This retrospective study was conducted at the Second Affiliated Hospital of Hainan Medical University, a large, comprehensive, tertiary Grade A hospital that integrates medical care, teaching, research, rehabilitation, and preventive healthcare. The hospital’s organ transplant center is capable of independently performing transplants of major organs such as the heart, liver, lungs, kidneys, and pancreas, completing approximately 200 organ transplant surgeries each year.

Participants were diagnosed with COVID-19 based on a positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 from throat swab specimens or next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF). Infection severity was categorized as mild, moderate, severe, or critical, with criteria defined as follows (Yang et al., 2020): (1) Mild: no findings of pneumonia on HRCT and presence of mild clinical symptoms; (2) Moderate disease: HRCT manifestations compatible with viral pneumonia and presence of respiratory symptoms and fever; (3) Severe: respiratory rate ≥30 beats per minute or respiratory distress, O₂ saturation ≤93% in a resting state, or oxygen concentration (FiO₂) or partial pressure of arterial blood oxygen (PaO₂) ≤300 mmHg; (4) Critical: respiratory failure requiring mechanical ventilation (MV), shock, or other organ failure requiring ICU admission and monitoring.

This retrospective study aimed to statistically analyze demographic data, clinical symptoms, laboratory results, and short-term prognosis of KTRs with COVID-19 pneumonia. The objective was to provide data support for the standardization of treatment for post-transplant COVID-19 pneumonia and to assess the extent of harm to KTRs during the current wave of the pandemic. All KTRs included in this study signed informed consent forms, and the study was approved by the Ethics Committee of the Second Affiliated Hospital of Hainan Medical University (Approval Number: 2024-KCSN-02).

The immunosuppression adjustment strategy was based on recommendations from Descartes (Maggiore et al., 2020), while general management strategies were derived from guidelines published by our health ministry (National Health Commission, 2023). Due to limited availability, not all KTRs received antiviral treatment; some were administered paxlovid, and others molnupiravir. The choice of antiviral medication was influenced by availability rather than the severity of infection.

Clinical information of KTRs, including the transplantation vintage, gender, age, BMI, number of kidney transplants, vaccine doses, clinical symptoms, SpO2 at admission, antiviral drugs used, pathogen types, underlying diseases, viral shedding time, rejection reactions, and other relevant information were recorded. We also included laboratory indicators at admission, including C-reactive protein (CRP), procalcitonin (PCT), cystatin C, D-dimer (DDP), blood cell counts, and baseline creatinine. RT-PCR assay using the Novel Coronavirus (2019-nCoV) nucleic acid diagnostic kit PCR-Fluorescence Probing (DaAn Gene Co., Ltd, Guangzhou, China) was performed according to the manufacturer’s instructions. Reactions were completed with the Cap Fluorescent Quantitative Polymerase Chain Reaction detection system (FQD-96A). A Ct value less than 35 on either open reading frame (ORF) and/or nucleocapsid protein (N) genes is considered positive.

Stable kidney function was defined as a stable serum creatinine level within the follow-up and no apparent abnormalities in transplant kidney ultrasound. COVID-19 pneumonia was identified by positive pharyngeal swab or BALF NGS tests, combined with typical chest CT imaging changes. Typical chest CT changes for COVID-19 pneumonia included peripheral or peripheral and central ground glass opacities (GGOs) in the early phase. As the disease progressed, GGOs with a crazy-paving appearance and consolidations were evident along with subpleural and parenchymal bands. There was also a predominance of architectural distortion; in the peak stage, these findings had progressed, while the later stage demonstrated their resolution (Brogna et al., 2023).

Follow-up continued until death, graft failure, or the cutoff date (October 31, 2023). This involved monitoring nucleic acid conversion time, serum creatinine, total lymphocyte count, serum albumin, and other factors when the KTRs were admitted to our hospital. Post-discharge, outpatient follow-ups occurred weekly for the first three months, then bi-weekly for the subsequent three months. Comprehensive case data were maintained throughout the follow-up process, with no loss to follow-up.

All patients underwent pulmonary CT examinations when admitted to the hospital (Ai et al., 2020). The pulmonary CT scans were evaluated by two experienced radiologists. Consensus was achieved through discussion in instances of scoring disagreement, and the duration of manual CT scoring completion by the two physicians was documented. In each of the five lung lobes, a CT severity score was assigned based on the degree of involvement: 0 point for no involvement, 1 point for <5% involvement, 2 points for 5–25% involvement, 3 points for 26–50% involvement, 4 points for 50–75% involvement, and 5 points for over 75%. The total CT severity score was the sum of the scores of all five lung lobes, ranging from 0 (no involvement) to 25 (maximum involvement) (Monfared et al., 2021).

Allograft dysfunction and death were considered as negative indicators.

Data are presented as mean ± standard deviation (SD) or median ± interquartile range (IQR), according to normality. The continuous variables were compared using t-test or Mann-Whitney U test. Categorical data were compared using the Fisher’s exact test and t -tests, as appropriate. All statistical analyses were conducted using IBM SPSS Version 23. p < 0.05 was considered statistically significant.Significance was adjusted post hoc, using Bonferroni’s correction, to reduce the chance of a type I error occurring. The threshold for significance was adjusted from p<0.05 to p<0.0167 as multiple analyses were conducted with effect of antiviral drugs use duration on viral shedding time and efficacy on COVID-19 pneumonia between the different antiviral drugs.

