Skip to main content
Download PDF

Outcomes of COVID-19 in 24 hospitalized liver transplant recipients: an observational study

BMC Infectious Diseases volume 24, Article number: 1019 (2024) Cite this article

Abstract

Background

Although liver transplant (LT) recipients are considered a population at risk of severe features of coronavirus disease 2019 (COVID-19), data in this regard are scarce and controversial. In this study, we reported the outcome of 24 cases of LT recipients who were hospitalized due to COVID-19 and investigated the role-playing factors in the severity of the disease.

Methods

In this single-center, analytic case-series study, eligible patients were among LT recipients who were hospitalized due to the diagnosis of COVID-19 based on positive results of polymerase chain reaction. Participants were categorized as severe COVID-19 if they were admitted to the intensive care unit, experienced respiratory failure demanding mechanical ventilation, or eventually died. Demographic and clinical data, COVID-19 symptoms and specific treatments, laboratory biomarkers, and immunosuppressive regimens and their alteration during the admission were recorded. Analysis was done using SPSS software.

Results

Twenty-four hospitalized LT patients were included, of which nine had severe and fifteen had non-severe COVID-19. Out of 9 patients with severe COVID-19, four sadly died. The analysis and comparison between the two groups revealed longer hospital stays (P = 0.02), lower lymphocyte counts (P = 0.002), and higher levels of C-reactive protein (CRP) (P = 0.006) in patients with severe COVID-19. Patients with non-severe COVID-19 had higher doses of tacrolimus and mycophenolate in their baseline immunosuppressive regimen (both P = 0.02).

Conclusion

Lymphopenia and high CRP levels are associated with more severe forms of COVID-19 in LT patients. Mycophenolate may have protective properties against severe COVID-19. The role of severity indicators in LT patients with COVID-19 needs to be systematically recognized.

Peer Review reports

Introduction

Severe acute respiratory syndrome coronavirus-2 (SARS‑CoV‑2) is responsible for coronavirus disease 2019 (COVID-19) which was declared a pandemic by Word Health Organization (WHO) On 11 March 2020. COVID-19 presentations vary from mild flu-like symptoms to more severe forms and life-threatening conditions such as multi-organ failure (MOF) and acute respiratory distress syndrome (ARDS) [1]. Notably, certain demographic groups, including the elderly, males, individuals with underlying disorders including hypertension and diabetes, and those with immune dysfunction, are at higher risk of experiencing severe features of COVID-19 [2].

Current evidence suggests the cytokine storm as the key underlying mechanism attributed to the severe COVID-19, characterized by the unleased production of inflammatory cytokines such as IL-1, IL-6, and TNF-α [3]. Following the invasion of SARS‑CoV‑2 to respiratory epithelial cells, it provokes the synthesis of proinflammatory cytokines in an uncontrolled manner leading to cytokine storm and subsequent deleterious events such as MOF and ARDS [3, 4].

As liver transplant (LT) recipients undergo lifelong immunosuppression, they should be under special consideration due to impaired immunity [5]. Remarkably, multiple studies have indicated that LT recipients do not necessarily face a higher risk of COVID-19 infection or associated complications and mortality compared to the general population [6,7,8,9]. Evidence also indicates that chronic treatment with immunosuppressive agents in LT recipients may inhibit the inflammatory cascade and cytokine storm, potentially preventing severe forms of COVID-19 [10]. Nonetheless, immunosuppressives may prolong the replication phase of virus infections, increase the viral load, and delay the full recovery [10, 11]. In a meta-analysis in 2021, the comparison of mortality rates between 610 LT recipients and 239,704 non-LT patients with COVID-19 from 4 studies revealed no significant difference (odds ratio [OR] = 0.8, p = 0.14). Although the hospitalization rate was reported higher in LT recipients compared to non-LT patients (OR = 1.99, p < 0.001), the ICU admission rates were almost similar (OR = 1.35, p = 0.55) [8].

Some studies have tried to investigate the contributing factors to the prognosis and severity of COVID-19 in LT recipients, including demographic characteristics, blood biomarkers, comorbidities, and immunosuppressive regimens [1, 11, 12]. High levels of C-reactive protein (CRP) and IL-6 and low absolute lymphocyte count, as well as older age and concomitant diabetes and hypertension, have been shown to be significantly associated with worse outcomes of COVID-19 in LT recipients [11, 12].

