| Abstract|| |
Coronavirus disease-2019 (COVID-19) has become a public health concern and global threat with high morbidity and mortality among kidney transplant recipients. However, risk factors and manifestations in this group of patients remain poorly understood. We aimed to study the clinical characteristics, laboratory parameters, and disease course of kidney transplant recipients with COVID-19 pneumonia. We enrolled 35 kidney transplant patients with COVID-19 pneumonia from March 2020 to November 2020 and studied their clinical records, laboratory results, radiological characteristics, and outcome. Their mean age was 44.82 ± 11.69 years (range: 17-65). The most common symptom was fever (94.28%) followed by cough (54.28%), fatigue (48.57%), shortness of breath (34.28%), and diarrhea/nausea/vomiting (22.85%). Leukopenia was seen in two patients (20.8%), and three patients had leukocytosis, while 75% of the patients had a white cell count in the normal range. Lymphopenia (<1100 per mm3) was seen in 23 patients (79%). All patients had elevated levels of C-reactive protein (CRP) with a range of 6-239.9 mg/L. An increase in serum creatinine from the baseline was seen in 25 patients (71.42%) with a mean of 2.62 mg/dL. Computerized tomography scan of the chest of 30 patients (85.71%) showed typical findings of multifocal ground glass shadows in both lung fields. Injection remdesivir was given in 28 patients (80%), and tocilizumab was given to three patients. Mortality was seen in six patients (17.14%), higher in those with O2 saturation <95% on admission (odds ratio: 6.29). Patients with kidney transplants display a high risk of mortality. The presence of multiple coexisting comorbidities, hypoxia at the time of admission, and high level of inflammatory markers (lactate dehydrogenase, CRP, D-dimer, and ferritin) is predictive of poorer outcomes.
|How to cite this article:|
Parikh M, Shah M, Hirapara J, Vaishnav B, Patel S, Prajapati AM, Prajapati D, Patel RJ. Clinical Profile and Outcome of Coronavirus Disease-2019 Pneumonia in Kidney Transplant Recipients: A Single-center Study from Western India. Saudi J Kidney Dis Transpl 2021;32:1679-88
|How to cite this URL:|
Parikh M, Shah M, Hirapara J, Vaishnav B, Patel S, Prajapati AM, Prajapati D, Patel RJ. Clinical Profile and Outcome of Coronavirus Disease-2019 Pneumonia in Kidney Transplant Recipients: A Single-center Study from Western India. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 Aug 15];32:1679-88. Available from: https://www.sjkdt.org/text.asp?2021/32/6/1679/352429
| Introduction|| |
Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with the coronavirus 2 (SARS-CoV-2). The infection ranges from mild disease to severe, acute respiratory distress syndrome characterized by a hyperinflammatory syndrome, multiorgan dysfunction, and death., In December 2019, the COVID-19 outbreak emerged in China, spread rapidly over the globe, emerged as an immense public health challenge. On March 11, 2020, the World Health Organization (WHO) declared it as a pandemic.
The information on COVID-19 is both limited and rapidly evolving due to the short time elapsed since the start of the outbreak as well as the resulting immense medical, social, and economic strain. Multiple risk factors predicting unfavorable outcomes, including old age, diabetes, hypertension, chronic kidney disease, coronary heart disease, and chronic lung disease, have been identified. In addition, accumulating clinical, laboratory, and pathology data suggest that an aberrant host immune response and the inflammatory cytokine storm play a key role for progression and mortality in COVID-19 patients., Multiple trials are underway assessing the role of various immunomodulating and immunosuppressive strategies to ameliorate the dysregulation of the immune response.,
Kidney transplant recipients frequently have multiple risk factors particularly hypertension and cardiovascular diseases and hence are at a high risk for unfavorable outcome. Moreover, they are on combinations of immunosuppressive drugs, including calcineurin inhibitors, antimetabolites, and steroids, which alter both the innate and adaptive immunity and render them more susceptible to bacterial and viral infections. On the other hand, the immunosuppressive medication may theoretically modulate and reduces the inflammatory response following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Aside from a few small case series, a more extensive analysis of COVID-19 in this population is lacking.,,,,,,,,,,, Whereas the mortality of COVID-19 in the general population is unclear and under intense scrutiny and debate,, the most extensive analysis to date from a mixed transplant population indicates an early mortality of 24% for inpatients. In contrast, a recent study of 8910 inpatients with COVID-19 in the general population and similar median age, showed a mortality rate of 5.8%.
