen were eligible. Randomization was stratified for risk factors of poor outcome and oxygen needs at inclusion. Participants were allocated to standard of care (SOC), or to standard of care plus ozanimod (OZA). Ozanimod (oral, once daily, incremental dosage) was administered for a maximum of 14 days. Primary endpoint investigated for size effect and variance over time was the assessment of safety and efficacy, evaluated by the daily score on the WHO-adapted 6-points ordinal scale for clinical improvement analyzed under the intention-to-treat principle. ResultsTwenty-three patients were randomized to SOC arm and 20, in the OZA arm from September 2020 to February 2022. Evaluation of efficacy showed non-significant reductions of median duration of respiratory support (6 (3-10) vs 9 (4-12) days, P=0.34), median duration of hospitalization (9 (6-12) vs 10 (6-18) days, P=0.20) and median time to clinical improvement (4 (3-7) vs 7 (3-11) days, P=0.12) for OZA compared to SOC. Heart rate was significantly lower with ozanimod (65 (63-67) vs. 71 (69-72) bpm, P<0.0001). However, QT and PR intervals were not affected. No severe adverse drug reaction was reported. InterpretationSRLs utility in severe pneumonia had never been tested in patients. We show for the first time that this new pharmacological agent can safely be administered to patients hospitalized for viral pneumonia, with potential clinical benefits. Bradycardia was frequent but well tolerated. Clinical Trial RegistrationClinicalTrials.gov number NCT04405102

Serum KL-6 as a Candidate Predictor of Outcome in Patients with SARS-CoV-2 Pneumonia.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-infection is associated with an extremely variable disease course. When interstitial pneumonia (IP) occurs, it can lead to acute respiratory distress syndrome and death. Serum Krebs von den Lungen-6 (KL-6) is an established marker of IP, but its role as a marker of SARS-CoV-2 pneumonia is debated. This bicentric study included 157 patients with SARS-CoV-2 pneumonia. The WHO Ordinal Scale for Clinical Improvement (0-10 points) was used to classify the clinical course. Serum samples were collected at admission, and on days 3 and 7 of hospitalization. KL-6 was measured by using automated chemiluminescence immunoassay. A total of 68 patients developed a severe SARS-CoV-2 pneumonia, 135 of them required oxygen, and 15 died during hospitalization. The patients requiring non-invasive ventilation, invasive ventilation, or extracorporeal membrane oxygenation had significantly higher serum KL-6 levels at admission. The serum KL-6 levels were tendentially higher in patients who died than in those who survived. Logistic regression identified serum KL-6 at a cut-off of 335 U/mL at admission as a significant predictor of severe SARS-CoV-2 pneumonia outcome. Serum KL-6 seems to be a candidate biomarker for the clinical routine to stratify patients with SARS-CoV-2 pneumonia for the risk of a severe disease outcome or death.

Factors Associated with 28-day Critical Illness Development During the First Wave of COVID-19.

This study aimed to define the predictors of critical illness development within 28 days postadmission during the first wave of the COVID-19 pandemic. We conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020. The most common presenting symptoms were cough, dyspnea, and fatigue. Critical illness developed in 45 (9.4%; 95% CI=7.0%-12.4%) patients. In the multivariable analysis, age (hazard ratio (HR)=1.05, p<0.001), number of comorbidities (HR=1.33, p=0.02), procalcitonin ≥0.25 µg/L (HR=2.12, p=0.03) and lactate dehydrogenase (LDH) ≥350 U/L (HR=2.04, p=0.03) were independently associated with critical illness development. The World Health Organization (WHO) ordinal scale for clinical improvement on admission was the strongest predictor of critical illness (HR=4.15, p<0.001). The patients hospitalized at the end of the study period had a much better prognosis compared to the patients hospitalized at the beginning (HR=0.14; p=0.02). The C-index of the model was 0.92. Age, comorbidity number, the WHO scale, LDH, and procalcitonin were independently associated with critical illness development. Mortality from COVID-19 seemed to be decreasing as the first wave of the pandemic advanced. Graphic Abstract.