However, the role of immunosuppressives in LT recipients with COVID-19 has been a matter of debate. Although the use of calcineurin inhibitors (CNIs) is generally accepted and seemingly not associated with worse outcomes [13], Colmenero et al. declared that mycophenolate mofetil may increase the risk of severe COVID-19 and they encouraged mycophenolate withdrawal or switching to CNIs [11]. Similarly, Forns and colleagues recommended mycophenolate withdrawal in LT patients with COVID-19 at any stage of the disease [14]. On the other hand, in a study in India, the administration of open-label mycophenolate 360 mg daily for a month in patients with COVID-19 was associated with a significant reduction in mortality and hospital stay [15]. Furthermore, the anti-viral effect of mycophenolate against SARS‑CoV‑2 has been observed in an in vitro study [16].

In spite of current findings, the role of immunosuppression and other clinical/laboratory parameters in the outcome of COVID-19 in LT recipients is not systematically recognized and demands further investigations. In this case-series study, we explored the outcomes of 24 LT patients who were hospitalized due to COVID-19. Additionally, we have investigated the potential contributing factors to the severity of COVID-19 among our LT patients.

Methods

This is a single-center, analytic case series study conducted at Firouzgar University Hospital in Tehran, Iran. The transplantation unit of Firouzgar Hospital began liver transplantation in July 2019. Eligible participants were adult (above 16 y/o) LT recipients who were hospitalized due to COVID-19, from July 2020 to July 2022, at Firouzgar Hospital. The diagnosis of COVID-19 was based on a positive result of real-time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) for SARS‑CoV‑2, from the nasopharyngeal swab. Patients were admitted to the hospital at the discretion of an infectious disease specialist based on clinical status and laboratory findings. All 24 patients have had their liver transplantation at Firouzgar Hospital and have been under lifelong surveillance by the transplant unit. All transplant recipients undergo life-long monitoring through regular visits and laboratory check-ups by the transplant team and physicians. Furthermore, patients are well-instructed to inform the transplant team in case of emerging any medical conditions. All data regarding each patient were accessible in electronic or physical files and were extracted by the research team. We made phone calls to patients or their reliable relatives in case of missing information/data in their hospital medical files.

We recorded demographic/clinical data, laboratory parameters, vaccination history, underlying diseases, etiology of liver damage, interval since transplantation, immunosuppressive regimen at baseline and during admission with adjustments, and COVID-specific treatments for all patients. Vaccinated patients were among those who received at least one dose, prior to the COVID-19 infection, of one of the WHO-approved vaccines available in Iran. Based on the severity of COVID-19 patients were classified into severe and non-severe groups. Patients who were admitted to the intensive care unit (ICU), experienced acute respiratory distress syndrome (ARDS) requiring mechanical ventilation, or eventually expired have been classified as severe. This classification of severity has been supported by previous studies [11]. The primary endpoint of our study was to report the outcome of COVID-19 in our patients. The assessment and comparison of clinical/laboratory findings in our patients in severe and non-severe COVID-19 groups were the secondary endpoints.

Statistical analysis

Qualitative variables are reported as frequencies and continuous variables are expressed as mean ± SD or median as needed. The analysis of categorical variables or proportions was done using Fisher’s exact test. For continuous variables, we performed independent samples T-test or Mann-Whitney U-test depending on the normality of data distribution. Statistical analysis was performed using IBM SPSS Statistics 18.0 (SPSS, Inc., Chicago, IL, USA). The significance level in all tests is P-value < 0.05.

Results

All 24 participants were Iranian adult liver transplant recipients with a positive PCR for SARS-CoV-2. Participants were between 17 and 68 y/o with a mean age of 48.29 ± 13.55. Sixteen patients (66.7%) were male and 8 (33.3%) were female. Only 1 patient in the non-severe group was a smoker. The frequencies of diabetes and hypertension in our patients were 6 (25%) and 3 (12.5%), respectively. The history of vaccination against COVID-19 was positive in 10 (41.6%) patients which 7 (70%) of them were vaccinated before transplantation.

