COVID-19 Infection in Transplant Patients: Difference between revisions

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{{CMG}}; {{AE}}  
{{CMG}}; {{AE}}  
=COVID-19 Infection in Transplant Patients=


Risk of COVID-19 in renal transplant patients is higher because of immunosuppression, underlying chronic kidney disease, and other co morbidities such as diabetes and hypertension, which are presently perceived as noteworthy components impacting the results in patients with COVID-19.<ref name="pmid32171076">{{cite journal |vauthors=Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B |title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study |journal=Lancet |volume=395 |issue=10229 |pages=1054–1062 |date=March 2020 |pmid=32171076 |pmc=7270627 |doi=10.1016/S0140-6736(20)30566-3 |url=}}</ref>.It is realized that any transplant recipient presented to the infection would result in a high level of cases; however the risk of donor to recipient transmission is unknown. The chances of a donor to recipient infection might be affected by exposure of the donor, infectivity of the the donor during the incubation period and the degree of viremia as well as the viability of virus in specific organ system.In this manner, in spite of the conceivable negative outcomes, temporary interruption of kidney transplantation might be fundamental in regions where the rate of infection is high.<ref name="MichaelsLa Hoz2020">{{cite journal|last1=Michaels|first1=Marian G.|last2=La Hoz|first2=Ricardo M.|last3=Danziger-Isakov|first3=Lara|last4=Blumberg|first4=Emily A.|last5=Kumar|first5=Deepali|last6=Green|first6=Michael|last7=Pruett|first7=Timothy L.|last8=Wolfe|first8=Cameron R.|title=Coronavirus disease 2019: Implications of emerging infections for transplantation|journal=American Journal of Transplantation|year=2020|issn=1600-6135|doi=10.1111/ajt.15832}}</ref>
== Overview ==
[[Kidney transplantation|Renal transplant]] patients are under [[immunosuppression]] to modulate the [[immune response]] to [[graft]]. Moreover these patients have various underlying [[chronic kidney diseases]] and other co-morbidities such as [[Diabetes mellitus|diabetes]] and [[hypertension]], which can impact the results in [[COVID-19 infection]]. Hence these patients are at a higher risk of developing [[COVID-19]] associated complications.<ref name="pmid32171076">{{cite journal |vauthors=Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B |title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study |journal=Lancet |volume=395 |issue=10229 |pages=1054–1062 |date=March 2020 |pmid=32171076 |pmc=7270627 |doi=10.1016/S0140-6736(20)30566-3 |url=}}</ref> The clinical manifestations, treatment and prognosis of COVID-19 infection may be different from the general population.<ref name="ZhuXu2020">{{cite journal|last1=Zhu|first1=Lan|last2=Xu|first2=Xizhen|last3=Ma|first3=Ke|last4=Yang|first4=Junling|last5=Guan|first5=Hanxiong|last6=Chen|first6=Song|last7=Chen|first7=Zhishui|last8=Chen|first8=Gang|title=Successful recovery of COVID‐19 pneumonia in a renal transplant recipient with long‐term immunosuppression|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1859–1863|issn=1600-6135|doi=10.1111/ajt.15869}}</ref> It is believed that any [[Organ transplant|transplant]] recipient presented to the [[infection]] would result in a high level of cases; however the risk of donor to [[recipient]] transmission is unknown. The chances of a [[donor]] to recipient infection might be affected by exposure of the donor, infectivity of the the donor during the incubation period and the degree of [[viremia]] as well as the viability of virus in specific organ system.Hence, in spite of the conceivable negative outcomes, temporary interruption of [[kidney transplantation]] might be needed in regions where the rate of [[infection]] is high.<ref name="MichaelsLa Hoz2020">{{cite journal|last1=Michaels|first1=Marian G.|last2=La Hoz|first2=Ricardo M.|last3=Danziger-Isakov|first3=Lara|last4=Blumberg|first4=Emily A.|last5=Kumar|first5=Deepali|last6=Green|first6=Michael|last7=Pruett|first7=Timothy L.|last8=Wolfe|first8=Cameron R.|title=Coronavirus disease 2019: Implications of emerging infections for transplantation|journal=American Journal of Transplantation|year=2020|issn=1600-6135|doi=10.1111/ajt.15832}}</ref>


= Epidemiology and Demographics =
==Historical Perspectives==
*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.<ref name="YangYu2020">{{cite journal|last1=Yang|first1=Xiaobo|last2=Yu|first2=Yuan|last3=Xu|first3=Jiqian|last4=Shu|first4=Huaqing|last5=Xia|first5=Jia'an|last6=Liu|first6=Hong|last7=Wu|first7=Yongran|last8=Zhang|first8=Lu|last9=Yu|first9=Zhui|last10=Fang|first10=Minghao|last11=Yu|first11=Ting|last12=Wang|first12=Yaxin|last13=Pan|first13=Shangwen|last14=Zou|first14=Xiaojing|last15=Yuan|first15=Shiying|last16=Shang|first16=You|title=Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study|journal=The Lancet Respiratory Medicine|volume=8|issue=5|year=2020|pages=475–481|issn=22132600|doi=10.1016/S2213-2600(20)30079-5}}</ref>  
The etiological agent involved is [[SARS-CoV-2|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.<ref>{{cite journal|doi=10.23750/abm.v91i1.9397}}</ref> The earlier [[SARS-CoV|SARS]] epidemic of Hong Kong  is known to affect both pediatric and adult [[Kidney transplantation|renal transplant]] patients where the severity of disease in adult patients was more than that in pediatric patients<ref name="Chiu2003">{{cite journal|last1=Chiu|first1=Man-Chun|title=Suggested management of immunocompromized kidney patients suffering from SARS|journal=Pediatric Nephrology|volume=18|issue=12|year=2003|pages=1204–1205|issn=0931-041X|doi=10.1007/s00467-003-1325-8}}</ref> The first reported case of [[COVID-19]] infection in [[Kidney transplantation|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.<ref name="ZhuXu2020">{{cite journal|last1=Zhu|first1=Lan|last2=Xu|first2=Xizhen|last3=Ma|first3=Ke|last4=Yang|first4=Junling|last5=Guan|first5=Hanxiong|last6=Chen|first6=Song|last7=Chen|first7=Zhishui|last8=Chen|first8=Gang|title=Successful recovery of COVID‐19 pneumonia in a renal transplant recipient with long‐term immunosuppression|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1859–1863|issn=1600-6135|doi=10.1111/ajt.15869}}</ref>
*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. <ref name="NaickerYang2020">{{cite journal|last1=Naicker|first1=Saraladevi|last2=Yang|first2=Chih-Wei|last3=Hwang|first3=Shang-Jyh|last4=Liu|first4=Bi-Cheng|last5=Chen|first5=Jiang-Hua|last6=Jha|first6=Vivekanand|title=The Novel Coronavirus 2019 epidemic and kidneys|journal=Kidney International|volume=97|issue=5|year=2020|pages=824–828|issn=00852538|doi=10.1016/j.kint.2020.03.001}}</ref>
 
*.The risk is further increased in patients having chronic kidney disease(CKD), patients on chronic replacement therapies, and patients with kidney transplants.<ref name="NaickerYang2020">{{cite journal|last1=Naicker|first1=Saraladevi|last2=Yang|first2=Chih-Wei|last3=Hwang|first3=Shang-Jyh|last4=Liu|first4=Bi-Cheng|last5=Chen|first5=Jiang-Hua|last6=Jha|first6=Vivekanand|title=The Novel Coronavirus 2019 epidemic and kidneys|journal=Kidney International|volume=97|issue=5|year=2020|pages=824–828|issn=00852538|doi=10.1016/j.kint.2020.03.001}}</ref>
==Classification==
Classification of [[COVID-19]] infection in [[Kidney transplantation|renal transplant]] patients depends on the severity of [[COVID-19]] manifestations. [[COVID-19]] infection classification according to WHO is following<ref name="urlClinical management of COVID-19">{{cite web |url=https://www.who.int/publications/i/item/clinical-management-of-covid-19 |title=Clinical management of COVID-19 |format= |work= |accessdate=}}</ref>:
<br />
{| class="wikitable"
|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
 
SpO<sub>2</sub> > 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 ([[Radiography|radiograph]], [[Computed tomography|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''
 
''SpO<sub>2</sub>'' < 90%
 
'''Child'''
 
[[Pneumonia]] plus at least one of following
 
''Central [[cyanosis]] or SpO<sub>2</sub> < 90%''
 
''Severe respiratory distress'' (fast breathing, grunting, severe  chest indrawing)
 
''General danger'' signs such as inability to [[Breastfeeding|breastfeed]] or drink,  [[lethargy]], or unconsciousness or [[Seizure|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 ([[Radiography|radiograph]], [[Computed tomography|CT scan]],  [[Ultrasound]]) may assist in diagnosis.
|-
|Critical Disease
|[[Acute respiratory distress syndrome|Acute Respiratory Distress Syndrome]] (ARDS)
|''Onset'': within 1 week of [[pneumonia]] or new worsening respiratory  symptoms.
 
''Chest imaging'':
 
([[Radiography|radiograph]], [[Computed tomography|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 [[Hypervolemia|fluid overload]].
 
''Oxygenation impairment in adults'':
 
-Mild [[Acute respiratory distress syndrome|ARDS]]: 200 mmHg < PaO<sub>2</sub>/FiO<sub>2</sub><sup>a</sup>  ≤ 300 mmHg (with PEEP or CPAP ≥ 5 cmH<sub>2</sub>O)
 
-Moderate [[Acute respiratory distress syndrome|ARDS]]: 100 mmHg < PaO<sub>2</sub>/FiO<sub>2</sub> ≤ 200  mmHg (with PEEP ≥ 5 cmH<sub>2</sub>O)
 
-Severe [[Acute respiratory distress syndrome|ARDS]]: PaO<sub>2</sub>/FiO<sub>2</sub> ≤ 100 mmHg (with PEEP ≥  5 cmH<sub>2</sub>O)
 
'''Oxygenation impairment in children''': note OI and OSI.
 
Use OI when available. If PaO<sub>2</sub>  not available, wean FiO<sub>2</sub> to maintain SpO<sub>2</sub> ≤ 97% to calculate  OSI or SpO<sub>2</sub>/FiO<sub>2</sub> ratio:
 
• Bilevel (NIV or CPAP) ≥ 5 cmH<sub>2</sub>O via full face mask: PaO<sub>2</sub>/FiO<sub>2</sub>
 
≤ 300 mmHg or SpO<sub>2</sub>/FiO<sub>2</sub> ≤ 264.
 
• Mild [[Acute respiratory distress syndrome|ARDS]] (invasively ventilated): 4 ≤ OI < 8 or 5 ≤ OSI <  7.5.
 
• Moderate [[Acute respiratory distress syndrome|ARDS]] (invasively ventilated): 8 ≤ OI < 16 or 7.5 ≤ OSI <  12.3.
 
