Clinical features and outcomes in kidney transplant recipients with COVID-19 pneumonia: a single center retrospective cohort study

doi:10.21203/rs.3.rs-3931620/v1

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Clinical features and outcomes in kidney transplant recipients with COVID-19 pneumonia: a single center retrospective cohort study

https://doi.org/10.21203/rs.3.rs-3931620/v1

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Objective

This retrospective cohort study aimed to assess the clinical characteristics, treatment outcomes, and short-term prognosis of kidney transplant recipients (KTRs) with concurrent coronavirus disease 2019 (COVID-19) pneumonia.

Methods

KTRs with COVID-19 pneumonia who were admitted to our hospital from December 28, 2022, to March 28, 2023 were included in the study, and their clinical symptoms, response to antiviral medications, and short-term prognosis were analyzed.

Results

A total of 64 KTRs with initial diagnosis of COVID-19 pneumonia were included in this study. The primary symptoms were fever, cough, and myalgia, with an incidence of 79.7%, 89.1%, and 46.9%, respectively. The administration of antiviral drugs (paxlovid or molnupiravir) within 1–5 days and for over 5 days demonstrated a statistically significant reduction in viral shedding time compared to the group without antiviral medication (P = 0.002). Both the paxlovid and molnupiravir treatment groups exhibited a significantly shorter duration of viral shedding time in comparison to the group without antiviral drugs (P = 0.002). After 6 months of recovery, there was no significantly negative impact on transplant kidney function (P = 0.294).

Conclusion

Fever, cough, and myalgia remain common initial symptoms of concurrent COVID-19 pneumonia in KTRs. The earlier use of antiviral drugs (the paxlovid or molnupiravir) is associated with better therapeutic outcomes. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had limited impact on short-term renal function of the KTRs with concurrent moderate or severe COVID-19 pneumonia.

kidney transplant

COVID-19 pneumonia

antiviral drugs

prognosis

Throughout the duration of the four-year coronavirus disease 2019 (COVID-19) pandemic, the virus has inflicted catastrophic calamities upon individuals worldwide, resulting in the loss of thousands of lives [1]. Through extensive research and the accumulation of clinical cases over this period, efficacious treatment protocols for the general populace have been discerned [2, 3]. Regrettably, in comparison to the general population afflicted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), kidney transplant recipients (KTRs) manifest notably elevated frequencies of grave affliction (44% vs. 6.1%) and mortality (24–28% vs. 1.4–4.3%) [4]. Unfortunately, our comprehension of the optimal approach to effectively manage COVID-19 infection in KTRs remains limited [5].

As of early 2023, the Omicron variant continues to be the prevailing strain in China. Extensive domestic and international evidence indicates a notable decrease in the pathogenicity of the Omicron variant within the pulmonary system, resulting in a shift in clinical presentations from predominantly pneumonia to upper respiratory tract infections [6]. Consequently, our country's epidemic prevention strategy has been transformed from centralized isolation to a comprehensive opening. However, there exists a dearth of pertinent clinical researches pertaining to the effects of COVID-19 pneumonia on individuals who have undergone kidney transplantation, particularly in terms of post-treatment monitoring and evaluation. There exists a pressing necessity for novel scientific evidence to inform the formulation of treatment protocols and preventive measures that are specifically customized for individuals with compromised immune systems.

Therefore, this study endeavors to amass clinical data pertaining to KTRs who have contracted COVID-19 pneumonia and received treatment at our medical facility between December 2022 and March 2023. The objective is to examine their clinical attributes, diagnostic and therapeutic approaches, and prognosis, thereby furnishing indispensable clinical backing for the formulation of preventive strategies targeting immunocompromised populations.

Study setting

This retrospective study was conducted entirely at the Second Affiliated Hospital of Hainan Medical University. The Second Affiliated Hospital of Hainan Medical University is a large, comprehensive, tertiary Grade A hospital that integrates medical care, teaching, research, rehabilitation, and preventive healthcare. Its 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.

Study population

The diagnosis of COVID-19 infection was confirmed 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). The patients were categorized into groups of mild, moderate, severe, and critical based on the severity of the infection [7]. Criteria for judging the severity of the infection were as follows: (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: patients with any of the following evidence: 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: having any of the following evidence: occurrence of respiratory failure and requiring mechanical ventilation (MV), shock, and other organ failure requiring ICU admission and monitoring.

Study design

This retrospective study aimed to statistically analyze demographic data, clinical symptoms, laboratory results, and short-term prognosis of KTRs who were hospitalized due to 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 obtained approval from the Ethics Committee of the Second Affiliated Hospital of Hainan Medical University (Approval Number: 2024-KCSN-02).

