Viral Pneumonia is Associated with Increased Risk and Earlier Development of Post-Inflammatory Pulmonary Fibrosis

Severe inflammatory response, acute respiratory distress syndrome, and death are established serious consequences of the acute phase of severe viral pneumonia. However, the long-term respiratory outcomes of severe viral pneumonia, including its association with pulmonary fibrosis, are less known. ObjectiveTo determine whether viral pneumonia is associated with an increased incidence of post-inflammatory pulmonary fibrosis. DesignWe performed two retrospective observational cohort studies using longitudinal hospitalization records from the States of California (2005-2011) and Florida (2009-2015) for the discovery and validation studies, respectively. Patients who were 85-years-old and younger with at least two hospital encounters but without a prior diagnosis of pulmonary fibrosis were included. International Classification of Diseases-9 (ICD9) codes of primary and secondary diagnoses and procedures were used to identify the exposure: diagnosis of viral pneumonia; the outcome: incidence of post-inflammatory pulmonary fibrosis [PIPF, ICD9: 515]; and the confounders. MethodsChronological age was used as the study time scale. Non-parametric Kaplan-Meier (KM) estimator and semiparametric Cox Proportional Hazard modelling were used to assessing the risk of PIPF. P-values < 10-3 were considered significant. ResultsAmong 9,802,565 patients from California and 8,741,345 patients in Florida cohorts, the prevalence of PIPF was 0.61% and 0.62% over 7 and 6.75 years, respectively. Patients with incident PIPF were older than those without [68(SD: 11) vs. 40(22) years]; among patients with PIPF, those with viral pneumonia diagnosis were younger than those without [63(12) versus 68(11) years]. Incidence of PIPF was higher for those with viral pneumonia diagnosis versus those without [1.6 (CI:1.51-1.69) vs. 0.91 (CI:0.86-0.96)] cases per 1000 person-years in California and in Florida [1.11 (CI:1.06 -1.16) vs, 0.93 (CI:0.89-0.98)]. Viral pneumonia was associated with increased risk of incident PIPF in both California aHR = 1.49 (1.38, 1.61), and Florida aHR of 1.26 (1.20, 1.33) cohorts (Table). Among patients who developed PIPF, the median time to diagnosis was 7.41 (6.16 -8.66) and 4.80 (4.34 - 5.26) years earlier for patients with viral pneumonia versus without in California and Florida cohorts. The association of viral pneumonia was not found for idiopathic pulmonary fibrosis [ICD9: 516.3]. Our findings suggest that patients hospitalized with viral pneumonia may have long term respiratory sequela that is often overlooked and suggest a need for additional studies focusing on phenotyping susceptible patients. This finding is especially important in light of the current COVID-19 pandemic because viral pneumonia is the most common manifestations of the disease, which could lead to subsequent fibrosis. O_TBL View this table: org.highwire.dtl.DTLVardef@90feb1org.highwire.dtl.DTLVardef@141251dorg.highwire.dtl.DTLVardef@1ebce08org.highwire.dtl.DTLVardef@238cedorg.highwire.dtl.DTLVardef@1f93031_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable:C_FLOATNO O_TABLECAPTIONFrequency of Viral Pneumonia and Post Inflammatory Pulmonary Fibrosis and confounders in the California and Florida cohorts, Incidence, Attributable Risk in the population and patients exposed to Viral Pneumonia in California and Florida cohorts are presented along with Risk Ratio, Univariate and multivariable Cox model hazard ratios. C_TABLECAPTION C_TBL