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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords:
Overview
| Admitted Patients | |||||||||||||||||||||||||||||||||||||||
| O2 Saturation <93% | O2 saturation >93% | S. Creaitnine is raised,Then Consider Kidney Biospy | •If there are signs of kidney rejection • Stop Anti Metabolite Drug • Prednisolone: 20 mg/d • Cyclosporine Trough Level: 75-150ng/ml • Tacrolimus Trough Level: 4 to 6 ng/mL • IVIG: 1-2 g/kg Divided Doses in 5 Days • Anti Viral Therapy According to Protocol • Azithromycin: 500 mg Stat and 250 mg • Daily for 4 Days | ||||||||||||||||||||||||||||||||||||
| • Stop Anti Metabolite Drug • Stop CNI • IV Methyl Prednisolone: 40mg/d • IVIG: 1-2 g/kg Divided Doses in 5 Days • Anti Viral Therapy According to Protocol • Azithromycin: 500 mg Stat and 250 mg • Daily for 4 Days | • If S.Creatinine is Normal • Stop Anti Metabolite Drug • Prednisolone: 20 mg/d • Cyclosporine Trough Level: 75-150ng/ml • Tacrolimus Trough Level: 4 to 6 ng/mL • Anti Viral Therapy According to Protocol • Azithromycin: 500 mg Stat and 250 mg • Daily for 4 Days | If No Sign of rejection then same protocol as for Normal Serum Creatinine and O2 sat. >93% | |||||||||||||||||||||||||||||||||||||
Historical Perspectives
The etiological agent involved is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), first detected in Wuhan, China. On March 12, 2020 the World Health Organization declared the COVID-19 outbreak a pandemic.[1] The earlier SARS epidemic of Hong Kong is known to affect both pediatric and adult renal transplant patients where the severity of disease in adult patients was more than that in pediatric patients[2] The first reported case of COVID-19 infection in renal transplant patient, was a 52‐year‐old man who received living‐related kidney transplantation 12 years for chronic glomerulonephritis, in Wuhan, China. He made a successful recovery and was discharged on day 13.[3]
Classification
Classification of COVID-19 infection in renal transplant patients depends on the severity of COVID-19 manifestations. COVID-19 infection classification according to WHO is following[4]:
| Mild Disease | Symptomatic patients meeting the case definition for COVID-19
No pneumonia No hypoxia | |
| Moderate Disease | Adolescent or adult
Pneumonia with fever, dyspnea, cough, and fast breathing SpO2 > or = 90% Child Signs of non-severe pneumonia (cough, difficulty breathing, fast breathing or chest indrawing) Fast breathing(breaths/min) <2 months: > or = 60 2-11 months: > or = 50 1-5 years: > or = 40 Diagnosis can be made clinically, Chest Imaging (radiograph, CT scan, Ultrasound) may assist in diagnosis. | |
| Severe Disease | Severe Pneumonia | Adolescent or adult
Signs of Pneumonia plus one of following: Respiratory rate > 30 breaths/min Severe Respiratory Distress SpO2 < 90% Child Pneumonia plus at least one of following Central cyanosis or SpO2 < 90% Severe respiratory distress (fast breathing, grunting, severe chest indrawing) General danger signs such as inability to breastfeed or drink, lethargy, or unconsciousness or convulsions Fast breathing(breaths/min) <2 months: > or = 60 2-11 months: > or = 50 1-5 years: > or = 40 Diagnosis can be made clinically, Chest Imaging (radiograph, CT scan, Ultrasound) may assist in diagnosis. |
| Critical Disease | Acute Respiratory Distress Syndrome (ARDS) | Onset: within 1 week of pneumonia or new worsening respiratory symptoms.
