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.

The impact of the Implementation of a Surgical Antibiotic Use Guideline in the Practice of Antibiotic Use in the Department of Surgery, Philippine General Hospital

@#Objective. This study aimed to assess compliance with current best practice guidelines on the use of antibiotics in the Department of Surgery in the Philippine General Hospital and to determine the impact of the dissemination of an institution-based guideline on compliance and on patient outcomes. Methods. Two antibiotic use surveys were performed 4 weeks before and 4 weeks after the implementation and dissemination of the PGH Surgical Antibiotic Use Guidelines in the Department of Surgery. The medical records of eligible patients were reviewed regarding patient and case characteristics, details on the administration of antibiotics and the collection of specimen for culture studies. Data relating to the occurrence of surgical site infection within 30 days of the operation was extracted. Compliance with antibiotic use guidelines was assessed for each case. The compliance rates in the pre- and post-intervention periods were compared. Results. The study included a total of 477 patients, 213 in the pre-implementation and 264 in the post-implementation period. Compared with the pre-intervention period, rates of compliance with guidelines improved for all parameters in the post-implementation period except for correct dosing. The greatest improvement was seen in the selection of the recommended drug, and proper duration. There was modest improvement in the timing of the preoperative drug administration. There was poor compliance with recommendations for appropriate specimen collection for culture studies, with marked improvement in collection in the pediatric group post-intervention. Overall, the in-hospital SSI rate was reduced from 6.8% to 1.1%, while there was little change in the 30-day SSI rate, post-intervention. Conclusion. A simple intervention to raise awareness of institutional guidelines on antibiotic use in the surgical setting lead to a modest improvement on overall compliance, although rates of total compliance with all relevant guidance on antibiotic use, choice, dose, timing and duration remained low. The impact on surgical site infection rates based on such compliance was modest.

Are vaccines effective and safe for the prevention of COVID-19 infections? A living systematic review

@#Introduction. In the attempt to control the spread of the disease and the pandemic, numerous COVID-19 vaccines are in development. A review of the evidence on their efficacy and safety are critical. Methods. A search for trials was done using the COVID-19 Living OVerview of Evidence (L·OVE) platform. We also searched for relevant authorization documents and trial reports for COVID-19 vaccines of the US-Food and Drug Authority (US-FDA), the European Medicines Agency (EMA), the United Kingdom Medicines and Health Products Regulatory Agency (MHRA), and the WHO website. We included studies that fulfilled the following inclusion criteria: population – humans; intervention – COVID-19 vaccines; comparison – control or placebo; outcomes – efficacy and adverse events; methods – phase 3 randomized trials. Two reviewers independently screened the reports, assessed the methodological quality, and extracted the data on the trial characteristics and results on vaccine efficacy and safety. The date of last search was March 11, 2021. Results. Interim results of trials investigating five vaccines were identified and included in the review. All five vaccines demonstrated satisfactory vaccine efficacy (VE) against symptomatic COVID-19 infection among adults in the short term with moderate certainty of evidence: BNT162b2, VE 95% (95% CI 90.3, 97.6); mRNA-1273, VE 93.6% (95% CI 88.6, 96.5); ChAdOx1, VE 66.7% (95% CI 57.4, 74.0), Gam-COVID-Vac, VE 91.1% (95% CI 83.6, 95.1); and Ad26.CoV2.S, VE 67.2% (95% CI 59.3, 73.7). Data on the efficacy against severe COVID-19 infection and asymptomatic COVID-19 infection are still inconclusive, except for Ad26.CoV2.S, which demonstrated good efficacy in preventing moderate and/or severe COVID-19 infection and acceptable protection against asymptomatic COVID-19 infection 28 days after vaccination (moderate certainty of evidence). Efficacy data on preventing death from COVID-19 infection are still inconclusive. Very limited phase 3 trial data is available to inform vaccine efficacy against the different variants of SARS-CoV-2. Vaccination with these five vaccines was associated with higher adverse reactions compared to control. These adverse events, due to reactions to the vaccines, were mild to moderate and of short duration. Available evidence on vaccine efficacy and safety is limited, mainly due to the short follow up and the small sample size of specific populations. Conclusion. BNT162b2, mRNA-1273, ChAdOx1, Gam-COVID-Vac and Ad26.CoV.S vaccines demonstrated satisfactory vaccine efficacy against symptomatic COVID-19 infection among adults in the short term with moderate certainty of evidence. Data on the efficacy against severe COVID-19 infection, asymptomatic COVID-19 infection, and death from COVID-19 infection are still inconclusive. Long-term efficacy and safety data, and data on the efficacy against variant strains of SARS-CoV-2 are still lacking.

