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1.
BMJ Open ; 12(1): e055367, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1622061

ABSTRACT

OBJECTIVES: The COVID-19 pandemic significantly affected the provisions of health services to necessary but deprioritised fields, such as transplantation. Many programmes had to ramp-down their activity, which may significantly affect transplant volumes. We aimed to pragmatically analyse measures of transplant activity and compare them by a country's income level and cumulative COVID-19 incidence (CCI). DESIGN, SETTING AND PARTICIPANTS: From June to September 2020, we surveyed transplant physicians identified as key informants in their programmes. Of the 1267 eligible physicians, 40.5% from 71 countries participated. OUTCOME: Four pragmatic measures of transplant activity. RESULTS: Overall, 46.5% of the programmes from high-income countries anticipate being able to maintain >75% of their transplant volume compared with 31.6% of the programmes from upper-middle-income countries, and with 21.7% from low/lower-middle-income countries (p<0.001). This could be because more programmes in high-income countries reported being able to perform transplantation/s (86.8%%-58.5%-67.9%, p<0.001), maintain prepandemic deceased donor offers (31.0%%-14.2%-26.4%, p<0.01) and avoid a ramp down phase (30.9%%-19.7%-8.3%, p<0.001), respectively. In a multivariable analysis that adjusted for CCI, programmes in upper-middle-income countries (adjusted OR, aOR=0.47, 95% CI 0.27 to 0.81) and low/lower-middle-income countries (aOR 0.33, 95% CI 0.16 to 0.67) had lower odds of being able to maintain >75% of their transplant volume, compared with programmes in high-income countries. Again, this could be attributed to lower-income being associated with 3.3-3.9 higher odds of performing no transplantation/s, 66%-68% lower odds of maintaining prepandemic donor offers and 37%-76% lower odds of avoiding ramp-down of transplantation. Overall, CCI was not associated with these measures. CONCLUSIONS: The impact of the pandemic on transplantation was more in lower-income countries, independent of the COVID-19 burden. Given the lag of 1-2 years in objective data being reported by global registries, our findings may inform practice and policy. Transplant programmes in lower-income countries may need more effort to rebuild disrupted services and recuperate from the pandemic even if their COVID-19 burden was low.


Subject(s)
COVID-19 , Humans , Income , Pandemics , SARS-CoV-2 , Tissue Donors
2.
Cells ; 10(12)2021 11 23.
Article in English | MEDLINE | ID: covidwho-1538383

ABSTRACT

Dendritic cells (DCs) are the most potent antigen-presenting cells, and their function is essential to configure adaptative immunity and avoid excessive inflammation. DCs are predicted to play a crucial role in the clinical evolution of the infection by the severe acute respiratory syndrome (SARS) coronavirus (CoV)-2. DCs interaction with the SARS-CoV-2 Spike protein, which mediates cell receptor binding and subsequent fusion of the viral particle with host cell, is a key step to induce effective immunity against this virus and in the S protein-based vaccination protocols. Here we evaluated human DCs in response to SARS-CoV-2 S protein, or to a fragment encompassing the receptor binding domain (RBD) challenge. Both proteins increased the expression of maturation markers, including MHC molecules and costimulatory receptors. DCs interaction with the SARS-CoV-2 S protein promotes activation of key signaling molecules involved in inflammation, including MAPK, AKT, STAT1, and NFκB, which correlates with the expression and secretion of distinctive proinflammatory cytokines. Differences in the expression of ACE2 along the differentiation of human monocytes to mature DCs and inter-donor were found. Our results show that SARS-CoV-2 S protein promotes inflammatory response and provides molecular links between individual variations and the degree of response against this virus.