Two case series of kidney transplants with COVID19 infection came from New York including 36 and 15 patients from Montefiore Medical Center and the Columbia University, respectively. Three additional series from Europe have shown an unusually high mortality rate among kidney transplant recipients with COVID-19, fluctuating between 20% and 28% compared with the report of 1%-5% mortality among patients with COVID-19 in the general population. These case series included seven patients, 20 patients, and eight patients from St. George’s University Hospital National Health Service Foundation Trust in London, United Kingdom; Spedali Civili University Hospital in Brescia, Italy; and Instituto de Investigación Sanitaria Hospital “12 de Octubre” (imas12), Madrid, Spain, respectively. In the general population, age, men, smoking, and cardiometabolic comorbidities have been associated with adverse outcomes as per early Chinese and Italian reports, while there is paucity of data regarding the prevalence and risk factors related to COVID-19 disease in the kidney transplant population. Case series have inherent limitations such as small sample size and center bias which do not allow in-depth analysis and firm conclusions.
The patients’ symptomatology includes fever (98%), cough (76%), dyspnea (55%), myalgia, and fatigue (44%). The most commonly involved system is respiratory, however, involvement of other organs systems such as cardiac, gastrointestinal, kidney, and nervous system involvement, has been reported too.,,,
In kidney transplant patients, the clinical manifestation, course of the disease, and prognosis of COVID-19 pneumonia may differ from the general population because of their immunosuppressed status. Furthermore, renal transplant patients might have lymphopenia due to their immunosuppressant medications so we cannot get help from this finding in diagnosis unlike the general population that has lymphopenia up to 63%.
In this study, we present data analysis of 35 kidney transplant recipients with suspected/ confirmed COVID-19 pneumonia who had been hospitalized from April 2020 to November 2020 at Shree Krishna Hospital, Bhaikaka University, Karamsad, Gujarat, India.
| Materials and Methods|| |
Study design and patients
This is a cross-sectional study that was carried out in Shree Krishna Hospital, Karamsad, Gujarat, India. During the period of eight months (April 1, 2020-November 30, 2020), we enrolled 35 kidney transplant recipients with suspected/confirmed COVID- 19 pneumonia who were admitted to our hospital. SARS-CoV-2 pneumonia was diagnosed based on a report of positive quantitative reverse transcription polymerase chain reaction (RT-PCR) from a nasopharyngeal sample and/or typical findings of COVID-19 on the computerized tomography scan of the chest in the presence of clinical scenario of acute respiratory illness. The Ethical Committee (Institutional Ethical Committee, H M Patel Centre For Medical Care and Education) approved this study with approval taken from Clinical Trial Registry of India. Written informed consent was waived off as this was a retrospective study without disclosure of any personal information of enrolled patients.
For all the patients with confirmed/suspected COVID-19 disease, we collected initial clinical manifestations, laboratory tests, computed tomographic scans of the chest, patient medications (including antiviral therapy, immunosuppression modification, oxygen support, invasive mechanical ventilation, and renal replacement therapy), and clinical outcomes (acute kidney injury, discharge, and mortality).
According to the WHO guidance and European Center for Disease Control and Prevention, patients were divided into suspected/possible, probable, and confirmed case of COVID-19 infection. If first quantitative RT-PCR came negative, a second nasopharyngeal swab was performed if the patient had a clinical presentation or radiologic images compatible with COVID-19 pneumonia.
Any person with at least one of the following symptoms: cough, fever, shortness of breath, sudden onset of anosmia, ageusia, or dysgeusia.
