Factors Associated with Adverse Outcomes among SARS-CoV-2 Positive Children in a Tertiary Government COVID-19 Referral Hospital in the Philippines.

Background and Objective: Pediatric COVID-19 epidemiology and factors associated with adverse outcomes - mortality, need for invasive mechanical ventilation, and ICU admission, are largely unstudied. We described the clinico-demographic characteristics of Filipino pediatric COVID-19 patients and determined the factors associated with adverse outcomes. Methods: This is a retrospective cohort study of 180 hospitalized SARS-CoV-2-confirmed cases 0-18 years old from April 2020 to August 2021 in a tertiary COVID-19 referral hospital in Manila, National Capital Region. Crude associations were determined using chi-squared or Fisher's exact tests; and medians were compared using the Mann-Whitney test. Factors predictive of mortality were determined using Cox proportional hazards regression analysis. The survivor functions were depicted in graphs. Results: About 41.67% had mild disease, 58.33% were males, 39.4% aged 0-4 years, and 69.44% had at least one comorbidity. About 9.44% died (adjusted 9.2 persons per 1000 patient-days, 95% CI 5.5%-15.2%), 17.78% needed invasive mechanical ventilation, and 20% needed ICU admission. Independently, severe-critical COVID-19 (HRc 11.51, 95% CI 3.23, 41.06), retractions (HRc 10.30, 95% CI 3.27, 32.47), alar flaring (HRc 4.39, 95% CI 1.53, 12.58), cyanosis (HRc 4.39, 95% CI 1.72, 14.11), difficulty of breathing (HRc 7.99, 95% CI 2.25, 28.71), poor suck/appetite (HRc 4.46, 95% CI 1.59, 12.40), ferritin (HRc 1.01, 95% CI 1.00, 1.01), IL-6 (HRc 1.01, 95% CI 1.00, 1.01), aPTT (HRc 1.05, 95% CI 1.01, 1.10), IVIg (HRc 4.00, 95% CI 1.07, 14.92) and corticosteroid (HRc 6.01, 95% CI 2.04, 17.67) were significant hazards for mortality. In adjusted Cox analysis, only retractions (HRa 34.96, 95% CI 3.36, 363.79), seizure (HRa 9.98, 95% CI 1.76, 56.55), and corticosteroids (HRa 8.21, 95% CI 1.12, 60.38) were significantly associated with mortality while alar flaring appeared to be protective (HRa 0.10, 95% CI 0.01, 0.95). Several clinical characteristics were consistently associated with adverse outcomes. Conclusions: Majority of hospitalized pediatric COVID-19 patients were very young, males, had mild disease, and had at least one comorbidity. Mortality, invasive mechanical ventilation, and ICU admission were relatively low. Except for alar flaring which appeared to be protective, retractions, seizure, and use of corticosteroids were associated with adverse outcomes.

Strategic Optimization of Patient Flow and Staffing Schemes during the COVID-19 Pandemic through Operations Management in a Neonatal Intensive Care Unit.

Background: The COVID-19 pandemic posed challenges in making time-bound hospital management decisions. The University of the Philippines -Philippine General Hospital (UP-PGH) is a tertiary COVID-19 referral center located in Manila, Philippines. The mismatch of increasing suspected or confirmed COVID-19 infected mothers with few documented cases of infected infants has caused significant patient overflow and manpower shortage in its NICU. Objective: We present an evaluated scheme for NICU bed reallocation to maximize capacity performance, staff rostering, and resource conservation, while preserving COVID-19 infection prevention and control measures. Methods: Existing process workflows translated into operational models helped create a solution that modified cohorting and testing schemes. Staffing models were transitioned to meet patient flow. Outcome measurements were obtained, and feedback was monitored during the implementation phase. Results: The scheme evaluation demonstrated benefits in (a) achieving shorter COVID-19 subunit length of stay; (b) better occupancy rates with minimal overflows; (c) workforce shortage mitigation with increased non-COVID workforce pool; (d) reduced personal protective equipment requirements; and (e) zero true SARS-CoV-2 infections. Conclusion: Designed for hospital operations leaders and stakeholders, this operations process can aid in hospital policy formulation in modifying cohorting schemes to maintain quality NICU care and service during the COVID-19 pandemic.