• Severe [[Acute respiratory distress syndrome|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 [[Jaundice|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 [[Coronavirus|SARS-Cov]] and [[Middle East respiratory syndrome coronavirus infection|MERS-CoV]]<ref name="LiMoore2003">{{cite journal|last1=Li|first1=Wenhui|last2=Moore|first2=Michael J.|last3=Vasilieva|first3=Natalya|last4=Sui|first4=Jianhua|last5=Wong|first5=Swee Kee|last6=Berne|first6=Michael A.|last7=Somasundaran|first7=Mohan|last8=Sullivan|first8=John L.|last9=Luzuriaga|first9=Katherine|last10=Greenough|first10=Thomas C.|last11=Choe|first11=Hyeryun|last12=Farzan|first12=Michael|title=Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus|journal=Nature|volume=426|issue=6965|year=2003|pages=450–454|issn=0028-0836|doi=10.1038/nature02145}}</ref><ref name="RajMou2013">{{cite journal|last1=Raj|first1=V. Stalin|last2=Mou|first2=Huihui|last3=Smits|first3=Saskia L.|last4=Dekkers|first4=Dick H. W.|last5=Müller|first5=Marcel A.|last6=Dijkman|first6=Ronald|last7=Muth|first7=Doreen|last8=Demmers|first8=Jeroen A. A.|last9=Zaki|first9=Ali|last10=Fouchier|first10=Ron A. M.|last11=Thiel|first11=Volker|last12=Drosten|first12=Christian|last13=Rottier|first13=Peter J. M.|last14=Osterhaus|first14=Albert D. M. E.|last15=Bosch|first15=Berend Jan|last16=Haagmans|first16=Bart L.|title=Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC|journal=Nature|volume=495|issue=7440|year=2013|pages=251–254|issn=0028-0836|doi=10.1038/nature12005}}</ref> 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<ref name="ShangYe2020">{{cite journal|last1=Shang|first1=Jian|last2=Ye|first2=Gang|last3=Shi|first3=Ke|last4=Wan|first4=Yushun|last5=Luo|first5=Chuming|last6=Aihara|first6=Hideki|last7=Geng|first7=Qibin|last8=Auerbach|first8=Ashley|last9=Li|first9=Fang|title=Structural basis of receptor recognition by SARS-CoV-2|journal=Nature|volume=581|issue=7807|year=2020|pages=221–224|issn=0028-0836|doi=10.1038/s41586-020-2179-y}}</ref> <ref name="YanZhang2020">{{cite journal|last1=Yan|first1=Renhong|last2=Zhang|first2=Yuanyuan|last3=Li|first3=Yaning|last4=Xia|first4=Lu|last5=Guo|first5=Yingying|last6=Zhou|first6=Qiang|title=Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2|journal=Science|volume=367|issue=6485|year=2020|pages=1444–1448|issn=0036-8075|doi=10.1126/science.abb2762}}</ref> <ref>{{cite journal|doi=10.1016/j.cell.2020.1002.1058}}</ref> <ref name="WrappWang2020">{{cite journal|last1=Wrapp|first1=Daniel|last2=Wang|first2=Nianshuang|last3=Corbett|first3=Kizzmekia S.|last4=Goldsmith|first4=Jory A.|last5=Hsieh|first5=Ching-Lin|last6=Abiona|first6=Olubukola|last7=Graham|first7=Barney S.|last8=McLellan|first8=Jason S.|title=Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation|journal=Science|volume=367|issue=6483|year=2020|pages=1260–1263|issn=0036-8075|doi=10.1126/science.abb2507}}</ref> <ref name="ChenGuo2020">{{cite journal|last1=Chen|first1=Yun|last2=Guo|first2=Yao|last3=Pan|first3=Yihang|last4=Zhao|first4=Zhizhuang Joe|title=Structure analysis of the receptor binding of 2019-nCoV|journal=Biochemical and Biophysical Research Communications|volume=525|issue=1|year=2020|pages=135–140|issn=0006291X|doi=10.1016/j.bbrc.2020.02.071}}</ref>ACE2: ACE ratio is higher in the [[Kidney|kidneys]] compared to the [[respiratory system]]. (1:1 in the [[Kidney|kidneys]] VS 1:20 in the [[respiratory system]]).<ref name="MalhaMueller2020">{{cite journal|last1=Malha|first1=Line|last2=Mueller|first2=Franco B.|last3=Pecker|first3=Mark S.|last4=Mann|first4=Samuel J.|last5=August|first5=Phyllis|last6=Feig|first6=Peter U.|title=COVID-19 and the Renin-Angiotensin System|journal=Kidney International Reports|volume=5|issue=5|year=2020|pages=563–565|issn=24680249|doi=10.1016/j.ekir.2020.03.024}}</ref>These receptors are found in the proximal tubules of [[kidney]]<ref name="LiMoore2003">{{cite journal|last1=Li|first1=Wenhui|last2=Moore|first2=Michael J.|last3=Vasilieva|first3=Natalya|last4=Sui|first4=Jianhua|last5=Wong|first5=Swee Kee|last6=Berne|first6=Michael A.|last7=Somasundaran|first7=Mohan|last8=Sullivan|first8=John L.|last9=Luzuriaga|first9=Katherine|last10=Greenough|first10=Thomas C.|last11=Choe|first11=Hyeryun|last12=Farzan|first12=Michael|title=Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus|journal=Nature|volume=426|issue=6965|year=2003|pages=450–454|issn=0028-0836|doi=10.1038/nature02145}}</ref><ref name="RajMou2013">{{cite journal|last1=Raj|first1=V. Stalin|last2=Mou|first2=Huihui|last3=Smits|first3=Saskia L.|last4=Dekkers|first4=Dick H. W.|last5=Müller|first5=Marcel A.|last6=Dijkman|first6=Ronald|last7=Muth|first7=Doreen|last8=Demmers|first8=Jeroen A. A.|last9=Zaki|first9=Ali|last10=Fouchier|first10=Ron A. M.|last11=Thiel|first11=Volker|last12=Drosten|first12=Christian|last13=Rottier|first13=Peter J. M.|last14=Osterhaus|first14=Albert D. M. E.|last15=Bosch|first15=Berend Jan|last16=Haagmans|first16=Bart L.|title=Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC|journal=Nature|volume=495|issue=7440|year=2013|pages=251–254|issn=0028-0836|doi=10.1038/nature12005}}</ref>[[SARS-CoV-2|SARS-CoV2]] spike(S) protein is cleaved and activated by transmembrane serine protease family (TMPRSS) after attaching to [[Angiotensin-converting enzyme 2|angiotensin-converting enzyme]] 2 (ACE2) receptors. This allows the virus to release fusion peptide that aides in membrane fusion..<ref name="PanXu2020">{{cite journal|last1=Pan|first1=Xiu-wu|last2=Xu|first2=Da|last3=Zhang|first3=Hao|last4=Zhou|first4=Wang|last5=Wang|first5=Lin-hui|last6=Cui|first6=Xin-gang|title=Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis|journal=Intensive Care Medicine|volume=46|issue=6|year=2020|pages=1114–1116|issn=0342-4642|doi=10.1007/s00134-020-06026-1}}</ref>
 
=== Associated Conditions===
 
==== Acute Kidney Injury ====
 
*[[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 [[Acute kidney injury|AKI]] which may indicate that [[Kidney transplantation|renal transplant]] patients are at higher risk [[Acute kidney injury|AKI]] on being infected with [[COVID-19]] whereas only 29% [[Acute kidney injury|AKI]] was seen in critically ill patients of general population.<ref name="YangYu2020">{{cite journal|last1=Yang|first1=Xiaobo|last2=Yu|first2=Yuan|last3=Xu|first3=Jiqian|last4=Shu|first4=Huaqing|last5=Xia|first5=Jia'an|last6=Liu|first6=Hong|last7=Wu|first7=Yongran|last8=Zhang|first8=Lu|last9=Yu|first9=Zhui|last10=Fang|first10=Minghao|last11=Yu|first11=Ting|last12=Wang|first12=Yaxin|last13=Pan|first13=Shangwen|last14=Zou|first14=Xiaojing|last15=Yuan|first15=Shiying|last16=Shang|first16=You|title=Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study|journal=The Lancet Respiratory Medicine|volume=8|issue=5|year=2020|pages=475–481|issn=22132600|doi=10.1016/S2213-2600(20)30079-5}}</ref>
*[[Acute kidney injury|Acute Kidney Injury]] seen in [[COVID-19]] infection can be from the cytotropic effect (Uptake of [[COVID-19|SARS-Cov-2]] virus into proximal tubule cells is possible explanation for the [[Acute kidney injury|AKI]] seen in [[COVID-19|COVID]] patients<ref name="LiMoore2003">{{cite journal|last1=Li|first1=Wenhui|last2=Moore|first2=Michael J.|last3=Vasilieva|first3=Natalya|last4=Sui|first4=Jianhua|last5=Wong|first5=Swee Kee|last6=Berne|first6=Michael A.|last7=Somasundaran|first7=Mohan|last8=Sullivan|first8=John L.|last9=Luzuriaga|first9=Katherine|last10=Greenough|first10=Thomas C.|last11=Choe|first11=Hyeryun|last12=Farzan|first12=Michael|title=Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus|journal=Nature|volume=426|issue=6965|year=2003|pages=450–454|issn=0028-0836|doi=10.1038/nature02145}}</ref><ref name="RajMou2013">{{cite journal|last1=Raj|first1=V. Stalin|last2=Mou|first2=Huihui|last3=Smits|first3=Saskia L.|last4=Dekkers|first4=Dick H. W.|last5=Müller|first5=Marcel A.|last6=Dijkman|first6=Ronald|last7=Muth|first7=Doreen|last8=Demmers|first8=Jeroen A. A.|last9=Zaki|first9=Ali|last10=Fouchier|first10=Ron A. M.|last11=Thiel|first11=Volker|last12=Drosten|first12=Christian|last13=Rottier|first13=Peter J. M.|last14=Osterhaus|first14=Albert D. M. E.|last15=Bosch|first15=Berend Jan|last16=Haagmans|first16=Bart L.|title=Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC|journal=Nature|volume=495|issue=7440|year=2013|pages=251–254|issn=0028-0836|doi=10.1038/nature12005}}</ref>) of the viral particles as well as systemic inflammatory response induced by the cytokines. Patients admitted with severe disease, [[acute respiratory distress syndrome]] ([[Acute respiratory distress syndrome|ARDS]]) or in patients admitted to ICU have a higher incidence of [[Acute kidney injury|AKI]] . <ref name="ZhouYu2020">{{cite journal|last1=Zhou|first1=Fei|last2=Yu|first2=Ting|last3=Du|first3=Ronghui|last4=Fan|first4=Guohui|last5=Liu|first5=Ying|last6=Liu|first6=Zhibo|last7=Xiang|first7=Jie|last8=Wang|first8=Yeming|last9=Song|first9=Bin|last10=Gu|first10=Xiaoying|last11=Guan|first11=Lulu|last12=Wei|first12=Yuan|last13=Li|first13=Hui|last14=Wu|first14=Xudong|last15=Xu|first15=Jiuyang|last16=Tu|first16=Shengjin|last17=Zhang|first17=Yi|last18=Chen|first18=Hua|last19=Cao|first19=Bin|title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study|journal=The Lancet|volume=395|issue=10229|year=2020|pages=1054–1062|issn=01406736|doi=10.1016/S0140-6736(20)30566-3}}</ref>.  Other possible reasons that can play a role in [[Acute kidney injury|AKI]] development, are multi-organ failure resulting in [[acute tubular necrosis]] ([[Acute tubular necrosis|ATN]]), volume reduction causing prerenal [[Acute tubular necrosis|ATN]], high [[fever]], drug toxicity, [[hypotension]], and contrast exposure. <ref name="Beddhu2004">{{cite journal|last1=Beddhu|first1=Srinivasan|title=Hypothesis: The Body Mass Index Paradox and an Obesity, Inflammation, and Atherosclerosis Syndrome in Chronic Kidney Disease|journal=Seminars in Dialysis|volume=17|issue=3|year=2004|pages=229–232|issn=08940959|doi=10.1111/j.0894-0959.2004.17311.x}}</ref> <ref name="MohamedLukitsch2020">{{cite journal|last1=Mohamed|first1=Muner MB|last2=Lukitsch|first2=Ivo|last3=Torres-Ortiz|first3=Aldo E|last4=Walker|first4=Joseph B|last5=Varghese|first5=Vipin|last6=Hernandez-Arroyo|first6=Cesar F|last7=Alqudsi|first7=Muhannad|last8=LeDoux|first8=Jason R|last9=Velez|first9=Juan Carlos Q|title=Acute Kidney Injury Associated with Coronavirus Disease 2019 in Urban New Orleans|journal=Kidney360|year=2020|pages=10.34067/KID.0002652020|issn=2641-7650|doi=10.34067/KID.0002652020}}</ref>
 
* Pro-inflammatory [[cytokine]] levels are elevated in the [[COVID-19]] infection and there is activation of [[T cell|T-cell]] response.  <ref name="HuangWang20202">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref>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.<ref name="PanXu20203">{{cite journal|last1=Pan|first1=Xiu-wu|last2=Xu|first2=Da|last3=Zhang|first3=Hao|last4=Zhou|first4=Wang|last5=Wang|first5=Lin-hui|last6=Cui|first6=Xin-gang|title=Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis|journal=Intensive Care Medicine|volume=46|issue=6|year=2020|pages=1114–1116|issn=0342-4642|doi=10.1007/s00134-020-06026-1}}</ref> According to an autopsy report of six patients, the light microscopy indicated CD68+ macrophage infiltration of the tubulointerstitium and severe [[Acute tubular necrosis|ATN]]. The tubules showed complement 5b-9 deposition in all six cases, but deposition in glomeruli and capillaries were seldom seen. Some [[Cytotoxic T cell|CD8+]] T lymphocyte cells and CD56+ ([[Natural killer cell|natural killer]]) cells were seen in kidney tissue<ref name="DiaoWang20202">{{cite journal|last1=Diao|first1=Bo|last2=Wang|first2=Chenhui|last3=Wang|first3=Rongshuai|last4=Feng|first4=Zeqing|last5=Tan|first5=Yingjun|last6=Wang|first6=Huiming|last7=Wang|first7=Changsong|last8=Liu|first8=Liang|last9=Liu|first9=Ying|last10=Liu|first10=Yueping|last11=Wang|first11=Gang|last12=Yuan|first12=Zilin|last13=Ren|first13=Liang|last14=Wu|first14=Yuzhang|last15=Chen|first15=Yongwen|year=2020|doi=10.1101/2020.03.04.20031120}}</ref>
 
==== General COVID-19 Pathophysiology in Renal Transplant Patients ====
The overall presentation of [[COVID-19]] in renal [[Kidney transplantation|transplant]] patients is similar to that in general population<ref name="WangHu2020">{{cite journal|last1=Wang|first1=Dawei|last2=Hu|first2=Bo|last3=Hu|first3=Chang|last4=Zhu|first4=Fangfang|last5=Liu|first5=Xing|last6=Zhang|first6=Jing|last7=Wang|first7=Binbin|last8=Xiang|first8=Hui|last9=Cheng|first9=Zhenshun|last10=Xiong|first10=Yong|last11=Zhao|first11=Yan|last12=Li|first12=Yirong|last13=Wang|first13=Xinghuan|last14=Peng|first14=Zhiyong|title=Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China|journal=JAMA|volume=323|issue=11|year=2020|pages=1061|issn=0098-7484|doi=10.1001/jama.2020.1585}}</ref>.However, the [[Kidney transplantation|renal transplant]] recipients are at remain at higher risk to catch [[COVID-19]]<ref name="ZhouYu2020">{{cite journal|last1=Zhou|first1=Fei|last2=Yu|first2=Ting|last3=Du|first3=Ronghui|last4=Fan|first4=Guohui|last5=Liu|first5=Ying|last6=Liu|first6=Zhibo|last7=Xiang|first7=Jie|last8=Wang|first8=Yeming|last9=Song|first9=Bin|last10=Gu|first10=Xiaoying|last11=Guan|first11=Lulu|last12=Wei|first12=Yuan|last13=Li|first13=Hui|last14=Wu|first14=Xudong|last15=Xu|first15=Jiuyang|last16=Tu|first16=Shengjin|last17=Zhang|first17=Yi|last18=Chen|first18=Hua|last19=Cao|first19=Bin|title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study|journal=The Lancet|volume=395|issue=10229|year=2020|pages=1054–1062|issn=01406736|doi=10.1016/S0140-6736(20)30566-3}}</ref>
and develop severe complications due to chronic immunosuppressed state which is implicated in various viral infections such as [[cytomegalovirus]], [[herpes zoster]], [[norovirus]] infections<ref name="KaruthuBlumberg2012">{{cite journal|last1=Karuthu|first1=Shamila|last2=Blumberg|first2=Emily A.|title=Common Infections in Kidney Transplant Recipients|journal=Clinical Journal of the American Society of Nephrology|volume=7|issue=12|year=2012|pages=2058–2070|issn=1555-9041|doi=10.2215/CJN.04410512}}</ref><ref name="AulagnonScemla2014">{{cite journal|last1=Aulagnon|first1=Florence|last2=Scemla|first2=Anne|last3=DeWolf|first3=Susan|last4=Legendre|first4=Christophe|last5=Zuber|first5=Julien|title=Diarrhea After Kidney Transplantation|journal=Transplantation|volume=98|issue=8|year=2014|pages=806–816|issn=0041-1337|doi=10.1097/TP.0000000000000335}}</ref>etc.
 
