{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:32:51Z","timestamp":1760146371355,"version":"build-2065373602"},"reference-count":81,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>PPHN is a common cause of neonatal respiratory failure and is still a serious condition that is associated with high mortality. Objectives: To analyze the clinical characteristics and outcomes of SARS-CoV-2 infection in neonates with PPHN to identify neonatal cases at risk to develop severe illness. Methods: For this systematic review, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched Medline, Embase, CINAHL, and PubMed for studies on the development of COVID-19 in neonates with PPHN, published from 1 December 2019 to 29 February 2024, with an English language restriction. Results: Of the 2406 papers that were identified, 21 articles were included in the systematic review. Studies involving thirty-six neonates with PPHN and infected with SARS-CoV-2 were analyzed (twenty-nine survived, six died, and one is still hospitalized). The main causes of PPHN in neonates who had COVID-19 were neonatal respiratory distress syndrome (NRDS) (41.7%), meconium-stained amniotic fluid (MSAF) (16.7%), preterm premature rupture of membranes (PPROM) (11.1%), hypoxic ischemic encephalopathy (HIE) (5.5%), pneumonia (5.5%), and idiopathic (2.8%). Most of those neonates were male (33.3%), belonged to Indian ethnicity (50%), and were delivered via caesarean section (44.4%). COVID-19 in cases with PPHN commonly occurred in neonates born with a pregnancy range from 32 to &lt;37 weeks (moderate to late preterm) (36.1%). The maternal severity of COVID-19 was reported to be severe in three cases only (8.3%); however, SARS-CoV-2 infection in neonates with PPHN was either severe (44.4%) or critical (22.2%). Most of these neonates experienced acute respiratory distress syndrome (ARDS) (58.3%). Early and late multisystem inflammatory syndrome in neonates (MIS-N) were reported in 50% and 11.1%, respectively. A high proportion of neonates were admitted to the intensive care unit (ICU) (58.3%) or needed mechanical ventilation (MV) (47.2%). Neonates with concurrent PPHN and SARS-CoV-2 infection who died had worse severity of COVID-19 [i.e., severity of COVID-19 was critical in 10% (neonates with PPHN who survived group) vs. 83.3% (neonates with PPHN who died group); p = 0.026]. Neonates with PPHN and COVID-19 had a higher relative risk of death if they received more antibiotics (RR 4.14, 95% CI 0.64\u20136.88) and if their COVID-19 was defined as critical (RR 2.84, 95% CI 0.86\u20139.39). Male neonates with PPHN and COVID-19 (RR 2.60, 95% CI 0.30\u20131.17) and those requiring prolonged invasive positive pressure ventilation (RR 2.22, 95% CI 0.64\u20137.73) also showed an increased relative risk for death. Conclusions: COVID-19 in neonates with PPHN is challenging and may be associated with increased mortality, severity, ICU admission, ARDS, MIS-N, and MV usage. The results should be interpreted with caution owing to the small number of studies and substantial heterogeneity and indicate a need for future research in this area. Due to its benefits, testing for SARS-CoV-2 should be encouraged for newborns with symptoms consistent with COVID-19, especially in neonates with a history of SARS-CoV-2 exposure. Effective protection measures should be implemented during delivery and post-delivery care as necessary.<\/jats:p>","DOI":"10.3390\/children11111305","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T07:04:04Z","timestamp":1730099044000},"page":"1305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Characteristics and Outcomes of SARS-CoV-2 Infection in Neonates with Persistent Pulmonary Hypertension of the Newborn (PPHN): A Systematic Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4552-4513","authenticated-orcid":false,"given":"Saad","family":"Alhumaid","sequence":"first","affiliation":[{"name":"School of Pharmacy, University of Tasmania, Hobart 7000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muneera","family":"Alabdulqader","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Specialty, Pediatric Department, Medical College, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zainab","family":"Al Alawi","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed A.","family":"Al Ghamdi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, King Fahad Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed A","family":"Alabdulmuhsin","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa 36422, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan I","family":"Al Hassar","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Aljafr General Hospital, Ministry of Health, Al-Ahsa 7110, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hussain Ahmed","family":"Alsouaib","sequence":"additional","affiliation":[{"name":"Medical Store Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa 36422, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hussain Ali","family":"Alhassan","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa 36422, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan","family":"Al-Helal","sequence":"additional","affiliation":[{"name":"Division of Laboratory, Medical Microbiology Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa 36422, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sameer Ahmed","family":"Almoraihel","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Aljafr General Hospital, Ministry of Health, Al-Ahsa 7110, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed Jaber","family":"Alomran","sequence":"additional","affiliation":[{"name":"Medical Department, Aljafr General Hospital, Ministry of Health, Al-Ahsa 7110, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassan Redha","family":"AL-Tarfi","sequence":"additional","affiliation":[{"name":"Medical Store Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa 36422, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbas Radi","family":"Al-Makinah","sequence":"additional","affiliation":[{"name":"Dental Department, Aljafr General Hospital, Ministry of Health, Al-Ahsa 7110, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tariq T.","family":"Alghareeb","sequence":"additional","affiliation":[{"name":"Administration of Pharmaceutical Care, Al-Ahsa Health Cluster, Ministry of Health, Al-Ahsa 36421, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Abdullah","family":"Alkhwaitem","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Rumah General Hospital, Ministry of Health, Riyadh 11981, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murtadha","family":"Alsuliman","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hereditary Blood Diseases Centre, Ministry of Health, Al-Ahsa 36422, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali N.","family":"Bukhamseen","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa 36422, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khulood Khaled","family":"Alajmi","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Al-Ahsa Mental Health Hospital, Ministry of Health, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed Salman","family":"Al Majhad","sequence":"additional","affiliation":[{"name":"Medical Store Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa 36422, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariam Ali","family":"Almajhad","sequence":"additional","affiliation":[{"name":"Nursing Department, Maternity and Children Hospital, Ministry of Health, Al-Ahsa 36422, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayat Hussain","family":"Alhmed","sequence":"additional","affiliation":[{"name":"Administration of Nursing Care, Maternity and Children Hospital, Ministry of Health, Al-Ahsa 36422, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulrahman A.","family":"Alnaim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jpeds.2019.06.053","article-title":"Morbidity of persistent pulmonary hypertension of the newborn in the first year of life","volume":"213","author":"Steurer","year":"2019","journal-title":"J. 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