Characteristics and factors associated with mortality of 200 COVID-19 patients at a Philippine COVID-19 tertiary referral center

@# Objectives: To describe the clinical profile and factors associated with mortality among the first 200 patients confirmed to have COVID-19 infection admitted in the University of the Philippines – Philippine General Hospital (UP-PGH) Methodology: We conducted a retrospective review of adult patients with confirmed COVID-19 infection admitted in PGH, a designated COVID-19 referral center. Demographic, clinical data, and clinical outcomes were extracted from medical records. Frequencies and distributions of various clinical characteristics were described, and factors associated with mortality were investigated. Results: Of the 200 patients in our cohort, majority were male (55.5%), and more than half (58%) were over 60 years old. Underlying co-morbid illnesses (67.5%) included hypertension (49.5%), diabetes mellitus (26.5%), and cardiovascular disease (20.5%). Most frequent presenting symptoms were cough (69.0%), fever (58.5%), or shortness of breath (53.0%). Most patients presented with mild (n=41, 20.5%) to moderate illness (n=99, 49.5%) and only 60 were considered severely (n=32, 16.0%) or critically ill (n=28, 14.0%). Many (61%) received empiric antibiotics, while 44.5% received either repurposed drugs or investigational therapies for COVID-19. Bacterial co-infection was documented in 11%, with Klebsiella pneumoniae commonly isolated. In-hospital mortality was 17.5%, which was highest for critical COVID-19 (71.4%). Mortality was observed to be higher among patients age 60 and above, those requiring oxygen, ventilatory support and ICU admission, and among those who developed acute kidney injury, acute stroke, sepsis, and nosocomial pneumonia. Conclusion: Our study confirms that COVID-19 affects males, older individuals and those with underlying co-morbid conditions. Empiric antimicrobial treatment was given for majority of patients, despite documentation of bacterial infection in only 11%. K. pneumoniae was commonly isolated, reflecting local epidemiology. Mortality rate during this early period of the pandemic was high and comparable to other institutions. Factors associated with mortality were related to critical COVID-19 and are similar to other studies.

The use of preoperative clinical risk assessment in COVID-19 screening among asymptomatic individuals, its cost-effectiveness and impact on surgical outcomes and management decisions: A rapid review

Objective@#This rapid review aimed to summarize data on the accuracy, benefits, harms, and cost-effectiveness of preoperative COVID-19 clinical risk assessment for asymptomatic individuals. @*Methods@#A comprehensive search in MEDLINE, Cochrane CENTRAL, ChinaXiv, medRxiv, and bioRxiv was done until March 10, 2021, using the keywords “COVID-19”, “surgery”, “RT-PCR”, “clinical risk assessment” and “cost-effectiveness”. We searched for studies that assessed the diagnostic accuracy of preoperative clinical risk assessment in COVID-19 screening among asymptomatic individuals, its cost-effectiveness, and its impact on surgical outcomes and management decisions. Risk of bias was assessed using Evaluation of Articles on Diagnosis (Painless Evidence Based Medicine)10 for accuracy studies, Newcastle-Ottawa Scale11 for cohort studies, and Drummond’s checklist12 for economic evaluations. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to evaluate the overall evidence. Data from included studies were collated qualitatively using summary tables and analyzed in Review Manager 5.4. Pooling of sensitivity and specificity, odds ratio or adjusted odds ratio, and cost-effectiveness measures using a random-effects model was planned. Heterogeneity was determined using I2. Subgroup and sensitivity analyses were preplanned in case significant heterogeneity was found. @*Results@#Three observational studies were included. Preoperative clinical risk assessment for COVID-19 demonstrated a sensitivity of 0.42 (95% CI 0.15-0.72) and a specificity of 0.85 (95% CI 0.76-0.92), using RT-PCR as a reference standard. Indirect evidence showed that any positive clinical risk assessment, COVID-19 antigen or RT-PCR test is done within 0–7 weeks from surgery was associated with a higher 30-day postoperative mortality (RR 3.96, 95% CI 3.41, 4.59) and pulmonary complications (RR 3.41, 95% CI 3.04, 3.83). Delaying surgery at least seven weeks from COVID-19 diagnosis was associated with lower post-surgical complications. Universal pre-endoscopy virus testing using the antigen rapid diagnostic test (Ag-RDT) (ICER = -26,286 €), standard RT-PCR (ICER = -11,128€), or rapid PCR (ICER = -13,703 €) combined with high-risk personal protective equipment (PPE) use in all patients irrespective of test results were found to be more cost-effective compared to no pre-endoscopy testing and no high-risk PPE use, at an, assumed COVID-19 prevalence of 1% or higher among asymptomatic individuals. Overall certainty of evidence was very low. @*Conclusion@#Preoperative clinical risk assessment has poor sensitivity but high specificity for detecting COVID-19 among asymptomatic individuals undergoing elective surgery. Objective diagnostic tests such as RT-PCR or Ag-RDT may still be needed to inform surgery schedules. @*@#