COVID-19 Pathophysiology<br />
 
== Causes ==
 
===Life Threatening Causes===
Even though the CT findings in [[COVID-19]] [[pneumonia]] were similar in [[Kidney transplantation|renal transplant]] recipients and general population<ref name="AiYang2020">{{cite journal|last1=Ai|first1=Tao|last2=Yang|first2=Zhenlu|last3=Hou|first3=Hongyan|last4=Zhan|first4=Chenao|last5=Chen|first5=Chong|last6=Lv|first6=Wenzhi|last7=Tao|first7=Qian|last8=Sun|first8=Ziyong|last9=Xia|first9=Liming|title=Correlation of Chest CT and RT-PCR Testing in Coronavirus Disease                    2019 (COVID-19) in China: A Report of 1014 Cases|journal=Radiology|year=2020|pages=200642|issn=0033-8419|doi=10.1148/radiol.2020200642}}</ref>
, due to chronic immunosuppression, the clinical features of [[COVID-19]] in [[Kidney transplantation|renal transplant]] patients may be atypical<ref name="MichaelsLa Hoz2020">{{cite journal|last1=Michaels|first1=Marian G.|last2=La Hoz|first2=Ricardo M.|last3=Danziger-Isakov|first3=Lara|last4=Blumberg|first4=Emily A.|last5=Kumar|first5=Deepali|last6=Green|first6=Michael|last7=Pruett|first7=Timothy L.|last8=Wolfe|first8=Cameron R.|title=Coronavirus disease 2019: Implications of emerging infections for transplantation|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1768–1772|issn=1600-6135|doi=10.1111/ajt.15832}}</ref>
. In one of the study, nine of the 10 patients had [[fever]], [[cough]], [[Dyspnea|shortness of breath]], and [[fatigue]]; three had [[diarrhea]]; eight had [[Lymphocytopenia|lymphopenia]]; six had [[renal injury]]; and six had liver function damage<ref name="ChenZhou2020">{{cite journal|last1=Chen|first1=Nanshan|last2=Zhou|first2=Min|last3=Dong|first3=Xuan|last4=Qu|first4=Jieming|last5=Gong|first5=Fengyun|last6=Han|first6=Yang|last7=Qiu|first7=Yang|last8=Wang|first8=Jingli|last9=Liu|first9=Ying|last10=Wei|first10=Yuan|last11=Xia|first11=Jia'an|last12=Yu|first12=Ting|last13=Zhang|first13=Xinxin|last14=Zhang|first14=Li|title=Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study|journal=The Lancet|volume=395|issue=10223|year=2020|pages=507–513|issn=01406736|doi=10.1016/S0140-6736(20)30211-7}}</ref>
<ref>{{cite journal|doi=10.1016/ S2213-2600(20)30079-5}}</ref>
<ref name="WangHu2020">{{cite journal|last1=Wang|first1=Dawei|last2=Hu|first2=Bo|last3=Hu|first3=Chang|last4=Zhu|first4=Fangfang|last5=Liu|first5=Xing|last6=Zhang|first6=Jing|last7=Wang|first7=Binbin|last8=Xiang|first8=Hui|last9=Cheng|first9=Zhenshun|last10=Xiong|first10=Yong|last11=Zhao|first11=Yan|last12=Li|first12=Yirong|last13=Wang|first13=Xinghuan|last14=Peng|first14=Zhiyong|title=Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China|journal=JAMA|volume=323|issue=11|year=2020|pages=1061|issn=0098-7484|doi=10.1001/jama.2020.1585}}</ref>
. 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<ref name="WuMcGoogan2020">{{cite journal|last1=Wu|first1=Zunyou|last2=McGoogan|first2=Jennifer M.|title=Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China|journal=JAMA|volume=323|issue=13|year=2020|pages=1239|issn=0098-7484|doi=10.1001/jama.2020.2648}}</ref>
. And, in report from study in [[Kidney transplantation|renal transplant]] patients, the number of severe cases were 80% compared to only 10% in their infected family members and 19% in general population<ref name="WuMcGoogan2020">{{cite journal|last1=Wu|first1=Zunyou|last2=McGoogan|first2=Jennifer M.|title=Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China|journal=JAMA|volume=323|issue=13|year=2020|pages=1239|issn=0098-7484|doi=10.1001/jama.2020.2648}}</ref>
.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.<ref name="WuMcGoogan2020">{{cite journal|last1=Wu|first1=Zunyou|last2=McGoogan|first2=Jennifer M.|title=Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China|journal=JAMA|volume=323|issue=13|year=2020|pages=1239|issn=0098-7484|doi=10.1001/jama.2020.2648}}</ref><ref name="WangHu2020">{{cite journal|last1=Wang|first1=Dawei|last2=Hu|first2=Bo|last3=Hu|first3=Chang|last4=Zhu|first4=Fangfang|last5=Liu|first5=Xing|last6=Zhang|first6=Jing|last7=Wang|first7=Binbin|last8=Xiang|first8=Hui|last9=Cheng|first9=Zhenshun|last10=Xiong|first10=Yong|last11=Zhao|first11=Yan|last12=Li|first12=Yirong|last13=Wang|first13=Xinghuan|last14=Peng|first14=Zhiyong|title=Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China|journal=JAMA|volume=323|issue=11|year=2020|pages=1061|issn=0098-7484|doi=10.1001/jama.2020.1585}}</ref>
 
<br />
 
==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.<ref name="YangYu20202">{{cite journal|last1=Yang|first1=Xiaobo|last2=Yu|first2=Yuan|last3=Xu|first3=Jiqian|last4=Shu|first4=Huaqing|last5=Xia|first5=Jia'an|last6=Liu|first6=Hong|last7=Wu|first7=Yongran|last8=Zhang|first8=Lu|last9=Yu|first9=Zhui|last10=Fang|first10=Minghao|last11=Yu|first11=Ting|last12=Wang|first12=Yaxin|last13=Pan|first13=Shangwen|last14=Zou|first14=Xiaojing|last15=Yuan|first15=Shiying|last16=Shang|first16=You|title=Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study|journal=The Lancet Respiratory Medicine|volume=8|issue=5|year=2020|pages=475–481|issn=22132600|doi=10.1016/S2213-2600(20)30079-5}}</ref>
*[[Acute kidney injury|AKI]] is seen in 5-15% of the [[Coronavirus|SARS-CoV]] and [[Middle East respiratory syndrome coronavirus infection causes|MERS-CoV]] infection, and the mortality rate is reported to be higher than in general population at 60-90% as per the literature. <ref name="NaickerYang2020">{{cite journal|last1=Naicker|first1=Saraladevi|last2=Yang|first2=Chih-Wei|last3=Hwang|first3=Shang-Jyh|last4=Liu|first4=Bi-Cheng|last5=Chen|first5=Jiang-Hua|last6=Jha|first6=Vivekanand|title=The Novel Coronavirus 2019 epidemic and kidneys|journal=Kidney International|volume=97|issue=5|year=2020|pages=824–828|issn=00852538|doi=10.1016/j.kint.2020.03.001}}</ref>
*.The risk is further increased in patients having [[Chronic renal failure|chronic kidney disease]](CKD), patients on chronic replacement therapies, and patients with kidney transplants.<ref name="NaickerYang2020" />
*In an analysis of 14 articles<ref name="BussalinoDe Maria2020">{{cite journal|last1=Bussalino|first1=Elisabetta|last2=De Maria|first2=Andrea|last3=Russo|first3=Rodolfo|last4=Paoletti|first4=Ernesto|title=Immunosuppressive therapy maintenance in a kidney transplant recipient with SARS‐CoV‐2 pneumonia: A case report|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1922–1924|issn=1600-6135|doi=10.1111/ajt.15920}}</ref>
 
<ref name="SeminariColaneri2020">{{cite journal|last1=Seminari|first1=Elena|last2=Colaneri|first2=Marta|last3=Sambo|first3=Margherita|last4=Gallazzi|first4=Ilaria|last5=Di Matteo|first5=Angela|last6=Roda|first6=Silvia|last7=Bruno|first7=Raffaele|last8=Mondelli|first8=Mario U.|last9=Brunetti|first9=Enrico|last10=Maiocchi|first10=Laura|last11=Zuccaro|first11=Valentina|last12=Pagnucco|first12=Layla|last13=Mariani|first13=Bianca|last14=Ludovisi|first14=Serena|last15=Lissandrin|first15=Raffaella|last16=Parisi|first16=Aldo|last17=Sacchi|first17=Paolo|last18=Patruno|first18=Savino F. A.|last19=Michelone|first19=Giuseppe|last20=Gulminetti|first20=Roberto|last21=Zanaboni|first21=Domenico|last22=Novati|first22=Stefano|last23=Maserati|first23=Renato|last24=Orsolini|first24=Paolo|last25=Vecchia|first25=Marco|last26=Sciarra|first26=Marco|last27=Asperges|first27=Erika|last28=Di Filippo|first28=Alessandro|last29=Biscarini|first29=Simona|last30=Lupi|first30=Matteo|last31=Pieri|first31=Teresa C.|last32=Sachs|first32=Michele|last33=Valsecchi|first33=Pietro|last34=Perlini|first34=Stefano|last35=Alfano|first35=Claudia|last36=Bonzano|first36=Marco|last37=Briganti|first37=Federica|last38=Crescenzi|first38=Giuseppe|last39=Falchi|first39=Anna G.|last40=Guarnone|first40=Roberta|last41=Guglielmana|first41=Barbara|last42=Maggi|first42=Elena|last43=Martino|first43=Ilaria|last44=Pettenazza|first44=Pietro|last45=Pioli di Marco|first45=Serena|last46=Quaglia|first46=Federica|last47=Sabena|first47=Anna|last48=Salinaro|first48=Francesco|last49=Speciale|first49=Francesco|last50=Zunino|first50=Ilaria|last51=De Lorenzo|first51=Marzia|last52=Secco|first52=Gianmarco|last53=Dimitry|first53=Lorenzo|last54=Cappa|first54=Giovanni|last55=Maisak|first55=Igor|last56=Chiodi|first56=Benedetta|last57=Sciarrini|first57=Massimiliano|last58=Barcella|first58=Bruno|last59=Resta|first59=Flavia|last60=Moroni|first60=Luca|last61=Vezzoni|first61=Giulia|last62=Scattaglia|first62=Lorenzo|last63=Boscolo|first63=Elisa|last64=Zattera|first64=Caterina|last65=Fidel|first65=Tassi M.|last66=Vincenzo|first66=Capozza|last67=Vignaroli|first67=Damiano|last68=Bazzini|first68=Marco|last69=Iotti|first69=Giorgio|last70=Mojoli|first70=Francesco|last71=Belliato|first71=Mirko|last72=Perotti|first72=Luciano|last73=Mongodi|first73=Silvia|last74=Tavazzi|first74=Guido|last75=Marseglia|first75=Gianluigi|last76=Licari|first76=Amelia|last77=Brambilla|first77=Ilaria|last78=Daniela|first78=Barbarini|last79=Antonella|first79=Bruno|last80=Patrizia|first80=Cambieri|last81=Giulia|first81=Campanini|last82=Giuditta|first82=Comolli|last83=Marta|first83=Corbella|last84=Rossana|first84=Daturi|last85=Milena|first85=Furione|last86=Bianca|first86=Mariani|last87=Roberta|first87=Maserati|last88=Enza|first88=Monzillo|last89=Stefania|first89=Paolucci|last90=Maurizio|first90=Parea|last91=Elena|first91=Percivalle|last92=Antonio|first92=Piralla|last93=Francesca|first93=Rovida|last94=Antonella|first94=Sarasini|last95=Maurizio|first95=Zavattoni|last96=Guy|first96=Adzasehoun|last97=Laura|first97=Bellotti|last98=Ermanna|first98=Cabano|last99=Giuliana|first99=Casali|last100=Luca|first100=Dossena|last101=Gabriella|first101=Frisco|last102=Gabriella|first102=Garbagnoli|last103=Alessia|first103=Girello|last104=Viviana|first104=Landini|last105=Claudia|first105=Lucchelli|last106=Valentina|first106=Maliardi|last107=Simona|first107=Pezzaia|last108=Marta|first108=Premoli|last109=Alice|first109=Bonetti|last110=Giacomo|first110=Caneva|last111=Irene|first111=Cassaniti|last112=Alfonso|first112=Corcione|last113=Di Martino|first113=Raffella|last114=Di Napoli|first114=Annapia|last115=Alessandro|first115=Ferrari|last116=Guglielmo|first116=Ferrari|last117=Loretta|first117=Fiorina|last118=Federica|first118=Giardina|last119=Alessandra|first119=Mercato|last120=Federica|first120=Novazzi|last121=Giacomo|first121=Ratano|last122=Beatrice|first122=Rossi|last123=Maria|first123=Sciabica I.|last124=Monica|first124=Tallarita|last125=Edoardo|first125=Vecchio N.|last126=Cerino|first126=Antonella|last127=Varchetta|first127=Stefania|last128=Oliviero|first128=Barbara|last129=Mantovani|first129=Stefania|last130=Mele|first130=Dalila|last131=Calvi|first131=Monica|last132=Tizzonis|first132=Michela|last133=Nicora|first133=Carlo|last134=Triarico|first134=Antonio|last135=Petronella|first135=Vincenzo|last136=Marena|first136=Carlo|last137=Muzzi|first137=Alba|last138=Lago|first138=Paolo|last139=Comandatore|first139=Francesco|last140=Bissignandi|first140=Gherard|last141=Gaiarsa|first141=Stefano|last142=Rettani|first142=Marco|last143=Band|first143=Claudio|title=SARS Cov‐2 infection in a renal‐transplanted patient: A case report|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1882–1884|issn=1600-6135|doi=10.1111/ajt.15902}}</ref>
<ref name="MarxMoulin2020">{{cite journal|last1=Marx|first1=David|last2=Moulin|first2=Bruno|last3=Fafi‐Kremer|first3=Samira|last4=Benotmane|first4=Ilies|last5=Gautier|first5=Gabriela|last6=Perrin|first6=Peggy|last7=Caillard|first7=Sophie|title=First case of COVID‐19 in a kidney transplant recipient treated with belatacept|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1944–1946|issn=1600-6135|doi=10.1111/ajt.15919}}</ref>
<ref name="GandolfiniDelsante2020">{{cite journal|last1=Gandolfini|first1=Ilaria|last2=Delsante|first2=Marco|last3=Fiaccadori|first3=Enrico|last4=Zaza|first4=Gianluigi|last5=Manenti|first5=Lucio|last6=Degli Antoni|first6=Anna|last7=Peruzzi|first7=Licia|last8=Riella|first8=Leonardo V.|last9=Cravedi|first9=Paolo|last10=Maggiore|first10=Umberto|title=COVID‐19 in kidney transplant recipients|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1941–1943|issn=1600-6135|doi=10.1111/ajt.15891}}</ref>
<ref name="GuillenPineiro2020">{{cite journal|last1=Guillen|first1=Elena|last2=Pineiro|first2=Gaston J.|last3=Revuelta|first3=Ignacio|last4=Rodriguez|first4=Diana|last5=Bodro|first5=Marta|last6=Moreno|first6=Asunción|last7=Campistol|first7=Josep M.|last8=Diekmann|first8=Fritz|last9=Ventura‐Aguiar|first9=Pedro|title=Case report of COVID‐19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation?|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1875–1878|issn=1600-6135|doi=10.1111/ajt.15874}}</ref>
<ref>{{cite journal|doi=10.1016/ S2213-2600(20)30182-X}}</ref>
<ref name="Haberal2020">{{cite journal|last1=Haberal|first1=Mehmet|title=COVID-19 UPDATE|journal=Experimental and Clinical Transplantation|volume=18|issue=2|year=2020|pages=139–140|issn=13040855|doi=10.6002/ect.2020.000e}}</ref>
<ref name="urlbts.org.uk">{{cite web |url=https://bts.org.uk/wp-content/uploads/2020/03/Clinical_management_transplant_recipients.pdf |title=bts.org.uk |format= |work= |accessdate=}}</ref><ref name="urlwww.europeanurology.com">{{cite web |url=https://www.europeanurology.com/article/S0302-2838(20)30211-6/pdf |title=www.europeanurology.com |format= |work= |accessdate=}}</ref>,  Median interval of transplantation - 4 years. (range .25-30.1)  Fatality rate: 17.4% (4/23)


