A year on from the start of COVID-19 in Wuhan it is time to reflect on what we know about SARS-COV2 infection in transplant recipient. In this issue you will find series reported from many different parts of the world and from recipients with different organ transplants. It is also a time to reflect on what we dont know and why we don’t know it. What protocols work and what do not, to help us manage every aspect of our work. When SARS-CoV-3 or some variant of it, comes around in due course, what will we do better and quicker? In short - what have we learned from 2020?
Dr. Jeremy R. Chapman, Editor-in-Chief, Transplantation
Kute VB, Bhalla AK, Guleria S, et al.
Transplantation: December 21, 2020 - Volume Online First
January issue of Transplantation contains a wealth of new information on the impact of COVID-19 on our populations of at risk patients. Here we also publish one of the largest studies of the disease profile in an emerging economy from 13 centers in India. 250 kidney transplant recipients proven to have COVID-19, 47 of whom were treated in ICU and 29 (11.6%) died. Risk factors for mortality were older age, obesity, pre-existing allograft dysfunction; and on presentation AKI, dyspnoea, ‘severe disease’, higher inflammatory markers (CRP, IL6, procalcitonin), CXR abnormalities and of course early ventilation requirements. The therapeutic strategies used in these patients is described in some detail.
This study investigated the incidence of SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) in seropositive and seronegative health care workers attending testing of asymptomatic and symptomatic staff at Oxford University Hospitals in the United Kingdom. A total of 12,541 health care workers participated and had anti-spike IgG measured; 11,364 were followed up after negative antibody results and 1265 after positive results, including 88 in whom seroconversion occurred during follow-up. A total of 223 anti-spike–seronegative health care workers had a positive PCR test (1.09 per 10,000 days at risk), 100 during screening while they were asymptomatic and 123 while symptomatic, whereas 2 anti-spike–seropositive health care workers had a positive PCR test (0.13 per 10,000 days at risk), and both workers were asymptomatic when tested (adjusted incidence rate ratio, 0.11; 95% confidence interval, 0.03 to 0.44; P=0.002). There were no symptomatic infections in workers with anti-spike antibodies. This study concluded that the presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months.
This cohort study assessed 38 517 adults who were admitted with COVID-19 to 955 US hospitals from January 1, 2020, to June 30, 2020, and a subset of 27 801 adults (72.2%) who were admitted to 398 of these hospitals that treated at least 10 patients with COVID-19 during 2 periods (January 1 to April 30, 2020, and May 1 to June 30, 2020). The primary outcome was the hospital’s risk-standardized event rate (RSER) of 30-day in-hospital mortality or referral to hospice. The mean (SD) age among participants (18 888 men [49.0%]) was 70.2 (15.5) years. The mean (SD) hospital-level RSER for the 955 hospitals was 11.8% (2.5%). The mean RSER in the worst-performing quintile of hospitals was 15.65% compared with 9.06% in the best-performing quintile (absolute difference, 6.59 percentage points; 95% CI, 6.38%-6.80%; P < .001). Mean RSERs in all but 1 of the 398 hospitals improved; 376 (94%) improved by at least 25%. The overall mean (SD) RSER declined from 16.6% (4.0%) to 9.3% (2.1%). The absolute difference in rates of mortality or referral to hospice between the worst and best-performing quintiles of hospitals decreased from 10.54 percentage points (95% CI, 10.03%-11.05%; P < .001) to 5.59 percentage points (95% CI, 5.33%-5.86%; P < .001). Higher county-level COVID-19 case rates were associated with worse RSERs, and case rate declines were associated with improvement in RSERs. This study concluded that over the first months of the pandemic, COVID-19 mortality rates in this cohort of US hospitals declined. Hospitals did better when the prevalence of COVID-19 in their surrounding communities was lower.
LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019. Hospitalized patients who had Covid-19 without end-organ failure were randomly assigned in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including the antiviral drug remdesivir and, when indicated, supplemental oxygen and glucocorticoids. On October 26, 2020, the data and safety monitoring board recommended stopping enrollment for futility after 314 patients (163 in the LY-CoV555 group and 151 in the placebo group) had undergone randomization and infusion.
This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. 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 mRNA1273 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). In summary, 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.
This study used mass cytometry and targeted proteomics to profile the innate immune response of patients with mild or severe COVID-19 and of healthy individuals. A surge of CD169+ monocytes associated with an IFNγ +MCP-2+ signature rapidly followed symptom onset. At later stages, a persistent inflammatory phenotype was observed in patients with severe disease, dominated by high CCL3 and CCL4 abundance correlating with the reappearance of CD16+ monocytes, whereas the response of mild COVID-19 patients normalizes. This study provides insights into the dynamic nature of inflammatory responses in COVID-19 patients and identifies sustained innate immune responses as a likely mechanism in severe patients, thus supporting investigation of targeted interventions in severe COVID-19.
Women in Transplantation (WIT) initiative of The Transplantation Society will provide funding to an Early Career Researcher to support research focusing on sex and gender issues relevant to solid organ transplantation.
This initiative was made possible with support with One Lambda, a Thermo Fisher Scientific brand, and Sanofi, with each supporting one award.
The spectrum of studies includes basic, clinical and translational. This individual should have spent two years or less performing research relevant to solid organ transplantation since obtaining their last degree (PhD, MD, MSc, PharmD, or equivalent). This work may represent a continuation of current research or a novel aspect of work. The mentor should have expertise in transplantation or immunology but need not be an investigator with known expertise in gender or sex.
Read the first issue of the DICG newsletter. This is brought to you on behalf of the executive council of the Declaration of Istanbul Custodian Group (www.declarationofistanbul.org) which works to protect and promote the principles enunciated in the Declaration of Istanbul (DOI), a landmark document in the history of global transplantation.
Dec. 31 - There was a 30 per cent reduction in the number of transplants carried out this year, as a result of the Covid-19 pandemic, new figures from the Health Service Executive (HSE) show. Between January and December 28th, 2020, there were 190 transplants carried out in the Republic, down from the 274 transplants in 2019.
Jan. 1 - An up-and-coming gene therapy for blood disorders. A new class of medications for cystic fibrosis. Increased access to telemedicine. These are some of the innovations that will enhance healing and change healthcare in the coming year, according to a distinguished panel of clinicians and researchers from Cleveland Clinic.
Dec. 30 - Women awaiting liver transplants in the United States are known to be about one-third more likely than men to become too ill to undergo surgery or die before receiving a liver. Now a study headed by UC San Francisco and Columbia University highlights the role that frailty plays in this gender gap.
Dec. 31 - Patients pursuing solid organ transplantation are encouraged to receive many vaccines on an accelerated timeline. Vaccination prior to transplantation offers the best chance of developing immunity and may expand the pool of donor organs that candidates can accept without needing post-transplant therapy.