{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:15:32Z","timestamp":1793736932759,"version":"4.6.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:p>\n                    Following the COVID-19 pandemic, the clinical patterns of pediatric respiratory infections have undergone significant changes, with increasing attention on the immunological imprint left by Post-Acute Sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID. A perplexing clinical phenomenon has been observed: some children with a history of Long COVID exhibit a disproportionately severe inflammatory response and extensive lung injury when encountering common community-acquired pneumonia, such as that caused by\n                    <jats:italic>Mycoplasma pneumoniae<\/jats:italic>\n                    or\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    , inconsistent with their pathogen load. This review aims to dissect this phenomenon and proposes the \u201cImmune Priming and Two-Hit\u201d model as its core pathophysiological framework. This model posits that the Long COVID state constitutes the \u201cfirst hit,\u201d establishing a \u201cprimed\u201d or \u201chyper-reactive\u201d immune baseline through viral persistence, trained immunity-induced monocyte reprogramming, and sustained endothelial dysfunction. Upon the \u201csecond hit\u201d of a bacterial infection, this primed immune system triggers a dysregulated, synergistically amplified inflammatory cascade. The mechanisms involve the exponential release of cytokines such as Interleukin-6 (IL-6), IL-1\u03b2, and Tumor Necrosis Factor-\n                    <jats:italic>\u03b1<\/jats:italic>\n                    (TNF-\u03b1), inflammation-mediated immunothrombosis, and excessive activation of Neutrophil Extracellular Trap formation (NETosis), ultimately leading to severe outcomes like Acute Respiratory Distress Syndrome (ARDS) and necrotizing pneumonia. Consequently, identifying and defining this \u201cHyper-inflammatory endotype\u201d is of critical clinical importance. We define it as an \u201cendotype\u201d to emphasize the distinct, host-determined pathophysiological mechanisms underlying it, rather than merely a collection of clinical manifestations. By monitoring biomarkers such as ferritin, D-dimer, lactate dehydrogenase (LDH), and lymphocyte counts, clinicians may be able to perform early risk stratification of these children. This approach not only facilitates a shift in therapeutic strategy from purely antimicrobial therapy to \u201chost-directed therapy\u201d\u2014emphasizing the necessity of early, adequate corticosteroid use and consideration of anticoagulation\u2014but also provides a new theoretical basis and intervention window for preventing long-term sequelae such as pulmonary fibrosis.\n                  <\/jats:p>","DOI":"10.3389\/fpubh.2026.1782871","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T05:24:43Z","timestamp":1776662683000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The \u201ctwo-hit\u201d storm: a hyper-inflammatory endotype in pediatric long COVID and its role in the severity of secondary bacterial pneumonia\u2014a mechanistic review and clinical implications"],"prefix":"10.3389","volume":"14","author":[{"given":"Hong","family":"Huang","sequence":"first","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Fang","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingtao","family":"Ma","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojuan","family":"Dong","sequence":"additional","affiliation":[{"name":"Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"45599","DOI":"10.1038\/s41598-025-29616-9","article-title":"Changes in spectrum of respiratory pathogens infections among hospitalized patients post COVID-19 pandemic in Jinan, Shandong Province","volume":"15","author":"Li","year":"2025","journal-title":"Sci Rep"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1186\/s12890-025-04026-9","article-title":"Epidemiology of severe acute respiratory infections in South Korea: a nationwide surveillance study","volume":"25","author":"Kang","year":"2025","journal-title":"BMC 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