We recorded the initial presentations of COVID-19 at the time patients were referred to the infectious diseases outpatient clinic, or primary COVID-19 manifestations during transplant hospitalization. Gastrointestinal symptoms were the most frequent complaints (33%), and then cough (29.2%), dyspnea (29.2%), fever (25%), malaise (20.8%), headache (16.7%), and sore throat (12.5%).

The causes of liver damage in study subjects included primary sclerosing cholangitis (PSC) in 7 (29.2%), hepatitis B in 5 (20.8%), hepatitis C in 1 (4.2%), Wilson disease in 1 (4.2%), non-alcoholic steatohepatitis (NASH) in 4 (16.7%), alcoholic hepatitis in 2 (8.3%), and other etiologies of liver damage in 4 (16.7%) patients. None of our patients had a diagnosed cardiovascular or lung disease.

Ten patients (41.6%) were infected during the admission for transplantation and none of them was infected by donor liver.

Based on the severity of COVID-19, 9(37.5%) patients were categorized in the severe group which 5(55.5%) of them were ICU admitted, and unfortunately, 4(44.4%) were expired. The comparison of demographics and clinical data between severe and non-severe groups revealed no statistically significant differences, except for the length of hospitalization which was significantly longer in the severe group (P = 0.02) (Table 1).

Table 1 Demographics and clinical data of 24 hospitalized LT recipients with COVID-19 in severe and non-severe groups
Full size table

The key findings regarding each patient within severe and non-severe COVID-19 groups are demonstrated in additional file 1 and additional file 2, respectively. All mortality cases were among new LT recipients who were infected with SARS‑CoV‑2 during the admission for transplantation.

The values of laboratory biomarkers measured in non-severe and severe COVID-19 groups during their admission are summarized in Table 2. Patients with severe COVID-19 had significantly higher levels of CPR compared to the non-severe group (P = 0.006). We measured the absolute lymphocyte counts of our patients at the beginning of admission and also the lowest (minimum) lymphocyte counts all through the admission. Although no significant difference at the beginning (onset) counts were reported (P = 0.1), patients in the severe group had significantly lower lymphocyte counts at the minimum levels compared to the non-severe group (P = 0.002). Among COVID-19-specific treatments, significantly more patients in the severe group received IVIG compared to non-severe (4 vs. 1, respectively, P = 0.04).

Table 2 Laboratory biomarkers and immunosuppressive regimens in 24 hospitalized LT recipients with COVID-19 in severe and non-severe COVID-19 groups
Full size table

We recorded the baseline immunosuppressives and their daily dose in addition to immunosuppressive regimens during hospital admission for patients within each group. Significantly more patients with non-severe COVID-19 had mycophenolate in their baseline regimen (P = 0.02). Furthermore, the mean baseline dose of mycophenolate and tacrolimus were significantly higher in the non-severe group compared to the severe group (both P = 0.02) (Table 2).

Of all LT patients, 13 (54.2%) had mycophenolate at their baseline immunosuppressive regimen. During the COVID-19 admission, mycophenolate in 9 (69.2%) patients were completely withdrawn, in 2 (15.4%) was reduced, and in 2 (15.4%) was continued without dose alteration. Only 2 (15.4%) patients from those who had baseline mycophenolate developed severe COVID-19; one of them was completely withdrawn from mycophenolate, and in one another, mycophenolate was continued without dose reduction.

Discussion

In this article, we have evaluated the outcomes and a wide range of potential role-playing factors in the severity of COVID-19 in 24 hospitalized LT patients. We had 15 LT patients with non-severe COVID-19 who did not experience respiratory failure demanding mechanical ventilation or critical clinical status leading to ICU admission or death. The remaining 9 patients were considered severe COVID-19 in which 4 of them sadly expired.

