Background: Although coronavirus disease 2019 (COVID-19) is no longer classified as a Public Health Emergency of International Concern by World Health Organization, its global impact persists. Data on its impact in lung transplant recipients (LTRs) from China remain limited. This study aims to share clinical experiences and provide insights into managing LTRs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Methods: We conducted a study on LTRs with COVID-19 caused by the Omicron variant from November 17, 2022, to May 1, 2023. Clinical information was gathered retrospectively through electronic medical records, questionnaires, or follow-up telephone calls.

Results: A total of 227 LTRs were reviewed for infection with Omicron variant. After excluding 49 cases without confirmed SARS-CoV-2 infection, this left a final cohort of 178 infected LTRs, accounting for an infection rate of 78.4% (178/227). Of the patients, 50% (89/178) required hospitalization, with an average hospital stay of 16 days [interquartile range (IQR): 9.5–25.5 days]. Of the 89 hospitalized patients, 41.6% (37/89) eventually progressed to severe or critical disease, forming the severe/critical group (S/C group), while the remaining 58.4% (52/89) had mild or moderate disease (M/M group). In comparison to the M/M group, the S/C group had higher C-reactive protein (CRP) (59.6 vs. 16.8 mg/L, P<0.001), Erythrocyte sedimentation rate (45.5 vs. 22.5 mm/h, P=0.005) and D-dimer level (1.09 vs. 0.65 mg/L, P=0.01), but lower CD4⁺ T lymphocytes count (217 vs. 427 cells/µL, P=0.004). The S/C group had significantly higher rates of combined pulmonary bacterial infection (67.6% vs. 38.5%, P=0.006) and pulmonary fungal infection (73.0% vs. 38.5%, P=0.001) during the course of COVID-19, nearly double that of the M/M group. In a multivariate logistic analysis, elevated CRP (>41.8 mg/L), combined pulmonary fungal infection, and interstitial lung disease (ILD) as primary disease emerged as high-risk factors for developing the severe disease phenotype following Omicron variant infection in LTRs, with respective odds ORs values of 4.23 [95% confidence interval (CI): 1.68–11.23], 4.76 (95% CI: 1.59–15.64), and 5.13 (95% CI: 1.19–29.17). Receiver operating characteristic (ROC) curve analysis showed that CD4⁺ T lymphocyte count may be a strong marker for predicting death. At a cutoff of 404 cells/µL, sensitivity was 0.509, specificity 0.999, and area under the curve (AUC) was 0.806 (95% CI: 0.678–0.934). Ultimately, 13 recipients succumbed to COVID-19 related respiratory failure or secondary multiple organ dysfunction, resulting in an overall mortality rate of 7.3% (13/178).

Conclusions: LTRs are at high risk of secondary lung infections after Omicron. Key risk factors for severe disease include CRP >41.8 mg/L, ILD as primary disease, and pulmonary fungal infection. CD4+ T lymphocyte count may predict mortality risk in LTRs with COVID-19.

Keywords: Lung transplantation; Omicron; coronavirus disease 2019 (COVID-19); coronavirus; risk factor