Treatment plans

The immunosuppression adjustment strategy was based on recommendations from Descartes [8], while general management strategies were derived from guidelines published by our health ministry [6]. As a consequence of a pervasive scarcity of antiviral medications amidst the upsurge of the pandemic, a minority of KTRs had not received antiviral treatment; a fraction of them were administered paxlovid, while the remainder were subjected to molnupiravir. The determination of whether to administer antiviral medications or what kind of the antiviral medication were not contingent upon the gravity of the patient's condition or the duration of infection, but rather hinged upon the accessibility of medications during that period. Detailed information can be found in the supplementary materials.

Observation indicators

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: levels of lab tests 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). The determination of positive is the Ct value less than 35 on either open reading frame (ORF) and/or nucleocapsid protein (N) genes.

Stable kidney function was defined as a stable serum creatinine level within the follow-up and no apparent abnormalities in transplant kidney ultrasound.

For COVID-19 pneumonia, we defined it as a positive result in the pharyngeal swab test for SARS-CoV-2 nucleic acid or positive results in NGS testing of BALF, 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 [9].

Follow-up for the entire study population 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.

Radiographic scores

All patients underwent a pulmonary CT examination when admitted to the hospital, as it is highly sensitive for diagnosing COVID-19 pneumonia [10]. The pulmonary CT scans were evaluated by two radiologists with over 10 years of experience each. 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).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) [11].

Outcome measures

Allograft dysfunction and death were considered as negative indicators.

Statistical analysis

Data are presented as mean ± standard deviation (SD) or median ± interquartile range (IQR), according to normality. The continuous variables were compared using a 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.

Comparison of clinical characteristics between moderate and severe COVID-19 pneumonia patients

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 by informants as the first symptom in 51 (79.7%) of the cases. Cough was present in 57 (89.1%) patients, muscle pain was present in 30 (46.9%) patients, and diarrhea was only present in 4. 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). Age, CT score, ICU admission or intubation, length of stay, CRP at admission, albumin levels at admission of severe group were all higher than the moderate COVID-19 patients with a statistically significant (P < 0.05). There were no statistically significant differences in the other indicators. The specific data are indicated in Table 1.

Table 1

Comparison of clinical features of COVID-19 between moderate disease and severe disease
	Moderate (n = 38)	Severe (n = 26)	P value
Gender (Male)	24	21	0.216
Age (years)	43.97 ± 11.92	51.9 ± 14.50	0.023
Interval time between kidney transplantation and onset of COVID-19 pneumonia (months)	39.97 ± 39.49	43.50 ± 59.18	0.776
BMI	21.46 ± 2.67	22.47 ± 3.20	0.179
COVID-19 vaccination	4	1	0.614
Hypertension	21	19	0.237
Diabetes	7	7	0.617
Coronary heart disease	4	6	0.314
CT score	6.84 ± 3.15	15.62 ± 4.10	0.000
WBC on admission (10⁹/L)	5.38 ± 3.22	6.86 ± 3.92	0.104
Lymphocyte counts on admission (10⁹/L)	0.58 ± 0.52	0.61 ± 0.37	0.776
Platelets on admission	186.42 ± 58.54	182.77 ± 72.67	0.825
DDP on admission	0.84 ± 1.55	1. 71 ± 2.07	0.061
CRP on admission (mg/L)	32.60 ± 58.23	71.58 ± 56.49	0.012
PCT on admission (ng/mL)	0.55 ± 1.81	1.89 ± 4.89	0.189
Albumin on admission (g/dL)	39.7 ± 3.7	36.6 ± 6.2	0.014
Baseline creatinine (mg/dL)	179.6 ± 171.1	207.9 ± 151.5	0.498
Viral shedding time (days)	12.9 ± 6.7	17.5 ± 9.9	0.030
Hospital admissions (days)	8.90 ± 3.79	17.54 ± 10.94	0.001
Intubated or admitted to the ICU	0	4	0.024
Data are presented as average ± SD or numbers. WBC, white cell counts; DDP, D-dimer; CRP, C-reaction protein; PCT, procalcitonin.

Effect of antiviral drugs use duration on the viral shedding time of COVID-19 pneumonia patients

The effectiveness of antiviral drug timing in this study was assessed based on the corrected viral shedding time, which is determined by subtracting the duration of antiviral drug use from the overall viral shedding time. Out of the 64 participants, 24 did not utilize antiviral drugs, while 10 used them within a period of 1–5 days, and 30 used them for over 5 days. The corrected viral shedding times for these groups were found to be 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 the use of antiviral drugs within 1–5 days and for over 5 days (P = 0.339). 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. Table 2 demonstrates the specific results.