This study comprised 64 individuals who had undergone their initial kidney transplant and were diagnosed with concurrent COVID-19 pneumonia. Among these individuals, there were 45 males and 19 females, with ages ranging from 15 to 82 years and an average age of 47.11 ± 13.47 years. The duration between kidney transplantation and onset of COVID-19 pneumonia varied from 1 month to 264 months, with an average of 41.41 ± 48.05 months. It is noteworthy that only 5 cases had received COVID-19 vaccination, while the remaining individuals were unvaccinated. Fever was reported as the first symptom in 51 (79.7%) of the cases. Cough was present in 57 (89.1%) patients, followed by muscle pain in 30 (46.9%) and diarrhea only in 4 patients. Additionally, 30 cases had respiratory distress, accounting for 46.9% of the total. Among the patients, 26 were classified in the severe group, with the remainder classified in the moderate group (n=38). Significant differences were observed in age, CT score, ICU admission or intubation, length of stay, CRP at admission, albumin levels at admission between severe and moderate COVID-19 patients (P<0.05). There were no statistically significant differences in the other indicators. The specific data are indicated in Table 1 .

The study evaluated the impact of antiviral drug timing on viral shedding time, corrected by subtracting the duration of drug use from the total shedding time. Out of the 64 participants, 24 did not utilize antiviral drugs, while 10 used them within 1–5 days, and 30 used them for over 5 days. The corrected viral shedding times for these groups were 19.46 (95% CI, 17.19–21.73) days, 12.10 (95% CI, 7.62–16.58) days, and 13.57 (95% CI, 10.82–16.31) days, respectively, indicating a statistically significant difference of three groups (P=0.002). However, there was no statistically significant distinction observed between 1–5 days and over 5 days groups (P=0.539). The three groups demonstrated consistency in various baseline characteristics, including gender, age, transplantation vintage (Interval time between kidney transplantation and onset of COVID-19 pneumonia), hypertension, diabetes, coronary heart disease, BMI, CT score, baseline creatinine, WBC at admission, lymphocyte counts on admission, albumin on admission, CRP, and PCT at admission, with no statistically significant differences observed, as shown in Table 2 .

Among the 64 recipients, 24 individuals did not receive antiviral drugs, 10 received molnupiravir, and 30 received paxlovid. The corrected viral shedding times for these groups were 19.52 (95% CI, 17.15–21.89) days, 14.70 (95% CI, 9.74–19.66) days, and 12.87 (95% CI, 10.28–15.46) days, respectively, displaying a statistically significant difference (P=0.002). The three groups demonstrated consistency in various baseline characteristics, including gender, age, transplantation vintage, hypertension, diabetes, coronary heart disease, BMI, CT score, baseline creatinine, albumin on admission, WBC at admission, CRP, and PCT at admission, with no statistically significant differences observed. The detailed results are shown in Table 3 .

Upon admission, a total of 31 recipients underwent NGS testing. Among these recipients, 30 specimens were obtained from BALF, one from blood, and another from sputum. Bacterial infections were identified in 20 specimens, including Staphylococcus argenteus, Acinetobacter baumannii, Pseudomonas aeruginosa, Tropheryma whipplei, Klebsiella pneumoniae, Streptococcus pneumoniae, Enterococcus faecalis, Escherichia coli, Hemophilus influenzae, Pseudomonas maltophilia, and Legionella pneumophila. Additionally, fungal infections, including Aspergillus flavus, Candida albicans, Pneumocystis jirovecii, Aspergillus fumigatus, Candida parapsilosis, and Candida tropicalis, were detected in 14 specimens. Furthermore, 11 specimens exhibited co-infection with Human betaherpesvirus 5. Notably, a significant proportion of recipients, accounting for 77.4% (24 out of 31), presented with mixed infections, involving bacteria or fungi in conjunction with COVID-19 pneumonia.

Four patients died within 6 months of follow-up, and 1 had kidney allograft dysfunction. A comparison of baseline creatinine (176.63 ± 149.62 μmol/L) and creatinine at 6 months (153.46 ± 76.25 μmol/L) in the remaining 59 recipients showed no statistically significant difference (P=0.173).

Our study reveals that fever (79.7%) and cough (89.1%) persist as the most prevalent clinical symptoms of post-transplant COVID-19 pneumonia, with an elevated occurrence compared with general population and exclusively COVID-19 infected KTRs (Belsky et al., 2021; Monfared et al., 2021). Furthermore, this study demonstrates higher incidence rates of muscle pain and shortness of breath compared to previous literature reports (Akalin et al., 2020). The different results may be attributed to the differences in patients enrollment and population selection. In our study, the incidence of diarrhea was 6.25%, which aligns with the findings of Monfared et al (Monfared et al., 2021). All participants in our study discontinued Mycophenolate Mofetil (MMF) and either reduced or stopped Calcineurin Inhibitors (CNI) based on the severity of infection. The duration of immunosuppressive drug discontinuation ranged from 6 to 33 days, with a median of 6 days (refer to Supplementary Materials for further details). However, no instances of acute rejection were observed in KTRs, potentially attributed to the increased utilization of corticosteroids during COVID-19 pneumonia treatment and the compromised immune systems of the patients (Maggiore et al., 2020; Monfared et al., 2021).

