Abstract: Objective To investigate the effect of herpesvirus infection on the clinical prognosis and the microbiota of the lower respiratory tract in patients with severe pneumonia. Methods According to the results of metagenomic next-generation sequencing(mNGS), 114 patients with severe pneumonia hospitalized in ICU were divided into herpesvirus-positive group and herpesvirus-negative group. The basic demographic and clinical characteristics were collected. Differences between the two sets of information were compared using the independent samples t test, Mann-Whitney U test, and χ2 test. Cox regression model was used to analyze the factors affecting prognosis. Kaplan-Meier method was used to conduct the survival analysis, and the Log-Rank test was applied to compare survival curves. Histograms and heat maps were generated to illustrate the differences in the lower respiratory tract microbiota between the two groups. Results The acute physiololgy and chronic health evaluation(APACHE II)score of the herpesvirus-positive group was higher than that of the negative group, and the difference was statistically significant(Z=-2.260, P=0.024). There were no significant differences in other clinical characteristics. Herpesvirus infection was an independent risk factor affecting the clinical prognosis of patients with severe pneumonia. The 30-day mortality rate of the herpesvirus-positive group was higher than that of the herpesvirus-negative group(44.64 % vs. 27.57 %, χ2=4.040, P=0.044), with a statistically significant difference. The 30-day mortality rate of herpes simplex virus-1(HSV-1),Epstein-Barr virus(EBV)and cytomegalovirus(CMV)positive groups were higher than that of the corresponding herpesvirus-negative groups, with a statistically significant difference(χ2=3.982, P=0.046; χ2=4.991, P=0.025; χ2=6.791, P=0.009). There were observable differences in the distribution of microbial flora between the herpesvirus-positive and herpesvirus-negative groups, with a distinct predominance of certain species in each group. The herpesvirus-positive group showed a higher likelihood of co-occurrence with pathogens such as Corynebacterium striatum, Legionella pneumophila, Aspergillus and Pneumocystis japonicus. Conclusion Herpesvirus infection is an independent risk factor for the clinical prognosis of patients with severe pneumonia, and is closely associated with the 30-day mortality of patients with severe pneumonia, particularly the presence of HSV-1, EBV, and CMV, which correlate with increased 30-day mortality rates. Furthermore, patients with severe pneumonia who were positive for herpesviruses tend to have a higher presence of conditional pathogenic bacteria in their respiratory tracts, suggesting that herpesviruses may influence disease prognosis by altering the microbiota.

Key words: Severe pneumonia, Herpesvirus infection, Lower respiratory tract microbiota, 30-day mortality, Metagenomic next-generation sequencing