The impact of COVID 19 on R.TX is unclear Risk factors in R.TX: Comorbidities, residual graft dysfunction, long term immunosuppression There are a very few case series in renal transplant recipients from mild to severe infection Aim: Equipoise between infection and rejection We don’t know the best approach for immunosuppressive drugs in these patients

1. COVID 19 and CNI inhibitors
Hoseini R
Associate Professor
IUMS
2020

2. Introduction
• To date, million patients with COVID 10 have
been reported
• Increased risk of viral infection and its
complications and death in immunocompromised
patients especially T cell dysfunction
• The risk of death increases in COVID 19 with
lymphopenia
• Increased risk of viral infection and its
complications and death in patients with
comorbidities

3. Introduction
• The impact of COVID 19 on R.TX is unclear
• Risk factors in R.TX: Comorbidities, residual graft
dysfunction, long term immunosuppression
• There are a very few case series in renal
transplant recipients from mild to severe infection
• Aim: Equipoise between infection and rejection
• We don’t know the best approach for
immunosuppressive drugs in these patients

4. What do we do?
Should we stop CNIs?
What is your recommendation; stopping
or reducing?

5. A single center observational study of the
clinical characteristics and short term outcome
of 20 kidney transplant patients admitted for
SARS-COV 2 pneumonia (Italy)
• 20 patients with fever, one with Res. distress
• Immunosuppression were hold in all
• Half abNl CXR at admission, 87% progression
• Five died after a median of 15 days
High risk of progression and significant mortality in kidney
transplant patients with SARS-COV 19 Pneumonia

6. COVID 19 Infection In Kidney Transplant
recipients (South London)
• 7 cases of adult kidney transplant
• 2 Outpatient, 1 ward admission, 4 ICU admission
• 3 of patients in ICU had Diabetes
• All patients had fever and respiratory distress
• 1 patient died
COVID 19 may lead to severe disease in R.TX recipients

7. Presentation and evolution of COVID 19 in
immunosuppressed patients, preliminary
evaluation in a north Italian cohort on CNIs
based therapy, preprint in BMJ
• 384 adult patients (331 S.O.TX, 53 rheumatic Dis.)
• All received CNIs (46 only CNIs)
• 14: confirmed COVID 19, 14 with clinical diagnosis
• 14 Hospitalized, no superinfection
• 1 with metastatic lung cancer died
COVID 19 showed a mild course with low mortality rate
in patients on CNIs regimen

8. COVID 19 in long term liver transplant
patients: preliminary experience from an
Italian transplant centre in Lombardy
• 141 liver transplant adult patients
• 111 people more than 10 years
• 40 people within the past two years
• Three people died (over65, HTN, Diabetes,
Hyperlipidemia, overweight) with low dose CsA.
Immunosuppressive medications should not be reduced or
stopped for liver transplant patients with COVID 19

9. COVID 19 and CNI inhibitors
Conclusion
• No benefits of immunosuppression withdrawal
and anti-inflammatory instead.
• Most believe: ↓immunosuppression is a fair idea
• The degree of reduction is not known

10. COVID 19 and CNI inhibitors
Cyclosporine or Tacrolimus?
• CsA: ↓expression of N-protein of SARS-COV 2
• N-protein is required for viral replication
• No data are for this in vitro finding for TAC
• CsA could be used as preferred CNI in R.TX???

11. The impact of CNI on Coronavirus

12. The impact of CNI on Coronavirus

13. COVID 19 and CNI inhibitors
Cyclosporine or Tacrolimus?
• Coronavirus use immunophylin pathway for
replication
• CSA inhibit immunophylin pathway and inhibit
coronavirus replication in vitro independently of its
immunosuppressive effect
• The inhibitory effect of CSA on coronavirus and HCV
was shown in 2011 in vitro.
• Clinical studies shows that CsA prolongs the HCV
recur after liver TX compared to TAC.

14. COVID 19 and CNI inhibitors
Cyclosporine or Tacrolimus?
• CsA significantly inhibit Treg, TAC does not inhibit
Treg.
• Treg induce intolerance
• Treg has a key role in viral persistence in HCV and
other viruses.

15. The impact of Antiviral agents on CNIs
• Some antiviral agents such as both Lopinavir and
ritonavir interact with CNI causing inhibition of
metabolism and potentially high readings
• Monitoring of trough levels of CsA and TAC is
necessary

16. Conclusion
• In Mild cases: antiproliferative drugs should be
stopped
• In mild to moderate cases: antiproliferative drugs
should be withdrawn, and CNIs reduce by 50%.
• Change TAC to CSA is controversial.
• In severe cases requiring ICU and mechanical
ventilation, antiproliferative and CNI should be
stopped immediately and the dose of
corticosteroids should be increased.
Interaction between CNIs with antiviral agents should be considered

17. Conclusion
• There is a mega trial done by WHO (Solidarity,
ISRCTN83971151)
• Test four approaches:
-Remdesivir
-Lopinavir-ritonavir
-Lopinavir-ritonavir with IFN-B1a
-Hydroxychloquine

18. References
1. Nature Reviews Nephrology, May, 2020
2. Massachusetts General Hospital COVID 19
Treatment Guideline
3. BMJ , 2020, preprint article
4. Journal of Am Society of Nephrology, 2020, 31 (6),
1145-1146.
5. NEJM, May 2020