Subject(s)
Dendritic Cells/pathology , Dendritic Cells/virology , Receptors, Virus/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Cell Adhesion Molecules/metabolism , Cell Differentiation , Cytokines/biosynthesis , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Inflammation/pathology , Lectins, C-Type/metabolism , Protein Domains , Proto-Oncogene Proteins c-akt/metabolism , Receptors, Cell Surface/metabolism , STAT Transcription Factors/metabolism , Signal Transduction , Tissue Donors
3.
Med Humanit ; 47(4): 397-406, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1533074

ABSTRACT

With a focus on Larissa Lai's The Tiger Flu, this article explores how transplantation is part of the ongoing transformation of being in a body that is of the world. That is, it examines how we may require other ways of thinking bodies as constituted by histories, spaces and times that may be ignored in the biomedical arena. The Tiger Flu, I argue, calls for an intra- and inter-connected way of thinking how we treat bodies, and thereby ways of working with bodies affected by environmental disasters (both acute and ongoing capitalist and colonial projects), multiple selves and time as more than linear. I turn to queercrip as a way of defying a curative imaginary that dominates transplantation and in so doing examine the colonial, capitalist violence of present day living. I move through Eve Hayward's and Karen Barad's work to examine how the cut of transplantation is a transformation, as integral to the ongoing experience of having a body in the world and yet potentially unique in its force of bringing inter- and intra-relatedness to the fore of one's existence. Rather than sick or cured, I argue that transplantation is a transformation that captures our bodily changes, how the environment constitutes the self, how parts may feel integral to the self or easily disposed of, how viscera may tie us to others, and how the future may only be forged through a re-turn to the past (of the donor and a pre-transplant self). Transplantation is not about loss of self or gaining of an other, but rather about rendering apparent our multispecies, multiworld ties, and thus how we are bound by the histories we forge and the futures we re-member.


Subject(s)
Tissue Donors , Violence , Humans
4.
Transplant Proc ; 53(4): 1126-1131, 2021 May.
Article in English | MEDLINE | ID: covidwho-1525970

ABSTRACT

Coronavirus disease 2019 drastically impacted solid organ transplantation. Lacking scientific evidence, a very stringent but safer policy was imposed on liver transplantation (LT) early in the pandemic. Restrictive transplant guidelines must be reevaluated and adjusted as data become available. Before LT, the prevailing policy requires a negative severe acute respiratory syndrome coronavirus 2 real-time polymerase chain reaction (RT-PCR) of donors and recipients. Unfortunately, prolonged viral RNA shedding frequently hinders transplantation. Recent data reveal that positive test results for viral genome are frequently due to noninfectious and prolonged convalescent shedding of viral genome. Moreover, studies demonstrated that the cycle threshold of quantitative RT-PCR could be leveraged to inform clinical transplant decision-making. We present an evidence-adjusted and significantly less restrictive policy for LT, where risk tolerance is tiered to recipient acuity. In addition, we delineate the pretransplant clinical decision-making, intra- and postoperative management, and early outcome of 2 recipients of a liver graft performed while their RT-PCR of airway swabs remained positive. Convalescent positive RT-PCR results are common in the transplant arena, and the proposed policy permits reasonably safe LT in many circumstances.


Subject(s)
COVID-19 Nucleic Acid Testing/standards , COVID-19/diagnosis , Health Policy , Liver Transplantation/legislation & jurisprudence , SARS-CoV-2/genetics , COVID-19/prevention & control , COVID-19 Nucleic Acid Testing/methods , Female , Humans , Infection Control/legislation & jurisprudence , Infection Control/methods , Liver Transplantation/adverse effects , Male , Middle Aged , Postoperative Complications/prevention & control , Postoperative Complications/virology , Preoperative Care/legislation & jurisprudence , Preoperative Care/methods , Reference Values , Tissue Donors , Virus Shedding
5.
J Am Soc Nephrol ; 32(3): 708-722, 2021 03.
Article in English | MEDLINE | ID: covidwho-1496675