Chest imaging: (radiograph, CT scan, or lung ultrasound): bilateral opacities, not related to volume overload, lobar or lung collapse, or nodules Origin of pulmonary infiltrates: Respiratory failure not explained by cardiac failure or fluid overload. Oxygenation impairment in adults: -Mild ARDS: 200 mmHg < PaO2/FiO2a ≤ 300 mmHg (with PEEP or CPAP ≥ 5 cmH2O) -Moderate ARDS: 100 mmHg < PaO2/FiO2 ≤ 200 mmHg (with PEEP ≥ 5 cmH2O) -Severe ARDS: PaO2/FiO2 ≤ 100 mmHg (with PEEP ≥ 5 cmH2O) Oxygenation impairment in children: note OI and OSI. Use OI when available. If PaO2 not available, wean FiO2 to maintain SpO2 ≤ 97% to calculate OSI or SpO2/FiO2 ratio: • Bilevel (NIV or CPAP) ≥ 5 cmH2O via full face mask: PaO2/FiO2 ≤ 300 mmHg or SpO2/FiO2 ≤ 264. • Mild ARDS (invasively ventilated): 4 ≤ OI < 8 or 5 ≤ OSI < 7.5. • Moderate ARDS (invasively ventilated): 8 ≤ OI < 16 or 7.5 ≤ OSI < 12.3. • Severe ARDS (invasively ventilated): OI ≥ 16 or OSI ≥ 12.3. |
| Sepsis | Adults:
Acute life-threatening organ dysfunction caused by a dysregulated host response to suspected or proven infection. Signs of organ dysfunction: altered mental status, difficult or fast breathing, low oxygen saturation, reduced urine output, fast heart rate, weak pulse, cold extremities or low blood pressure, skin mottling, laboratory evidence of coagulopathy, thrombocytopenia, acidosis, high lactate, or hyperbilirubinemia. Children Suspected or proven infection and ≥ 2 age-based systemic inflammatory response syndrome (SIRS) criteria, of which one must be abnormal temperature or white blood cell count. | |
| Septic shock | Adults:
Persistent hypotension despite volume resuscitation, requiring vasopressors to maintain MAP ≥ 65 mmHg and serum lactate level > 2 mmol/L Children: Any hypotension (SBP < 5th centile or > 2 SD below normal for age) or two or three of the following: altered mental status; bradycardia or tachycardia (HR < 90 bpm or > 160 bpm in infants and heart rate < 70 bpm or > 150 bpm in children); prolonged capillary refill (> 2 sec) or weak pulse; fast breathing; mottled or cool skin or petechial or purpuric rash; high lactate; reduced urine output; hyperthermia or hypothermia |
Pathophysiology
Genetics
Angiotensin-converting enzyme 2 and Dipeptidyl peptidase have been implicated in the uptake of SARS-Cov and MERS-CoV[5][6] Several studies have indicated that viral S-protein RBD interacts with host ACE2 receptor. S protein changes thus make the human cells permissive to SARS-CoV and SARS-CoV-2 infection[7] [8] [9] [10] [11]ACE2: ACE ratio is higher in the kidneys compared to the respiratory system. (1:1 in the kidneys VS 1:20 in the respiratory system).[12]These receptors are found in the proximal tubules of kidney[5][6]SARS-CoV2 spike(S) protein is cleaved and activated by transmembrane serine protease family (TMPRSS) after attaching to angiotensin-converting enzyme 2 (ACE2) receptors. This allows the virus to release fusion peptide that aides in membrane fusion..[13]
Associated Conditions
Acute Kidney Injury
- Acute Kidney Injury has been reported in patients with COVID-19 infection along with presence of proteinuria, hematuria. In a case observation, 4 out of 7 patients had AKI which may indicate that renal transplant patients are at higher risk AKI on being infected with COVID-19 whereas only 29% AKI was seen in critically ill patients of general population.[14]
- Acute Kidney Injury seen in COVID-19 infection can be from the cytotropic effect (Uptake of SARS-Cov-2 virus into proximal tubule cells is possible explanation for the AKI seen in COVID patients[5][6]) of the viral particles as well as systemic inflammatory response induced by the cytokines. Patients admitted with severe disease, acute respiratory distress syndrome (ARDS) or in patients admitted to ICU have a higher incidence of AKI . [15]. Other possible reasons that can play a role in AKI development, are multi-organ failure resulting in acute tubular necrosis (ATN), volume reduction causing prerenal ATN, high fever, drug toxicity, hypotension, and contrast exposure. [16] [17]
- Pro-inflammatory cytokine levels are elevated in the COVID-19 infection and there is activation of T-cell response. [18]There is higher cytokine levels and there is occurrence of cytokine storm in severe cases. In cytokine storm the, the immune system damages the healthy tissue rather than virus.[19] According to an autopsy report of six patients, the light microscopy indicated CD68+ macrophage infiltration of the tubulointerstitium and severe ATN. The tubules showed complement 5b-9 deposition in all six cases, but deposition in glomeruli and capillaries were seldom seen. Some CD8+ T lymphocyte cells and CD56+ (natural killer) cells were seen in kidney tissue[20]
General COVID-19 Pathophysiology in Renal Transplant Patients
The overall presentation of COVID-19 in renal transplant patients is similar to that in general population[21].However, the renal transplant recipients are at remain at higher risk to catch COVID-19[15] and develop severe complications due to chronic immunosuppressed state which is implicated in various viral infections such as cytomegalovirus, herpes zoster, norovirus infections[22][23]etc.
