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

Milan et al., Acta Medica Philippina, doi:10.47895/amp.v58i7.8392
Apr 2024  
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Mortality 47% Improvement Relative Risk Ventilation 21% ICU admission 16% Vitamin D for COVID-19  Milan et al.  LATE TREATMENT Is late treatment with vitamin D beneficial for COVID-19? Retrospective 180 patients in Philippines (April 2020 - August 2021) Lower mortality (p=0.18) and ventilation (p=0.53), not sig. c19early.org Milan et al., Acta Medica Philippina, Apr 2024 Favorsvitamin D Favorscontrol 0 0.5 1 1.5 2+
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
Retrospective 180 hospitalized pediatric COVID-19 patients in the Philippines showing lower mortality with vitamin D and zinc, and higher mortality with remdesivir, all without statistical significance. Remdesivir was given to few patients and authors do not provide information on the timing of treatment - confounding by indication may be significant.
Cholecalciferol was used in this study. Meta analysis shows that late stage treatment with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 69% [47‑82%] lower risk vs. 39% [27‑49%] lower risk. Cholecalciferol requires two hydroxylation steps to become activated - first in the liver to calcifediol, then in the kidney to calcitriol. Calcitriol, paricalcitol, and alfacalcidol are active vitamin D analogs that do not require conversion. This allows them to have more rapid onset of action compared to cholecalciferol. The time delay for cholecalciferol to increase serum calcifediol levels can be 2-3 days, and the delay for converting calcifediol to active calcitriol can be up to 7 days.
This is the 121st of 122 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 587 sextillion).
30 studies are RCTs, which show efficacy with p=0.0000032.
Study covers zinc, vitamin D, and remdesivir.
risk of death, 46.5% lower, RR 0.53, p = 0.18, treatment 9 of 122 (7.4%), control 8 of 58 (13.8%), NNT 16, day 45.
risk of mechanical ventilation, 20.8% lower, RR 0.79, p = 0.53, treatment 20 of 122 (16.4%), control 12 of 58 (20.7%), NNT 23, day 45.
risk of ICU admission, 15.9% lower, RR 0.84, p = 0.69, treatment 23 of 122 (18.9%), control 13 of 58 (22.4%), NNT 28, day 45.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Milan et al., 30 Apr 2024, retrospective, Philippines, peer-reviewed, median age 11.0, 5 authors, study period 1 April, 2020 - 31 August, 2021. Contact: markmilan31@gmail.com.
This PaperVitamin DAll
Factors Associated with Adverse Outcomes among SARS-CoV-2 Positive Children in a Tertiary Government COVID-19 Referral Hospital in the Philippines
Mark Jason Dc. Milan, Md, Al Joseph R Molina, Md, Anna Lisa T Ong-Lim, Md, Ma. Esterlita V Uy, Md, Ms, Herbert G Uy, Md
Acta Medica Philippina, doi:10.47895/amp.v58i7.8392
Background and Objective. Pediatric COVID-19 epidemiology and factors associated with adverse outcomesmortality, need for invasive mechanical ventilation, and ICU admission, are largely unstudied. We described the clinicodemographic 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.
Statement of Authorship All authors certified fulfillment of ICMJE authorship criteria. Author Disclosure All authors declared no conflicts of interest. Appendix. Survival functions after Cox regression analysis, adjusted
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This is a retrospective cohort study of 180 hospitalized SARS-CoV-2-confirmed cases ' '0-18 years oldfrom April 2020 to August 2021 in a tertiary COVID-19 referral hospital in ' 'Manila, National Capital Region. Crudeassociations 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.\r\n' 'Results. About 41.67% had mild disease, 58.33% were males, 39.4% aged 0-4 years, and 69.44% ' 'had at least onecomorbidity. 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) weresignificantly 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.\r\n' 'Conclusions. Majority of hospitalized pediatric COVID-19 patients were very young, males, had ' 'milddisease, and had at least one comorbidity. Mortality, invasive mechanical ventilation, ' 'and ICU admission wererelatively low. 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Late treatment
is less effective
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