ABSTRACT

BACKGROUND: Late antibody-mediated rejection (ABMR) is a leading cause of transplant failure. Blocking IL-6 has been proposed as a promising therapeutic strategy. METHODS: We performed a phase 2 randomized pilot trial to evaluate the safety (primary endpoint) and efficacy (secondary endpoint analysis) of the anti-IL-6 antibody clazakizumab in late ABMR. The trial included 20 kidney transplant recipients with donor-specific, antibody-positive ABMR ≥365 days post-transplantation. Patients were randomized 1:1 to receive 25 mg clazakizumab or placebo (4-weekly subcutaneous injections) for 12 weeks (part A), followed by a 40-week open-label extension (part B), during which time all participants received clazakizumab. RESULTS: Five (25%) patients under active treatment developed serious infectious events, and two (10%) developed diverticular disease complications, leading to trial withdrawal. Those receiving clazakizumab displayed significantly decreased donor-specific antibodies and, on prolonged treatment, modulated rejection-related gene-expression patterns. In 18 patients, allograft biopsies after 51 weeks revealed a negative molecular ABMR score in seven (38.9%), disappearance of capillary C4d deposits in five (27.8%), and resolution of morphologic ABMR activity in four (22.2%). Although proteinuria remained stable, the mean eGFR decline during part A was slower with clazakizumab compared with placebo (-0.96; 95% confidence interval [95% CI], -1.96 to 0.03 versus -2.43; 95% CI, -3.40 to -1.46 ml/min per 1.73 m2 per month, respectively, P=0.04). During part B, the slope of eGFR decline for patients who were switched from placebo to clazakizumab improved and no longer differed significantly from patients initially allocated to clazakizumab. CONCLUSIONS: Although safety data indicate the need for careful patient selection and monitoring, our preliminary efficacy results suggest a potentially beneficial effect of clazakizumab on ABMR activity and progression.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Graft Rejection/therapy , Interleukin-6/antagonists & inhibitors , Kidney Transplantation/adverse effects , Adult , Allografts , Antibodies, Monoclonal, Humanized/adverse effects , Double-Blind Method , Female , Glomerular Filtration Rate , Graft Rejection/immunology , Graft Rejection/physiopathology , Humans , Infections/etiology , Interleukin-6/immunology , Isoantibodies/blood , Male , Middle Aged , Tissue Donors , Treatment Outcome , Young Adult
7.
Nat Commun ; 12(1): 5839, 2021 10 05.
Article in English | MEDLINE | ID: covidwho-1454764

ABSTRACT

There is an urgent need to understand the nature of immune responses against SARS-CoV-2, to inform risk-mitigation strategies for people living with HIV (PLWH). Here we show that the majority of PLWH with ART suppressed HIV viral load, mount a detectable adaptive immune response to SARS-CoV-2. Humoral and SARS-CoV-2-specific T cell responses are comparable between HIV-positive and negative subjects and persist 5-7 months following predominately mild COVID-19 disease. T cell responses against Spike, Membrane and Nucleoprotein are the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. We further show that the overall magnitude of SARS-CoV-2-specific T cell responses relates to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH. These findings suggest that inadequate immune reconstitution on ART, could hinder immune responses to SARS-CoV-2 with implications for the individual management and vaccine effectiveness in PLWH.


Subject(s)
HIV Infections/immunology , HIV Infections/virology , Immunity, Humoral , SARS-CoV-2/physiology , T-Lymphocytes/immunology , Adult , Aged , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antibody Formation/immunology , Antigens, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Cohort Studies , Female , Genome, Human , HIV Infections/blood , Humans , Interferon-gamma/metabolism , Male , Middle Aged , Phenotype , Species Specificity , Tissue Donors
8.
Indian J Ophthalmol ; 69(10): 2559-2562, 2021 10.
Article in English | MEDLINE | ID: covidwho-1441287
9.
Indian J Ophthalmol ; 69(10): 2808-2811, 2021 10.
Article in English | MEDLINE | ID: covidwho-1441259

ABSTRACT

Purpose: To determine the postmortem positivity for COVID-19 among voluntary eye donors who had been certified to have died of non-COVID-19 causes. Methods: All donors who donated their corneas (from March 2021 onward) were assessed for COVID-19 positivity tested by nasopharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) test. Relevant screening history was taken prior to collection. Strict precautions were taken during the retrieval as per the guidelines issued by the National Program for Control of Blindness and Visual Impairment and the Eye Bank Association of India, and the tissues were handled as per standard operating protocol. Results: 85 eye calls were attended during this period, of which 56 were home-based and 29 were from a hospital setting. Samples from 12 of the former group of donors were found to be positive for COVID-19 (14%). Conclusion: This study highlights the possibility of postmortem RT-PCR positivity in voluntary corneal tissue donors without a prior history of symptoms, signs, or diagnosis of illness suggestive of COVID-19. It is recommended that postmortem testing of donors should be done by RT-PCR for retrievals made during the pandemic.