In our short-term follow-up of 64 KTRs with COVID-19 pneumonia, we observed no adverse events such as pulmonary embolism, possibly due to adequate administration of anticoagulant therapy and outpatient health education (Basic-Jukic et al., 2021). There were 1 patient had kidney allograft dysfunction, three died of COVID-19 pneumonia, and 1 dead of aspergillosis, resulting in an overall mortality and allograft dysfunction rate of 7.81% (5/64). Our findings suggest that personalized discontinuation of immunosuppressive drugs can be considered a safe and dependable approach for KTRs. In the present study, a significant statistical disparity was observed in the utilization of lung CT scans for the evaluation of moderate and severe COVID-19 pneumonia (P<0.05), thereby reinforcing the favorable contribution of lung CT scans in the assessment of this condition (Fields et al., 2020). Our data indicate no statistically significant difference (P=0.148) between the baseline mean serum creatinine levels (174.8 ± 150.3 μmol/L) and those at six months after discharge (149.9 ± 71.8 μmol/L), suggesting no detrimental impact of SARS-CoV-2 on transplant kidney function over six months. However, a marginal decline in mean serum creatinine levels at the six-month after discharge was observed, potentially attributable to compromised immunity in individuals previously afflicted with COVID-19 pneumonia (Zhu et al., 2020a; Cristelli et al., 2021), as well as reduced doses of CNI medications (Zhu et al., 2020b).

Our investigation revealed no noteworthy disparity in baseline creatinine levels between the moderate and severe COVID-19 pneumonia cohorts (P>0.05), aligning with the findings of Malinowska’s study (Malinowska et al., 2022). This suggests that the severity of SARS-CoV-2 does not exert an immediate influence on transplant kidney function, but rather manifests long-term consequences.

Our study revealed a significant correlation between the timing of antiviral drug administration and the effectiveness of treatment in KTRs with COVID-19 pneumonia (Hung et al., 2022; Sun et al., 2022). Individuals who received antiviral drugs within 1–5 days exhibited a shorter duration of viral shedding (12.10 days) compared to those who received antiviral drugs for over 5 days (13.57 days) or did not receive them at all (19.46 days). Both Paxlovid and Molnupiravir demonstrated similar efficacy in reducing viral shedding (12.87 ± 7.07 days vs. 14.70 ± 6.93 days), with Paxlovid exhibiting superiority over non-users (P<0.0167) (Park et al., 2023). However, the group receiving molnupiravir exhibited a shorter adjusted duration of viral shedding in comparison to the non-user group (14.70 ± 6.93 days vs. 19.52 ± 5.48 days), though this disparity did not reach statistical significance (P=0.055), likely due to the small sample size. During our short-term follow-up, we did not observe any immediate impact of antiviral medications on the functioning of the transplanted kidney, which aligns with the findings of Wen et al.’s investigation (Wen et al., 2022). Our data indicate that the early administration of antiviral drugs produces more favorable outcomes (Cegolon et al., 2023; Saravolatz et al., 2023).

The utilization of antibiotics in KTRs with COVID-19 pneumonia has been a subject of debate (Maggiore et al., 2020). In this retrospective investigation, we employed NGS technology to analyze a total of 31 specimens, revealing a notable prevalence of mixed infections (77.4%, 24/31), significantly higher than the general population rate of 26% (Pegoraro et al., 2023). The predominant bacteria were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Streptococcus pneumoniae (Antimicrobial Resistance C, 2022) Invasive fungal infections were also increasingly reported (Kanj et al., 2023). Mixed infections appear more common, emphasizing the necessity of judicious antibiotic prophylaxis. In comparison to conventional lung CT scans, the utilization of NGS detection enables the early detection of co-infections (Xu et al., 2023), thereby facilitating accurate clinical intervention and mitigating the inappropriate use of antibiotics. Regrettably, NGS does not encompass susceptibility testing, a feature commonly found in traditional pathogen detection methods. Nonetheless, the rapid and cost-effective generation of genome-scale sequence data associated with NGS presents a more comprehensive pathogen profile, thereby advancing our comprehension of real-world scenarios (Xuan et al., 2013).

Limitations exist with our study. First, this is a single-center, retrospective cohort study with a small sample size. Larger scale prospective studies are required to verify our findings. Second, the follow-up period was only six months, longer follow-ups and observations should be conducted in the future. Finally, the retrospective nature of the study introduced certain biases in the patient cohort structure.

Notwithstanding these constraints, our study demonstrates valuable insights into the management of KTRs with COVID-19 pneumonia. We observed that antiviral medications exhibit efficacy regardless of the disease stage, the early administration of prophylactic antibiotics is of utmost importance, and no infections or detrimental effects on graft function resulting from antiviral drugs were detected six months after recovery.