Considerations for vaccinating children against COVID-19.

COVID-19 vaccines have been introduced in children and adolescents in many countries. However, high levels of community transmission and infection-derived immunity make the decision to introduce COVID-19 vaccination of children in countries yet to do so particularly challenging. For example, other vaccine preventable diseases, including measles and polio, generally have far higher childhood morbidity and mortality in low-income and middle-income countries (LMICs) than COVID-19, and coverage with these vaccines has declined during the pandemic. Many countries are yet to introduce pneumococcal conjugate and rotavirus vaccines for children, which prevent common causes of childhood death, or human papillomavirus vaccine for adolescents. The Pfizer and Moderna COVID-19 vaccines that have been widely tested in children and adolescents have a positive risk-benefit profile. However, the benefit is less compared with other life-saving vaccines in this age group, particularly in LMICs and settings with widespread infection-derived immunity. The resources required for rollout may also pose a considerable challenge in LMICs. In this paper, we describe COVID-19 in children, with a focus on LMICs, and summarise the published literature on safety, efficacy and effectiveness of COVID-19 vaccination in children and adolescents. We highlight the complexity of decision-making regarding COVID-19 vaccination of children now that most of this low-risk population benefit from infection-derived immunity. We emphasise that at-risk groups should be prioritised for COVID-19 vaccination; and that if COVID-19 vaccines are introduced for children, the opportunity should be taken to improve coverage of routine childhood vaccines and preventative healthcare. Additionally, we highlight the paucity of epidemiological data in LMICs, and that for future epidemics, measures need to be taken to ensure equitable access to safe and efficacious vaccines before exposure to infection.

Expert review of global real-world data on COVID-19 vaccine booster effectiveness and safety during the omicron-dominant phase of the pandemic.

INTRODUCTION: COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. However, the emergence of the Omicron variant and subvariants as the globally dominant strains have raised doubts about the effectiveness of currently available vaccines and prompted debate about potential future vaccination strategies. AREAS COVERED: Using the publicly available IVAC VIEW-hub platform, we reviewed 52 studies on vaccine effectiveness (VE) after booster vaccinations. VE were reported for SARS-CoV-2 symptomatic infection, severe disease and death and stratified by vaccine schedule and age. In addition, a non-systematic literature review of safety was performed to identify single or multi-country studies investigating adverse event rates for at least two of the currently available COVID-19 vaccines. EXPERT OPINION: Booster shots of the current COVID-19 vaccines provide consistently high protection against Omicron-related severe disease and death. Additionally, this protection appears to be conserved for at least 3 months, with a small but significant waning after that. The positive risk-benefit ratio of these vaccines is well established, giving us confidence to administer additional doses as required. Future vaccination strategies will likely include a combination of schedules based on risk profile, as overly frequent boosting may be neither beneficial nor sustainable for the general population.

Invasive meningococcal disease in Malaysia, Philippines, Thailand, and Vietnam: An Asia-Pacific expert group perspective on current epidemiology and vaccination policies.

Invasive meningococcal disease (IMD) imposes a significant burden on the global community due to its high case fatality rate (4-20%) and the risk of long-term sequelae for one in five survivors. An expert group meeting was held to discuss the epidemiology of IMD and immunization policies in Malaysia, Philippines, Thailand, and Vietnam. Most of these countries do not include meningococcal immunization in their routine vaccination programs, except for high-risk groups such as immunocompromised people and pilgrims. It is difficult to estimate the epidemiology of IMD in the highly diverse Asia-Pacific region, but available evidence indicate serogroup B is increasingly dominant. Disease surveillance systems differ by country. IMD is not a notifiable disease in some of them. Without an adequate surveillance system in the region, the risk and the burden of IMD might well be underestimated. With the availability of new combined meningococcal vaccines and the World Health Organization roadmap to defeat bacterial meningitis by 2030, a better understanding of the epidemiology of IMD in the Asia-Pacific region is needed.

Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia.

BACKGROUND: Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP. METHODS: This phase 2/3, randomized, open-label, active-control, multicenter study randomly assigned solithromycin (capsules, suspension or intravenous) or an appropriate comparator antibiotic in a 3:1 ratio (planned n = 400) to children 2 months to 17 years of age with CABP. Primary safety endpoints included treatment-emergent adverse events (AEs) and AE-related drug discontinuations. Secondary effectiveness endpoints included clinical improvement following treatment without additional antimicrobial therapy. RESULTS: Unrelated to safety, the sponsor stopped the trial prior to completion. Before discontinuation, 97 participants were randomly assigned to solithromycin (n = 73) or comparator (n = 24). There were 24 participants (34%, 95% CI, 23%-47%) with a treatment-emergent AE in the solithromycin group and 7 (29%, 95% CI, 13%-51%) in the comparator group. Infusion site pain and elevated liver enzymes were the most common related AEs with solithromycin. Study drug was discontinued due to AEs in 3 subjects (4.3%) in the solithromycin group and 1 (4.2%) in the comparator group. Forty participants (65%, 95% CI, 51%-76%) in the solithromycin group achieved clinical improvement on the last day of treatment versus 17 (81%, 95% CI, 58%-95%) in the comparator group. The proportion achieving clinical cure was 60% (95% CI, 47%-72%) and 68% (95% CI, 43%-87%) for the solithromycin and comparator groups, respectively. CONCLUSIONS: Intravenous and oral solithromycin were generally well-tolerated and associated with clinical improvement in the majority of participants treated for CABP.

Expert review on global real-world vaccine effectiveness against SARS-CoV-2.

INTRODUCTION: COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. While primary series vaccination rates are generally high in Southeast Asian (SEA) countries, various factors have limited the rollout and impact of booster doses. AREAS COVERED: We reviewed 79 studies in the International Vaccine Access Center (IVAC) VIEW-hub platform on vaccine effectiveness (VE) after primary immunizations with two-dose schedules. VE data were reported for SARS-CoV-2 infection, COVID-19-related hospitalizations and deaths, and stratified across variants of concern, age, study design and prior SARS-CoV-2 infection for mRNA vaccines (BNT162b2, mRNA-1273, and combinations of both), vector vaccines (AstraZeneca, AZD1222 [ChAdOx1 nCoV-19] 'Vaxzevria'), and inactivated virus vaccines (CoronaVac). EXPERT OPINION: The most-studied COVID-19 vaccines provide consistently high (>90%) protection against serious clinical outcomes like hospitalizations and deaths, regardless of variant. Additionally, this protection appears equivalent for mRNA vaccines and vector vaccines like AZD1222, as supported by our analysis of Asian and relevant international data, and by insights from SEA experts. Given the continued impact of COVID-19 hospitalizations and deaths on health-care systems worldwide, encouraging vaccination strategies that reduce this burden is more relevant than attempting to prevent broader but milder infections with specific variants, including Omicron.

A Response to: Letter to the Editor Regarding "Cost-Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Versus Lower-Valent Alternatives in Filipino Infants".

This communication seeks to address the questions of Dhere and colleagues in their letter on our study "Cost-effectiveness of the 13-valent pneumococcal conjugate vaccine (PCV13) versus lower-valent alternatives in Filipino infants." We hope to provide clarity on each of the three potential misunderstandings of our cost-effectiveness analysis that were raised by Dhere and colleagues.

Safety and immunogenicity of 3 formulations of a Sabin inactivated poliovirus vaccine produced on the PER.C6® cell line: A phase 2, double-blind, randomized, controlled study in infants vaccinated at 6, 10 and 14 weeks of age.

