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
Mortality, COVID-19 66% improvement lower risk ← → higher risk Mortality, all cause 80% ICU admission 66% Hospitalization 90% Sotrovimab  Gleeson et al.  EARLY TREATMENT Is early treatment with sotrovimab beneficial for COVID-19? Prospective study of 116 patients in the United Kingdom (Dec 2021 - Feb 2022) Lower hospitalization with sotrovimab (p=0.0076) c19early.org Gleeson et al., medRxiv, May 2022 0 0.5 1 1.5 2+ RR
Sotrovimab for COVID-19
44th treatment shown to reduce risk in August 2022, now with p = 0.00054 from 28 studies, recognized in 42 countries. Efficacy is variant dependent.
Lower risk for mortality, ICU, and hospitalization.
No treatment is 100% effective. Protocols combine treatments.
6,200+ studies for 200+ treatments. c19early.org
Download Meta Analysis
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.
Efficacy is variant dependent. In Vitro studies predict lower efficacy for BA.11-3, BA.4, BA.54, XBB.1.9.3, XBB.1.5.24, XBB.2.9, CH.1.15, and no efficacy for BA.26, XBB, XBB.1.5, ХВВ.1.9.17, XBB.1.16, BQ.1.1.45, and CL.15. US EUA has been revoked.
Standard of Care (SOC) for COVID-19 in the study country, the United Kingdom, is very poor with very low average efficacy for approved treatments8. The United Kingdom focused on expensive high-profit treatments, approving only one low-cost early treatment, which required a prescription and had limited adoption. The high-cost prescription treatment strategy reduces the probability of early treatment due to access and cost barriers, and eliminates complementary and synergistic benefits seen with many low-cost treatments.
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Study covers molnupiravir and sotrovimab.
risk of death, 66.4% lower, RR 0.34, p = 1.00, treatment 0 of 47 (0.0%), control 1 of 48 (2.1%), NNT 48, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), COVID-19.
risk of death, 79.8% lower, RR 0.20, p = 0.49, treatment 0 of 47 (0.0%), control 2 of 48 (4.2%), NNT 24, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), all cause.
risk of ICU admission, 66.4% lower, RR 0.34, p = 1.00, treatment 0 of 47 (0.0%), control 1 of 48 (2.1%), NNT 48, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of hospitalization, 89.8% lower, RR 0.10, p = 0.008, treatment 1 of 47 (2.1%), control 10 of 48 (20.8%), NNT 5.3.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
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.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 United Kingdom Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines Spain Brazil Italy France Japan Canada China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR The United Kingdom favored high-profit treatments.The average efficacy of treatments was very low.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2025 United Kingdom Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines Spain Brazil Italy France Japan Canada China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Zambia Fiji Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore New Zealand Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia Syria The UK favored high-profit treatments.The average efficacy was very low.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
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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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.</jats:p><jats:p>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.</jats:p><jats:p>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. 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