Comparison of COVID-19 hospitalization costs across care pathways: a patient-level time-driven activity-based costing analysis in a Brazilian hospital

BackgroundThe COVID-19 pandemic raised awareness of the need to better understand where and how patient-level costs are incurred in health care organizations, as health managers and other decision-makers need to plan and quickly adapt to the increasing demand for health care services to meet patients’ care needs. Time-driven activity-based costing offers a better understanding of the drivers of cost throughout the care pathway, providing information that can guide decisions on process improvement and resource optimization. This study aims to estimate COVID-19 patient-level hospital costs and to evaluate cost variability considering the in-hospital care pathways of COVID-19 management and the patient clinical classification.MethodsThis is a prospective cohort study that applied time-driven activity-based costing (TDABC) in a Brazilian reference center for COVID-19. Patients hospitalized during the first wave of the disease were selected for their data to be analyzed to estimate in-hospital costs. The cost information was calculated at the patient level and stratified by hospital care pathway and Ordinal Scale for Clinical Improvement (OSCI) category. Multivariable analyses were applied to identify predictors of cost variability in the care pathways that were evaluated.ResultsA total of 208 patients were included in the study. Patients followed five different care pathways, of which Emergency + Ward was the most followed (n = 118, 57%). Pathways which included the intensive care unit presented a statistically significant influence on costs per patient (p < 0.001) when compared to Emergency + Ward. The median cost per patient was I$2879 (IQR 1215; 8140) and mean cost per patient was I$6818 (SD 9043). The most expensive care pathway was the ICU only, registering a median cost per patient of I$13,519 (IQR 5637; 23,373) and mean cost per patient of I$17,709 (SD 16,020). All care pathways that included the ICU unit registered a higher cost per patient.ConclusionsThis is one of the first microcosting study for COVID-19 that applied the TDABC methodology and demonstrated how patient-level costs vary as a function of the care pathways followed by patients. These findings can be used to develop value reimbursement strategies that will inform sustainable health policies in middle-income countries such as Brazil.

A prospective study of pulmonary outcomes and chest computed tomography in the first year after COVID-19.

COVID-19 primarily affects the respiratory system. We aimed to evaluate how pulmonary outcomes develop after COVID-19 by assessing participants from the first pandemic wave prospectively 3 and 12 months following hospital discharge. Pulmonary outcomes included self-reported dyspnoea assessed with the modified Medical Research Council dyspnoea scale, 6-min walk distance (6MWD), spirometry, diffusing capacity of the lung for carbon monoxide (D LCO), body plethysmography and chest computed tomography (CT). Chest CT was repeated at 12 months in participants with pathological findings at 3 months. The World Health Organization (WHO) ordinal scale for clinical improvement defined disease severity in the acute phase. Of 262 included COVID-19 patients, 245 (94%) and 222 (90%) participants attended the 3- and 12-month follow-up, respectively. Self-reported dyspnoea and 6MWD remained unchanged between the two time points, while D LCO and total lung capacity improved (0.28 mmol·min-1·kPa-1, 95% CI 0.12-0.44, and 0.13 L, 95% CI 0.02-0.24, respectively). The prevalence of fibrotic-like findings on chest CT at 3 and 12 months in those with follow-up chest CT was unaltered. Those with more severe disease had worse dyspnoea, D LCO and total lung capacity values than those with mild disease. There was an overall positive development of pulmonary outcomes from 3 to 12 months after hospital discharge. The discrepancy between the unaltered prevalence of self-reported dyspnoea and the improvement in pulmonary function underscores the complexity of dyspnoea as a prominent factor of long-COVID. The lack of increase in fibrotic-like findings from 3 to 12 months suggests that SARS-CoV-2 does not induce a progressive fibrotic process in the lungs.

Efficacy and Safety of Direct Hemoperfusion Using Polymyxin B-Immobilized Polystyrene Column for Patients With COVID-19: Protocol for an Exploratory Study.