A prospective cohort study conducted by Colmenero et al. in 2020 included 111 LT recipients, of which 35(31.5%) met the criteria of severe COVID-19. Older age (P = 0.038), dyspnea as an initial COVID-19 presentation (P < 0.001), receiving bolus corticosteroids and tocilizumab for COVID-19 treatment (P = 0.007 and P < 0.001, respectively), and lower lymphocyte counts (P = 0.013) were significantly more common in the severe COVID-19 group. Regarding immunosuppressive, they reported mycophenolate in the baseline regimen more commonly in patients with severe COVID-19 compared to the non-severe group (P = 0.014). Besides, mycophenolate was identified as an independent predictor of severe COVID-19 (relative risk (RR): 3.94, 95% confidence interval (CI): 1.59–9.74) [11]. We had the same results regarding lymphocyte counts in our subjects, but surprisingly, we found that mycophenolate was significantly more frequent in the baseline regimen of non-severe group (P = 0.03), furthermore, they had a higher mean dose of baseline mycophenolate compared to the severe COVID-19 group (P = 0.02) (Table 2).

Mycophenolate mofetil impedes lymphocytic proliferation by inhibiting DNA replication in T and B lymphocytes; adding to the COVID-19-induced lymphopenia and lymphocyte dysfunction, continuing mycophenolate in LT patients with COVID-19 might lead to poor outcomes and serious risks [5, 17]. However, some studies have shown the antiviral properties and beneficial effects of mycophenolate in patients with COVID-19 including faster recovery, reduced mortality, and COVID-19 complications [15, 18]. In a study by Kato et al., significant anti-SARS-COV-2 activity for mycophenolic acid was observed, which suggests the potential clinical use of mycophenolate in the treatment of COVID-19 [16].

A meta-analysis in 2020 comprising 24 studies and 3099 patients showed a significantly lower lymphocyte count in patients with COVID-19 who experienced ARDS (P < 0.001), were admitted to ICU (P = 0.02), and died (P < 0.001). Their results also indicate that patients with lymphopenia are more likely to experience severe COVID-19 (OR:3.70, 95%CI:2.44–5.63, p < 0.001) [19]. Various mechanisms have been hypothesized to explain the lymphopenia in severe cases of COVID-19, including SARS-COV-2-induced apoptosis/proptosis of lymphocytes, bone marrow and thymus suppression, immune-mediated elimination of infected lymphocytes, sequestration of lymphocytes in target organs, and lymphopenia induced by cytokine storm and high levels of blood lactic acid [20, 21].

Regarding calcineurin inhibitors (CNIs), according to the previous studies on LT patients with COVID-19, starting or continuing CNIs or switching to CNI from other immunosuppressives is not associated with any poor outcome or increased mortality [10, 13]. We found that the average dose of tacrolimus in baseline regimen of non-severe COVID-19 group was significantly higher than severe group (P = 0.02), and more patients in non-severe group had tacrolimus in their baseline regimen than in severe group, even though statistically not significant (P = 0.09) (Table 2).

The results yielded by previous studies regarding the treatment with systemic corticosteroids in COVID-19 have been highly controversial [22, 23]. This controversy might be attributed to the use of different types of corticosteroids in studies, the stage of the disease during which corticosteroids were administered, other concomitant treatments received by patients, the incidence of adverse events associated with corticosteroids (such as hyperglycemia, delayed wound healing, and an increased risk of infection and gastrointestinal bleeding), variations in hospital facilities between low-income and high-income countries, and other confounding factors [23]. While the administration of corticosteroids during the inflammatory phase of COVID-19 has established a significant reduction in mortality and incidence of ARDS [24], patients who were under chronic corticosteroid therapy at the time of COVID-19 infection, seem to have a greater risk of mortality and severe COVID-19 [10]. In a multicenter cohort study on 1726 patients with non-severe COVID-19, the administration of corticosteroids was associated with worse clinical outcomes [25]. Overall, using systemic corticosteroids might be more beneficial in severe cases of COVID-19 [26]. We did not yield any results indicating worse outcomes with corticosteroids (Table 2).

The records of vaccination among our patients revealed no statistical difference between the two groups of severe and non-severe COVID-19 (Table 1). However, the beneficial effects of vaccination against COVID-19 in LT recipients are well established [27,28,29]. According to the previous meta-analysis studies, the humoral response rate following the first dose of vaccination has been estimated to be 22.4–22.5% in LT recipients, and this rate increases over 90% after the third dose [27]. Besides, LT patients seem to have a better response to vaccination compared to other solid organ recipients [28]. However, a study involving 143 LT recipients and 58 control subjects conducted by Toniutto and colleagues, revealed that the immunogenicity of anti-SARS-COV-2 vaccine in LT patients without a previous history of COVID-19 was significantly lower compared to controls. They have also identified mycophenolate as the main predictor of vaccination failure in LT recipients [30]. In addition to mycophenolate mofetil, male gender, coexisting comorbidities, and using more than two immunosuppressants have been associated with poor response to vaccination against COVID-19 in LT recipients [27, 29].

