Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Covid 19 and cni inhibitors

137 views

Published on

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

Published in: Education
  • Be the first to comment

Covid 19 and cni inhibitors

  1. 1. COVID 19 and CNI inhibitors Hoseini R Associate Professor IUMS 2020
  2. 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. 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. 4. What do we do? Should we stop CNIs? What is your recommendation; stopping or reducing?
  5. 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. 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. 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. 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. 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. 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. 11. The impact of CNI on Coronavirus
  12. 12. The impact of CNI on Coronavirus
  13. 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. 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. 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. 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. 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. 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

×