Convalescent plasma as adjunctive therapy for hospitalized patients with COVID-19:The Co-CLARITY Trial

Background and Objective@#Convalescent plasma therapy (CPT) may reduce the risk of disease progression among patients with COVID-19. This study was undertaken to evaluate the efficacy and safety of CPT in preventing ICU admission among hospitalized COVID-19 patients.@*Methods@#In this open-label randomized controlled trial, we randomly assigned hospitalized adult patients with COVID-19 in a 1:1 ratio to receive convalescent plasma as an adjunct to standard of care or standard of care alone. The primary endpoint was ICU admission within first 28 days of enrolment. Primary safety endpoints include rapid deterioration of respiratory or clinical status within four hours of convalescent plasma transfusion and cumulative incidence of serious adverse events during the study period including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), severe allergic reactions, and transfusion-related infections.@*Results@#A total of 22 patients were assigned to receive convalescent plasma as an adjunct to standard of care and 22 to receive standard of care alone. The median time from onset of COVID-19 symptoms to study enrolment was eight days (IQR, 4 to 10). Two patients (9.1%) in the CPT group and one patient (4.5%) in the control group were admitted to the ICU. The primary outcome measure, ICU admission, was not different between the two groups (q-value >0.9). No patient who received convalescent plasma had rapid deterioration of respiratory/clinical status within four hours of transfusion and none developed TRALI, TACO, anaphylaxis, severe allergic reactions, or transfusion-related infections. There was also no significant difference in the secondary outcomes of 28-day mortality (two patients in the CPT group and none in the control group, q-value >0.90), dialysis-free days, vasopressor-free days, and ICU-free days.@*Conclusions@#Among hospitalized COVID-19 patients, no significant differences were observed in the need for ICU admission between patients given CPT as adjunct to standard of care and those who received standard of care alone. Interpretation is limited by early termination of the trial which may have been underpowered to detect a clinically important difference.

Intravenous tocilizumab versus standard of care in the treatment of severe and critical COVID-19-related pneumonia: A single center, double-blind, placebo controlled, phase 3 trial

Background@#Severe and critical COVID-19 disease is characterized by hyperinflammation involving pro-inflammatory cytokines, particularly IL-6. Tocilizumab is a monoclonal antibody that blocks IL-6 receptors. @*Objectives@#This study evaluated the efficacy of tocilizumab in Filipino patients with severe to critical COVID-19 disease. @*Methods@#This phase 3 randomized double-blind trial, included patients hospitalized for severe or critical COVID-19 in a 1:1 ratio to receive either tocilizumab plus local standard of care or placebo plus standard of care. Patients were eligible for a repeat IV infusion within 24-48 hours if they deteriorated or did not improve. Treatment success or clinical improvement was defined as at least two categories of improvement from baseline in the WHO 7-point Ordinal Scale of patient status, in an intention-to-treat manner. @*Results@#Forty-nine (49) patients were randomized in the tocilizumab arm and 49 in the placebo arm. There was no significant difference in age, comorbidities, COVID-19 severity, need for mechanical ventilation, presence of acute respiratory distress syndrome, or biomarker levels between groups. Use of adjunctive therapy was similar between groups, with corticosteroid used in 91.8% in tocilizumab group and 81.6% in the placebo group, while remdesivir was used in 98% of participants in both groups. There was no significant difference between groups in terms of treatment success in both the intention-to-treat analysis (relative risk=1.05, 95% CI: 0.85-1.30) and per-protocol analysis (relative risk=0.98, 95% CI: 0.80 to 1.21). There was no significant difference in time to improvement of at least two categories relative to baseline on the 7-point Ordinal Scale of clinical status. @*Conclusion@#The use of tocilizumab on top of standard of care in the management of patients with severe to critical COVID-19 did not result in significant improvement as defined by the WHO 7-point Ordinal Scale of patient status, nor in significant improvement in incidence of mechanical ventilation, incidence of ICU admission, length of ICU stay, and mortality rate.

In vitro quorum quenching activity of eleusine indica crude ethanolic extract against pseudomonas aeruginosa and serratia marcescens