===Age===
===Age===
*Renal transplant patients of all ages are at a higher risk of COVID-19 due to immunosuppression.
 
*In general population, COVID-19 associated AKI has higher incidence in elderly.<ref name="PeiZhang2020">{{cite journal|last1=Pei|first1=Guangchang|last2=Zhang|first2=Zhiguo|last3=Peng|first3=Jing|last4=Liu|first4=Liu|last5=Zhang|first5=Chunxiu|last6=Yu|first6=Chong|last7=Ma|first7=Zufu|last8=Huang|first8=Yi|last9=Liu|first9=Wei|last10=Yao|first10=Ying|last11=Zeng|first11=Rui|last12=Xu|first12=Gang|title=Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia|journal=Journal of the American Society of Nephrology|volume=31|issue=6|year=2020|pages=1157–1165|issn=1046-6673|doi=10.1681/ASN.2020030276}}</ref>
*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.<ref name="BussalinoDe Maria2020">{{cite journal|last1=Bussalino|first1=Elisabetta|last2=De Maria|first2=Andrea|last3=Russo|first3=Rodolfo|last4=Paoletti|first4=Ernesto|title=Immunosuppressive therapy maintenance in a kidney transplant recipient with SARS‐CoV‐2 pneumonia: A case report|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1922–1924|issn=1600-6135|doi=10.1111/ajt.15920}}</ref>
 
<ref name="SeminariColaneri2020">{{cite journal|last1=Seminari|first1=Elena|last2=Colaneri|first2=Marta|last3=Sambo|first3=Margherita|last4=Gallazzi|first4=Ilaria|last5=Di Matteo|first5=Angela|last6=Roda|first6=Silvia|last7=Bruno|first7=Raffaele|last8=Mondelli|first8=Mario U.|last9=Brunetti|first9=Enrico|last10=Maiocchi|first10=Laura|last11=Zuccaro|first11=Valentina|last12=Pagnucco|first12=Layla|last13=Mariani|first13=Bianca|last14=Ludovisi|first14=Serena|last15=Lissandrin|first15=Raffaella|last16=Parisi|first16=Aldo|last17=Sacchi|first17=Paolo|last18=Patruno|first18=Savino F. A.|last19=Michelone|first19=Giuseppe|last20=Gulminetti|first20=Roberto|last21=Zanaboni|first21=Domenico|last22=Novati|first22=Stefano|last23=Maserati|first23=Renato|last24=Orsolini|first24=Paolo|last25=Vecchia|first25=Marco|last26=Sciarra|first26=Marco|last27=Asperges|first27=Erika|last28=Di Filippo|first28=Alessandro|last29=Biscarini|first29=Simona|last30=Lupi|first30=Matteo|last31=Pieri|first31=Teresa C.|last32=Sachs|first32=Michele|last33=Valsecchi|first33=Pietro|last34=Perlini|first34=Stefano|last35=Alfano|first35=Claudia|last36=Bonzano|first36=Marco|last37=Briganti|first37=Federica|last38=Crescenzi|first38=Giuseppe|last39=Falchi|first39=Anna G.|last40=Guarnone|first40=Roberta|last41=Guglielmana|first41=Barbara|last42=Maggi|first42=Elena|last43=Martino|first43=Ilaria|last44=Pettenazza|first44=Pietro|last45=Pioli di Marco|first45=Serena|last46=Quaglia|first46=Federica|last47=Sabena|first47=Anna|last48=Salinaro|first48=Francesco|last49=Speciale|first49=Francesco|last50=Zunino|first50=Ilaria|last51=De Lorenzo|first51=Marzia|last52=Secco|first52=Gianmarco|last53=Dimitry|first53=Lorenzo|last54=Cappa|first54=Giovanni|last55=Maisak|first55=Igor|last56=Chiodi|first56=Benedetta|last57=Sciarrini|first57=Massimiliano|last58=Barcella|first58=Bruno|last59=Resta|first59=Flavia|last60=Moroni|first60=Luca|last61=Vezzoni|first61=Giulia|last62=Scattaglia|first62=Lorenzo|last63=Boscolo|first63=Elisa|last64=Zattera|first64=Caterina|last65=Fidel|first65=Tassi M.|last66=Vincenzo|first66=Capozza|last67=Vignaroli|first67=Damiano|last68=Bazzini|first68=Marco|last69=Iotti|first69=Giorgio|last70=Mojoli|first70=Francesco|last71=Belliato|first71=Mirko|last72=Perotti|first72=Luciano|last73=Mongodi|first73=Silvia|last74=Tavazzi|first74=Guido|last75=Marseglia|first75=Gianluigi|last76=Licari|first76=Amelia|last77=Brambilla|first77=Ilaria|last78=Daniela|first78=Barbarini|last79=Antonella|first79=Bruno|last80=Patrizia|first80=Cambieri|last81=Giulia|first81=Campanini|last82=Giuditta|first82=Comolli|last83=Marta|first83=Corbella|last84=Rossana|first84=Daturi|last85=Milena|first85=Furione|last86=Bianca|first86=Mariani|last87=Roberta|first87=Maserati|last88=Enza|first88=Monzillo|last89=Stefania|first89=Paolucci|last90=Maurizio|first90=Parea|last91=Elena|first91=Percivalle|last92=Antonio|first92=Piralla|last93=Francesca|first93=Rovida|last94=Antonella|first94=Sarasini|last95=Maurizio|first95=Zavattoni|last96=Guy|first96=Adzasehoun|last97=Laura|first97=Bellotti|last98=Ermanna|first98=Cabano|last99=Giuliana|first99=Casali|last100=Luca|first100=Dossena|last101=Gabriella|first101=Frisco|last102=Gabriella|first102=Garbagnoli|last103=Alessia|first103=Girello|last104=Viviana|first104=Landini|last105=Claudia|first105=Lucchelli|last106=Valentina|first106=Maliardi|last107=Simona|first107=Pezzaia|last108=Marta|first108=Premoli|last109=Alice|first109=Bonetti|last110=Giacomo|first110=Caneva|last111=Irene|first111=Cassaniti|last112=Alfonso|first112=Corcione|last113=Di Martino|first113=Raffella|last114=Di Napoli|first114=Annapia|last115=Alessandro|first115=Ferrari|last116=Guglielmo|first116=Ferrari|last117=Loretta|first117=Fiorina|last118=Federica|first118=Giardina|last119=Alessandra|first119=Mercato|last120=Federica|first120=Novazzi|last121=Giacomo|first121=Ratano|last122=Beatrice|first122=Rossi|last123=Maria|first123=Sciabica I.|last124=Monica|first124=Tallarita|last125=Edoardo|first125=Vecchio N.|last126=Cerino|first126=Antonella|last127=Varchetta|first127=Stefania|last128=Oliviero|first128=Barbara|last129=Mantovani|first129=Stefania|last130=Mele|first130=Dalila|last131=Calvi|first131=Monica|last132=Tizzonis|first132=Michela|last133=Nicora|first133=Carlo|last134=Triarico|first134=Antonio|last135=Petronella|first135=Vincenzo|last136=Marena|first136=Carlo|last137=Muzzi|first137=Alba|last138=Lago|first138=Paolo|last139=Comandatore|first139=Francesco|last140=Bissignandi|first140=Gherard|last141=Gaiarsa|first141=Stefano|last142=Rettani|first142=Marco|last143=Band|first143=Claudio|title=SARS Cov‐2 infection in a renal‐transplanted patient: A case report|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1882–1884|issn=1600-6135|doi=10.1111/ajt.15902}}</ref>
<ref name="MarxMoulin2020">{{cite journal|last1=Marx|first1=David|last2=Moulin|first2=Bruno|last3=Fafi‐Kremer|first3=Samira|last4=Benotmane|first4=Ilies|last5=Gautier|first5=Gabriela|last6=Perrin|first6=Peggy|last7=Caillard|first7=Sophie|title=First case of COVID‐19 in a kidney transplant recipient treated with belatacept|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1944–1946|issn=1600-6135|doi=10.1111/ajt.15919}}</ref>
<ref name="GandolfiniDelsante2020">{{cite journal|last1=Gandolfini|first1=Ilaria|last2=Delsante|first2=Marco|last3=Fiaccadori|first3=Enrico|last4=Zaza|first4=Gianluigi|last5=Manenti|first5=Lucio|last6=Degli Antoni|first6=Anna|last7=Peruzzi|first7=Licia|last8=Riella|first8=Leonardo V.|last9=Cravedi|first9=Paolo|last10=Maggiore|first10=Umberto|title=COVID‐19 in kidney transplant recipients|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1941–1943|issn=1600-6135|doi=10.1111/ajt.15891}}</ref>
<ref name="GuillenPineiro2020">{{cite journal|last1=Guillen|first1=Elena|last2=Pineiro|first2=Gaston J.|last3=Revuelta|first3=Ignacio|last4=Rodriguez|first4=Diana|last5=Bodro|first5=Marta|last6=Moreno|first6=Asunción|last7=Campistol|first7=Josep M.|last8=Diekmann|first8=Fritz|last9=Ventura‐Aguiar|first9=Pedro|title=Case report of COVID‐19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation?|journal=American Journal of Transplantation|volume=20|issue=7|year=2020|pages=1875–1878|issn=1600-6135|doi=10.1111/ajt.15874}}</ref>
<ref>{{cite journal|doi=10.1016/ S2213-2600(20)30182-X}}</ref>
<ref name="Haberal2020">{{cite journal|last1=Haberal|first1=Mehmet|title=COVID-19 UPDATE|journal=Experimental and Clinical Transplantation|volume=18|issue=2|year=2020|pages=139–140|issn=13040855|doi=10.6002/ect.2020.000e}}</ref>
<ref name="urlbts.org.uk">{{cite web |url=https://bts.org.uk/wp-content/uploads/2020/03/Clinical_management_transplant_recipients.pdf |title=bts.org.uk |format= |work= |accessdate=}}</ref><ref name="urlwww.europeanurology.com">{{cite web |url=https://www.europeanurology.com/article/S0302-2838(20)30211-6/pdf |title=www.europeanurology.com |format= |work= |accessdate=}}</ref>
*In general population, [[COVID-19]] associated [[Acute kidney injury|AKI]] has higher incidence in elderly.<ref name="PeiZhang2020">{{cite journal|last1=Pei|first1=Guangchang|last2=Zhang|first2=Zhiguo|last3=Peng|first3=Jing|last4=Liu|first4=Liu|last5=Zhang|first5=Chunxiu|last6=Yu|first6=Chong|last7=Ma|first7=Zufu|last8=Huang|first8=Yi|last9=Liu|first9=Wei|last10=Yao|first10=Ying|last11=Zeng|first11=Rui|last12=Xu|first12=Gang|title=Renal Involvement and Early Prognosis in Patients with COVID-19 Pneumonia|journal=Journal of the American Society of Nephrology|volume=31|issue=6|year=2020|pages=1157–1165|issn=1046-6673|doi=10.1681/ASN.2020030276}}</ref>