Diagnostic imaging criteria
Radiological evidence showing lesions compatible with COVID-19.
Detection of SARS-CoV-2 nucleic acid or antigen in a clinical specimen
At least one of the following two epidemiological links:
1. Close contact with a confirmed COVID-19 case in the 14 days prior to the onset of symptoms
2. Having been a resident or a staff member in the 14 days prior to the onset of symptoms, in a residential institution for vulnerable people where ongoing COVID- 19 transmission has been confirmed.
1. Possible case: Any person meeting the clinical criteria
2. Probable case: Any person meeting the clinical criteria with an epidemiological link odds ratio (OR) any person meeting the diagnostic imaging criteria
3. Confirmed case: Any person meeting the laboratory criterion.
| Statistical Analysis|| |
Statistical analysis was done with IBM SPSS Statistics version 20.0 (IBM Corp., Armonk, NY, USA). We expressed continuous variables as a range and categorical variables as the number.
| Results|| |
Among the 35 enrolled transplant patients, 31 were male. The mean age of patient was 44.82 ± 11.69 years (range: 17-65). The time range after transplantation was nine months to 32 years, with the mean time of 6.8 years. Thirty-four recipients (97.14%) had received a live donor kidney, one had a history of deceased donor transplantation, and four recipients had undergone ABO-incompatible transplant.
As shown in [Figure 1], the main etiology of underlying end-stage renal disease was undetermined followed by glomerulonephritis and diabetic nephropathy.
[Table 1] shows the detailed clinical characteristics of 35 patients. Hypertension was present in 97.14%, 28.57% had diabetes mellitus and 5.71% had a history of ischemic heart disease.
|Table 1. Clinical and radiological characteristics in kidney transplant recipients.|
MMF: Mycophenolate mofetil, COVID-19: Coronavirus disease 2019, WBC: White blood cells, CRP: C-reactive protein, LDH: Lactate dehydrogenase, IL-6: interleukin-6, RT-PCR: Reverse transcription polymerase chain reaction, CT scan: Computerized tomography scan.
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Among immunosuppressive medications, all patients were on prednisolone (100%), antimetabolites in 97.4% (80% were receiving mycophenolate mofetil (MMF), and 17.4% were receiving azathioprine), calcineurin inhibitors (CNIs) in 88.57% (80% tacrolimus, and 8.57% cyclosporine). 5.71% of recipients were on sirolimus, while 2.75% were on everolimus.
The most common symptom was fever [in 33 patients (94.28%)], followed by cough (54.28%), fatigue (48.57%), shortness of breath (34.28%), and diarrhea/nausea/vomiting (22.85%).
Laboratory tests showed that two patients with COVID-19 pneumonia (20.8%) had leukopenia (<4000 per mm3) and three patients had leukocytosis (>11,000 per mm3) while 75% of the patients had a white cell count in the normal range. Lymphopenia (<1100 per mm3) was seen in 23 patients (79%), and the lowest lymphocyte count was 216 per mm3, with the mean of 929.11 lymphocytes per mm3. All of the patients had an elevated concentration of C-reactive protein (CRP) (>6 mg/L) with a range of (6-239.9 mg/L). At admission, 15 recipients (42.85%) had baseline chronic graft dysfunction (serum creatinine >1.5 mg/dL). In addition, an increase in serum creatinine levels from baseline levels was also observed in 25 patients (71.42%) with a mean of 2.62 mg/dL.
On admission, 11 patients (31.42 %) had an O2 saturation of less than 95% while 24 recipients were on room air; however, during the course of hospitalization, among those 24 patients, two required high-flow nasal oxygen, three required oxygen though nasal prongs, one required NRBM support while one recipient progressed to required invasive mechanical ventilation and eventually succumbed to death. Nasal prongs were used in seven patients out of which one worsened to require invasive ventilation while six recovered to room air. There were two recipients who required noninvasive ventilation at the time of admission, unfortunately they worsened to require invasive ventilation and succumbed to death.
