Preventing Coronavirus Disease 2019 in Kidney Transplant Recipients: Where Should We Begin?

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Abstract

Context

Chronic immunosuppression is associated with an increased risk of opportunistic infections. Although kidney transplant recipients with coronavirus disease 2019 (COVID-19) have higher mortality than the general population, data on their risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are unknown.

Subject of Review

A recent single-center screening study from the UK ( Transplantation. 2021 Jan 1;105(1):151–7) showed that 89 (10.4%) of 855 consecutive kidney transplant recipients tested positive for SARS-CoV-2 antibodies. Risk factors for infection included a nonwhite background, diabetes, and a history of allograft rejection. Risk factors for mortality in individuals who developed COVID-19 were older age and receiving steroids.

Second Opinion

This study shows that the rate of SARS-CoV-2 infection in kidney transplant recipients is similar to the one observed in the general population in the same area (13%), indicating that transplant recipients are not at increased risk of COVID-19. However, the investigators raise the interesting point that since transplant individuals were advised to shelter earlier than the general population, they may be in fact more susceptible. This statement is hard to substantiate, but the identification of specific risk factors for infection and poor outcomes is crucial to tailor strategies to prevent spread of the infection. This is particularly important, considering that kidney transplant recipients may be at increased risk of prolonged viral spread and in-host viral mutations, making them not just a particularly fragile population for COVID-19 but also a potentially major source of further contagions.

Related collections

Most cited references 25

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Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

Edward E Walsh, Robert W Frenck, Ann Falsey … (2021)

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States. Methods In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle–formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor–binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose. Results A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2–neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. Conclusions The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)

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Clinical Characteristics of Covid-19 in New York City

Parag Goyal, Justin J Choi, Laura C Pinheiro … (2020)

To the Editor: The world is in the midst of the coronavirus disease 2019 (Covid-19) pandemic, 1,2 and New York City has emerged as an epicenter. Here, we characterize the first 393 consecutive patients with Covid-19 who were admitted to two hospitals in New York City. This retrospective case series includes adults 18 years of age or older with confirmed Covid-19 who were consecutively admitted between March 3 (date of the first positive case) and March 27, 2020, at an 862-bed quaternary referral center and an affiliated 180-bed nonteaching community hospital in Manhattan. Both hospitals adopted an early-intubation strategy with limited use of high-flow nasal cannulae during this period. Cases were confirmed through reverse-transcriptase–polymerase-chain-reaction assays performed on nasopharyngeal swab specimens. Data were manually abstracted from electronic health records with the use of a quality-controlled protocol and structured abstraction tool (details are provided in the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). Among the 393 patients, the median age was 62.2 years, 60.6% were male, and 35.8% had obesity (Table 1). The most common presenting symptoms were cough (79.4%), fever (77.1%), dyspnea (56.5%), myalgias (23.8%), diarrhea (23.7%), and nausea and vomiting (19.1%) (Table S1 in the Supplementary Appendix). Most of the patients (90.0%) had lymphopenia, 27% had thrombocytopenia, and many had elevated liver-function values and inflammatory markers. Between March 3 and April 10, respiratory failure leading to invasive mechanical ventilation developed in 130 patients (33.1%); to date, only 43 of these patients (33.1%) have been extubated. In total, 40 of the patients (10.2%) have died, and 260 (66.2%) have been discharged from the hospital; outcome data are incomplete for the remaining 93 patients (23.7%). Patients who received invasive mechanical ventilation were more likely to be male, to have obesity, and to have elevated liver-function values and inflammatory markers (ferritin, d-dimer, C-reactive protein, and procalcitonin) than were patients who did not receive invasive mechanical ventilation. Of the patients who received invasive mechanical ventilation, 40 (30.8%) did not need supplemental oxygen during the first 3 hours after presenting to the emergency department. Patients who received invasive mechanical ventilation were more likely to need vasopressor support (95.4% vs. 1.5%) and to have other complications, including atrial arrhythmias (17.7% vs. 1.9%) and new renal replacement therapy (13.3% vs. 0.4%). Among these 393 patients with Covid-19 who were hospitalized in two New York City hospitals, the manifestations of the disease at presentation were generally similar to those in a large case series from China 1 ; however, gastrointestinal symptoms appeared to be more common than in China (where these symptoms occurred in 4 to 5% of patients). This difference could reflect geographic variation or differential reporting. Obesity was common and may be a risk factor for respiratory failure leading to invasive mechanical ventilation. 3 The percentage of patients in our case series who received invasive mechanical ventilation was more than 10 times as high as that in China; potential contributors include the more severe disease in our cohort (since testing and hospitalization in the United States is largely limited to patients with more severe disease) and the early-intubation strategy used in our hospitals. Regardless, the high demand for invasive mechanical ventilation has the potential to overwhelm hospital resources. Deterioration occurred in many patients whose condition had previously been stable; almost a third of patients who received invasive mechanical ventilation did not need supplemental oxygen at presentation. The observations that the patients who received invasive mechanical ventilation almost universally received vasopressor support and that many also received new renal replacement therapy suggest that there is also a need to strengthen stockpiles and supply chains for these resources.

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A serological assay to detect SARS-CoV-2 seroconversion in humans

Fatima Amanat, Daniel Stadlbauer, Shirin Strohmeier … (2020)

Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.

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Author and article information

Journal

Journal ID (nlm-ta): Nephron Clin Pract

Journal ID (iso-abbrev): Nephron Clin Pract

Journal ID (publisher-id): NEF

Title: Nephron. Clinical Practice

Publisher: S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )

ISSN (Print): 1660-8151

ISSN (Electronic): 1660-2110

Publication date (Electronic): 31 March 2021

Volume: 145

Issue: 3

Pages: 280-284

Affiliations

[1 ] ^aRenal Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

[2 ] ^bCenter for Transplantation Sciences, Massachusetts General Hospital, Boston, Massachusetts, USA

[3 ] ^cRenal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

[4 ] ^dTransplantation Research Center, Brigham and Women's Hospital, Boston, Massachusetts, USA

[5 ] ^eDepartment of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA

Author notes

* Paolo Cravedi, paolo.cravedi@ 123456mssm.edu

Article

Publisher ID: nef-0145-0280

DOI: 10.1159/000515165

PMC ID: 8089451

PubMed ID: 33789316

SO-VID: 59a0035a-c517-4bbd-a79a-51c1ea212c90

License:

This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

History

Date received : 1 February 2021

Date accepted : 11 February 2021

Date: 2021

Page count

References: 25, Pages: 5

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