CRP is primarily produced by hepatocytes in response to inflammatory cytokines and is known as a biomarker of acute inflammation. An increased level of CRP is usually observed in inflammatory conditions, mainly in infections [31]. Our laboratory results showed significantly higher levels of CRP among LT patients with severe COVID-19, which is consistent with previous studies [12, 32]. Interestingly, the role of CRP in COVID-19 might go further than a simple indicator of severe inflammation, and CRP could intensify the disease severity by immune dysregulation and organ damage [33]. In addition to CRP, high levels of lactate dehydrogenase (LDH), D-dimer, IL-6, and IL-10 have also been known as severity markers of COVID-19 [12, 34].

Conclusion

lymphopenia and high levels of CRP are associated with more severe forms of COVID-19 in LT patients. Mycophenolate mofetil does not necessarily aggravate the clinical status in LT patients with COVID-19, and may even have protective properties against severe COVID-19. The role of severity indicators, including clinical, paraclinical, and laboratory parameters, along with the role of immunosuppressives in LT patients with COVID-19 needs to be systematically recognized.

Data availability

All data supporting the findings of this study are available within the paper and its Supplementary Information.

References

  1. Becchetti C, Zambelli MF, Pasulo L, Donato MF, Invernizzi F, Detry O, et al. COVID-19 in an international European liver transplant recipient cohort. Gut. 2020;69(10):1832–40.

    Article  CAS  PubMed  Google Scholar 

  2. Wolff D, Nee S, Hickey NS, Marschollek M. Risk factors for Covid-19 severity and fatality: a structured literature review. Infection. 2021;49:15–28.

    Article  CAS  PubMed  Google Scholar 

  3. Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol. 2021;93(1):250–6.

    Article  CAS  PubMed  Google Scholar 

  4. Kalinina O, Golovkin A, Zaikova E, Aquino A, Bezrukikh V, Melnik O, et al. Cytokine storm signature in patients with moderate and severe COVID-19. Int J Mol Sci. 2022;23(16):8879.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Philips CA, Rela M, Soin AS, Gupta S, Surendran S, Augustine P. Critical update on the diagnosis and management of COVID-19 in advanced cirrhosis and liver transplant recipients. J Clin Translational Hepatol. 2021;9(6):947.

    Google Scholar 

  6. Lai Q, Spoletini G, Bianco G, Graceffa D, Agnes S, Rossi M, Lerut J. SARS-CoV2 and immunosuppression: a double‐edged sword. Transpl Infect Disease. 2020;22(6):e13404.

    Article  CAS  Google Scholar 

  7. Khazaaleh S, Alomari M, Sharma S, Kapila N, Zervos XB, Gonzalez AJ. COVID-19 in liver transplant patients: impact and considerations. World J Transplantation. 2023;13(1):1.

    Article  Google Scholar 

  8. Kulkarni AV, Tevethia HV, Premkumar M, Arab JP, Candia R, Kumar K et al. Impact of COVID-19 on liver transplant recipients–A systematic review and meta-analysis. EClinicalMedicine. 2021;38.

  9. Heldman MR, Kates OS. COVID-19 in solid organ transplant recipients: a review of the current literature. Curr Treat Options Infect Dis. 2021;13(3):67–82.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Calderón-Parra J, Cuervas-Mons V, Moreno-Torres V, Rubio-Rivas M, Agudo-de Blas P, Pinilla-Llorente B, et al. Influence of chronic use of corticosteroids and calcineurin inhibitors on COVID-19 clinical outcomes: analysis of a nationwide registry. Int J Infect Dis. 2022;116:51–8.