Benefits and risks of prolonged cotrimoxazole prophylaxis among people living with HIV in immune reconstitution phase: A retrospective cohort study

@#<p style="text-align: justify;"><strong>OBJECTIVES:</strong> To determine the effect of prolonged cotrimoxazole prophylaxis (CP) in reducing hospitalization and opportunistic infection rates among people living with HIV (PLHIV) with CD4 count >200 cells/mm3.<br /> <strong>METHODS:</strong>  We retrospectively reviewed 349 medical charts of PLHIV with CD4 count (or T-cell count) of >200 cells/mm3 enrolled in an HIV treatment hub in Manila, Philippines, from January 2004 to July 2016. Demographic, clinical characteristics and outcomes were extracted. Descriptive statistics were generated. Chi-square test for two proportions was done to compare the difference in outcomes between the CP and non-CP groups.<br /> <strong>RESULTS:</strong>  Of the 349 patients, majority (96.6%) were male with a mean age of 28 years (SD 6.4) and mean CD4 count of 373 cells/mm3 (SD 148). CP was continued in 103 patients (29.5%) with mean duration of 1.7 (SD 1.9) years. The prolonged CP group had more events of adverse drug reactions (p<0.001), specifically minor cutaneous reactions (p<0.001) and immunologic failures (p<0.001), compared to the non-CP group. There were no statistically significant differences in the frequency of hospitalization, PJP (Pneumocystis jirovecii pneumonia), non-PJP, other respiratory illnesses, diarrhea, toxoplasmosis, tuberculosis, stage 3/4 events and mortality, between the prolonged CP and non-CP groups.<br /> <strong>CONCLUSION:</strong> We did not observe any additional benefit in giving prolonged CP among PLHIV with CD4 count >200 cells/mm3. More adverse effects were also seen in the CP group.</p>

Estimating the burden of dengue in the Philippines using a dynamic transmission model

@#<p style="text-align: justify;"><b>OBJECTIVE:</b> This study aimed to describe dengue burden in the Philippines. Specifically, health and economic costs of the disease were estimated.</p><p style="text-align: justify;"><b>METHODS:</b> A published serotype-specific and age-stratified dengue dynamic transmission model was populated with Philippine-specific dengue epidemiology and cost data. Data were gathered from literature and record reviews. Dengue experts were consulted to validate the model parameters. Sensitivity analyses were performed to test the uncertainty of input parameters on model outcomes.</p><p style="text-align: justify;"><strong>RESULTS:</strong> By 2016 to 2020, it is estimated that annually, average hospitalized cases will amount to 401,191 and ambulatory cases will amount to 239,497; resulting to USD 139 million (PhP 5.9 billion) and USD 19 million (PhP 827 million) worth of aggregate costs shouldered by the public payer for hospitalized and ambulatory cases, respectively. Average annual productivity losses may amount to USD 19 million (PhP 821 million) and DALY lost is expected to be 50,622.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> The cost of dengue is high especially since the Philippines is an endemic country. Thus, there is a need to optimize government interventions such as vector control and vaccination that aim to prevent dengue infections.</p>