Previous SARS-CoV-2 infection or a third dose of vaccine elicited cross-variant neutralising antibodies in vaccinated solid-organ transplant recipients.

Objectives: The SARS-CoV-2 pandemic poses a great threat to global health, particularly in solid organ transplant recipients (SOTRs). A 3-dose mRNA vaccination protocol has been implemented for the majority of SOTRs, yet their immune responses are less effective compared to healthy controls (HCs). Methods: We analyzed the humoral immune responses against the vaccine strain and variants of concern (VOC), including the highly mutated-omicron variant in 113 SOTRs, of whom 44 had recovered from COVID-19 (recovered-SOTRs) and 69 had not contracted the virus (COVID-naïve). In addition, 30 HCs, 8 of whom had recovered from COVID-19, were also studied. Results: Here, we report that three doses of the mRNA vaccine had only a modest effect in eliciting anti-viral antibodies against all viral strains in the fully vaccinated COVID-naive SOTRs (n = 47). Only 34.0% of this group of patients demonstrated both detectable anti-RBD IgG with neutralization activities against alpha, beta, and delta variants, and only 8.5% of them showed additional omicron neutralizing capacities. In contrast, 79.5% of the recovered-SOTRs who received two doses of vaccine demonstrated both higher anti-RBD IgG levels and neutralizing activities against all VOC, including omicron. Conclusion: These findings illustrate a significant impact of previous infection on the development of anti-SARS-CoV-2 immune responses in vaccinated SOTRs and highlight the need for alternative strategies to protect a subset of a lesser-vaccine responsive population.

Tocilizumab for severe COVID-19 in solid organ transplant recipients: a matched cohort study.

The safety and efficacy of tocilizumab for the treatment of severe respiratory symptoms due to COVID-19 remain uncertain, in particular among solid organ transplant (SOT) recipients. Thus, we evaluated the clinical characteristics and outcomes of 29 hospitalized SOT recipients who received tocilizumab for severe COVID-19, compared to a matched control group who did not. Among a total of 117 total SOT recipients hospitalized with COVID-19, 29 (24.8%) received tocilizumab. The 90-day mortality was significantly higher among patients who received tocilizumab (41%) compared to those who did not (20%, P = .03). When compared to control patients matched by age, hypertension, chronic kidney disease, and administration of high dose corticosteroids, there was no significant difference in mortality (41% vs 28%, P = .27), hospital discharge (52% vs 72%, P = .26), or secondary infections (34% vs 24%, P = .55). Among patients who received tocilizumab, there was also no difference in mortality based on the level of oxygen support (intubated vs not intubated) at the time of tocilizumab initiation. In this matched cohort study, tocilizumab appeared to be safe but was not associated with decreased 90-day mortality. Larger randomized studies are needed to identify whether there are subsets of SOT recipients who may benefit from tocilizumab for treatment of COVID-19.

Kidney Biopsy Findings in Patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is thought to cause kidney injury by a variety of mechanisms. To date, pathologic analyses have been limited to patient reports and autopsy series. METHODS: We evaluated biopsy samples of native and allograft kidneys from patients with COVID-19 at a single center in New York City between March and June of 2020. We also used immunohistochemistry, in situ hybridization, and electron microscopy to examine this tissue for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: The study group included 17 patients with COVID-19 (12 men, 12 black; median age of 54 years). Sixteen patients had comorbidities, including hypertension, obesity, diabetes, malignancy, or a kidney or heart allograft. Nine patients developed COVID-19 pneumonia. Fifteen patients (88%) presented with AKI; nine had nephrotic-range proteinuria. Among 14 patients with a native kidney biopsy, 5 were diagnosed with collapsing glomerulopathy, 1 was diagnosed with minimal change disease, 2 were diagnosed with membranous glomerulopathy, 1 was diagnosed with crescentic transformation of lupus nephritis, 1 was diagnosed with anti-GBM nephritis, and 4 were diagnosed with isolated acute tubular injury. The three allograft specimens showed grade 2A acute T cell-mediated rejection, cortical infarction, or acute tubular injury. Genotyping of three patients with collapsing glomerulopathy and the patient with minimal change disease revealed that all four patients had APOL1 high-risk gene variants. We found no definitive evidence of SARS-CoV-2 in kidney cells. Biopsy diagnosis informed treatment and prognosis in all patients. CONCLUSIONS: Patients with COVID-19 develop a wide spectrum of glomerular and tubular diseases. Our findings provide evidence against direct viral infection of the kidneys as the major pathomechanism for COVID-19-related kidney injury and implicate cytokine-mediated effects and heightened adaptive immune responses.

COVID-19 in pancreas transplant recipients.

Coronavirus disease 2019 (COVID-19) has become a pandemic since first being described in January 2020. Clinical manifestations in non-transplant patients range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome, multiorgan system failure, and death. Limited reports in kidney transplant recipients suggest similar characteristics in that population. We report here the first case series of COVID-19 infection occurring in pancreas transplant recipients.

COVID-19 in solid organ transplant recipients: Initial report from the US epicenter.

Solid organ transplant recipients may be at a high risk for SARS-CoV-2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty-six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual-organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty-two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non-rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID-19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID-19 has the potential to severely impact solid organ transplant recipients.