===Gender===
===Gender===
*Men are more likely to be affected by COVID_19 than women.<ref name="SharmaVolgman2020">{{cite journal|last1=Sharma|first1=Garima|last2=Volgman|first2=Annabelle Santos|last3=Michos|first3=Erin D.|title=Sex Differences in Mortality From COVID-19 Pandemic|journal=JACC: Case Reports|year=2020|issn=26660849|doi=10.1016/j.jaccas.2020.04.027}}</ref>
 
*Women dying from COVID-19 are generally elder than men(median age: 82 vs. 79 years for women vs. men, respectively).<ref name="SharmaVolgman2020">{{cite journal|last1=Sharma|first1=Garima|last2=Volgman|first2=Annabelle Santos|last3=Michos|first3=Erin D.|title=Sex Differences in Mortality From COVID-19 Pandemic|journal=JACC: Case Reports|year=2020|issn=26660849|doi=10.1016/j.jaccas.2020.04.027}}</ref>
*Men are more likely to be affected by [[COVID-19]] than women.<ref name="SharmaVolgman2020">{{cite journal|last1=Sharma|first1=Garima|last2=Volgman|first2=Annabelle Santos|last3=Michos|first3=Erin D.|title=Sex Differences in Mortality From COVID-19 Pandemic|journal=JACC: Case Reports|year=2020|issn=26660849|doi=10.1016/j.jaccas.2020.04.027}}</ref>
*Women dying from [[COVID-19]] are generally elder than men(median age: 82 vs. 79 years for women vs. men, respectively).<ref name="SharmaVolgman2020">{{cite journal|last1=Sharma|first1=Garima|last2=Volgman|first2=Annabelle Santos|last3=Michos|first3=Erin D.|title=Sex Differences in Mortality From COVID-19 Pandemic|journal=JACC: Case Reports|year=2020|issn=26660849|doi=10.1016/j.jaccas.2020.04.027}}</ref>
 
===Race===
===Race===
*There is no racial predilection for COVID-19 infection in renal transplant patients.
<nowiki>*</nowiki>According to study done in New York, 14 recipients (39%) were black, and 15 recipients (42%) were Hispanic.<ref name="AkalinAzzi2020">{{cite journal|last1=Akalin|first1=Enver|last2=Azzi|first2=Yorg|last3=Bartash|first3=Rachel|last4=Seethamraju|first4=Harish|last5=Parides|first5=Michael|last6=Hemmige|first6=Vagish|last7=Ross|first7=Michael|last8=Forest|first8=Stefanie|last9=Goldstein|first9=Yitz D.|last10=Ajaimy|first10=Maria|last11=Liriano-Ward|first11=Luz|last12=Pynadath|first12=Cindy|last13=Loarte-Campos|first13=Pablo|last14=Nandigam|first14=Purna B.|last15=Graham|first15=Jay|last16=Le|first16=Marie|last17=Rocca|first17=Juan|last18=Kinkhabwala|first18=Milan|title=Covid-19 and Kidney Transplantation|journal=New England Journal of Medicine|volume=382|issue=25|year=2020|pages=2475–2477|issn=0028-4793|doi=10.1056/NEJMc2011117}}</ref>


=Pathophysiology=
== Risk Factors ==
There are various factors that can predispose renal transplant patients to COVID-19.


* Acute Kidney Injury has been reported in patients with COVID-19 infection and presence of proteinuria, hematuria has also been reported. 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.<ref name="YangYu2020">{{cite journal|last1=Yang|first1=Xiaobo|last2=Yu|first2=Yuan|last3=Xu|first3=Jiqian|last4=Shu|first4=Huaqing|last5=Xia|first5=Jia'an|last6=Liu|first6=Hong|last7=Wu|first7=Yongran|last8=Zhang|first8=Lu|last9=Yu|first9=Zhui|last10=Fang|first10=Minghao|last11=Yu|first11=Ting|last12=Wang|first12=Yaxin|last13=Pan|first13=Shangwen|last14=Zou|first14=Xiaojing|last15=Yuan|first15=Shiying|last16=Shang|first16=You|title=Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study|journal=The Lancet Respiratory Medicine|volume=8|issue=5|year=2020|pages=475–481|issn=22132600|doi=10.1016/S2213-2600(20)30079-5}}</ref>
* Immunosuppression<ref name="ZhouYu2020">{{cite journal|last1=Zhou|first1=Fei|last2=Yu|first2=Ting|last3=Du|first3=Ronghui|last4=Fan|first4=Guohui|last5=Liu|first5=Ying|last6=Liu|first6=Zhibo|last7=Xiang|first7=Jie|last8=Wang|first8=Yeming|last9=Song|first9=Bin|last10=Gu|first10=Xiaoying|last11=Guan|first11=Lulu|last12=Wei|first12=Yuan|last13=Li|first13=Hui|last14=Wu|first14=Xudong|last15=Xu|first15=Jiuyang|last16=Tu|first16=Shengjin|last17=Zhang|first17=Yi|last18=Chen|first18=Hua|last19=Cao|first19=Bin|title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study|journal=The Lancet|volume=395|issue=10229|year=2020|pages=1054–1062|issn=01406736|doi=10.1016/S0140-6736(20)30566-3}}</ref>
*Acute Kidney Injury seen in COVID-19 infection can be from the cytotropic effect 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 . <ref name="ZhouYu2020">{{cite journal|last1=Zhou|first1=Fei|last2=Yu|first2=Ting|last3=Du|first3=Ronghui|last4=Fan|first4=Guohui|last5=Liu|first5=Ying|last6=Liu|first6=Zhibo|last7=Xiang|first7=Jie|last8=Wang|first8=Yeming|last9=Song|first9=Bin|last10=Gu|first10=Xiaoying|last11=Guan|first11=Lulu|last12=Wei|first12=Yuan|last13=Li|first13=Hui|last14=Wu|first14=Xudong|last15=Xu|first15=Jiuyang|last16=Tu|first16=Shengjin|last17=Zhang|first17=Yi|last18=Chen|first18=Hua|last19=Cao|first19=Bin|title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study|journal=The Lancet|volume=395|issue=10229|year=2020|pages=1054–1062|issn=01406736|doi=10.1016/S0140-6736(20)30566-3}}</ref>.  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, hemodynamic instability, and contrast exposure. <ref name="Beddhu2004">{{cite journal|last1=Beddhu|first1=Srinivasan|title=Hypothesis: The Body Mass Index Paradox and an Obesity, Inflammation, and Atherosclerosis Syndrome in Chronic Kidney Disease|journal=Seminars in Dialysis|volume=17|issue=3|year=2004|pages=229–232|issn=08940959|doi=10.1111/j.0894-0959.2004.17311.x}}</ref> <ref name="MohamedLukitsch2020">{{cite journal|last1=Mohamed|first1=Muner MB|last2=Lukitsch|first2=Ivo|last3=Torres-Ortiz|first3=Aldo E|last4=Walker|first4=Joseph B|last5=Varghese|first5=Vipin|last6=Hernandez-Arroyo|first6=Cesar F|last7=Alqudsi|first7=Muhannad|last8=LeDoux|first8=Jason R|last9=Velez|first9=Juan Carlos Q|title=Acute Kidney Injury Associated with Coronavirus Disease 2019 in Urban New Orleans|journal=Kidney360|year=2020|pages=10.34067/KID.0002652020|issn=2641-7650|doi=10.34067/KID.0002652020}}</ref>
* Chronic Renal Failure<ref name="ZhouYu2020">{{cite journal|last1=Zhou|first1=Fei|last2=Yu|first2=Ting|last3=Du|first3=Ronghui|last4=Fan|first4=Guohui|last5=Liu|first5=Ying|last6=Liu|first6=Zhibo|last7=Xiang|first7=Jie|last8=Wang|first8=Yeming|last9=Song|first9=Bin|last10=Gu|first10=Xiaoying|last11=Guan|first11=Lulu|last12=Wei|first12=Yuan|last13=Li|first13=Hui|last14=Wu|first14=Xudong|last15=Xu|first15=Jiuyang|last16=Tu|first16=Shengjin|last17=Zhang|first17=Yi|last18=Chen|first18=Hua|last19=Cao|first19=Bin|title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study|journal=The Lancet|volume=395|issue=10229|year=2020|pages=1054–1062|issn=01406736|doi=10.1016/S0140-6736(20)30566-3}}</ref><ref name="BanerjeePopoola2020">{{cite journal|last1=Banerjee|first1=Debasish|last2=Popoola|first2=Joyce|last3=Shah|first3=Sapna|last4=Ster|first4=Irina Chis|last5=Quan|first5=Virginia|last6=Phanish|first6=Mysore|title=COVID-19 infection in kidney transplant recipients|journal=Kidney International|volume=97|issue=6|year=2020|pages=1076–1082|issn=00852538|doi=10.1016/j.kint.2020.03.018}}</ref>
*Uptake of SARS-Cov-2 virus into proximal tubule cells is possible explanation for the AKI seen in COVID patients. Angiotensin-converting enzyme 2 and Dipeptidyl peptidase have been implicated in the uptake of SARS-Cov and MERS-CoV. These receptors are found in the proximal tubules of kidney..<ref name="LiMoore2003">{{cite journal|last1=Li|first1=Wenhui|last2=Moore|first2=Michael J.|last3=Vasilieva|first3=Natalya|last4=Sui|first4=Jianhua|last5=Wong|first5=Swee Kee|last6=Berne|first6=Michael A.|last7=Somasundaran|first7=Mohan|last8=Sullivan|first8=John L.|last9=Luzuriaga|first9=Katherine|last10=Greenough|first10=Thomas C.|last11=Choe|first11=Hyeryun|last12=Farzan|first12=Michael|title=Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus|journal=Nature|volume=426|issue=6965|year=2003|pages=450–454|issn=0028-0836|doi=10.1038/nature02145}}</ref><ref name="RajMou2013">{{cite journal|last1=Raj|first1=V. Stalin|last2=Mou|first2=Huihui|last3=Smits|first3=Saskia L.|last4=Dekkers|first4=Dick H. W.|last5=Müller|first5=Marcel A.|last6=Dijkman|first6=Ronald|last7=Muth|first7=Doreen|last8=Demmers|first8=Jeroen A. A.|last9=Zaki|first9=Ali|last10=Fouchier|first10=Ron A. M.|last11=Thiel|first11=Volker|last12=Drosten|first12=Christian|last13=Rottier|first13=Peter J. M.|last14=Osterhaus|first14=Albert D. M. E.|last15=Bosch|first15=Berend Jan|last16=Haagmans|first16=Bart L.|title=Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC|journal=Nature|volume=495|issue=7440|year=2013|pages=251–254|issn=0028-0836|doi=10.1038/nature12005}}</ref>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)).<ref name="MalhaMueller2020">{{cite journal|last1=Malha|first1=Line|last2=Mueller|first2=Franco B.|last3=Pecker|first3=Mark S.|last4=Mann|first4=Samuel J.|last5=August|first5=Phyllis|last6=Feig|first6=Peter U.|title=COVID-19 and the Renin-Angiotensin System|journal=Kidney International Reports|volume=5|issue=5|year=2020|pages=563–565|issn=24680249|doi=10.1016/j.ekir.2020.03.024}}</ref>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..<ref name="PanXu2020">{{cite journal|last1=Pan|first1=Xiu-wu|last2=Xu|first2=Da|last3=Zhang|first3=Hao|last4=Zhou|first4=Wang|last5=Wang|first5=Lin-hui|last6=Cui|first6=Xin-gang|title=Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis|journal=Intensive Care Medicine|volume=46|issue=6|year=2020|pages=1114–1116|issn=0342-4642|doi=10.1007/s00134-020-06026-1}}</ref>
* Co-Morbidities<ref name="ZhouYu2020">{{cite journal|last1=Zhou|first1=Fei|last2=Yu|first2=Ting|last3=Du|first3=Ronghui|last4=Fan|first4=Guohui|last5=Liu|first5=Ying|last6=Liu|first6=Zhibo|last7=Xiang|first7=Jie|last8=Wang|first8=Yeming|last9=Song|first9=Bin|last10=Gu|first10=Xiaoying|last11=Guan|first11=Lulu|last12=Wei|first12=Yuan|last13=Li|first13=Hui|last14=Wu|first14=Xudong|last15=Xu|first15=Jiuyang|last16=Tu|first16=Shengjin|last17=Zhang|first17=Yi|last18=Chen|first18=Hua|last19=Cao|first19=Bin|title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study|journal=The Lancet|volume=395|issue=10229|year=2020|pages=1054–1062|issn=01406736|doi=10.1016/S0140-6736(20)30566-3}}</ref>
*Pro-inflammatory cytokine levels are elevated in the COVID-19 infection and there is activation of T-call response.  <ref name="HuangWang2020">{{cite journal|last1=Huang|first1=Chaolin|last2=Wang|first2=Yeming|last3=Li|first3=Xingwang|last4=Ren|first4=Lili|last5=Zhao|first5=Jianping|last6=Hu|first6=Yi|last7=Zhang|first7=Li|last8=Fan|first8=Guohui|last9=Xu|first9=Jiuyang|last10=Gu|first10=Xiaoying|last11=Cheng|first11=Zhenshun|last12=Yu|first12=Ting|last13=Xia|first13=Jiaan|last14=Wei|first14=Yuan|last15=Wu|first15=Wenjuan|last16=Xie|first16=Xuelei|last17=Yin|first17=Wen|last18=Li|first18=Hui|last19=Liu|first19=Min|last20=Xiao|first20=Yan|last21=Gao|first21=Hong|last22=Guo|first22=Li|last23=Xie|first23=Jungang|last24=Wang|first24=Guangfa|last25=Jiang|first25=Rongmeng|last26=Gao|first26=Zhancheng|last27=Jin|first27=Qi|last28=Wang|first28=Jianwei|last29=Cao|first29=Bin|title=Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China|journal=The Lancet|volume=395|issue=10223|year=2020|pages=497–506|issn=01406736|doi=10.1016/S0140-6736(20)30183-5}}</ref>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.<ref name="PanXu2020">{{cite journal|last1=Pan|first1=Xiu-wu|last2=Xu|first2=Da|last3=Zhang|first3=Hao|last4=Zhou|first4=Wang|last5=Wang|first5=Lin-hui|last6=Cui|first6=Xin-gang|title=Identification of a potential mechanism of acute kidney injury during the COVID-19 outbreak: a study based on single-cell transcriptome analysis|journal=Intensive Care Medicine|volume=46|issue=6|year=2020|pages=1114–1116|issn=0342-4642|doi=10.1007/s00134-020-06026-1}}</ref> According to an autopsy report of six patients, the light microscopy revealed cluster of differentiation 68 (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<ref name="DiaoWang2020">{{cite journal|last1=Diao|first1=Bo|last2=Wang|first2=Chenhui|last3=Wang|first3=Rongshuai|last4=Feng|first4=Zeqing|last5=Tan|first5=Yingjun|last6=Wang|first6=Huiming|last7=Wang|first7=Changsong|last8=Liu|first8=Liang|last9=Liu|first9=Ying|last10=Liu|first10=Yueping|last11=Wang|first11=Gang|last12=Yuan|first12=Zilin|last13=Ren|first13=Liang|last14=Wu|first14=Yuzhang|last15=Chen|first15=Yongwen|year=2020|doi=10.1101/2020.03.04.20031120}}</ref>
** Diabetes
** Hypertension
** Hyperlipidemia
** H/o Heart Disease
* Male Sex<ref name="AkalinAzzi2020">{{cite journal|last1=Akalin|first1=Enver|last2=Azzi|first2=Yorg|last3=Bartash|first3=Rachel|last4=Seethamraju|first4=Harish|last5=Parides|first5=Michael|last6=Hemmige|first6=Vagish|last7=Ross|first7=Michael|last8=Forest|first8=Stefanie|last9=Goldstein|first9=Yitz D.|last10=Ajaimy|first10=Maria|last11=Liriano-Ward|first11=Luz|last12=Pynadath|first12=Cindy|last13=Loarte-Campos|first13=Pablo|last14=Nandigam|first14=Purna B.|last15=Graham|first15=Jay|last16=Le|first16=Marie|last17=Rocca|first17=Juan|last18=Kinkhabwala|first18=Milan|title=Covid-19 and Kidney Transplantation|journal=New England Journal of Medicine|volume=382|issue=25|year=2020|pages=2475–2477|issn=0028-4793|doi=10.1056/NEJMc2011117}}</ref><ref name="NacifZanini2020">{{cite journal|last1=Nacif|first1=Lucas Souto|last2=Zanini|first2=Leonardo Y.|last3=Waisberg|first3=Daniel R.|last4=Pinheiro|first4=Rafael S.|last5=Galvão|first5=Flávio|last6=Andraus|first6=Wellington|last7=D'Albuquerque|first7=Luiz Carneiro|title=COVID-19 in solid organ transplantation patients: A systematic review|journal=Clinics|volume=75|year=2020|issn=1807-5932|doi=10.6061/clinics/2020/e1983}}</ref>
* Old Age<ref name="AkalinAzzi2020">{{cite journal|last1=Akalin|first1=Enver|last2=Azzi|first2=Yorg|last3=Bartash|first3=Rachel|last4=Seethamraju|first4=Harish|last5=Parides|first5=Michael|last6=Hemmige|first6=Vagish|last7=Ross|first7=Michael|last8=Forest|first8=Stefanie|last9=Goldstein|first9=Yitz D.|last10=Ajaimy|first10=Maria|last11=Liriano-Ward|first11=Luz|last12=Pynadath|first12=Cindy|last13=Loarte-Campos|first13=Pablo|last14=Nandigam|first14=Purna B.|last15=Graham|first15=Jay|last16=Le|first16=Marie|last17=Rocca|first17=Juan|last18=Kinkhabwala|first18=Milan|title=Covid-19 and Kidney Transplantation|journal=New England Journal of Medicine|volume=382|issue=25|year=2020|pages=2475–2477|issn=0028-4793|doi=10.1056/NEJMc2011117}}</ref><ref name="NacifZanini2020">{{cite journal|last1=Nacif|first1=Lucas Souto|last2=Zanini|first2=Leonardo Y.|last3=Waisberg|first3=Daniel R.|last4=Pinheiro|first4=Rafael S.|last5=Galvão|first5=Flávio|last6=Andraus|first6=Wellington|last7=D'Albuquerque|first7=Luiz Carneiro|title=COVID-19 in solid organ transplantation patients: A systematic review|journal=Clinics|volume=75|year=2020|issn=1807-5932|doi=10.6061/clinics/2020/e1983}}</ref>
* Current or h/o smoking tobacco<ref name="AkalinAzzi2020">{{cite journal|last1=Akalin|first1=Enver|last2=Azzi|first2=Yorg|last3=Bartash|first3=Rachel|last4=Seethamraju|first4=Harish|last5=Parides|first5=Michael|last6=Hemmige|first6=Vagish|last7=Ross|first7=Michael|last8=Forest|first8=Stefanie|last9=Goldstein|first9=Yitz D.|last10=Ajaimy|first10=Maria|last11=Liriano-Ward|first11=Luz|last12=Pynadath|first12=Cindy|last13=Loarte-Campos|first13=Pablo|last14=Nandigam|first14=Purna B.|last15=Graham|first15=Jay|last16=Le|first16=Marie|last17=Rocca|first17=Juan|last18=Kinkhabwala|first18=Milan|title=Covid-19 and Kidney Transplantation|journal=New England Journal of Medicine|volume=382|issue=25|year=2020|pages=2475–2477|issn=0028-4793|doi=10.1056/NEJMc2011117}}</ref>