Polymyxin B-immobilized fiber column (PMX; Toraymyxin column) was approved for the relief of systemic inflammatory response syndrome caused by bacterial infection or endotoxemia. PMX reduces lung damage by removing leukocytes and cytokines in addition to endotoxin removal in the setting of idiopathic pulmonary fibrosis. Acute exacerbation of interstitial pneumonia pathologically presents with diffuse alveolar damage (DAD). PMX direct hemoperfusion (PMX-DHP) demonstrated efficacy, improving oxygenation. The SARS-CoV-2 virus causes COVID-19, which emerged in December 2019. The condition may become severe about 1 week after onset, and respiratory failure rapidly develops, requiring intensive care management. A characteristic of COVID-19-related severe pneumonia is ground-glass opacities rapidly progressing in both lungs, which subsequently turn into infiltrative shadows. This condition could be classified as DAD. As for the congealing fibrinogenolysis system, D-dimer, fibrin/fibrinogen degradation product quantity, and prolonged prothrombin time were significant factors in nonsurviving COVID-19 cases, associated with aggravated pneumonia. Clinical trials are being conducted, but except for remdesivir and dexamethasone, no treatments have yet been approved. COVID-19 aggravates with the deterioration of oxygen saturation, decrease in lymphocytes, and the occurrence of an abnormal congealing fibrinogenolysis system, leading to diffuse lung damage. Once the condition transitions from moderate to severe, it is necessary to prevent further exacerbation by providing treatment that will suppress the aforementioned symptoms as soon as possible. This study aims to access treatment options to prevent the transition from acute exacerbation of interstitial pneumonia to DAD. The mechanism of action envisioned for PMX-DHP is to reduce congealing fibrinogenolysis system abnormalities and increase oxygenation by removing activated leukocytes and cytokines, which are risk factors for the aggravation of COVID-19-related pneumonia. We will conduct a multicenter, prospective, intervention, single-group study to evaluate the efficacy and safety of direct hemoperfusion using PMX-DHP for patients with COVID-19. Efficacy will be evaluated by the primary end point, which is the rate of Ordinal Scale for Clinical Improvement after PMX-DHP of at least 1 point from a status of 4, 5, or 6 on day 15. The effect of PMX-DHP will be estimated by setting a control group with background factors from non-PMX-DHP patients enrolled in the COVID-19 registry. This study will be carried out as a single-group open-label study and will be compared with a historical control. The historical control will be selected from the COVID-19 registry according to age, gender, and severity of pneumonia. The study period is scheduled from September 28, 2020, through April 30, 2023. Patient enrollment was scheduled from the Japan Registry of Clinical Trials publication for March 31, 2022. Data fixation is scheduled for October 2022, with the publication of the results by March 2023. From a clinical perspective, PMX-DHP is expected to become an adjunctive therapy to address unmet medical needs and prevent the exacerbation from moderate to severe acute respiratory distress syndrome in COVID-19 cases. DERR1-10.2196/37426.

Clinical characteristics and outcomes of incident cases of COVID-19 in unvaccinated adult cystic fibrosis patients in southern Brazil: a prospective cohort study conducted during the first year of the COVID-19 pandemic.

There is still limited information on the clinical characteristics and outcomes of cystic fibrosis (CF) patients with COVID-19 in Brazil. The objective of this study was to describe the cumulative incidence of COVID-19 in CF patients, as well as their clinical characteristics and outcomes. This was a prospective cohort study involving unvaccinated adult CF patients and conducted during the first year of the SARS-CoV-2 pandemic in the city of Porto Alegre, in southern Brazil. The clinical course of the disease was rated on the WHO Ordinal Scale for Clinical Improvement. The primary outcome was the number of incident cases of COVID-19. Between April 30, 2020 and April 29, 2021, 98 CF patients were included in the study. Seventeen patients were diagnosed with COVID-19. For the CF patients, the annual cumulative incidence of COVID-19 was 17.3%, similar to that for the general population, adjusted for age (18.5%). The most common symptoms at diagnosis of COVID-19 were cough (in 59%), dyspnea (in 53%), fatigue (in 53%), and fever (in 47%). Only 6 (35%) of the patients required hospitalization, and 3 (17.6%) required oxygen support. Only 1 patient required mechanical ventilation, having subsequently died. During the first year of the SARS-CoV-2 pandemic in southern Brazil, the cumulative incidence rate of COVID-19 was similar between CF patients and the general population. More than 50% of the CF patients with SARS-CoV-2 infection had a mild clinical presentation, without the need for hospital admission, and almost the entire sample recovered completely from the infection, the exception being 1 patient who had advanced lung disease and who died.

Corticosteroid effectiveness among hospitalised COVID-19 patients in Malaysia.