Table 2

Comparison of clinical features between the patients who did not receive antiviral drugs, used antiviral drugs within 1–5 days and used antiviral drugs over 5 days.
	None (n = 24)	1–5 days (n = 10)	> 5 days (n = 30)	P value
Viral shedding time (days)	19.46 ± 5.37	12.10 ± 6.26	13.57 ± 7.34	0.002
Interval time between kidney transplantation and onset of COVID-19 pneumonia (months)	47.54 ± 40.97	25.00 ± 34.62	41.97 ± 56.46	0.465
Gender (Male)	16	7	22	0.932
Hypertension	14	5	21	0.449
Diabetes	6	1	7	0.722
Coronary heart disease	5	3	2	0.139
Age (years)	48.79 ± 14.31	42.20 ± 14.17	47.40 ± 12.59	0.431
BMI	21.73 ± 3.17	21.65 ± 3.37	22.06 ± 2.62	0.889
CT score	9.46 ± 5.60	8.50 ± 4.67	11.80 ± 5.70	0.157
Baseline creatinine (mg/dL)	150.79 ± 102.01	209.47 ± 196.34	217.15 ± 187.63	0.311
WBC on admission (10⁹/L)	5.72 ± 0.36	6.97 ± 5.94	5.86 ± 3.40	0.633
Lymphocyte counts on admission (10⁹/L)	0.50 ± 2.43	0.48 ± 0.23	0.70 ± 0.57	0.239
CRP on admission (mg/L)	49.86 ± 71.14	45.37 ± 44.16	48.67 ± 57.9	0.981
PCT on admission (ng/mL)	1.04 ± 2.49	0.33 ± 0.13	1.39 ± 4.53	0.706
Albumin on admission (g/dL)	38.13 ± 5.16	39.59 ± 4.63	38.25 ± 5.23	0.731
Data are presented as average ± SD or numbers. WBC, white cell counts; CRP, C-reaction protein; PCT, procalcitonin.

Efficacy on COVID-19 pneumonia between the different antiviral drugs

Utilizing the corrected viral shedding time as a measure of antiviral drug efficacy, 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.

Table 3

Treatment effect of different antiviral drugs on COVID-19.
	None (n = 24)	Molnupiravir (n = 10)	Paxlovid (n = 30)	P value
Viral shedding time (days)	19.52 ± 5.48	14.70 ± 6.93	12.87 ± 7.07	0.002
Interval time between kidney transplantation and onset of COVID-19 pneumonia (months)	47.2 ± 41.9	50.9 ± 88.0	101.8 ± 206.9	0.490
Gender (Male)	16	6	23	0.500
Hypertension	14	8	18	0.539
Diabetes	6	1	7	0.722
Coronary heart disease	5	0	5	0.386
Age (years)	48.35 ± 14.47	45.60 ± 16.07	46.68 ± 12.16	0.488
BMI	21.54 ± 3.10	21.86 ± 3.66	22.12 ± 2.57	0.764
CT score	9.52 ± 3.10	13.00 ± 5.56	10.23 ± 5.45	0.307
Baseline creatinine (mg/dL)	153.74 ± 103.25	223.40 ± 190.32	208.33 ± 187.78	0.765
WBC on admission (10⁹/L)	5.79 ± 2.45	6.80 ± 3.91	5.6 ± 4.17	0.793
CRP on admission (mg/L)	51.84 ± 72.16	74.18 ± 77.23	37.27 ± 39.70	0.401
PCT on admission (ng/mL)	1.08 ± 2.54	1.24 ± 2.78	1.05 ± 4.23	0.995
Albumin on admission (g/dL)	38.04 ± 5.26	38.30 ± 4.84	38.73 ± 5.13	0.400
Data are presented as average ± SD or numbers. WBC, white cell counts; CRP, C-reaction protein; PCT, procalcitonin; Cr, creatinine.

Pathogen spectrum of KTRs with COVID-19 pneumonia

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.

Short-term prognosis of KTRs with COVID-19 pneumonia

Four patients died within the study period of 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).