An inactivated poliovirus vaccine candidate using Sabin strains (sIPV) grown on the PER.C6® cell line was assessed in infants after demonstrated immunogenicity and safety in adults. The study recruited 300 infants who were randomized (1:1:1:1) to receive one of 3 dose levels of sIPV or a conventional IPV based on Salk strains (cIPV). Poliovirus-neutralizing antibodies were measured before the first dose and 28 days after the third dose. Reactogenicity was assessed for 7 days and unsolicited adverse events (AEs) for 28 days after each vaccination. Serious AEs (SAEs) were recorded throughout the study. Solicited AEs were mostly mild to moderate. None of the SAEs reported in the study were judged vaccine related, including one fatal SAE due to aspiration of vomitus that occurred 26 days after the third dose of low-dose sIPV. After 3 sIPV vaccinations and across all dose levels, seroconversion (SC) rates were at least 92% against Sabin poliovirus types and at least 80% against Salk types, with a dose-response in neutralizing antibody geometric mean titers (GMTs) observed across the 3 sIPV groups. Compared to cIPV, the 3 sIPV groups displayed similar or higher SC rates and GMTs against the 3 Sabin types but showed a lower response against Salk types 1 and 2; this was most visible for Salk type 1. While the PER.C6® cell line-based sIPV showed an acceptable safety profile and immunogenicity in infants, lower seroprotection against type 1 warrants optimization of dose level and additional clinical evaluation.

Safety of primary immunization with a DTwP-HBV/Hib vaccine in healthy infants: a prospective, open-label, interventional, phase IV clinical study.

OBJECTIVE: This study aimed to assess the safety of a fully liquid DTwP-HBV/Hib pentavalent vaccine (EupentaTM) based on the occurrence of adverse events (AEs) following vaccination. METHODS: This was a prospective, open-label, single-arm, interventional phase IV study. A single intramuscular injection of the study vaccine was administered to infants at approximately 6, 10, and 14 weeks of age, and an end-of-study follow-up visit was scheduled at 18 weeks. RESULTS: In all, 3000 subjects were enrolled and received at least one dose of the study vaccine. Of these, 2717 (90.6%) experienced at least one AE. Immediate reactions, solicited and unsolicited AEs were respectively identified in 224 (7.5%), 2,652 (88.4%), and 1,099 (36.6%) subjects. The most prevalent solicited and unsolicited AEs comprised pain/tenderness and upper respiratory tract infection, respectively. Most AEs were mildly or moderately severe. Forty-one (1.4%) subjects had at least one serious AE (SAE); of these, two (0.1%) had two SAEs each, considered related to the study vaccine. Six (0.2%) subjects died due to unsolicited AEs, none of which were considered related to the study vaccine. No AEs were reported at the end-of-study follow-up visit. CONCLUSIONS: The study vaccine  had a safety profile similar to that reported in a previous clinical study, and did not result in an increased risk of AEs known to be associated with DTwP-based vaccines or previously unrecognized SAEs.

What is the true burden of diphtheria, tetanus, pertussis and poliovirus in children aged 3-18 years in Asia? A systematic literature review.

OBJECTIVES: In recent years, outbreaks and a rising incidence of diphtheria, tetanus, and pertussis have occurred in Asia, particularly in older children. METHODS: A systematic search of MEDLINE and Embase was conducted from January 2000 to October 2020 to identify the epidemiology of diphtheria, tetanus, pertussis, and poliomyelitis in children and adolescents (aged 3-18 years) in Asia. The results were then related to vaccination schedules, booster coverage rates, pertussis source of infection, and booster immunogenicity, as identified by a pragmatic review. The International Prospective Register of Systematic Reviews (PROSPERO) registration: #CRD42020222445. RESULTS: A total of 35 studies were included in this review. Limited data were reported on the epidemiology of diphtheria, tetanus, pertussis, and poliomyelitis. Data from studies reporting the incidence of diphtheria and pertussis exemplify the shift in epidemiology to older children/adolescents. Seroprevalence data suggest that immunity to pertussis and diphtheria is below the level of herd immunity in several Asian countries in this population. CONCLUSION: The true burden of diphtheria, pertussis, and tetanus in children aged 3-18 years in Asia is unknown because of weak or absent nationwide surveillance systems. The available evidence highlights the inadequacies in immunity, either by gaps in a recommendation or suboptimal booster coverage, supporting the public health need for booster vaccinations in this population.