Using steroids to manage hospitalised coronavirus disease 2019 (COVID-19) patients caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has been shown to reduce the need for mechanical ventilation and mortality. To date, low-dose dexamethasone and methylprednisolone corticosteroids have been effective in reducing the infection's progress in hospitalised patients. However, it is unknown if high dosages of corticosteroids can achieve a better clinical outcome. This study aims to compare the clinical outcomes of hospitalised COVID-19 patients who are given a 10-day low-dose corticosteroid treatment (IV 2 mg/kg/day methylprednisolone loading dose (LD) then 0.25 mg/kg four times a day (q.i.d.)) with patients given a 10-day high-dose corticosteroid treatment (IV 20 mg dexamethasone once daily (o.d.) or a 1.5 mg/kg prednisolone tablet o.d.). Retrospective data on hospitalised COVID-19 patients were collected for this study, and the primary outcome measure was the patients' clinical status based on the World Health Organization's (WHO) Ordinal Scale for Clinical Improvement (OSCI) on Day-5 and Day-10 post-steroid. The results demonstrated that using steroids significantly improved patients' clinical outcomes from a WHO OSCI level of 4 (0.1) on Day-1 to 2.6 (2.5) on Day-5 (p < 0.001). There was no significant difference in clinical outcome between low-dose and high-dose corticosteroid treatment on Day-5 (H = 2.15; p = 0.34) and Day-10 (H = 1.12; p = 0.58). This study concludes that using low-dose corticosteroids is recommended for hospitalised COVID-19 patients to ensure clinical outcomes are optimised.

Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: a randomised clinical trial (RESIST trial)

BackgroundStatins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial.MethodsIn this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I.ResultsThe primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41–2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27–1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events.ConclusionsAmong patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration.Trial Registry Number CTRI/2020/07/026791 (http://ctri.nic.in; registered on 25/07/2020)

Secondary Organising Pneumonia Among COVID-19 Patients: A Retrospective Case-Control Study.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Secondary organising pneumonia (OP) induced by SARS-CoV-2 infection is a recently recognised complication of COVID-19. We aimed to evaluate the prevalence of OP among hospitalised patients with COVID-19 pneumonia and to assess whether disease severity and other clinical factors and comorbidities are correlated with OP development.We conducted a retrospective case-control study including hospitalised patients due to COVID-19 who performed a chest CT scan during hospitalisation and compared patients with clinical and radiological evidence of OP to patients without evidence of OP. Demographics, comorbidities, disease severity, dexamethasone/remdesivir treatment, laboratory results, and outcomes were compared between groups.One hundred fifteen patients were included, of whom 48 (41.7%) fulfilled clinical and imaging criteria for OP. Among OP patients, the most common chest CT-scan findings were consolidations, arciform condensations, and subpleural bands. OP patients had longer hospitalisation (19.5 vs 10 days, p=0.002) and more frequent ICU admission, but no significant differences in readmittance or mortality rates within 180 days compared to controls. In the adjusted effects model, the need for supplementary oxygen on the 21st day after symptom onset, the presence of Ordinal Scale for Clinical Improvement (OSCI) = 4, when compared to OSCI ≤ 3, and higher C-reactive protein on admission, were significantly associated with higher odds for OP. No other differences were identified between OP and controls after adjusting for other factors. The use of remdesivir or dexamethasone did not impact the diagnosis of OP. Only 38% of OP patients required treatment with high-dose corticosteroids.In conclusion, SARS-CoV-2-induced OP may be more frequent than previously thought, especially among hospitalised patients and patients with a more severe disease, particularly those who fail to improve after the second week of disease or who present higher inflammatory markers on admission. It increases the length of stay, but not all patients require specific treatment and OP may improve despite the absence of high-dose corticosteroid treatment.

Double-Blind, Randomized, Placebo-Controlled Study on hzVSF-v13, a Novel Anti-Vimentin Monoclonal Antibody Drug as Add-on Standard of Care in the Management of Patients with Moderate to Severe COVID-19.