COVID-19 Pathophysiology
Causes
Life Threatening Causes
Even though the CT findings in COVID-19 pneumonia were similar in renal transplant recipients and general population[24] , due to chronic immunosuppression, the clinical features of COVID-19 in renal transplant patients may be atypical[25] . In one of the study, nine of the 10 patients had fever, cough, shortness of breath, and fatigue; three had diarrhea; eight had lymphopenia; six had renal injury; and six had liver function damage[26] [27] [21] . It needs to be verified whether the severity of COVID-19 pneumonia differs in immunocompromised transplant patients than non-immunocompromised population. According to a report from China’s Infectious Disease Information system, out of 72,314 COVID-19 cases in general population, 81% were reported as mild, whereas 19% were either severe or critical[28] . And, in report from study in renal transplant patients, the number of severe cases were 80% compared to only 10% in their infected family members and 19% in general population[28] .Moreover, average duration of illness was nearly twice i.e. 35 days compared to 18 days in control group and 17-20 days reported in general population.[28][21]
Differentiating type page name here from other Diseases
Epidemiology and Demographics
- Epidemiological date indicates that the rate of severe complications of COVID-19 is almost 25%, and kidney is also one of the main organs affected in severe illness.[29]
- AKI is seen in 5-15% of the SARS-CoV and MERS-CoV infection, and the mortality rate is reported to be higher than in general population at 60-90% as per the literature. [30]
- .The risk is further increased in patients having chronic kidney disease(CKD), patients on chronic replacement therapies, and patients with kidney transplants.[30]
- In an analysis of 14 articles[31]
[32] [33] [34] [35] [36] [37] [38][39], Median interval of transplantation - 4 years. (range .25-30.1) Fatality rate: 17.4% (4/23)
Age
- Renal transplant patients of all ages are at a higher risk of COVID-19 due to immunosuppression.
- The youngest renal transplant patient who died of COVID-19 according to analysis of 14 studies was 71 years old.[31]
[32] [33] [34] [35] [40] [37] [38][39]
Gender
- Men are more likely to be affected by COVID-19 than women.[42]
- Women dying from COVID-19 are generally elder than men(median age: 82 vs. 79 years for women vs. men, respectively).[42]
Race
*According to study done in New York, 14 recipients (39%) were black, and 15 recipients (42%) were Hispanic.[43]
Risk Factors
There are various factors that can predispose renal transplant patients to COVID-19.
- Immunosuppression[15]
- Chronic Renal Failure[15][44]
- Co-Morbidities[15]
- Diabetes
- Hypertension
- Hyperlipidemia
- H/o Heart Disease
- Male Sex[43][45]
- Old Age[43][45]
- Current or h/o smoking tobacco[43]
- Possible a/w donor COVID-19 infection[45]
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Criteria
If available, the diagnostic criteria are provided here.
Symptoms
Presenting symptoms in renal transplant patients are similar to those of non-renal transplant patients.
- Respiratory symptons
- Cough
- Chest Pain
- Dysnea
- Fever
- Hypoxia
- Lymphopenia
- High C-Reactive Protein[46]
Valuable prognostic blood tests that can be done are
- Lymphocyte count
- Renal transplant patients generally have a low lymphocyte count due to immunosuppression, hence finding a further drop in the lymphocyte count can be of prognostic value.
- D-dimer
- Ferritin
- Troponin
- Microvascular thrombosis and disseminated intravascular coagulation( with gut ischemia) can occur later in the course of illness. They are characterized by marked increase in the levels of D-dimer particularly. D dimer, ferritin, and troponin should be measured in all patients with severe COVID-19 infection on admission and in those who fail to show any clinical improvement.[46]
Past Medical History
Laboratory Findings
Electrolyte and Biomarker Studies
Electrocardiogram
Chest X Ray
CT
MRI
Echocardiography or Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Pharmacotherapy
Acute Pharmacotherapies
Chronic Pharmacotherapies
Immunotherapy
In renal transplant patients, the immune responses are altered, especially the T cell response, due to generalized immunosuppression. Due to recent timeframe of outbreak of COVID-19 and insufficient scientific evidence, there is limited evidence on decreasing or changing the pattern of immunosuppression in renal transplant patients who have been infected with COVID-19. [47]
- Clinical presentation of COVID-19 infection in renal transplant patients are like the clinical presentations of infection in general population. [47].Moreover, renal transplant patients are generally immunocompromised, and this predisposes them to severe infection with COVID-19. Rejection of the graft can occur if immunosuppression is reduced in these patients. Hence given the high rate of mortality in COVID-19 infections, it is suggested that a careful risk vs benefits assessment of whether to continue immunosuppression should be done.[48]
- Managing the immunosuppression in renal transplant patients is difficult and should be based on[48]
- Age
- Severity of COVID-19 infection
- Presence of Co-Morbidities
- Time since the transplant
- In patients with mild to moderate infection, it has been a practice to continue or decrease the doses of immunosuppressive drugs, however this approach can cause high mortality in patients having COVID-19 infection.[48]
Immuno Drugs
- Antiproliferative agents such as MMF and azathioprine [49]
- Should be stopped at the time of admission to hospital
- Prednisolone[49]
- The dosage can be either increased or left unchanged. These can provide immunological protection to the renal graft.