All patients underwent a noncontrast chest computerized tomography (CT) scan of lungs. Chest CT images of 30 patients (85.71%) showed typical findings of multifocal ground glass shadows in the both lung fields [Table 2]. Bilateral pulmonary involvement was seen in 25 patients (71.4%), predominantly on the left side [Figure 2]. Most of the CT scan showed peripheral involvement. The mean CT severity was 12.28 while 24 (68.57%) patients had severity score more 10. CORADs grade 5 was noted in 27 recipients. Four recipients had negative reports for both rapid antigen test and RT-PCR; however, based on their high-resolution CT (HRCT) findings and clinical suspicion, they were treated on lines of atypical pneumonia COVID-19.
|Table 2. Treatment and outcomes of our patients.|
COVID-19: Coronavirus disease 2019, MMF/AZA: Mycophenolate mofetil/azathioprine, CNIs: Calcineurin inhibitors, mTOR: Mammalian target of rapamycin, RRT: Renal replacement therapy.
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|Figure 2. Chest computerized tomography scan of one of our patient showing bilateral ground glass opacities, more in peripheral distribution.|
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On admission, the dose of immunosuppressive agents was reduced under close monitoring [Table 2]. All of the patients received vitamin C, zinc and azithromycin 500 mg. Anticoagulation in the form of heparin was given in 27 patients (77.14%) with elevated D-dimer levels while antiviral-injectable remdesivir (200 mg on day 1 followed by 100 mg once a day for 4 more days) was given in 28 patients (80%) with persistent fever/hypoxemia/high CT severity scores on CT thorax. Oral favipiravir was given to one patient (2.85%). Tocilizumab was given to three patients with very high IL-6 levels and worsening clinical condition [Table 2]. Oral steroids were continued in eight patients while 27 recipients were shifted to injectable methylprednisolone. Antimetabolites-MMF and azathioprine were discontinued in all patients, also everolimus and sirolimus was discontinued in two and one patient each. Four patients required discontinuation of CNIs while eight recipients required discontinuation of all immune suppressants (except steroids).
The median time of stay among the discharged patients was eight days (range 4-31 days) while for those who died, it was 12.5 days with the maximum duration of stay being 21 days.
In patients with more than one underlying disease, the rate of mortality was higher than in patients with one or without the underlying disease (30% vs. 12%, OR: 3.14, 95% confidence interval CI: 0.51 to 19.5, P = 0.32). The mortality rate among patients who had O2 saturation less than 95% on admission also was higher than those with O2 saturation more than 95% (36% vs. 9%, OR: 6.29, 95% CI: 0. 94 to 41.96, P = 0.06).
Inflammatory markers were checked every 48 h during patients’ hospitalization at our institution. When peak laboratory values and inflammatory markers were compared [Table 2] , nonsurvivors had lower mean lymphocyte counts (558 per mm3 vs. 701 per mm3, P = 0.19) and platelet counts (145 per mm3 vs. 192 per mm3, P = 0.05); and higher levels of C-reactive protein (170 mg/L vs. 73 mg/L, P = 0.005), ferritin (1330 ug/mL vs. 648 ug/mL, P= 0.001), D-dimer (3296 ng/mL vs. 1190 ng/mL, P = 002), IL-6 (157 pg/mL vs. 111 pg/mL, P = 0.38), lactate dehydrogenase (LDH) (766 IU/L vs 323 IU/L, P = 0.00001) while procalcitonin levels were almost similar between both groups (0.4 nL/mL)
| Discussion|| |
Multiple studies have shown COVID-19 causing fatal respiratory tract infections and extra pulmonary manifestation. T cells play an essential antiviral role, viral replication in SARS-CoV infection is not delayed by reduction of CD8+T cells, and depletion of CD4+T cells results in an immune-mediated interstitial pneumonitis and delayed clearance of COVID-19 from lungs. Transplant patients are at high risk for complications if they become infected with COVID-19 as they suffer from immunosuppression due to their drugs.