Humanized Virus Suppressing Factor-variant 13 (hzVSF-v13), a monoclonal IgG4 antibody against vimentin, was investigated in moderate to severe COVID-19 pneumonia through a Phase II study. Patients were randomized to two different IV doses of the test drug or saline with standard of care. Overall, 64 patients were recruited, and 62 entered the efficacy assessment in the full analysis set. Primary endpoint: The clinical failure rate at day 28 was 15.8% for placebo, 9.1% for low-dose hzVSF-v13 and 9.5% for high-dose hzVSF-v13 (not significant). A trend toward better efficacy was shown in several secondary endpoints, with statistical significance between low-dose hzVSF-v13 and placebo in terms of the rate of improved patients on the ordinal scale for clinical improvement (OSCI): 90.0% vs. 52.63% (p = 0.0116). In the severe stratum, the results of low-dose hzVSF-v13 vs. placebo were 90.0% and 22.2% for OSCI (p = 0.0092), 9 days and 14 days for time to discontinuation of oxygen therapy (p = 0.0308), 10 days and 15 days for both time to clinical improvement (TTCI) and time to recovery (TTR) and p = 0.0446 for both TTCI and TTR. Change from baseline of NEWS2 score at day 28 was −3.4 vs. + 0.4 (p = 0.0441). The results propose hzVSF-v13 as a candidate in the treatment of severe COVID-19.

Impact of AYUSH 64 as an adjunctive to standard of care in mild COVID 19 - An open-label randomized controlled pilot study

BackgroundAyurveda herbal formulation AYUSH-64, proven to treat malaria and influenza-like illness in india was repurposed for COVID-19 patients considering preliminary evidances, however, scientific data was not available. AimTo evaluate the preliminary efficacy and safety of AYUSH 64 as an add-on to standard of care in mild COVID19 patients. Materials and methodsA single centre, randomized, open-labeled, controlled, pilot study were conducted on mild COVID 19 confirmed patients. Patients allotted in interventional group (n = 41) recieved AYUSH 64, 3 gm per day in three divided dose for 14 days as an adjuvant to standard of care (SOC) whereas control group received SOC (n = 39) alone. Outcomes were reduction in WHO ordinal scale for clinical improvement, all-cause mortality, incidence of COVID19 symptoms among asymptomatic patients at baseline, use for oxygen therapy, use for a mechanical ventilator, the total duration of symptomatic phase and adverse events. ResultsMean score of WHO ordinal scale was reduced as time lapse in both the groups (f (1) = 20.5, p < 0.001) indicating clinical improvement among groups. There was no statistically significant difference in mean WHO ordinal scale between groups (f (1) = 0.98, p = 0.32). The proportion of asymptomatic patients progressing to the symptomatic stage is lower in AYUSH 64 group [OR, 0.68 (CI, 0.17–2.66)]. Mean days for the total duration of the symptomatic phase was also short in AYUSH 64 group (4.68 ± 3.29 days) compared to SOC group (5.81 ± 3.5 days). No incidence of the requirement of a mechanical ventilator, adverse drug reaction and death were observed in either of the groups. ConclusionThe findings of this pilot study show that an integrated approach of AYUSH 64 with SOC provide early trends of benefit by reduction in disease progression and in total symptom duration. However, its effects remains inconclusive on outcomes such as all cause mortality, use of oxygen therapy, invasive ventilator due to sparse outcomes.

The impact of obesity and dyslipidemia on Remdesivir effectiveness in hospitalized patients with SARS-CoV-2-related pneumonia: An observational study

Background and aimsRemdesivir (GS-5734), an inhibitor of the viral RNA-dependent, RNA polymerase was early identified as a promising therapeutic candidate against COVID-19. Our aim was to evaluate the impact of several metabolic parameters on Remdesivir effectiveness among hospitalized COVID-19 patients. Methods and resultsWe conducted an observational study on patients with SARS-CoV-2-related pneumonia admitted between May 2020 and September 2021 to the COVID-19 Units of Internal Medicine, Pneumology and Intensive Care of Garibaldi Hospital, Catania, Italy, and treated with Remdesivir. The “Ordinal Scale For Clinical Improvement” was used to assess patients’ clinical improvement within 28 days of hospitalization. Short-term mortality rate was also evaluated.A total of 142 patients with SARS-CoV-2-related pneumonia were studied. The prevalence of obesity (20.7% vs. 41.9%, p = 0.03), the average BMI (27.1 ± 4.4 vs. 31.1 ± 6.1, p < 0.01) and the mean LDL-C levels (78 ± 19 mg/dl vs. 103 ± 18 mg/dl, p = 0.03) were significantly lower in early-improved (EI) compared to not-improved (NI) individuals. Obesity was negatively associated to clinical improvement after Remdesivir (OR 0.48, 95%CI 0.17–0.97, p = 0.04). Both obesity (OR 2.82, 95% CI 1.05–7.71, p = 0.04) and dyslipidemia (OR 2.78, 95%CI 1.17–7.16, p = 0.03) were significantly related to patients’ mortality. Dyslipidemic subjects experienced a slower clinical improvement than non-dyslipidemic ones (Long-Rank p = 0.04). ConclusionOur study showed that unfavorable metabolic conditions such as obesity and dyslipidemia could predict a worse clinical response to Remdesivir as well as the mortality in hospitalized COVID-19 patients. Further prospective and larger-scale studies are needed to confirm these preliminary findings.

Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: a randomised controlled trial (COVERAGE)

ObjectivesTo assess the efficacy of inhaled ciclesonide in reducing the risk of adverse outcomes in COVID-19 outpatients at risk of developing severe illness. MethodsCOVERAGE is an open-label, randomized controlled trial. Outpatients with documented COVID-19, risk factors for aggravation, symptoms for ≤7 days, and absence of criteria for hospitalization are randomly allocated to either a control arm or one of several experimental arms, including inhaled ciclesonide. The primary efficacy endpoint is COVID-19 worsening (hospitalization, oxygen therapy at home, or death) by Day 14. Other endpoints are adverse events, maximal follow-up score on the WHO Ordinal Scale for Clinical Improvement, sustained alleviation of symptoms, cure, and RT-PCR and blood parameter evolution at Day 7. The trial's Safety Monitoring Board reviewed the first interim analysis of the ciclesonide arm and recommended halting it for futility. The results of this analysis are reported here. ResultsThe analysis involved 217 participants (control 107, ciclesonide 110), including 111 women and 106 men. Their median age was 63 years (interquartile range 59–68), and 157 of 217 (72.4%) had at least one comorbidity. The median time since first symptom was 4 days (interquartile range 3–5). During the 28-day follow-up, 2 participants died (control 2/107 [1.9%], ciclesonide 0), 4 received oxygen therapy at home and were not hospitalized (control 2/107 [1.9%], ciclesonide 2/110 [1.8%]), and 24 were hospitalized (control 10/107 [9.3%], ciclesonide 14/110 [12.7%]). In intent-to-treat analysis of observed data, 26 participants reached the composite primary endpoint by Day 14, including 12 of 106 (11.3%, 95% CI: 6.0%–18.9%) in the control arm and 14 of 106 (13.2%; 95% CI: 7.4–21.2%) in the ciclesonide arm. Secondary outcomes were similar for both arms. DiscussionOur findings are consistent with the European Medicines Agency's COVID-19 task force statement that there is currently insufficient evidence that inhaled corticosteroids are beneficial for patients with COVID-19.

Convalescent plasma in the treatment of moderate to severe COVID-19 pneumonia: a randomized controlled trial (PROTECT-Patient Trial)

There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9% saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95% CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.

Predictive factors of clinical outcomes in patients with COVID-19 treated with tocilizumab: A monocentric retrospective analysis.

The aim of this retrospective observational study is to analyse clinical, serological and radiological predictors of outcome in patients with COVID-19 pneumonia treated with tocilizumab, providing clinical guidance to its use in real-life. This is a retrospective, monocentric observational cohort study. All consecutive patients hospitalized between February the 11th and April 14th 2020 for severe COVID-19 pneumonia at Reggio Emilia AUSL and treated with tocilizumab were enrolled. The patient's clinical status was recorded every day using the WHO ordinal scale for clinical improvement. Response to treatment was defined as an improvement of one point (from the status at the beginning of tocilizumab treatment) during the follow-up on this scale. Bivariate association of main patients' characteristics with outcomes was explored by descriptive statistics and Fisher or Kruskal Wallis tests (respectively for qualitative or quantitative variables). Each clinically significant predictor was checked by a loglikelihood ratio test (in univariate logistic models for each of the considered outcomes) against the null model. A total of 173 patients were included. Only hypertension, the use of angiotensin-converting enzyme inhibitors, PaO2/FiO2, respiratory rate and C-reactive protein were selected for the multivariate analysis. In the multivariable model, none of them was significantly associated with response. Evaluating a large number of clinical variables, our study did not find new predictors of outcome in COVID19 patients treated with tocilizumab. Further studies are needed to investigate the use of tocilizumab in COVID-19 and to better identify clinical phenotypes which could benefit from this treatment.

