Pediatric ARDS phenotypes in critical COVID-19: implications for therapies and outcomes

Purpose to describe lung mechanics in Pediatric Acute Respiratory Disease Syndrome (PARDS) associated with COVID-19. We hypothesize two phenotypes according to respiratory system mechanics and clinical diagnosis. Methods a concurrent multicenter observational study was performed, analyzing clinical variables and pulmonary mechanics of PARDS associated with COVID-19 in 4 Pediatric intensive care units (PICUs) of Perú. Subgroup analysis included PARDS associated with multisystem inflammatory syndrome in children (MIS-C), MIS-PARDS, and PARDS with COVID-19 primary respiratory infection, C-PARDS. In addition, receiver operator curve analysis (ROC) for mortality was performed. Results 30 patients were included. Age was 7.5(4-11) years, 60% male, and mortality 23%. 47% corresponded to MIS-PARDS and 53% to C-PARDS phenotypes. C-PARDS had positive RT-PCR in 67% and MIS-PARDS none (p<0.001). C-PARDS group had more profound hypoxemia (P/Fratio<100, 86%vs38%,p<0.01) and higher driving-pressure (DP) [14(10-22)vs10(10-12)cmH2O], and lower compliance of the respiratory system (CRS)[0.5(0.3-0.6)vs 0.7(0.6-0.8)ml/kg/cmH2O] compared to MIS-PARDS (all p<0.05). ROC-analysis for mortality showed that DP had the best performance [AUC 0.91(95%CI0.81-1.00), with the best cut-point of 15 cmH2O (100% sensitivity and 87% of specificity). Mortality in C-PARDS was 38% and 7% in MIS-PARDS(p=0.09). MV free-days were 12(0-23) in C-PARDS and 23(21-25) in MIS-PARDS(p=0.02) Conclusion critical pediatric COVID-19 is heterogeneous in children. COVID-19 PARDS had two phenotypes with distinctive pulmonary mechanics features. Characteristics of C-PARDS are like a classic primary PARDS, while a decoupling between compliance and hypoxemia was more frequent in MIS-PARDS. In addition, C-PARDS had fewer MV free-days. DP ≥ 15 cmH2O had the best performance of the quasi-static calculations to discriminate for mortality. Standardized pulmonary mechanics measurements in PARDS might reveal essential information to tailor the ventilatory strategy in pediatric critical COVID-19. ‘Take-home message’ Tweet Lung mechanics help to differentiate two different phenotypes in PARDS associated with COVID-19. C-PARDS associated with respiratory infection, and MIS-PARDS, associated with MIS-C. Also, lung mechanics variables were associated with mortality, being DP ≥ 15 cmH2O the best discriminator. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Approval letters 088-2021-CIEI-HNHU Hospital Nacional Hipolito Unanue, 011-2021-CIEI-HEVES Hospital de Emergencias de Villa El Salvador, 001-2021-COVID-HR Hospital Regional de Cusco, 42-IETSI-ESSALUD-2020 Hospital Edgardo Rebagliati Martins I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in this work are contained in the manuscript.