@#<p style="text-align: justify;"><strong>Introduction:</strong> Nosocomial contaminants such as Pseudomonas aeruginosa and Serratia marcescens are increasingly developing resistance to many antibiotics. One of the promising alternatives that may complement, if not substitute, the use of antibiotics is quorum quenching, the process of interfering with chemical signals that mediate communication between microorganisms. Eleusine indica, a ubiquitous grass used traditionally to treat infections, has been shown to contain metabolites, such as fatty acid derivatives and p-coumaric acid, capable of quorum quenching. To date, there has been no study on the quorum quenching activity of E. indica.</p><p style="text-align: justify;"><strong>Objectives:</strong> This study aimed to determine the in vitro activity of crude ethanolic extract of E. indica leaves against selected quorum-sensing regulated virulence factors of P. aeruginosa and S. marcescens.</p><p style="text-align: justify;"><strong>Methodology:</strong> E. indica leaves were collected, washed, air-dried, and homogenized. Following ethanolic extraction and rotary evaporation, the extract was screened for antimicrobial activity through disk diffusion test and broth microdilution assay. The quorum quenching activity of the extract against P. aeruginosa was measured through swarming motility assay, while the activity against S. marcescens was measured through swarming motility and pigment inhibition assays. The quorum quenching assays were conducted in triplicates, and analysis of variance (ANOVA) was performed to identify differences among the treatment groups.</p><p style="text-align: justify;"><strong>Results:</strong> Disk diffusion test revealed that no zones of inhibition formed against both P. aeruginosa and S. marcescens for varying concentrations of up to 200 mg/mL of the crude extract. Likewise, the MIC of the extract against both P. aeruginosa and S. marcescens was determined to be >200 mg/mL. However, it was shown that the extract, at 50 mg/mL, has statistically significant activity (p<0.05) against the swarming motility of P. aeruginosa, and it is 71.6% as effective in reducing the swarming area of the bacteria compared to cinnamaldehyde. This was not observed when the extract was tested against the swarming motility of and pigment production by S. marcescens.</p><p style="text-align: justify;"><strong>Conclusion:</strong> In this study, the quorum quenching activity of the crude ethanolic extract of E. indica leaves was found to be effective against P. aeruginosa but not against S. marcescens. The compounds that will be identified by further studies may conceivably be used as an adjunct therapy in P. aeruginosa infections and as coating agents in medical devices.</p>

Virgin Coconut Oil Attenuates Deficits in Rats Undergoing Transient Cerebral Ischemia

@#Background and Objectives. Neuroprotection agents may help improve the outcomes of large vessel ischemic stroke. This study aims to explore the role of Virgin Coconut Oil (VCO), with its well-documented anti-oxidant properties, in neuroprotection after transient occlusion of the extracranial internal carotid artery in a rat model of stroke. Methods. Twenty-three Sprague-Dawley rats were randomized into two groups: 1) control group (n=11) given distilled water, and 2) treatment group (n=12) given virgin coconut oil at 5.15 ml/kg body weight for seven days. Subsequently, the rats underwent transient right extracranial internal carotid artery occlusion (EICAO) for 5 minutes using non-traumatic aneurysm clips. At 4 and 24 hours after EICAO, the animals were examined for neurologic deficits by an observer blinded to treatment groups, then sacrificed. Eight brain specimens (4 from each group) were subjected to histopathologic examination (H & E staining) while the rest of the specimens were processed using triphenyltetrazolium chloride (TTC) staining to determine infarct size and area of hemispheric edema. Results. VCO treatment significantly improved the severity of neurologic deficit (1.42 ± 2.31) compared to the control distilled water group (4.09 ± 2.59) 24 hours after EICAO. Whereas, infarct size and percent hemispheric edema did not significantly differ between the two groups. Conclusion. Prophylactic treatment of VCO is protective against EICAO-induced neurologic deficits in a rat model. VCO shows great potential as a neuroprotective agent for large vessel ischemic stroke. However, more studies are necessary to elucidate the neuroprotective mechanisms of VCO therapy in ischemic stroke.

Association of rs17095355 polymorphism and extrahepatic biliary atresia among Filipinos

Background@#Extrahepatic biliary atresia (EHBA) causes a rare obstructive cholestasis in infants. Kasai portoenterostomy if done before the third month of life may relieve obstruction. Genetic predisposition has been implicated in EHBA etiopathogenesis with rs17095355 polymorphism having the strongest association. We determined the association between rs17095355 and EHBA susceptibility of Filipino children, and described the outcome in each genotype among timely operated patients. @*Methods@#Thirty-four histologically diagnosed EHBA patients and thirty-three age- and sex-matched controls were recruited. Genomic DNA was extracted from peripheral blood and subjected to PCR and direct sequencing. Success of surgery among patients operated before 90 days of life was assessed by jaundice clearance six months post-surgery and native liver survival two and five years post-surgery. @*Results@#There was no significant difference among individuals carrying T and C alleles in developing EHBA (OR:1.36; 95%CI:0.65–2.86). Jaundice persisted post-operatively in 75%, 33% and 27% of Kasai-operated homozygous T (T/T), homozygous C (C/C) and heterozygous (C/T) patients, respectively. Fifty percent of Kasai-operated C/C and C/T patients retained their native liver whereas all Kasai-operated T/T patients required liver transplantation two years post-surgery. @*Conclusion@#There is insufficient evidence to associate rs17095355 in EHBA development among Filipinos. Further investigation is warranted to elucidate genetic mechanisms in EHBA etiopathogenesis.