- Corticosteroids have beneficial effects such as
- Tacrolimus[49]
- Low doses of tacrolimus can be given but more evidence is required.[49]
- The dose should be reduced to 50%. Target levels for tacrolimus should be 3-5 ng/ml.[51]
- Tocilizumab.[49]
- COVID-19 infection has been found to cause cytokine storm and inflammation due to antiviral immune response, hence trials of anti-interleukin 6 monoclonal antibody Tocilizumab and continuing steroids in infected patients has been considered.
- Cyclosporine
- Cyclosporin A has been shown to have an inhibitory effect on proliferation of corona viruses and hepatitis C virus in vitro, not seen in tacrolimus. Cyclosporin A is thought to inhibit the replication of a diverse array of coronaviruses through its impact on cyclophilin A and B.[52][53]
- Cyclosporine levels should be targeted at 25-50 ng/ml.[51]
Surgery and Device Based Therapy
| Box 1 in Row 1 | |||||||||||||||||||||
| Box 2 in Row 2 | Box in Row 2 | ||||||||||||||||||||
Indications for Surgery
Pre-Operative Assessment
Post-Operative Management
Transplantation
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
References
- ↑ . doi:10.23750/abm.v91i1.9397. Missing or empty
|title=(help) - ↑ Chiu, Man-Chun (2003). "Suggested management of immunocompromized kidney patients suffering from SARS". Pediatric Nephrology. 18 (12): 1204–1205. doi:10.1007/s00467-003-1325-8. ISSN 0931-041X.
- ↑ Zhu, Lan; Xu, Xizhen; Ma, Ke; Yang, Junling; Guan, Hanxiong; Chen, Song; Chen, Zhishui; Chen, Gang (2020). "Successful recovery of COVID‐19 pneumonia in a renal transplant recipient with long‐term immunosuppression". American Journal of Transplantation. 20 (7): 1859–1863. doi:10.1111/ajt.15869. ISSN 1600-6135.
- ↑ "Clinical management of COVID-19".
- ↑ 5.0 5.1 5.2 Li, Wenhui; Moore, Michael J.; Vasilieva, Natalya; Sui, Jianhua; Wong, Swee Kee; Berne, Michael A.; Somasundaran, Mohan; Sullivan, John L.; Luzuriaga, Katherine; Greenough, Thomas C.; Choe, Hyeryun; Farzan, Michael (2003). "Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus". Nature. 426 (6965): 450–454. doi:10.1038/nature02145. ISSN 0028-0836.
- ↑ 6.0 6.1 6.2 Raj, V. Stalin; Mou, Huihui; Smits, Saskia L.; Dekkers, Dick H. W.; Müller, Marcel A.; Dijkman, Ronald; Muth, Doreen; Demmers, Jeroen A. A.; Zaki, Ali; Fouchier, Ron A. M.; Thiel, Volker; Drosten, Christian; Rottier, Peter J. M.; Osterhaus, Albert D. M. E.; Bosch, Berend Jan; Haagmans, Bart L. (2013). "Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC". Nature. 495 (7440): 251–254. doi:10.1038/nature12005. ISSN 0028-0836.
- ↑ Shang, Jian; Ye, Gang; Shi, Ke; Wan, Yushun; Luo, Chuming; Aihara, Hideki; Geng, Qibin; Auerbach, Ashley; Li, Fang (2020). "Structural basis of receptor recognition by SARS-CoV-2". Nature. 581 (7807): 221–224. doi:10.1038/s41586-020-2179-y. ISSN 0028-0836.
- ↑ Yan, Renhong; Zhang, Yuanyuan; Li, Yaning; Xia, Lu; Guo, Yingying; Zhou, Qiang (2020). "Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2". Science. 367 (6485): 1444–1448. doi:10.1126/science.abb2762. ISSN 0036-8075.
- ↑ . doi:10.1016/j.cell.2020.1002.1058. Missing or empty
|title=(help) - ↑ Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola; Graham, Barney S.; McLellan, Jason S. (2020). "Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation". Science. 367 (6483): 1260–1263. doi:10.1126/science.abb2507. ISSN 0036-8075.
- ↑ Chen, Yun; Guo, Yao; Pan, Yihang; Zhao, Zhizhuang Joe (2020). "Structure analysis of the receptor binding of 2019-nCoV". Biochemical and Biophysical Research Communications. 525 (1): 135–140. doi:10.1016/j.bbrc.2020.02.071. ISSN 0006-291X.
- ↑ Malha, Line; Mueller, Franco B.; Pecker, Mark S.; Mann, Samuel J.; August, Phyllis; Feig, Peter U. (2020). "COVID-19 and the Renin-Angiotensin System". Kidney International Reports. 5 (5): 563–565. doi:10.1016/j.ekir.2020.03.024. ISSN 2468-0249.