    Article  PubMed  Google Scholar 

  11. Colmenero J, Rodríguez-Perálvarez M, Salcedo M, Arias-Milla A, Muñoz-Serrano A, Graus J, et al. Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients. J Hepatol. 2021;74(1):148–55.

    Article  CAS  PubMed  Google Scholar 

  12. Keddie S, Ziff O, Chou MK, Taylor RL, Heslegrave A, Garr E, et al. Laboratory biomarkers associated with COVID-19 severity and management. Clin Immunol. 2020;221:108614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Becchetti C, Gschwend SG, Dufour J-F, Banz V. COVID-19 in liver transplant recipients: a systematic review. J Clin Med. 2021;10(17):4015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Forns X, Navasa M. Liver transplant immunosuppression during the covid-19 pandemic. Gastroenterología Y Hepatología (English Edition). 2020;43(8):457–63.

    Article  Google Scholar 

  15. Sajgure A, Kulkarni A, Joshi A, Sajgure V, Pathak V, Melinkeri R et al. Safety and efficacy of mycophenolate in COVID-19: a nonrandomised prospective study in western India. Lancet Reg Health-Southeast Asia. 2023;11.

  16. Kato F, Matsuyama S, Kawase M, Hishiki T, Katoh H, Takeda M. Antiviral activities of mycophenolic acid and IMD-0354 against SARS‐CoV‐2. Microbiol Immunol. 2020;64(9):635–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Parente A, Manzia TM, Angelico R, Tirotta F, Muiesan P, Tisone G. Framarino Dei Malatesta M. COVID-19, liver transplant, and immunosuppression: allies or foes? Transpl Infect Disease. 2021;23(1):e13417.

    Article  CAS  Google Scholar 

  18. Sajgure AD, Sajgure VA, Date GV, Kulkarni AP. Safety of mycophenolate in covid-19 infection: A case series.

  19. Huang I, Pranata R. Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis. J Intensive care. 2020;8:1–10.

    Article  Google Scholar 

  20. Lee J, Park S-S, Kim TY, Lee D-G, Kim D-W. Lymphopenia as a biological predictor of outcomes in COVID-19 patients: a nationwide cohort study. Cancers. 2021;13(3):471.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jafarzadeh A, Jafarzadeh S, Nozari P, Mokhtari P, Nemati M. Lymphopenia an important immunological abnormality in patients with COVID-19: possible mechanisms. Scand J Immunol. 2021;93(2):e12967.

    Article  CAS  PubMed  Google Scholar 

  22. Wagner C, Griesel M, Mikolajewska A, Metzendorf M-I, Fischer A-L, Stegemann M, et al. Systemic corticosteroids for the treatment of COVID-19: equity‐related analyses and update on evidence. Cochrane Database Syst Rev. 2022;2022:11.

    Google Scholar 

  23. Lu K, Leno RW, Brewster SR. Systemic corticosteroids for COVID-19. Acad Emerg Med. 2022;29(2):252–4.

    Article  PubMed  Google Scholar 

  24. Pulakurthi YS, Pederson JM, Saravu K, Gupta N, Balasubramanian P, Kamrowski S et al. Corticosteroid therapy for COVID-19: a systematic review and meta-analysis of randomized controlled trials. Medicine. 2021;100(20).

  25. Chen Z, Yin X, Tan X, Wang J, Jiang N, Tian M, et al. Effectiveness of systemic corticosteroids therapy for nonsevere patients with COVID-19: a multicenter, retrospective, longitudinal cohort study. Value Health. 2022;25(5):709–16.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Singh AK, Majumdar S, Singh R, Misra A. Role of corticosteroid in the management of COVID-19: a systemic review and a Clinician’s perspective. Diabetes Metabolic Syndrome: Clin Res Reviews. 2020;14(5):971–8.

    Article  CAS  Google Scholar 

  27. Gkoufa A, Saridaki M, Georgakopoulou VE, Spandidos DA, Cholongitas E. COVID–19 vaccination in liver transplant recipients. Experimental Therapeutic Med. 2023;25(6):1–9.

    Article  Google Scholar 

  28. Meshram HS, Kute V, Rane H, Dave R, Banerjee S, Mishra V, Chauhan S. Humoral and cellular response of COVID-19 vaccine among solid organ transplant recipients: a systematic review and meta‐analysis. Transpl Infect Disease. 2022;24(6):e13926.