Subject(s)
COVID-19 , Cornea , Eye Banks , Humans , SARS-CoV-2 , Tissue Donors
11.
Exp Clin Transplant ; 18(Suppl 2): 31-42, 2020 07.
Article in English | MEDLINE | ID: covidwho-1405517

ABSTRACT

Tamil Nadu, Gujarat, Telangana, Maharashtra, Kerala, Chandigarh, Karnataka, National Capital Territory of Delhi, and Rajasthan are states and union territories having active deceased-donor organ transplant programs in India. Transplant data (2013-2018) have been collected by the National Organ and Tissue Transplant Organization from all states and union territories of India and submitted to the Global Observatory on Donation and Transplantation. From 2013 to 2018, 49155 transplants were reported in India, including 39000 living-donor organ recipients and 10 155 deceased-donor organ recipients. These transplants were for kidney (living donor = 32584, deceased donor = 5748), liver (living donor = 6416, deceased donor = 2967), heart (deceased donor = 895), lung (deceased donor = 459), pancreas (deceased donor = 78), and small bowel (deceased donor = 8). According to 2018 data, India was the second largest transplanting country in the world in terms of the absolute number of transplants. Here, we discuss the status, progress, challenges, and solutions for deceaseddonor organ transplantation. The plan to increase rates of organ donation in India include the following points: teamwork and focus by intensive care unit doctors; public education on organ donation using social media; professional education and family donation conversation programs for brain death declaration and donor management; organ procurement organizations; international collaboration and regular meetings and updates for organizations working in the field of organ transplantation; grief counseling and reporting of potential donation for families of recently deceased people; nonfinancial incentivization to families of potential organ donors; expert committees and standard operating protocols for use of marginal donor organs, donation after circulatory death programs, and machine perfusion; maintenance of transparency and ethics in organ donation, allocation, and transplantation as directed by governmental, nongovernmental, and intergovernmental entities; and regular audit of progress and registry data.


Subject(s)
Brain Death , Organ Transplantation , Tissue Donors/supply & distribution , Tissue and Organ Procurement , Attitude to Death , COVID-19 , Health Education , Health Knowledge, Attitudes, Practice , Health Services Needs and Demand , Humans , India , Religion and Medicine , Time Factors
12.
JAMA Ophthalmol ; 139(8): 922-923, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1400716
13.
Neurol India ; 69(4): 995-996, 2021.
Article in English | MEDLINE | ID: covidwho-1403944

ABSTRACT

Formal brainstem reflex testing remains one of the most important procedures in identification and evaluation of patients who meet clinical criteria for brainstem death. Early identification of such patients is critical since willing donors may contribute to the organ donation process. During the first two waves of the coronavirus disease of 2019 (COVID-19) pandemic, organ transplantation from brainstem dead donors has declined significantly due to several reasons, including perceived increased risk of virus transmission to both physicians as well as patients as well as lack of awareness regarding donor workup in the context of the COVID-19 pandemic.


Subject(s)
Brain Death , COVID-19 , Brain Death/diagnosis , Humans , Pandemics , SARS-CoV-2 , Tissue Donors
14.
Cardiol Young ; 31(8): 1238-1240, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1397819

ABSTRACT

The growing unmet demand for suitable organ donors increases each year. Despite relative contraindications for thoracic organ donation after previous cardiac surgery, experienced programmes and surgeons can successfully utilise the lungs from select donors who have undergone prior cardiac surgery. This is the first reported case of double lung en bloc procurement from a donor who had a previous arterial switch operation as an infant.


Subject(s)
Arterial Switch Operation , Cardiac Surgical Procedures , Lung Transplantation , Tissue and Organ Procurement , Humans , Infant , Lung/diagnostic imaging , Lung/surgery , Tissue Donors
15.
Indian J Ophthalmol ; 69(6): 1598-1599, 2021 06.
Article in English | MEDLINE | ID: covidwho-1389642
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