=Lab Findings=
* Possible a/w donor COVID-19 infection<ref name="NacifZanini2020">{{cite journal|last1=Nacif|first1=Lucas Souto|last2=Zanini|first2=Leonardo Y.|last3=Waisberg|first3=Daniel R.|last4=Pinheiro|first4=Rafael S.|last5=Galvão|first5=Flávio|last6=Andraus|first6=Wellington|last7=D'Albuquerque|first7=Luiz Carneiro|title=COVID-19 in solid organ transplantation patients: A systematic review|journal=Clinics|volume=75|year=2020|issn=1807-5932|doi=10.6061/clinics/2020/e1983}}</ref>
 
== 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.
Presenting symptoms in renal transplant patients are similar to those of non-renal transplant patients.
*Respiratory symptons
*Respiratory symptons
**Cough
**Cough
Line 40: Line 247:
*Hypoxia
*Hypoxia
*Lymphopenia
*Lymphopenia
*High C-Reactive Protein<ref name="BanerjeePopoola2020">{{cite journal|last1=Banerjee|first1=Debasish|last2=Popoola|first2=Joyce|last3=Shah|first3=Sapna|last4=Ster|first4=Irina Chis|last5=Quan|first5=Virginia|last6=Phanish|first6=Mysore|title=COVID-19 infection in kidney transplant recipients|journal=Kidney International|volume=97|issue=6|year=2020|pages=1076–1082|issn=00852538|doi=10.1016/j.kint.2020.03.018}}</ref>
*High C-Reactive Protein<ref name="BanerjeePopoola20202">{{cite journal|last1=Banerjee|first1=Debasish|last2=Popoola|first2=Joyce|last3=Shah|first3=Sapna|last4=Ster|first4=Irina Chis|last5=Quan|first5=Virginia|last6=Phanish|first6=Mysore|title=COVID-19 infection in kidney transplant recipients|journal=Kidney International|volume=97|issue=6|year=2020|pages=1076–1082|issn=00852538|doi=10.1016/j.kint.2020.03.018}}</ref>


Valuable prognostic blood tests that can be done are
Valuable prognostic blood tests that can be done are
*Lymphocyte count
 
* 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.
**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
*D-dimer
*Ferritin
*Ferritin
*Troponin
*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.<ref name="BanerjeePopoola2020">{{cite journal|last1=Banerjee|first1=Debasish|last2=Popoola|first2=Joyce|last3=Shah|first3=Sapna|last4=Ster|first4=Irina Chis|last5=Quan|first5=Virginia|last6=Phanish|first6=Mysore|title=COVID-19 infection in kidney transplant recipients|journal=Kidney International|volume=97|issue=6|year=2020|pages=1076–1082|issn=00852538|doi=10.1016/j.kint.2020.03.018}}</ref>
**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.<ref name="BanerjeePopoola20202">{{cite journal|last1=Banerjee|first1=Debasish|last2=Popoola|first2=Joyce|last3=Shah|first3=Sapna|last4=Ster|first4=Irina Chis|last5=Quan|first5=Virginia|last6=Phanish|first6=Mysore|title=COVID-19 infection in kidney transplant recipients|journal=Kidney International|volume=97|issue=6|year=2020|pages=1076–1082|issn=00852538|doi=10.1016/j.kint.2020.03.018}}</ref>
 
 
===Past Medical History===
 
=== Laboratory Findings ===
 
==== Electrolyte and Biomarker Studies ====
 
==== Electrocardiogram ====
 
==== Chest X Ray ====


=Management of immunosuppression in Transplant patients=
====CT ====
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. <ref name="ZhuXu2020">{{cite journal|last1=Zhu|first1=Lan|last2=Xu|first2=Xizhen|last3=Ma|first3=Ke|last4=Yang|first4=Junling|last5=Guan|first5=Hanxiong|last6=Chen|first6=Song|last7=Chen|first7=Zhishui|last8=Chen|first8=Gang|title=Successful recovery of COVID‐19 pneumonia in a renal transplant recipient with long‐term immunosuppression|journal=American Journal of Transplantation|year=2020|issn=1600-6135|doi=10.1111/ajt.15869}}</ref>   


*Clinical presentation of COVID-19 infection in renal transplant patients are like the clinical presentations of infection in general population. <ref name="ZhuXu2020">{{cite journal|last1=Zhu|first1=Lan|last2=Xu|first2=Xizhen|last3=Ma|first3=Ke|last4=Yang|first4=Junling|last5=Guan|first5=Hanxiong|last6=Chen|first6=Song|last7=Chen|first7=Zhishui|last8=Chen|first8=Gang|title=Successful recovery of COVID‐19 pneumonia in a renal transplant recipient with long‐term immunosuppression|journal=American Journal of Transplantation|year=2020|issn=1600-6135|doi=10.1111/ajt.15869}}</ref>.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.<ref name="pmid32354637">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>  
==== MRI ====
 
==== Echocardiography or Ultrasound ====
 
==== Other Imaging Findings ====
 
=== Other Diagnostic Studies ===
 
== Treatment ==
=== Pharmacotherapy ===
 
==== Acute Pharmacotherapies ====
 
==== Chronic Pharmacotherapies ====
<br />
 
=== 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. <ref name="ZhuXu20202">{{cite journal|last1=Zhu|first1=Lan|last2=Xu|first2=Xizhen|last3=Ma|first3=Ke|last4=Yang|first4=Junling|last5=Guan|first5=Hanxiong|last6=Chen|first6=Song|last7=Chen|first7=Zhishui|last8=Chen|first8=Gang|title=Successful recovery of COVID‐19 pneumonia in a renal transplant recipient with long‐term immunosuppression|journal=American Journal of Transplantation|year=2020|issn=1600-6135|doi=10.1111/ajt.15869}}</ref>
 
*Clinical presentation of COVID-19 infection in renal transplant patients are like the clinical presentations of infection in general population. <ref name="ZhuXu20202">{{cite journal|last1=Zhu|first1=Lan|last2=Xu|first2=Xizhen|last3=Ma|first3=Ke|last4=Yang|first4=Junling|last5=Guan|first5=Hanxiong|last6=Chen|first6=Song|last7=Chen|first7=Zhishui|last8=Chen|first8=Gang|title=Successful recovery of COVID‐19 pneumonia in a renal transplant recipient with long‐term immunosuppression|journal=American Journal of Transplantation|year=2020|issn=1600-6135|doi=10.1111/ajt.15869}}</ref>.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.<ref name="pmid32354637">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>
*'''Managing the immunosuppression in renal transplant patients is difficult and should be based on'''<ref name="pmid32354637">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>
*'''Managing the immunosuppression in renal transplant patients is difficult and should be based on'''<ref name="pmid32354637">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>
**Age
**Age
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*''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.''<ref name="pmid32354637">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>
*''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.''<ref name="pmid32354637">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>


=Treatment=
=== Immuno Drugs ===
==Immunosuppresant Drugs==
<br />
*'''Antiproliferative agents such as MMF and azathioprine '''<ref name="pmid32354637">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>
 
**Should be stopped at the time of admission to hospital
*'''Antiproliferative agents such as MMF and azathioprine '''<ref name="pmid323546372">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>
*'''Prednisolone'''<ref name="pmid32354637">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>
** Should be stopped at the time of admission to hospital
*'''Prednisolone'''<ref name="pmid323546372">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>