We report clinical data of 35 kidney transplant recipients with COVID-19 pneumonia. Kidney transplant recipients may have varied clinical manifestation due to immunosuppression, but as per our study, they showed a similar pattern of clinical characteristics to the general population. The most common symptoms on admission included shortness of breath, fever, and cough, but the percentage of fever was higher than in other studies (94.28%) while in Envar Akalin’s report, diarrhea was the most common presenting symptom. Laboratory tests indicated leukopenia in 5.71% and lymphopenia in 65.71% of patients, and normal white blood cell count was more frequent in our study, similar to case series by Alireza Abrishami, while leukopenia was the characteristic finding in Fishman and Grossi’s study.
Even the most common pattern in chest CT scan in our patients was bilateral peripheral ground-glass opacity, similar to the general population.
It has always been a big challenge to manage patient’s immunosuppressive medication due to the lack of data about COVID-19 in renal transplant patients. Hence, it has to be decided on a case-by-case considering factors such as time since transplantation, baseline graft function, and age. Despite the apparent concern about the risk of rejection with the reduction in immunosuppression, due to the high mortality rate in hospitalized patients with COVID-19 pneumonia, we stopped or reduced the dose of immunosuppressive agents as previously reported in other studies did., Currently, it is unclear whether transplant recipients are more likely to develop severe forms of the disease.
In our study, in patients with more than one underlying disease and patients who had O2 saturation less than 95% on admission, the mortality rate was higher. Peak levels of CRP, D-dimer, LDH, and ferritin were significantly associated with mortality, but there was no significant association between mortality and lymphopenia (P = 0.19).
Enver Akalin reported a very high early mortality among kidney transplant recipients with COVID-19 (28% at 3 weeks) as compared with the general population,, and our study showed 17.14% mortality.
| Conclusion|| |
We conclude that COVID-19 is more severe in transplant patients and has poorer outcomes. The presence of multiple coexisting comorbidities, hypoxia at the time of admission and high level of inflammatory markers (LDH, CRP, D-dimer, and ferritin) are predictive of poorer outcomes. Typical respiratory symptoms such as fever, cough, and shortness of breath are common (>95%) presenting symptoms even in transplant patients despite their immunosuppressed state. Bilateral lung involvement is rule in transplant recipients. Reduction of immunosuppressant, continuation of steroids and antiviral (Remdesivir) is principal modality of treatment. Although this single center study with small sample size is a limitation, we believe that the findings we reported are going to help to understand the clinical characteristics and deciding management of COVID-19 in transplant patients.
| Acknowledgments|| |
The authors represent their thankfulness to the Departments of Medicine, Chest Medicine, Critical Care Medicine and Anesthesiology. Furthermore, we extend our gratefulness to the nephrologists from Muljibhai Patel Urological Hospital, Nadiad, for showing their faith in us in managing their renal transplant patients at our center.
Conflict of interest: None declared.
| References|| |
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020;395:507-13.
Giamarellos-Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe 2020;27:992- 1000.e3.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395:497-506.
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395: 1054-62.
Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection – A review of immune changes in patients with viral pneumonia. Emerg Microbes Infect 2020;9:727-32.
Toniati P, Piva S, Cattalini M, et al. Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy. Autoimmun Rev 2020;19:102568.
Mehta P, McAuley DF, Brown M, et al. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020;395:1033-4.
Abrishami A, Samavat S, Behnam B, Arab-Ahmadi M, Nafar M, Sanei Taheri M. Clinical course, imaging features, and outcomes of COVID-19 in kidney transplant recipients. Eur Urol 2020;78:281-6.
Akalin E, Azzi Y, Bartash Ret al. COVID-19 and kidney transplantation. N Engl J Med 2020;382:2475-7.
Alberici F, Delbarba E, Manenti C, et al. A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia. Kidney Int 2020;97:1083-8.
Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M. COVID-19 infection in kidney transplant recipients. Kidney Int 2020;97: 1076-82.
