Kidney Transplant Recipients and Omicron: Outcomes, effect of vaccines and the efficacy and safety of novel treatments

Gleeson et al., medRxiv, doi:10.1101/2022.05.03.22274524

May 2022

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Retrospective 116 kidney transplant recipients diagnosed with COVID-19 in the community during the Omicron era in the UK, showing lower hospitalization with sotrovimab, but no significant difference with molnupiravir. Two molnupiravir-treated patients requiring dialysis had features of thrombotic microangiopathy, raising potential safety concerns.

Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-10. Multiple analyses have identified variants potentially created by molnupiravir11-15.

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Study covers molnupiravir and sotrovimab.

risk of death, 128.6% higher, RR 2.29, p = 0.52, treatment 1 of 21 (4.8%), control 1 of 48 (2.1%), COVID-19.

risk of death, 14.3% higher, RR 1.14, p = 1.00, treatment 1 of 21 (4.8%), control 2 of 48 (4.2%), all-cause.

risk of ICU admission, 128.6% higher, RR 2.29, p = 0.52, treatment 1 of 21 (4.8%), control 1 of 48 (2.1%).

risk of hospitalization, 31.4% lower, RR 0.69, p = 0.74, treatment 3 of 21 (14.3%), control 10 of 48 (20.8%), NNT 15.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

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Gleeson et al., 3 May 2022, prospective, United Kingdom, preprint, 14 authors, study period 21 December, 2021 - 10 February, 2022. Contact: m.willicombe08@imperial.ac.uk.

This Paper Molnupiravir All

Kidney Transplant Recipients and Omicron: Outcomes, effect of vaccines and the efficacy and safety of novel treatments

Sarah Gleeson, Paul Martin, Tina Thomson, Amarpreet Thind, Maria Prendecki, Katrina J Spensley, Candice L Clarke, Candice Roufosse, Graham Pickard, David Thomas, Stephen P Mcadoo, Liz Lightstone, Peter Kelleher, Dr Michelle Willicombe

doi:10.1101/2022.05.03.22274524

We aimed to describe the outcomes of Omicron infection in kidney transplant recipients (KTR), compare the efficacy of the community therapeutic interventions and report the safety profile of molnupiravir. From 142 KTRs diagnosed with COVID-19 infection after Omicron had become the dominant variant in the UK, 116 (78.9%) cases were diagnosed in the community; 47 receiving sotrovimab, 21 molnupiravir and 48 no treatment. 10 (20.8%) non-treated patients were hospitalised following infection, which was significantly higher than the sotrovimab group (2.1%), p=0.0048, but not the molnupiravir treated group (14.3%), p=0.47. The only admission following sotrovimab occurred in a patient infected with BA.2. One patient from the molnupiravir and no-treatment groups required ICU support, and both subsequently died, with one other death in the no-treatment group. No patient receiving sotrovimab died. 6/116 (5.2%) patients required dialysis following their diagnosis; 2 (9.5%) patients receiving molnupiravir and 4 (8.3%) no-treatment. This requirement was significantly higher in the molnupiravir group compared with the sotrovimab treated patients, in whom no patient required dialysis, p=0.035. Both molnupiravir treated patients requiring dialysis had features of systemic thrombotic microangiopathy. Post-vaccination serostatus was available in 110 patients. Seropositive patients were less likely to require hospital admission compared with seronegative patients, 6 (7.0%) and 6 (25.0%) respectively, p=0.023. Seropositive patients were also less likely to require dialysis therapy, p=0.016. In conclusion, sotrovimab treatment in the community was associated with superior patient and transplant outcomes; it's clinical efficacy against the BA.2 variant requires a rapid review. The treatment benefit of molnupiravir was not evident, and wider safety reporting in transplant patients is needed.

risk group with poor infection outcomes, immunosuppressed people often with significant comorbidities, have been excluded from policy informing studies from the start of the pandemic. Relying on extrapolating data from these studies to inform management of transplant recipients, may and has led to suboptimal outcomes.

References

Benotmane, Pre-exposure prophylaxis with Evusheld™ elicits limited neutralizing activity against the omicron variant in kidney transplant patients, medRxiv

Bernal, Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients, N Engl J Med

Broecker, Clinical-pathological correlations in post-transplant thrombotic microangiopathy, Histopathology

Callaghan, Real-world Effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S Vaccines Against SARS-CoV-2 in Solid Organ and Islet Transplant Recipients, Transplantation

Chavarot, Early treatment with sotrovimab monoclonal antibody in kidney transplant recipients with Omicron infection

Extance, Covid-19: What is the evidence for the antiviral molnupiravir?, BMJ

Gupta, Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab, N Engl J Med

Iketani, Antibody evasion properties of SARS-CoV-2 Omicron sublineages, Nature

Kemp, SARS-CoV-2 evolution during treatment of chronic infection, Nature

Prendecki, Immunological responses to SARS-CoV-2 vaccines in kidney transplant recipients, Lancet

Villanego, Trends in COVID-19 Outcomes in Kidney Transplant Recipients During the Period of Omicron Variant Predominance, Transplantation

Willicombe, Scanlon, Miranda, Loud, Lightstone, Should we be clinically assessing antibody responses to covid vaccines in immunocompromised people?, BMJ

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