- ↑ Pan, Xiu-wu; Xu, Da; Zhang, Hao; Zhou, Wang; Wang, Lin-hui; Cui, Xin-gang (2020). "Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis". Intensive Care Medicine. 46 (6): 1114–1116. doi:10.1007/s00134-020-06026-1. ISSN 0342-4642.
- ↑ Yang, Xiaobo; Yu, Yuan; Xu, Jiqian; Shu, Huaqing; Xia, Jia'an; Liu, Hong; Wu, Yongran; Zhang, Lu; Yu, Zhui; Fang, Minghao; Yu, Ting; Wang, Yaxin; Pan, Shangwen; Zou, Xiaojing; Yuan, Shiying; Shang, You (2020). "Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study". The Lancet Respiratory Medicine. 8 (5): 475–481. doi:10.1016/S2213-2600(20)30079-5. ISSN 2213-2600.
- ↑ 15.0 15.1 15.2 15.3 15.4 Zhou, Fei; Yu, Ting; Du, Ronghui; Fan, Guohui; Liu, Ying; Liu, Zhibo; Xiang, Jie; Wang, Yeming; Song, Bin; Gu, Xiaoying; Guan, Lulu; Wei, Yuan; Li, Hui; Wu, Xudong; Xu, Jiuyang; Tu, Shengjin; Zhang, Yi; Chen, Hua; Cao, Bin (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". The Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. ISSN 0140-6736.
- ↑ Beddhu, Srinivasan (2004). "Hypothesis: The Body Mass Index Paradox and an Obesity, Inflammation, and Atherosclerosis Syndrome in Chronic Kidney Disease". Seminars in Dialysis. 17 (3): 229–232. doi:10.1111/j.0894-0959.2004.17311.x. ISSN 0894-0959.
- ↑ Mohamed, Muner MB; Lukitsch, Ivo; Torres-Ortiz, Aldo E; Walker, Joseph B; Varghese, Vipin; Hernandez-Arroyo, Cesar F; Alqudsi, Muhannad; LeDoux, Jason R; Velez, Juan Carlos Q (2020). "Acute Kidney Injury Associated with Coronavirus Disease 2019 in Urban New Orleans". Kidney360: 10.34067/KID.0002652020. doi:10.34067/KID.0002652020. ISSN 2641-7650.
- ↑ Huang, Chaolin; Wang, Yeming; Li, Xingwang; Ren, Lili; Zhao, Jianping; Hu, Yi; Zhang, Li; Fan, Guohui; Xu, Jiuyang; Gu, Xiaoying; Cheng, Zhenshun; Yu, Ting; Xia, Jiaan; Wei, Yuan; Wu, Wenjuan; Xie, Xuelei; Yin, Wen; Li, Hui; Liu, Min; Xiao, Yan; Gao, Hong; Guo, Li; Xie, Jungang; Wang, Guangfa; Jiang, Rongmeng; Gao, Zhancheng; Jin, Qi; Wang, Jianwei; Cao, Bin (2020). "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". The Lancet. 395 (10223): 497–506. doi:10.1016/S0140-6736(20)30183-5. ISSN 0140-6736.
- ↑ Pan, Xiu-wu; Xu, Da; Zhang, Hao; Zhou, Wang; Wang, Lin-hui; Cui, Xin-gang (2020). "Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis". Intensive Care Medicine. 46 (6): 1114–1116. doi:10.1007/s00134-020-06026-1. ISSN 0342-4642.
- ↑ Diao, Bo; Wang, Chenhui; Wang, Rongshuai; Feng, Zeqing; Tan, Yingjun; Wang, Huiming; Wang, Changsong; Liu, Liang; Liu, Ying; Liu, Yueping; Wang, Gang; Yuan, Zilin; Ren, Liang; Wu, Yuzhang; Chen, Yongwen (2020). doi:10.1101/2020.03.04.20031120. Missing or empty
|title=(help) - ↑ 21.0 21.1 21.2 Wang, Dawei; Hu, Bo; Hu, Chang; Zhu, Fangfang; Liu, Xing; Zhang, Jing; Wang, Binbin; Xiang, Hui; Cheng, Zhenshun; Xiong, Yong; Zhao, Yan; Li, Yirong; Wang, Xinghuan; Peng, Zhiyong (2020). "Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China". JAMA. 323 (11): 1061. doi:10.1001/jama.2020.1585. ISSN 0098-7484.
- ↑ Karuthu, Shamila; Blumberg, Emily A. (2012). "Common Infections in Kidney Transplant Recipients". Clinical Journal of the American Society of Nephrology. 7 (12): 2058–2070. doi:10.2215/CJN.04410512. ISSN 1555-9041.