**The dosage can be either increased or left unchanged. These can provide immunological protection to the renal graft.
**The dosage can be either increased or left unchanged. These can provide immunological protection to the renal graft.
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****Reduction of white blood cell traffic
****Reduction of white blood cell traffic
***''Vascular protective effects''
***''Vascular protective effects''
****Maintenance of integrity and permeability of endothelium.  <ref name="LansburyRodrigo2020">{{cite journal|last1=Lansbury|first1=Louise E.|last2=Rodrigo|first2=Chamira|last3=Leonardi-Bee|first3=Jo|last4=Nguyen-Van-Tam|first4=Jonathan|last5=Shen Lim|first5=Wei|title=Corticosteroids as Adjunctive Therapy in the Treatment of Influenza|journal=Critical Care Medicine|volume=48|issue=2|year=2020|pages=e98–e106|issn=0090-3493|doi=10.1097/CCM.0000000000004093}}</ref> <ref name="pmid32354637">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>
**** Maintenance of integrity and permeability of endothelium.  <ref name="LansburyRodrigo2020">{{cite journal|last1=Lansbury|first1=Louise E.|last2=Rodrigo|first2=Chamira|last3=Leonardi-Bee|first3=Jo|last4=Nguyen-Van-Tam|first4=Jonathan|last5=Shen Lim|first5=Wei|title=Corticosteroids as Adjunctive Therapy in the Treatment of Influenza|journal=Critical Care Medicine|volume=48|issue=2|year=2020|pages=e98–e106|issn=0090-3493|doi=10.1097/CCM.0000000000004093}}</ref> <ref name="pmid323546372">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>
*'''Tacrolimus'''<ref name="pmid32354637">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>
*'''Tacrolimus'''<ref name="pmid323546372">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>


**Low doses of tacrolimus can be given but more evidence is required.<ref name="pmid32354637">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>
**Low doses of tacrolimus can be given but more evidence is required.<ref name="pmid323546372">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>


**The dose should be reduced to 50%. Target levels for tacrolimus should be 3-5 ng/ml.<ref name="urlwww.massgeneral.org">{{cite web |url=https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/mass-general-COVID-19-treatment-guidance.pdf |title=www.massgeneral.org |format= |work= |accessdate=}}</ref>
**The dose should be reduced to 50%. Target levels for tacrolimus should be 3-5 ng/ml.<ref name="urlwww.massgeneral.org">{{cite web |url=https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/mass-general-COVID-19-treatment-guidance.pdf |title=www.massgeneral.org |format= |work= |accessdate=}}</ref>
*'''Tocilizumab'''.<ref name="pmid32354637">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>
*'''Tocilizumab'''.<ref name="pmid323546372">{{cite journal |vauthors=Banerjee D, Popoola J, Shah S, Ster IC, Quan V, Phanish M |title=COVID-19 infection in kidney transplant recipients |journal=Kidney Int. |volume=97 |issue=6 |pages=1076–1082 |date=June 2020 |pmid=32354637 |pmc=7142878 |doi=10.1016/j.kint.2020.03.018 |url=}}</ref>


**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.
**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.
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**Cyclosporine levels should be targeted at 25-50 ng/ml.<ref name="urlwww.massgeneral.org">{{cite web |url=https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/mass-general-COVID-19-treatment-guidance.pdf |title=www.massgeneral.org |format= |work= |accessdate=}}</ref>
**Cyclosporine levels should be targeted at 25-50 ng/ml.<ref name="urlwww.massgeneral.org">{{cite web |url=https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/mass-general-COVID-19-treatment-guidance.pdf |title=www.massgeneral.org |format= |work= |accessdate=}}</ref>


==Medical Therapy==
<br />
*With regard to specific antiviral therapies, although a recent trial showed no benefit of lopinavir-ritonavir in hospitalized patients with severe COVID-19, it remains possible that treatment with these drugs as well as hydroxychloroquine will be considered in patients with COVID-19 pneumonia.<ref name="CaoWang2020">{{cite journal|last1=Cao|first1=Bin|last2=Wang|first2=Yeming|last3=Wen|first3=Danning|last4=Liu|first4=Wen|last5=Wang|first5=Jingli|last6=Fan|first6=Guohui|last7=Ruan|first7=Lianguo|last8=Song|first8=Bin|last9=Cai|first9=Yanping|last10=Wei|first10=Ming|last11=Li|first11=Xingwang|last12=Xia|first12=Jiaan|last13=Chen|first13=Nanshan|last14=Xiang|first14=Jie|last15=Yu|first15=Ting|last16=Bai|first16=Tao|last17=Xie|first17=Xuelei|last18=Zhang|first18=Li|last19=Li|first19=Caihong|last20=Yuan|first20=Ye|last21=Chen|first21=Hua|last22=Li|first22=Huadong|last23=Huang|first23=Hanping|last24=Tu|first24=Shengjing|last25=Gong|first25=Fengyun|last26=Liu|first26=Ying|last27=Wei|first27=Yuan|last28=Dong|first28=Chongya|last29=Zhou|first29=Fei|last30=Gu|first30=Xiaoying|last31=Xu|first31=Jiuyang|last32=Liu|first32=Zhibo|last33=Zhang|first33=Yi|last34=Li|first34=Hui|last35=Shang|first35=Lianhan|last36=Wang|first36=Ke|last37=Li|first37=Kunxia|last38=Zhou|first38=Xia|last39=Dong|first39=Xuan|last40=Qu|first40=Zhaohui|last41=Lu|first41=Sixia|last42=Hu|first42=Xujuan|last43=Ruan|first43=Shunan|last44=Luo|first44=Shanshan|last45=Wu|first45=Jing|last46=Peng|first46=Lu|last47=Cheng|first47=Fang|last48=Pan|first48=Lihong|last49=Zou|first49=Jun|last50=Jia|first50=Chunmin|last51=Wang|first51=Juan|last52=Liu|first52=Xia|last53=Wang|first53=Shuzhen|last54=Wu|first54=Xudong|last55=Ge|first55=Qin|last56=He|first56=Jing|last57=Zhan|first57=Haiyan|last58=Qiu|first58=Fang|last59=Guo|first59=Li|last60=Huang|first60=Chaolin|last61=Jaki|first61=Thomas|last62=Hayden|first62=Frederick G.|last63=Horby|first63=Peter W.|last64=Zhang|first64=Dingyu|last65=Wang|first65=Chen|title=A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19|journal=New England Journal of Medicine|volume=382|issue=19|year=2020|pages=1787–1799|issn=0028-4793|doi=10.1056/NEJMoa2001282}}</ref>  
=== Surgery and Device Based Therapy ===  
*Remdesiver inhibits the viral replication by pre mature termination of RNA transcription, and have shown activity in vitro against the viral agent.<ref name="WangCao2020">{{cite journal|last1=Wang|first1=Manli|last2=Cao|first2=Ruiyuan|last3=Zhang|first3=Leike|last4=Yang|first4=Xinglou|last5=Liu|first5=Jia|last6=Xu|first6=Mingyue|last7=Shi|first7=Zhengli|last8=Hu|first8=Zhihong|last9=Zhong|first9=Wu|last10=Xiao|first10=Gengfu|title=Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro|journal=Cell Research|volume=30|issue=3|year=2020|pages=269–271|issn=1001-0602|doi=10.1038/s41422-020-0282-0}}</ref>Food and Drug Administration (FDA) in the USA has authorized its use in patients hospitalized with COVID-19.It is not recommended in patients with lower GFR (GFR < 30 mL/min).<ref name="SandersMonogue2020">{{cite journal|last1=Sanders|first1=James M.|last2=Monogue|first2=Marguerite L.|last3=Jodlowski|first3=Tomasz Z.|last4=Cutrell|first4=James B.|title=Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19)|journal=JAMA|year=2020|issn=0098-7484|doi=10.1001/jama.2020.6019}}</ref>
*The choice of calcineurin inhibitor may also be beneficial. For example, 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.<ref name="de WildeZevenhoven-Dobbe2011">{{cite journal|last1=de Wilde|first1=Adriaan H.|last2=Zevenhoven-Dobbe|first2=Jessika C.|last3=van der Meer|first3=Yvonne|last4=Thiel|first4=Volker|last5=Narayanan|first5=Krishna|last6=Makino|first6=Shinji|last7=Snijder|first7=Eric J.|last8=van Hemert|first8=Martijn J.|title=Cyclosporin A inhibits the replication of diverse coronaviruses|journal=
Journal of General Virology
|volume=92|issue=11|year=2011|pages=2542–2548|issn=0022-1317|doi=10.1099/vir.0.034983-0}}</ref><ref name="TanakaSato2013">{{cite journal|last1=Tanaka|first1=Yoshikazu|last2=Sato|first2=Yuka|last3=Sasaki|first3=Takashi|title=Suppression of Coronavirus Replication by Cyclophilin Inhibitors|journal=Viruses|volume=5|issue=5|year=2013|pages=1250–1260|issn=1999-4915|doi=10.3390/v5051250}}</ref>


==Primary Prevention==
==== Indications for Surgery ====
*Currently no vaccine has been developed against the SARS-CoV 2 virus.<ref name="AdapaChenna2020">{{cite journal|last1=Adapa|first1=Sreedhar|last2=Chenna|first2=Avantika|last3=Balla|first3=Mamtha|last4=Merugu|first4=Ganesh Prasad|last5=Koduri|first5=Narayana Murty|last6=Daggubati|first6=Subba Rao|last7=Gayam|first7=Vijay|last8=Naramala|first8=Srikanth|last9=Konala|first9=Venu Madhav|title=COVID-19 Pandemic Causing Acute Kidney Injury and Impact on Patients With Chronic Kidney Disease and Renal Transplantation|journal=Journal of Clinical Medicine Research|volume=12|issue=6|year=2020|pages=352–361|issn=1918-3003|doi=10.14740/jocmr4200}}</ref>


==General Measures for Renal transplant Patients==
==== Pre-Operative Assessment ====


