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Open accessJournal ArticleDOI: 10.1007/S40472-021-00322-5

Immune Responses to SARS-CoV-2 in Solid Organ Transplant Recipients.

04 Mar 2021-Current Transplantation Reports (Springer International Publishing)-Vol. 8, Iss: 2, pp 1-13
Abstract: Coronavirus disease 2019 (COVID-19) is caused by a complex interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics and host immune responses. Hosts with altered immunity, including solid organ transplant recipients, may be at increased risk of complications and death due to COVID-19. A synthesis of the available data on immune responses to SARS-CoV-2 infection is needed to inform therapeutic and preventative strategies in this special population. Few studies have directly compared immune responses to SARS-CoV-2 between transplant recipients and the general population. Like non-transplant patients, transplant recipients mount an exuberant inflammatory response following initial SARS-CoV2 infection, with IL-6 levels correlating with disease severity in some, but not all studies. Transplant recipients display anti-SARS-CoV-2 antibodies and activated B cells in a time frame and magnitude similar to non-transplant patients—limited data suggest these antibodies can be detected within 15 days of symptom onset and may be durable for several months. CD4+ and CD8+ T lymphopenia, a hallmark of COVID-19, is more profound in transplant recipients, but SARS-CoV-2–reactive T cells can be detected among patients with both mild and severe disease. The limited available data indicate that immune responses to SARS-CoV-2 are similar between transplant recipients and the general population, but no studies have been sufficiently comprehensive to understand nuances between organ types or level of immunosuppression to meaningfully inform individualized therapeutic decisions. The ongoing pandemic provides an opportunity to generate higher-quality data to support rational treatment and vaccination strategies in this population.

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Topics: Immunosuppression (55%), Population (54%), Immune system (53%)
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Open accessJournal ArticleDOI: 10.1111/AJT.16708
Abstract: Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2-specific T-cell-mediated immunity (SARS-CoV-2-CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS-CoV-2-CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)-γ FluoroSpot assay after a median of 103 days from COVID-19 diagnosis. Serum SARS-CoV-2 IgG antibodies were measured by ELISA. A control group of non-transplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post-transplant SARS-CoV-2-CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN-γ-producing CD4+ than CD8+ responses (93.5% versus 83.9%). Positive spike-specific and nucleoprotein-specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein-specific response was present in 83.3% (25/30). An inverse correlation was observed between the number of spike-specific IFN-γ-producing SFUs and time from diagnosis (Spearman's rho: -0.418; P-value = 0.024). Two recipients (6.5%) failed to mount either T-cell-mediated or IgG responses. There were no significant differences between LT recipients and non-transplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable -but declining over time- SARS-CoV-2-CMI after a median of 3 months from COVID-19, with no meaningful differences with immunocompetent patients.

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Topics: FluoroSpot (53%)

4 Citations


Open accessJournal ArticleDOI: 10.3390/V13091879
20 Sep 2021-Viruses
Abstract: Since its outbreak in December 2019, the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to an enormous rise in scientific response with an excess of COVID-19-related studies on the pathogenesis and potential therapeutic approaches. Solid organ transplant (SOT) recipients are a heterogeneous population with long-lasting immunosuppression as a joining element. Immunocompromised patients are a vulnerable population with a high risk of severe infections and an increased infection-related mortality rate. It was postulated that the hyperinflammatory state due to cytokine release syndrome during severe COVID-19 could be alleviated by immunosuppressive therapy in SOT patients. On the other hand, it was previously established that T cell-mediated immunity, which is significantly weakened in SOT recipients, is the main component of antiviral immune responses. In this paper, we present the current state of science on COVID-19 immunology in relation to solid organ transplantation with prospective therapeutic and vaccination strategies in this population.