    Article  CAS  Google Scholar 

  29. Luo D, Chen X, Du J, Mei B, Wang A, Kuang F, et al. Immunogenicity of COVID-19 vaccines in chronic liver disease patients and liver transplant recipients: a systematic review and meta‐analysis. Liver Int. 2023;43(1):34–48.

    Article  PubMed  Google Scholar 

  30. Toniutto P, Falleti E, Cmet S, Cussigh A, Veneto L, Bitetto D, et al. Past COVID-19 and immunosuppressive regimens affect the long-term response to anti-SARS-CoV-2 vaccination in liver transplant recipients. J Hepatol. 2022;77(1):152–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liu C, Zheng C, Shen X, Liang L, Li Q. Serum CRP interacts with SPARC and regulate immune response in severe cases of COVID-19 infection. Front Immunol. 2023;14.

  32. Sadeghi-Haddad-Zavareh M, Bayani M, Shokri M, Ebrahimpour S, Babazadeh A, Mehraeen R et al. C-reactive protein as a prognostic indicator in COVID-19 patients. Interdisciplinary perspectives on infectious diseases. 2021;2021.

  33. Mosquera-Sulbaran JA, Pedreañez A, Carrero Y, Callejas D. C‐reactive protein as an effector molecule in Covid‐19 pathogenesis. Rev Med Virol. 2021;31(6):e2221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Wang L, Yang LM, Pei SF, Chong YZ, Guo Y, Gao XL, et al. CRP, SAA, LDH, and DD predict poor prognosis of coronavirus disease (COVID-19): a meta-analysis from 7739 patients. Scand J Clin Lab Investig. 2021;81(8):679–86.

    Article  CAS  Google Scholar 

Download references

Funding

Not applicable.

Author information

Authors and Affiliations

  1. School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Amir M. Sadeghian, Sobhan Kazemi, Farrokhlagha Hosseini & Mohammad Hosein Mohammadi

  2. Division of Hepatopancreatobiliary Surgery & Abdominal Organ Transplantation, Firoozgar Hospital, Iran University of Medical Sciences, Beh Afarin St., Karim Khan Zand Blvd, Tehran, Iran

    Mohsenreza Mansourian & Seyed Yahya Zarghami

  3. Department of Infectious Diseases, School of Medicine, Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, Iran

    Mitra Ranjbar

  4. Preventive Medicine and Public Health Research Center, Department of Community and Family Medicine, School of Medicine, Psychosocial Health Research Institute, Iran University of Medical Sciences, Tehran, Iran

    Marzieh Nojomi

Authors
  1. Amir M. Sadeghian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohsenreza Mansourian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mitra Ranjbar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sobhan Kazemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marzieh Nojomi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Seyed Yahya Zarghami
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Farrokhlagha Hosseini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohammad Hosein Mohammadi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.S. writing and editing the original manuscript & data analysis & data curation & conceptualization & methodologyM.Mansourian. editing the manuscript & project administration & conceptualization & final approval of the manuscriptM.R. editing the manuscript & project administration & conceptualization & final approval of the manuscriptS.K. collecting data, writing the original manuscriptM.N. data analysisS.Z. editing the manuscript & conceptualizationF.H. collecting data & preparing tablesM.Mohammadi. collecting data & preparing tables.

Corresponding authors

Correspondence to Mohsenreza Mansourian or Mitra Ranjbar.

Ethics declarations

Ethics approval and consent to participate

This study is approved by the ethics committee of Iran University of Medical Sciences (Number: IR.IUMS.FMD.REC.1401.180.) informed consent to participate in this study was obtained from all subjects or their legal guardians.

Consent for publication

Not applicable.

Conflict of interest

Authors have no conflict of interest to declare .

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary Material 2

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sadeghian, A.M., Mansourian, M., Ranjbar, M. et al. Outcomes of COVID-19 in 24 hospitalized liver transplant recipients: an observational study. BMC Infect Dis 24, 1019 (2024). https://doi.org/10.1186/s12879-024-09879-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12879-024-09879-9

Keywords

BMC Infectious Diseases

ISSN: 1471-2334

Contact us