- ↑ Aulagnon, Florence; Scemla, Anne; DeWolf, Susan; Legendre, Christophe; Zuber, Julien (2014). "Diarrhea After Kidney Transplantation". Transplantation. 98 (8): 806–816. doi:10.1097/TP.0000000000000335. ISSN 0041-1337.
- ↑ Ai, Tao; Yang, Zhenlu; Hou, Hongyan; Zhan, Chenao; Chen, Chong; Lv, Wenzhi; Tao, Qian; Sun, Ziyong; Xia, Liming (2020). "Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases". Radiology: 200642. doi:10.1148/radiol.2020200642. ISSN 0033-8419.
- ↑ Michaels, Marian G.; La Hoz, Ricardo M.; Danziger-Isakov, Lara; Blumberg, Emily A.; Kumar, Deepali; Green, Michael; Pruett, Timothy L.; Wolfe, Cameron R. (2020). "Coronavirus disease 2019: Implications of emerging infections for transplantation". American Journal of Transplantation. 20 (7): 1768–1772. doi:10.1111/ajt.15832. ISSN 1600-6135.
- ↑ Chen, Nanshan; Zhou, Min; Dong, Xuan; Qu, Jieming; Gong, Fengyun; Han, Yang; Qiu, Yang; Wang, Jingli; Liu, Ying; Wei, Yuan; Xia, Jia'an; Yu, Ting; Zhang, Xinxin; Zhang, Li (2020). "Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study". The Lancet. 395 (10223): 507–513. doi:10.1016/S0140-6736(20)30211-7. ISSN 0140-6736.
- ↑ . doi:10.1016/ S2213-2600(20)30079-5 Check
|doi=value (help). Missing or empty|title=(help) - ↑ 28.0 28.1 28.2 Wu, Zunyou; McGoogan, Jennifer M. (2020). "Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China". JAMA. 323 (13): 1239. doi:10.1001/jama.2020.2648. ISSN 0098-7484.
- ↑ Yang, Xiaobo; Yu, Yuan; Xu, Jiqian; Shu, Huaqing; Xia, Jia'an; Liu, Hong; Wu, Yongran; Zhang, Lu; Yu, Zhui; Fang, Minghao; Yu, Ting; Wang, Yaxin; Pan, Shangwen; Zou, Xiaojing; Yuan, Shiying; Shang, You (2020). "Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study". The Lancet Respiratory Medicine. 8 (5): 475–481. doi:10.1016/S2213-2600(20)30079-5. ISSN 2213-2600.
- ↑ 30.0 30.1 Naicker, Saraladevi; Yang, Chih-Wei; Hwang, Shang-Jyh; Liu, Bi-Cheng; Chen, Jiang-Hua; Jha, Vivekanand (2020). "The Novel Coronavirus 2019 epidemic and kidneys". Kidney International. 97 (5): 824–828. doi:10.1016/j.kint.2020.03.001. ISSN 0085-2538.
- ↑ 31.0 31.1 Bussalino, Elisabetta; De Maria, Andrea; Russo, Rodolfo; Paoletti, Ernesto (2020). "Immunosuppressive therapy maintenance in a kidney transplant recipient with SARS‐CoV‐2 pneumonia: A case report". American Journal of Transplantation. 20 (7): 1922–1924. doi:10.1111/ajt.15920. ISSN 1600-6135.
- ↑ 32.0 32.1 Seminari, Elena; Colaneri, Marta; Sambo, Margherita; Gallazzi, Ilaria; Di Matteo, Angela; Roda, Silvia; Bruno, Raffaele; Mondelli, Mario U.; Brunetti, Enrico; Maiocchi, Laura; Zuccaro, Valentina; Pagnucco, Layla; Mariani, Bianca; Ludovisi, Serena; Lissandrin, Raffaella; Parisi, Aldo; Sacchi, Paolo; Patruno, Savino F. A.; Michelone, Giuseppe; Gulminetti, Roberto; Zanaboni, Domenico; Novati, Stefano; Maserati, Renato; Orsolini, Paolo; Vecchia, Marco; Sciarra, Marco; Asperges, Erika; Di Filippo, Alessandro; Biscarini, Simona; Lupi, Matteo; Pieri, Teresa C.; Sachs, Michele; Valsecchi, Pietro; Perlini, Stefano; Alfano, Claudia; Bonzano, Marco; Briganti, Federica; Crescenzi, Giuseppe; Falchi, Anna G.; Guarnone, Roberta; Guglielmana, Barbara; Maggi, Elena; Martino, Ilaria; Pettenazza, Pietro; Pioli di Marco, Serena; Quaglia, Federica; Sabena, Anna; Salinaro, Francesco; Speciale, Francesco; Zunino, Ilaria; De