Following an extensive four-year investigation into the SARS-CoV-2 and its ongoing mutations resulting in reduced virulence, the World Health Organization (WHO) officially announced on May 5, 2023, that the prevailing COVID-19 pandemic no longer qualified as a global public health emergency. Nevertheless, the WHO emphasized that although SARS-CoV-2 would not disappear entirely, it would endure in the long run and continue to affect the human population. Presently, there is limited research on the prognosis of KTRs concerning SARS-CoV-2. During our discussions, we have placed particular emphasis on four significant clinical concerns, in addition to the typical clinical characteristics and prognoses of KTRs.

Clinical Data

Our study reveals that fever (79.7%) and cough (89.1%) persist as the most prevalent clinical symptoms of post-transplant COVID-19 pneumonia, which had an elevated occurrence compared with general population and exclusively COVID-19 infected KTRs [11, 12]. Furthermore, this study demonstrates higher incidence rates of muscle pain and shortness of breath compared to previous literature reports [13]. The different results may be attributed to the patients enrolled and population selection. In our study, the incidence of diarrhea was found to be 6.25%, which aligns with the findings of Monfared et al. [11]. Furthermore, all participants in our study discontinued the use of Mycophenolate Mofetil (MMF) and either reduced or completely stopped the administration of Calcineurin Inhibitors (CNI) based on the severity of the 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 [8, 11].

In comparison to existing literature, our study conducted a short-term follow-up on a cohort of 64 KTRs who were infected with COVID-19 pneumonia. Notably, no instances of adverse events such as pulmonary embolism were observed, which may be attributed to the adequate administration of anticoagulant therapy and outpatient health education provided to the recipients [14]. 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). Consequently, 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 [15]. 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 in comparison to the baseline was observed, potentially attributable to compromised immunity in individuals previously afflicted with COVID-19 pneumonia [16, 17], as well as reduced doses of CNI medications [18], thereby mitigating CNI-related harm to the transplanted kidney.

Association of severe pneumonia with worsened transplant kidney function

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 [19]. 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.

Impact of antiviral drug duration and efficacy

Our study revealed a significant correlation between the timing of antiviral drug administration and the effectiveness of treatment in KTRs with COVID-19 pneumonia [20, 21]. Individuals who received antiviral drugs for a duration of 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, two different antiviral drugs, 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 < 0.05) [22]. However, within our retrospective cohort, 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), although this disparity did not reach statistical significance (P = 0.055), likely due to the smaller sample size of the molnupiravir group. 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 [23]. Our data indicate that the early administration of antiviral drugs produces more favorable outcomes, as their utilization proves to be more effective than abstaining from their use [24, 25].

Antibiotic use in KTRs with COVID-19 pneumonia

The utilization of antibiotics in individuals who have undergone kidney transplantation and are also afflicted with COVID-19 pneumonia has been a subject of debate [8]. In this retrospective investigation, we employed NGS technology to analyze a total of 31 specimens, comprising BALF(29 cases), sputum (1 case), and blood (1 case). The results revealed a notable prevalence of mixed infections (24/31), amounting to 77.4%, which significantly exceeds the observed rate of 26% in the general population [26]. The predominant bacteria were Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Streptococcus pneumoniae [27]. In addition to mixed infections caused by bacteria, invasive fungal infections were also increasingly reported [28], which is in concordance with this study. The diagnosis and treatment of pulmonary fungal infections has always been challenging for renal transplant recipients. In KTRs, 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 [29], 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 [30].

Limitations exist with our study. First, this is a single-center retrospective cohort study with a small sample size. Therefore, 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 greatest limitation of our study is that this is a retrospective study, and the patient cohort structure has a certain bias.

Notwithstanding these constraints, our examination demonstrates that among individuals who have undergone kidney transplantation and contracted COVID-19 (moderate or severe) pneumonia, the following findings were observed: 1) antiviral medications exhibit efficacy regardless of the disease stage; 2) the early administration of prophylactic antibiotics is of utmost importance; 3) no instances of infections or detrimental effects on graft function resulting from antiviral drugs were detected six months after recovery.

Data Availability

The data of metagenomic next-generation sequencing for this study have been deposited at National Genomics Data Center under BioProject number PRJCA022994.

Acknowledgments

The authors would like to thank all members of the co-author and patient involved in this article.

Author Contributions

HJ, JX and YW designed the study. LX, XC and XY draft and revised the manuscript. JW initially analyzed the data. LX,SC, MY, ZY and RC collected patient data and administered therapy. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and the writing of the paper.

Funding

This work was supported by the project supported by Hainan Province Clinical Medical Center and Hainan Province Health industry scientific research project (No. 21A200275).

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Clinical features and outcomes in kidney transplant recipients with COVID-19 pneumonia: a single center retrospective cohort study

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