Cost-Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Versus Lower-Valent Alternatives in Filipino Infants.

INTRODUCTION: The Philippines pediatric national immunization program (NIP) included the 13-valent pneumococcal conjugate vaccine manufactured by Pfizer (PCV13-PFE) since 2015. Uptake has been slow in particular regions, with coverage only reaching all regions in 2019. Given affordability challenges in the context of higher coverage, this study seeks to determine whether universal coverage across all regions of the Philippines with PCV13-PFE will provide good value for money compared with 10-valent PCV alternatives manufactured by GlaxoSmithKline (PCV10-GSK) or Serum Institute of India (PCV10-SII). METHODS: A decision analytic model is adapted for this cost-effectiveness analysis in the Philippines. Clinical and economic input parameters are taken from published sources. Future disease is predicted using age-stratified and population-level observed serotype dynamics. Total cases of pneumococcal disease, deaths, direct and indirect healthcare costs, and quality-adjusted life years (QALYs) gained are discounted 7% annually and modeled for each PCV. Given clinical uncertainty, PCV10-SII outcomes are reported as ranges. Incremental cost-effectiveness ratios (ICERs) are calculated for PCV13-PFE versus lower-valent PCVs (PCV10-GSK or PCV10-SII) from a societal perspective over 10 years. RESULTS: Nationwide PCV13-PFE use over 10 years is estimated to avert 375,831 more cases, save 53,189 additional lives, and gain 153,349 QALYs compared with PCV10-GSK. This equates to cost-savings of PHP 12.27 billion after vaccine costs are accounted for. Similarly, PCV13-PFE is more effective and cost-saving compared with PCV10-SII. Switching programs to PCV10-SII would result in more cases of disease (313,797 - 666,889), more deaths (22,759 - 72,435), and lost QALYs (108,061 - 266,108), equating to a net economic loss (PHP 359.82 million - 14.41 billion). PCV13-PFE remains cost-effective in the presence of parameter uncertainty. CONCLUSION: PCV13-PFE would prevent exceedingly more cases and deaths compared with lower-valent PCVs. Additionally, the PCV13-PFE program is estimated to continue providing cost-savings, offering the best value for money to achieve universal PCV coverage in the Philippines.

Detection and Genome Sequencing of SARS-CoV-2 Variants Belonging to the B.1.1.7 Lineage in the Philippines.

We report the sequencing and detection of 36 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutations specific to viruses belonging to the B.1.1.7 lineage in the Philippines.

Impact of COVID-19 on routine immunisation in South-East Asia and Western Pacific: Disruptions and solutions.

BACKGROUND: Data on COVID-19-induced disruption to routine vaccinations in the South-East Asia and Western Pacific regions (SEAR/WPR) have been sparse. This study aimed to quantify the impact of COVID-19 on routine vaccinations by country, antigen, and sector (public or private), up to 1 June 2020, and to identify the reasons for disruption and possible solutions. METHODS: Sanofi Pasteur teams from 19 countries in SEAR/WPR completed a structured questionnaire reporting on COVID-19 disruptions for 13-19 routinely delivered antigens per country, based on sales data, government reports, and regular physician interactions. Data were analysed descriptively, disruption causes ranked, and solutions evaluated using a modified public health best practices framework. FINDINGS: 95% (18/19) of countries reported vaccination disruption. When stratified by country, a median of 91% (interquartile range 77-94) of antigens were impacted. Infancy and school-entry age vaccinations were most impacted. Both public and private sector healthcare providers experienced disruptions. Vaccination rates had not recovered for 39% of impacted antigens by 1 June 2020. Fear of infection, movement/travel restrictions, and limited healthcare access were the highest-ranked reasons for disruption. Highest-scoring solutions were separating vaccination groups from unwell patients, non-traditional vaccination venues, virtual engagement, and social media campaigns. Many of these solutions were under-utilised. INTERPRETATION: COVID-19-induced disruption of routine vaccination was more widespread than previously reported. Adaptable solutions were identified which could be implemented in SEAR/WPR and elsewhere. Governments and private providers need to act urgently to improve coverage rates and plan for future waves of the pandemic, to avoid a resurgence of vaccine-preventable diseases. FUNDING: Sanofi Pasteur.