Lorenzo, Marzia; Secco, Gianmarco; Dimitry, Lorenzo; Cappa, Giovanni; Maisak, Igor; Chiodi, Benedetta; Sciarrini, Massimiliano; Barcella, Bruno; Resta, Flavia; Moroni, Luca; Vezzoni, Giulia; Scattaglia, Lorenzo; Boscolo, Elisa; Zattera, Caterina; Fidel, Tassi M.; Vincenzo, Capozza; Vignaroli, Damiano; Bazzini, Marco; Iotti, Giorgio; Mojoli, Francesco; Belliato, Mirko; Perotti, Luciano; Mongodi, Silvia; Tavazzi, Guido; Marseglia, Gianluigi; Licari, Amelia; Brambilla, Ilaria; Daniela, Barbarini; Antonella, Bruno; Patrizia, Cambieri; Giulia, Campanini; Giuditta, Comolli; Marta, Corbella; Rossana, Daturi; Milena, Furione; Bianca, Mariani; Roberta, Maserati; Enza, Monzillo; Stefania, Paolucci; Maurizio, Parea; Elena, Percivalle; Antonio, Piralla; Francesca, Rovida; Antonella, Sarasini; Maurizio, Zavattoni; Guy, Adzasehoun; Laura, Bellotti; Ermanna, Cabano; Giuliana, Casali; Luca, Dossena; Gabriella, Frisco; Gabriella, Garbagnoli; Alessia, Girello; Viviana, Landini; Claudia, Lucchelli; Valentina, Maliardi; Simona, Pezzaia; Marta, Premoli; Alice, Bonetti; Giacomo, Caneva; Irene, Cassaniti; Alfonso, Corcione; Di Martino, Raffella; Di Napoli, Annapia; Alessandro, Ferrari; Guglielmo, Ferrari; Loretta, Fiorina; Federica, Giardina; Alessandra, Mercato; Federica, Novazzi; Giacomo, Ratano; Beatrice, Rossi; Maria, Sciabica I.; Monica, Tallarita; Edoardo, Vecchio N.; Cerino, Antonella; Varchetta, Stefania; Oliviero, Barbara; Mantovani, Stefania; Mele, Dalila; Calvi, Monica; Tizzonis, Michela; Nicora, Carlo; Triarico, Antonio; Petronella, Vincenzo; Marena, Carlo; Muzzi, Alba; Lago, Paolo; Comandatore, Francesco; Bissignandi, Gherard; Gaiarsa, Stefano; Rettani, Marco; Band, Claudio (2020). "SARS Cov‐2 infection in a renal‐transplanted patient: A case report". American Journal of Transplantation. 20 (7): 1882–1884. doi:10.1111/ajt.15902. ISSN 1600-6135.
- ↑ 33.0 33.1 Marx, David; Moulin, Bruno; Fafi‐Kremer, Samira; Benotmane, Ilies; Gautier, Gabriela; Perrin, Peggy; Caillard, Sophie (2020). "First case of COVID‐19 in a kidney transplant recipient treated with belatacept". American Journal of Transplantation. 20 (7): 1944–1946. doi:10.1111/ajt.15919. ISSN 1600-6135.
- ↑ 34.0 34.1 Gandolfini, Ilaria; Delsante, Marco; Fiaccadori, Enrico; Zaza, Gianluigi; Manenti, Lucio; Degli Antoni, Anna; Peruzzi, Licia; Riella, Leonardo V.; Cravedi, Paolo; Maggiore, Umberto (2020). "COVID‐19 in kidney transplant recipients". American Journal of Transplantation. 20 (7): 1941–1943. doi:10.1111/ajt.15891. ISSN 1600-6135.
- ↑ 35.0 35.1 Guillen, Elena; Pineiro, Gaston J.; Revuelta, Ignacio; Rodriguez, Diana; Bodro, Marta; Moreno, Asunción; Campistol, Josep M.; Diekmann, Fritz; Ventura‐Aguiar, Pedro (2020). "Case report of COVID‐19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation?". American Journal of Transplantation. 20 (7): 1875–1878. doi:10.1111/ajt.15874. ISSN 1600-6135.
- ↑ . doi:10.1016/ S2213-2600(20)30182-X Check
|doi=value (help). Missing or empty|title=(help) - ↑ 37.0 37.1 Haberal, Mehmet (2020). "COVID-19 UPDATE". Experimental and Clinical Transplantation. 18 (2): 139–140. doi:10.6002/ect.2020.000e. ISSN 1304-0855.
- ↑ 38.0 38.1 "bts.org.uk" (PDF).
- ↑ 39.0 39.1 "www.europeanurology.com".