Efficacy and Safety of COVID-19 Convalescent Plasma in Hospitalized Patients

There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19. To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen. CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation. A unit of approximately 250 mL of CCP or equivalent volume of placebo (normal saline). The primary outcome was participant scores on the 11-point World Health Organization (WHO) Ordinal Scale for Clinical Improvement on day 14 after randomization; the secondary outcome was WHO scores determined on day 28. Subgroups were analyzed with respect to age, baseline WHO score, concomitant medications, symptom duration, CCP SARS-CoV-2 titer, baseline SARS-CoV-2 serostatus, and enrollment quarter. Outcomes were analyzed using a bayesian proportional cumulative odds model. Efficacy of CCP was defined as a cumulative adjusted odds ratio (cOR) less than 1 and a clinically meaningful effect as cOR less than 0.8. Of 941 participants randomized (473 to placebo and 468 to CCP), 556 were men (59.1%); median age was 63 years (IQR, 52-73); 373 (39.6%) were Hispanic and 132 (14.0%) were non-Hispanic Black. The cOR for the primary outcome adjusted for site, baseline risk, WHO score, age, sex, and symptom duration was 0.94 (95% credible interval [CrI], 0.75-1.18) with posterior probability (P[cOR<1] = 72%); the cOR for the secondary adjusted outcome was 0.92 (95% CrI, 0.74-1.16; P[cOR<1] = 76%). Exploratory subgroup analyses suggested heterogeneity of treatment effect: at day 28, cORs were 0.72 (95% CrI, 0.46-1.13; P[cOR<1] = 93%) for participants enrolled in April-June 2020 and 0.65 (95% CrI, 0.41 to 1.02; P[cOR<1] = 97%) for those not receiving remdesivir and not receiving corticosteroids at randomization. Median CCP SARS-CoV-2 neutralizing titer used in April to June 2020 was 1:175 (IQR, 76-379). Any adverse events (excluding transfusion reactions) were reported for 39 (8.2%) placebo recipients and 44 (9.4%) CCP recipients (P = .57). Transfusion reactions occurred in 2 (0.4) placebo recipients and 8 (1.7) CCP recipients (P = .06). In this trial, CCP did not meet the prespecified primary and secondary outcomes for CCP efficacy. However, high-titer CCP may have benefited participants early in the pandemic when remdesivir and corticosteroids were not in use. ClinicalTrials.gov Identifier: NCT04364737.

COVID‐19 and vaccination programme in one residential home

BackgroundApproximately 410 000 people live in care homes (CH) or residential settings in the UK, with the majority of this population being above the age of 85, making this group fall in the category of higher risk of more severe COVID‐19 symptoms and death. CH have been disproportionately affected by COVID‐19, people living and working in these settings have a higher risk of exposure to infection and higher risk of severe disease and mortality. CH residents and staff were prioritised for the vaccination programme in the UK due to increased risk of outbreaks, morbidity and mortality.MethodOne Residential home reported a COVID‐19 outbreak following the vaccination programme. Most staff vaccinated between 16‐18 December 2020, and most residents vaccinated on 30/12/2020. Residents were on isolation from 22/12/2020 prior to vaccination. The first positive COVID‐19 case was on 27th December. Staff and residents were scored according to the World Health Organisation (WHO) Ordinal Scale for Clinical Improvement (OSCI), table 1.ResultOf staff vaccinated, 20,83% (n=5) tested positive for COVID‐19. Nine staff members (27.28%) didn't have the vaccine, with 7 of these (77.78%) developing more limiting symptoms (OSCI score 2), compared to 8.33% (n=2) of those who had the vaccine. With 100% of residents vaccinated, 21 residents (65,63%) developed COVID‐19 symptoms, and 31.25% (n=10) developing more limiting COVID‐19 symptoms or death. Nineteen residents have a diagnosis of dementia and 63.16% (n=12) developed COVID‐19 symptoms and 50% (n=6) of those with dementia died, whilst those without dementia did not have any deaths reported.ConclusionAlthough this reflects the experience of a single CH, it is of relevance in suggesting substantial protection for staff who have been vaccinated, even though there was only 11 days between vaccination and the start of the outbreak.The experience in this CH starkly emphasizes the poor outcomes of COVID‐19 for residents, especially those with dementia, and unfortunately suggests that there are no benefits from vaccination as a secondary prevention approach once an outbreak has started. Ongoing evaluation will be important to optimize the delivery of the vaccination programme in CH settings, and to optimize staff take up of the vaccine.