A Narrative Review of Pneumococcal Disease in Children in the Philippines.

This narrative review describes the epidemiology of invasive pneumococcal diseases, nasopharyngeal carriage, and antibiotic resistance of Streptococcus pneumoniae serotypes, and vaccination coverage in children in the Philippines. Epidemiological data show that, despite the availability of the free-of-cost 13-valent pneumococcal conjugate vaccine for infants as part of the National Immunization Program, the burden of pneumococcal disease in young children remains high in the Philippines. The significant variability in data reported between studies highlights an urgent need for active and comprehensive disease surveillance for more accurate estimates of pneumococcal disease in the country. Although data from 2001 to 2013 show high rates of pneumococcal carriage in children in the Philippines aged < 5 years, contemporary data are lacking, again emphasizing the need for active surveillance programs. The introduction of pneumococcal conjugate vaccines has resulted in substantial declines in disease caused by pneumococcal serotypes included in the vaccines, but the emergence of pneumococcal disease due to nonvaccine serotypes is an ongoing concern. Surveillance of actively circulating serotypes is critical to better understand vaccine coverage. Antimicrobial resistance of S. pneumoniae remains a significant threat to public health worldwide; data regarding antibiotic resistance in young children in the Philippines are limited, but reports generally show low rates of antibiotic resistance in this group. National immunization rates have increased in recent years, yet many individuals are still unprotected from pneumococcal disease. Overall, there is a critical need for contemporary and accurate disease surveillance in the Philippines. Such data would provide better estimates of pneumococcal disease incidence, serotype distribution, and antibiotic resistance to better inform vaccination strategies and to ensure that children in the Philippines are best protected against pneumococcal disease.

Prevalence and molecular characteristics of MRSA nasal carriage among hospital care workers in a tertiary hospital in the Philippines.

BACKGROUND: Hospital-care workers (HCWs) are at risk for MRSA carriage, subsequent infection and potential transmission of nosocomial infection. Epidemiological typing of MRSA among HCWs would provide data that can be used for control measures. METHODS: This is a cross sectional study that involved 92 participants from pediatric and surgery department of a tertiary hospital. Nasal swabs were collected and inoculated onto MRSASelect Chromogenic Media. Samples characterized as MRSA underwent SCCmec typing and detection of Panton Valentine leucocidin (PVL) by PCR. RESULTS: The overall prevalence of MRSA was 13%. Six were from Pediatrics and another six were from Surgery. Seven out of 12 MRSA isolates carried SCCmec type I gene and five isolates carried SCCmec type IV gene. Six samples were found positive for PVL, four of which PVL-SSCmec IV, while the other two isolates were PVL-SCCmec I. The isolates were grouped into four main sequence types (STs) namely ST 1147, ST30, ST5 and ST97. Two samples from both departments were found to be PVL-positive SCCmec I ST 30; PVL-positive SCCmec IV ST 97 was found in two MRSA samples from Pediatrics and PVL-positive SCCmec IV ST 30 from Surgery. CONCLUSION: Data collected from a non-outbreak setting suggest the presence of different clones of MRSA from nasal swabs of HCWs belonging to the Department of Pediatrics and Surgery. The data collected by this study can be used as reference for other succeeding studies on the surveillance of MRSA among HCWs.