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      The Global Impact of COVID-19 on Solid Organ Transplantation: Two Years Into a Pandemic

      review-article
      , MBChB, MRCP 1 , , , MD, FFICM 2 , , MD, FRCPath 2 , , MD, FRCP 2 , , MD, FRCS, OBE 2
      Transplantation
      Lippincott Williams & Wilkins

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          Abstract

          The coronavirus disease 2019 (COVID-19) pandemic has had a major global impact on solid organ transplantation (SOT). An estimated 16% global reduction in transplant activity occurred over the course of 2020, most markedly impacting kidney transplant and living donor programs, resulting in substantial knock-on effects for waitlisted patients. The increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk and excess deaths in transplant candidates has resulted in substantial effort to prioritize the safe restart and continuation of transplant programs over the second year of the pandemic, with transplant rates returning towards prepandemic levels. Over the past 2 y, COVID-19 mortality in SOT recipients has fallen from 20%–25% to 8%–10%, attributed to the increased and early availability of SARS-CoV-2 testing, adherence to nonpharmaceutical interventions, development of novel treatments, and vaccination. Despite these positive steps, transplant programs and SOT recipients continue to face challenges. Vaccine efficacy in SOT recipients is substantially lower than the general population and SOT recipients remain at an increased risk of adverse outcomes if they develop COVID-19. SOT recipients and transplant teams need to remain vigilant and ongoing adherence to nonpharmaceutical interventions appears essential. In this review, we summarize the global impact of COVID-19 on transplant activity, donor evaluation, and patient outcomes over the past 2 y, discuss the current strategies aimed at preventing and treating SARS-CoV-2 infection in SOT recipients, and based on lessons learnt from this pandemic, propose steps the transplant community could consider as preparation for future pandemics.

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          Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

          Abstract Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle–encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.)
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            Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

            Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p interaction =0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. Funding UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
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              Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

              Summary Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.
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                Author and article information

                Journal
                Transplantation
                Transplantation
                TP
                Transplantation
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0041-1337
                1534-6080
                11 April 2022
                July 2022
                : 106
                : 7
                : 1312-1329
                Affiliations
                [1 ] Renal Department, Southmead Hospital, North Bristol NHS Trust, Bristol, United Kingdom.
                [2 ] NHS Blood and Transplant, Bristol, United Kingdom.
                Author notes
                Correspondence: Ailish Nimmo, MBChB, MRCP, Renal Department, Southmead Hospital, North Bristol NHS Trust, Bristol BS10 5NB, United Kingdom. ( ailish.nimmo@ 123456nhs.net ).
                Article
                00010
                10.1097/TP.0000000000004151
                9213067
                35404911
                6a2ed9a8-ad3d-4144-b2d0-67c2e6fa7a11
                Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                : 11 February 2022
                : 23 February 2022
                : 24 February 2022
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