Marón, Gabriela

ABSTRACT Background While vaccination is a key strategy to mitigate the severity of coronavirus disease 2019 (COVID‐19) in children, the risk factors for symptomatic, medically attended (hereon referred to as “symptomatic”) COVID‐19 and the impact of vaccination are not well defined among pediatric solid organ transplant recipients (PSOTR). Methods PSOTR aged six months through 21 years at 11 centers in the Pediatric Infectious Diseases Transplant Network (PIDTRAN) were analyzed retrospectively for symptomatic COVID‐19 between July 2021 and May 2023. Using a Cox proportional hazards model, risk factors associated with COVID‐19‐associated hospitalization, in‐hospital oxygen use, mechanical ventilation, and the impact of COVID‐19 vaccination were analyzed. Results Of 1370 PSOTR, 410 (29%) had symptomatic COVID‐19 infection. Among those with symptomatic infection, 115 (28%) were hospitalized, 35 required in‐hospital oxygen, and three required mechanical ventilation. In the study, 45% were unvaccinated against COVID‐19. Compared to unvaccinated PSOTR, incompletely vaccinated PSOTR had 56% lower hazard (95% CI 0.26, 0.72, p = 0.001) of COVID‐19‐associated hospitalization whereas completely vaccinated did not have a statistically significant difference in hazard of hospitalization. Receipt of at least one dose of the bivalent vaccine was also associated with 92.5% lower hazard (95% CI 0.010, 0.55, p = 0.011) of hospitalization. Risk factors for hospitalization included chronic kidney disease, underlying heart disease, neurodevelopmental delay, and lymphocytopenia. Conclusions Most PSOTR with symptomatic COVID‐19 did not require hospitalization or respiratory support. Several comorbidities and lymphocytopenia are associated with severe COVID‐19 in PSOTR. COVID‐19 vaccination, mostly, protected PSOTR against COVID‐19‐associated hospitalization, but vaccine uptake among PSOTR was low. image

Abstract Background Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy. Methods A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus. Results There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available.

Abstract Background Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience. Methods A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion. Results The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults. Conclusions Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities.

Abstract Background In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for 2 novel virus-neutralizing monoclonal antibody therapies, bamlanivimab and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products. Methods A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion. Results The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high-risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis. Conclusions Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence and ensure the implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.