Fernández-Ruiz M, Andrés A, Loinaz C, et al. COVID-19 in solid organ transplant recipients: A single-center case series from Spain. Am J Transplant 2020;20:1849-58.
Columbia University Kidney Transplant Program. Early description of coronavirus 2019 disease in kidney transplant recipients in New York. J Am Soc Nephrol 2020;31:1150-6.
Husain SA, Dube G, Morris H, , et al. Early outcomes of outpatient management of kidney transplant recipients with coronavirus disease 2019. Clin J Am Soc Nephrol 2020;15:1174-8.
Montagud-Marrahi E, Cofan F, Torregrosa JV, et al. Preliminary data on outcomes of SARS-CoV-2 infection in a Spanish single center cohort of kidney recipients. Am J Transplant 2020;20:2958-9.
Nair V, Jandovitz N, Hirsch JS, et al. COVID- 19 in kidney transplant recipients. Am J Transplant 2020;20:1819-25.
Trujillo H, Caravaca-Fontán F, Sevillano Á, et al. SARS-CoV-2 infection in hospitalized patients with kidney disease. Kidney Int Rep 2020;5:905-9.
Zhang H, Chen Y, Yuan Q, et al. Identification of kidney transplant recipients with corona-virus disease 2019. Eur Urol 2020;77:742-7.
Zhu L, Gong N, Liu B, et al. Coronavirus disease 2019 pneumonia in immunosuppressed renal transplant recipients: A summary of 10 confirmed cases in Wuhan, China. Eur Urol 2020;77:748-54.
Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020;323:2052-9.
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323:1239-42.
Pereira MR, Mohan S, Cohen DJ, et al. COVID-19 in solid organ transplant recipients: Initial report from the US epicenter. Am J Transplant 2020;20:1800-8.
Available from: https://www.who.int/docs/ default-source/coronaviruse/situation-reports/ 20200604-covid-19-sitrep 136.pdf?sfvrsn= fd36550b_2.
Coates PT, Wong G, Drueke T, Rovin B, Ronco P; Associate Editors, for the Entire Editorial Team. Early experience with COVID-19 in kidney transplantation. Kidney Int 2020;97:1074-5.
Liang W, Guan W, Chen R, et al. Cancer patients in SARS-CoV-2 infection: A nationwide analysis in China. Lancet Oncol 2020; 21:335-7.
Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A review. JAMA 2020;323:1824-36.
Clinical Insights for Hepatology and Liver Transplant Providers during the COVID-19 Pandemic. 2020 American Association for the Study of Liver Diseases; Released April 07, 2020. Available from: https://www.aasld.org/ sites/default/files/2020-04/AASLD-COVID19- ClinicalInsights-4.07.2020-Final.pdf.
Sharifi-Razavi A, Karimi N, Zarvani A, Cheraghmakani H, Baghbanian SM. Ischemic stroke associated with novel coronavirus 2019: A report of three cases. Int J Neurosci 2021;131:1243-7.
Sharifi-Razavi A, Karimi N, Rouhani N. COVID-19 and intracerebral haemorrhage: Causative or coincidental? New Microbes New Infect 2020;35:100669.
World Health Organization: Coronavirus Disease (COVID-19) Advice for the Public; 2020. Available from: .[Last accessed on 2020 May 08].
Caselli D, Aricò M. 2019-nCoV: Polite with children! Pediatr Rep 2020;12:8495.
Liu H, He X, Wang Y, J, et al. Management of COVID-19 in patients after liver transplantation: Beijing working party for liver transplantation. Hepatol Int 2020;14:432-6.
Fishman JA, Grossi PA. Novel Coronavirus-19 (COVID-19) in the immunocompromised transplant recipient: #Flatteningthecurve. Am J Transplant 2020;20:1765-7.
Mital Dipakkumar Parikh
Corresponding author: Dr. Mital Dipakkumar Parikh, Department of Medicine, Shree Krishna Hospital, Pramukhswami Medical College Karamsad, Anand, Gujarat, India.
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]