*The kidney transplant population must comply with the recommended measures of protection in the general population. Physicians can recommend the use of a mask on an individual basis, especially when the patient goes to health center or other place with agglomeration. People who show symptoms of being infected with SARS-CoV-2 should wear masks to prevent the spread of the disease to others..<ref name="LópezVázquez2020">{{cite journal|last1=López|first1=Verónica|last2=Vázquez|first2=Teresa|last3=Alonso-Titos|first3=Juana|last4=Cabello|first4=Mercedes|last5=Alonso|first5=Angel|last6=Beneyto|first6=Isabel|last7=Crespo|first7=Marta|last8=Díaz-Corte|first8=Carmen|last9=Franco|first9=Antonio|last10=González-Roncero|first10=Francisco|last11=Gutiérrez|first11=Elena|last12=Guirado|first12=Luis|last13=Jiménez|first13=Carlos|last14=Jironda|first14=Cristina|last15=Lauzurica|first15=Ricardo|last16=Llorente|first16=Santiago|last17=Mazuecos|first17=Auxiliadora|last18=Paul|first18=Javier|last19=Rodríguez-Benot|first19=Alberto|last20=Ruiz|first20=Juan Carlos|last21=Sánchez-Fructuoso|first21=Ana|last22=Sola|first22=Eugenia|last23=Torregrosa|first23=Vicente|last24=Zárraga|first24=Sofía|last25=Hernández|first25=Domingo|title=Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients|journal=Nefrología (English Edition)|year=2020|issn=20132514|doi=10.1016/j.nefroe.2020.03.017}}</ref>
==== Post-Operative Management ====
*It is prudent to approve a sick leave in patients whose profession involves a high hazard for disease.<ref name="LópezVázquez2020">{{cite journal|last1=López|first1=Verónica|last2=Vázquez|first2=Teresa|last3=Alonso-Titos|first3=Juana|last4=Cabello|first4=Mercedes|last5=Alonso|first5=Angel|last6=Beneyto|first6=Isabel|last7=Crespo|first7=Marta|last8=Díaz-Corte|first8=Carmen|last9=Franco|first9=Antonio|last10=González-Roncero|first10=Francisco|last11=Gutiérrez|first11=Elena|last12=Guirado|first12=Luis|last13=Jiménez|first13=Carlos|last14=Jironda|first14=Cristina|last15=Lauzurica|first15=Ricardo|last16=Llorente|first16=Santiago|last17=Mazuecos|first17=Auxiliadora|last18=Paul|first18=Javier|last19=Rodríguez-Benot|first19=Alberto|last20=Ruiz|first20=Juan Carlos|last21=Sánchez-Fructuoso|first21=Ana|last22=Sola|first22=Eugenia|last23=Torregrosa|first23=Vicente|last24=Zárraga|first24=Sofía|last25=Hernández|first25=Domingo|title=Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients|journal=Nefrología (English Edition)|year=2020|issn=20132514|doi=10.1016/j.nefroe.2020.03.017}}</ref>
*It is recommended to screen kidney transplant patients through teleconsultation so as to decrease the time spent in healthcare centers and decrease the risk of infection <ref name="LópezVázquez2020">{{cite journal|last1=López|first1=Verónica|last2=Vázquez|first2=Teresa|last3=Alonso-Titos|first3=Juana|last4=Cabello|first4=Mercedes|last5=Alonso|first5=Angel|last6=Beneyto|first6=Isabel|last7=Crespo|first7=Marta|last8=Díaz-Corte|first8=Carmen|last9=Franco|first9=Antonio|last10=González-Roncero|first10=Francisco|last11=Gutiérrez|first11=Elena|last12=Guirado|first12=Luis|last13=Jiménez|first13=Carlos|last14=Jironda|first14=Cristina|last15=Lauzurica|first15=Ricardo|last16=Llorente|first16=Santiago|last17=Mazuecos|first17=Auxiliadora|last18=Paul|first18=Javier|last19=Rodríguez-Benot|first19=Alberto|last20=Ruiz|first20=Juan Carlos|last21=Sánchez-Fructuoso|first21=Ana|last22=Sola|first22=Eugenia|last23=Torregrosa|first23=Vicente|last24=Zárraga|first24=Sofía|last25=Hernández|first25=Domingo|title=Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients|journal=Nefrología (English Edition)|year=2020|issn=20132514|doi=10.1016/j.nefroe.2020.03.017}}</ref>
*Maintenance of general hygiene. Washing your hands as often as possible with cleanser and water, or with a alcohol based hand sanitizer (60% alc), particularly: after utilizing the restroom, before eating, in the wake of blowing, coughing or sneezing and after direct contact with patient or their surroundings. Abstain from touching your eyes, nose and mouth before washing your hands.<ref name="LópezVázquez2020">{{cite journal|last1=López|first1=Verónica|last2=Vázquez|first2=Teresa|last3=Alonso-Titos|first3=Juana|last4=Cabello|first4=Mercedes|last5=Alonso|first5=Angel|last6=Beneyto|first6=Isabel|last7=Crespo|first7=Marta|last8=Díaz-Corte|first8=Carmen|last9=Franco|first9=Antonio|last10=González-Roncero|first10=Francisco|last11=Gutiérrez|first11=Elena|last12=Guirado|first12=Luis|last13=Jiménez|first13=Carlos|last14=Jironda|first14=Cristina|last15=Lauzurica|first15=Ricardo|last16=Llorente|first16=Santiago|last17=Mazuecos|first17=Auxiliadora|last18=Paul|first18=Javier|last19=Rodríguez-Benot|first19=Alberto|last20=Ruiz|first20=Juan Carlos|last21=Sánchez-Fructuoso|first21=Ana|last22=Sola|first22=Eugenia|last23=Torregrosa|first23=Vicente|last24=Zárraga|first24=Sofía|last25=Hernández|first25=Domingo|title=Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients|journal=Nefrología (English Edition)|year=2020|issn=20132514|doi=10.1016/j.nefroe.2020.03.017}}</ref>
*Regular cleaning of home with disinfection of objects and surfaces.<ref name="LópezVázquez2020">{{cite journal|last1=López|first1=Verónica|last2=Vázquez|first2=Teresa|last3=Alonso-Titos|first3=Juana|last4=Cabello|first4=Mercedes|last5=Alonso|first5=Angel|last6=Beneyto|first6=Isabel|last7=Crespo|first7=Marta|last8=Díaz-Corte|first8=Carmen|last9=Franco|first9=Antonio|last10=González-Roncero|first10=Francisco|last11=Gutiérrez|first11=Elena|last12=Guirado|first12=Luis|last13=Jiménez|first13=Carlos|last14=Jironda|first14=Cristina|last15=Lauzurica|first15=Ricardo|last16=Llorente|first16=Santiago|last17=Mazuecos|first17=Auxiliadora|last18=Paul|first18=Javier|last19=Rodríguez-Benot|first19=Alberto|last20=Ruiz|first20=Juan Carlos|last21=Sánchez-Fructuoso|first21=Ana|last22=Sola|first22=Eugenia|last23=Torregrosa|first23=Vicente|last24=Zárraga|first24=Sofía|last25=Hernández|first25=Domingo|title=Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients|journal=Nefrología (English Edition)|year=2020|issn=20132514|doi=10.1016/j.nefroe.2020.03.017}}</ref>
*Keep a distance of at least two metres from people with general symptoms such as fever, cough, malaise, sore throat or dyspnea). Abstain from sharing personal belongings.<ref name="LópezVázquez2020">{{cite journal|last1=López|first1=Verónica|last2=Vázquez|first2=Teresa|last3=Alonso-Titos|first3=Juana|last4=Cabello|first4=Mercedes|last5=Alonso|first5=Angel|last6=Beneyto|first6=Isabel|last7=Crespo|first7=Marta|last8=Díaz-Corte|first8=Carmen|last9=Franco|first9=Antonio|last10=González-Roncero|first10=Francisco|last11=Gutiérrez|first11=Elena|last12=Guirado|first12=Luis|last13=Jiménez|first13=Carlos|last14=Jironda|first14=Cristina|last15=Lauzurica|first15=Ricardo|last16=Llorente|first16=Santiago|last17=Mazuecos|first17=Auxiliadora|last18=Paul|first18=Javier|last19=Rodríguez-Benot|first19=Alberto|last20=Ruiz|first20=Juan Carlos|last21=Sánchez-Fructuoso|first21=Ana|last22=Sola|first22=Eugenia|last23=Torregrosa|first23=Vicente|last24=Zárraga|first24=Sofía|last25=Hernández|first25=Domingo|title=Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients|journal=Nefrología (English Edition)|year=2020|issn=20132514|doi=10.1016/j.nefroe.2020.03.017}}</ref>
*During the lockdown circumstance you should stay at home aside from the specified exemptions, as indicated by the standards built up by the political and wellbeing specialists. Telephone the kidney transplant facility at your referral community or the telephone numbers approved by the wellbeing specialists.<ref name="LópezVázquez2020">{{cite journal|last1=López|first1=Verónica|last2=Vázquez|first2=Teresa|last3=Alonso-Titos|first3=Juana|last4=Cabello|first4=Mercedes|last5=Alonso|first5=Angel|last6=Beneyto|first6=Isabel|last7=Crespo|first7=Marta|last8=Díaz-Corte|first8=Carmen|last9=Franco|first9=Antonio|last10=González-Roncero|first10=Francisco|last11=Gutiérrez|first11=Elena|last12=Guirado|first12=Luis|last13=Jiménez|first13=Carlos|last14=Jironda|first14=Cristina|last15=Lauzurica|first15=Ricardo|last16=Llorente|first16=Santiago|last17=Mazuecos|first17=Auxiliadora|last18=Paul|first18=Javier|last19=Rodríguez-Benot|first19=Alberto|last20=Ruiz|first20=Juan Carlos|last21=Sánchez-Fructuoso|first21=Ana|last22=Sola|first22=Eugenia|last23=Torregrosa|first23=Vicente|last24=Zárraga|first24=Sofía|last25=Hernández|first25=Domingo|title=Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients|journal=Nefrología (English Edition)|year=2020|issn=20132514|doi=10.1016/j.nefroe.2020.03.017}}</ref>
*Attempt to follow a right eating routine. Abstain from smoking and liquor. These substances weaken the immune system, and increase the risk of infectious diseases.<ref name="LópezVázquez2020">{{cite journal|last1=López|first1=Verónica|last2=Vázquez|first2=Teresa|last3=Alonso-Titos|first3=Juana|last4=Cabello|first4=Mercedes|last5=Alonso|first5=Angel|last6=Beneyto|first6=Isabel|last7=Crespo|first7=Marta|last8=Díaz-Corte|first8=Carmen|last9=Franco|first9=Antonio|last10=González-Roncero|first10=Francisco|last11=Gutiérrez|first11=Elena|last12=Guirado|first12=Luis|last13=Jiménez|first13=Carlos|last14=Jironda|first14=Cristina|last15=Lauzurica|first15=Ricardo|last16=Llorente|first16=Santiago|last17=Mazuecos|first17=Auxiliadora|last18=Paul|first18=Javier|last19=Rodríguez-Benot|first19=Alberto|last20=Ruiz|first20=Juan Carlos|last21=Sánchez-Fructuoso|first21=Ana|last22=Sola|first22=Eugenia|last23=Torregrosa|first23=Vicente|last24=Zárraga|first24=Sofía|last25=Hernández|first25=Domingo|title=Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients|journal=Nefrología (English Edition)|year=2020|issn=20132514|doi=10.1016/j.nefroe.2020.03.017}}</ref>


=Specific recommendations for kidney transplant patients suspected of SARS-CoV-2 infection=
==== Transplantation ====
All kidney transplant patients with suspected symptoms of COVID-19 are advised to contact their healthcare provider (ideally by phone), to discuss the full course of their treatment and other chronic conditions that they are having. Depending upon the symptoms :-
*Mild symptoms ie
**without Dyspnea or Tachypnea
**Temperature <38°C
**Kidney receptor with adequate functional reserves
***The patient can be asked to remain in contact via teleconsultation to have the diagnostic tests performed, monitor the symptoms and communicate alarming to the transplant team every 24–48h.
*Moderate/Severe symptoms
**Temperature >38°C
**Presence of Dyspnea
**Presence of Tachypnea
**Fragile Kidney receptor
***Patient can be asked to report to Emergency Department for clinical evaluation..<ref name="LópezVázquez2020">{{cite journal|last1=López|first1=Verónica|last2=Vázquez|first2=Teresa|last3=Alonso-Titos|first3=Juana|last4=Cabello|first4=Mercedes|last5=Alonso|first5=Angel|last6=Beneyto|first6=Isabel|last7=Crespo|first7=Marta|last8=Díaz-Corte|first8=Carmen|last9=Franco|first9=Antonio|last10=González-Roncero|first10=Francisco|last11=Gutiérrez|first11=Elena|last12=Guirado|first12=Luis|last13=Jiménez|first13=Carlos|last14=Jironda|first14=Cristina|last15=Lauzurica|first15=Ricardo|last16=Llorente|first16=Santiago|last17=Mazuecos|first17=Auxiliadora|last18=Paul|first18=Javier|last19=Rodríguez-Benot|first19=Alberto|last20=Ruiz|first20=Juan Carlos|last21=Sánchez-Fructuoso|first21=Ana|last22=Sola|first22=Eugenia|last23=Torregrosa|first23=Vicente|last24=Zárraga|first24=Sofía|last25=Hernández|first25=Domingo|title=Recommendations on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant patients|journal=Nefrología (English Edition)|year=2020|issn=20132514|doi=10.1016/j.nefroe.2020.03.017}}</ref>


=== Primary Prevention ===
=== Secondary Prevention ===
=== Cost-Effectiveness of Therapy ===
=== Future or Investigational Therapies ===


==References==
==References==
<references />
{{Reflist|2}}
 
[[Category:Disease]]

Revision as of 02:45, 15 July 2020

For COVID-19 frequently asked inpatient questions, click here
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COVID-19 Infection in Transplant Patients On the Web

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

Renal transplant patients are under immunosuppression to modulate the immune response to graft. Moreover these patients have various underlying chronic kidney diseases and other co-morbidities such as diabetes and hypertension, which can impact the results in COVID-19 infection. Hence these patients are at a higher risk of developing COVID-19 associated complications.[1] The clinical manifestations, treatment and prognosis of COVID-19 infection may be different from the general population.[2] It is believed that any transplant recipient presented to the infection would result in a high level of cases; however the risk of donor to recipient transmission is unknown. The chances of a donor to recipient infection might be affected by exposure of the donor, infectivity of the the donor during the incubation period and the degree of viremia as well as the viability of virus in specific organ system.Hence, in spite of the conceivable negative outcomes, temporary interruption of kidney transplantation might be needed in regions where the rate of infection is high.[3]

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.[4] 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[5] 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.[2]

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[6]:

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[7][8] 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[9] [10] [11] [12] [13]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).[14]These receptors are found in the proximal tubules of kidney[7][8]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..[15]

Associated Conditions

Acute Kidney Injury

  • Pro-inflammatory cytokine levels are elevated in the COVID-19 infection and there is activation of T-cell response. [20]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.[21] 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[22]

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[23].However, the renal transplant recipients are at remain at higher risk to catch COVID-19[17] and develop severe complications due to chronic immunosuppressed state which is implicated in various viral infections such as cytomegalovirus, herpes zoster, norovirus infections[24][25]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[26] , due to chronic immunosuppression, the clinical features of COVID-19 in renal transplant patients may be atypical[3] . 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[27] [28] [23] . 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[29] . 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[29] .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.[29][23]


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.[30]
  • 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. [31]
  • .The risk is further increased in patients having chronic kidney disease(CKD), patients on chronic replacement therapies, and patients with kidney transplants.[31]
  • In an analysis of 14 articles[32]

[33] [34] [35] [36] [37] [38] [39][40], 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.[32]

[33] [34] [35] [36] [41] [38] [39][40]

  • In general population, COVID-19 associated AKI has higher incidence in elderly.[42]

Gender

  • Men are more likely to be affected by COVID-19 than women.[43]
  • Women dying from COVID-19 are generally elder than men(median age: 82 vs. 79 years for women vs. men, respectively).[43]

Race

*According to study done in New York, 14 recipients (39%) were black, and 15 recipients (42%) were Hispanic.[44]

Risk Factors

There are various factors that can predispose renal transplant patients to COVID-19.

  • Immunosuppression[17]
  • Chronic Renal Failure[17][45]
  • Co-Morbidities[17]
    • Diabetes
    • Hypertension
    • Hyperlipidemia
    • H/o Heart Disease
  • Male Sex[44][46]
  • Old Age[44][46]
  • Current or h/o smoking tobacco[44]
  • Possible a/w donor COVID-19 infection[46]

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[47]

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.[47]


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. [48]

  • Clinical presentation of COVID-19 infection in renal transplant patients are like the clinical presentations of infection in general population. [48].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.[49]
  • Managing the immunosuppression in renal transplant patients is difficult and should be based on[49]
    • 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.[49]

Immuno Drugs


  • Antiproliferative agents such as MMF and azathioprine [50]
    • Should be stopped at the time of admission to hospital
  • Prednisolone[50]
    • The dosage can be either increased or left unchanged. These can provide immunological protection to the renal graft.
    • Corticosteroids have beneficial effects such as
      • Immunomodulation and anti-inflammatory properties
        • Inhibition of proinflammatory cytokines
        • Reduction of white blood cell traffic
      • Vascular protective effects
        • Maintenance of integrity and permeability of endothelium. [51] [50]
  • Tacrolimus[50]
    • Low doses of tacrolimus can be given but more evidence is required.[50]
    • The dose should be reduced to 50%. Target levels for tacrolimus should be 3-5 ng/ml.[52]
  • Tocilizumab.[50]
    • 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.[53][54]
    • Cyclosporine levels should be targeted at 25-50 ng/ml.[52]


Surgery and Device Based Therapy

Indications for Surgery

Pre-Operative Assessment

Post-Operative Management

Transplantation

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

References

  1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B (March 2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. PMC 7270627 Check |pmc= value (help). PMID 32171076 Check |pmid= value (help).
  2. 2.0 2.1 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. 20 (7): 1859–1863. doi:10.1111/ajt.15869. ISSN 1600-6135.
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