- ↑ . doi:10.1016/ S2213-2600(20)30182-X Check
|doi=value (help). Missing or empty|title=(help) - ↑ Pei, Guangchang; Zhang, Zhiguo; Peng, Jing; Liu, Liu; Zhang, Chunxiu; Yu, Chong; Ma, Zufu; Huang, Yi; Liu, Wei; Yao, Ying; Zeng, Rui; Xu, Gang (2020). "Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia". Journal of the American Society of Nephrology. 31 (6): 1157–1165. doi:10.1681/ASN.2020030276. ISSN 1046-6673.
- ↑ 42.0 42.1 Sharma, Garima; Volgman, Annabelle Santos; Michos, Erin D. (2020). "Sex Differences in Mortality From COVID-19 Pandemic". JACC: Case Reports. doi:10.1016/j.jaccas.2020.04.027. ISSN 2666-0849.
- ↑ 43.0 43.1 43.2 43.3 Akalin, Enver; Azzi, Yorg; Bartash, Rachel; Seethamraju, Harish; Parides, Michael; Hemmige, Vagish; Ross, Michael; Forest, Stefanie; Goldstein, Yitz D.; Ajaimy, Maria; Liriano-Ward, Luz; Pynadath, Cindy; Loarte-Campos, Pablo; Nandigam, Purna B.; Graham, Jay; Le, Marie; Rocca, Juan; Kinkhabwala, Milan (2020). "Covid-19 and Kidney Transplantation". New England Journal of Medicine. 382 (25): 2475–2477. doi:10.1056/NEJMc2011117. ISSN 0028-4793.
- ↑ Banerjee, Debasish; Popoola, Joyce; Shah, Sapna; Ster, Irina Chis; Quan, Virginia; Phanish, Mysore (2020). "COVID-19 infection in kidney transplant recipients". Kidney International. 97 (6): 1076–1082. doi:10.1016/j.kint.2020.03.018. ISSN 0085-2538.
- ↑ 45.0 45.1 45.2 Nacif, Lucas Souto; Zanini, Leonardo Y.; Waisberg, Daniel R.; Pinheiro, Rafael S.; Galvão, Flávio; Andraus, Wellington; D'Albuquerque, Luiz Carneiro (2020). "COVID-19 in solid organ transplantation patients: A systematic review". Clinics. 75. doi:10.6061/clinics/2020/e1983. ISSN 1807-5932.
- ↑ 46.0 46.1 Banerjee, Debasish; Popoola, Joyce; Shah, Sapna; Ster, Irina Chis; Quan, Virginia; Phanish, Mysore (2020). "COVID-19 infection in kidney transplant recipients". Kidney International. 97 (6): 1076–1082. doi:10.1016/j.kint.2020.03.018. ISSN 0085-2538.
- ↑ 47.0 47.1 Zhu, Lan; Xu, Xizhen; Ma, Ke; Yang, Junling; Guan, Hanxiong; Chen, Song; Chen, Zhishui; Chen, Gang (2020). "Successful recovery of COVID‐19 pneumonia in a renal transplant recipient with long‐term immunosuppression". American Journal of Transplantation. doi:10.1111/ajt.15869. ISSN 1600-6135.
- ↑ 48.0 48.1 48.2 Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M (June 2020). "COVID-19 infection in kidney transplant recipients". Kidney Int. 97 (6): 1076–1082. doi:10.1016/j.kint.2020.03.018. PMC 7142878 Check
|pmc=value (help). PMID 32354637 Check|pmid=value (help). - ↑ 49.0 49.1 49.2 49.3 49.4 49.5 Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M (June 2020). "COVID-19 infection in kidney transplant recipients". Kidney Int. 97 (6): 1076–1082. doi:10.1016/j.kint.2020.03.018. PMC 7142878 Check
|pmc=value (help). PMID 32354637 Check|pmid=value (help). - ↑ Lansbury, Louise E.; Rodrigo, Chamira; Leonardi-Bee, Jo; Nguyen-Van-Tam, Jonathan; Shen Lim, Wei (2020). "Corticosteroids as Adjunctive Therapy in the Treatment of Influenza". Critical Care Medicine. 48 (2): e98–e106. doi:10.1097/CCM.0000000000004093. ISSN 0090-3493.
- ↑ 51.0 51.1 "www.massgeneral.org" (PDF).
- ↑ de Wilde, Adriaan H.; Zevenhoven-Dobbe, Jessika C.; van der Meer, Yvonne; Thiel, Volker; Narayanan, Krishna; Makino, Shinji; Snijder, Eric J.; van Hemert, Martijn J. (2011). "Cyclosporin A inhibits the replication of diverse coronaviruses". Journal of General Virology. 92 (11): 2542–2548. doi:10.1099/vir.0.034983-0. ISSN 0022-1317.
- ↑ Tanaka, Yoshikazu; Sato, Yuka; Sasaki, Takashi (2013). "Suppression of Coronavirus Replication by Cyclophilin Inhibitors". Viruses. 5 (5): 1250–1260. doi:10.3390/v5051250. ISSN 1999-4915.
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