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Topics: Organ transplantation (56%), Population (54%), Immunosuppression (54%) ... read more

1 Citations


Open accessJournal ArticleDOI: 10.37536/RIECS.2021.6.1.253
31 May 2021-
Abstract: Los pacientes con enfermedad renal cronica en hemodialisis tienen una respuesta inmune humoral alterada y una baja respuesta de seroconversion a vacunas. Hasta el momento, no se conoce su capacidad de generar respuesta inmune frente al coronavirus 2019 (COVID-19). Mediante este estudio analizamos la capacidad de respuesta inmunitaria frente al COVID-19 en los pacientes de una unidad de hemodialisis hospitalaria. Realizamos un estudio observacional descriptivo retrospectivo de 69 pacientes de la unidad de hemodialisis del Hospital Universitario de Guadalajara. A los 3 meses se les realizo test rapido Ac Wondfo Biotech en 62 pacientes y a los 11 meses el test serologico IgG de Abbott en 55 pacientes. Se diagnosticaron 19 casos COVID-19: 13 con PCR y 6 con test rapido. 11 de ellos sufrieron enfermedad COVID-19 grave. A los 3 meses 12 pacientes tenian Ac detectable, de los cuales 6 habian sido asintomaticos. A los 11 meses 9 pacientes tuvieron Ac IgG a nivel optimo y dos tercios de ellos habian sufrido COVID-19 grave. Todos los pacientes que sufrieron COVID-19 grave mantenian titulo de Ac IgG a los 11 meses. Por otro lado, los pacientes COVID-19 en los que no se detecto Ac IgG a los 11 meses habian sufrido la enfermedad de forma leve. En nuestra poblacion la presencia y mantenimiento de respuesta inmunitaria frente a SARS Cov2 se asocio al antecedente COVID-19 grave. Los resultados serologicos indeterminados se asociaron a casos oligosintomaticos.

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1 Citations



Open accessJournal ArticleDOI: 10.1111/AJT.16843
Abstract: Organ transplant recipients may not mount an adequate immune response to COVID-19 infection and therefore may benefit greatly from passive immunization with anti-spike monoclonal antibodies (mAbs), which have been shown to decrease hospitalization rates in the general outpatient population. We evaluated the efficacy of mAb therapy in decreasing hospitalizations or emergency room (ER) visits among kidney transplant recipients (KTR) with COVID-19. We identified KTR with COVID-19 between March 1, 2020 and April 30, 2021. Patients were excluded if they had multi-organ transplant or hospital-acquired COVID-19. We studied 95 KTR; 20 received mAb. mAb administration was associated with a significant decrease in hospitalizations or ER visits (15% vs. 76%, p < 0.001). This association remained significant after adjustment for potential confounders, and analysis of mAb administration as a time-dependent variable, with day of symptom onset as day 1 (adjusted HR 0.216, p = 0.04). Black or Hispanic patients were less likely to receive mAb and more likely to be admitted to the hospital or visit the ER. In our KTR population, mAb therapy for COVID-19 may have helped decrease hospitalizations and ER visits. Healthcare inequities, including access to investigational treatments, have been exacerbated by the COVID-19 pandemic. Antiviral mAbs are a promising therapeutic modality, especially for immunocompromised patients.

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Topics: Population (52%)

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94 results found


Open accessJournal ArticleDOI: 10.1016/S0140-6736(20)30183-5
Chaolin Huang1, Yeming Wang2, Xingwang Li3, Lili Ren4  +25 moreInstitutions (8)
24 Jan 2020-The Lancet
Abstract: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.

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26,390 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2021436
Abstract: BackgroundCoronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.MethodsIn this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the final results of this assessment.ResultsA total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.92 to 1.55).ConclusionsIn patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936. opens in new tab; ISRCTN number, 50189673. opens in new tab.)

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Topics: Lung injury (55%), Mechanical ventilation (52%), Randomized controlled trial (52%) ... read more

4,501 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2034577
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...

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4,222 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2035389
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 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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Topics: Vaccine efficacy (62%), Breakthrough infection (53%), Placebo (50%)

2,721 Citations


Open accessJournal ArticleDOI: 10.1038/S41577-020-0311-8
Matthew Zirui Tay1, Chek Meng Poh1, Laurent Rénia2, Laurent Rénia1  +4 moreInstitutions (3)
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.

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2,055 Citations


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