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1.
Anaesthesist ; 71(4): 311-317, 2022 Apr.
Article in German | MEDLINE | ID: covidwho-1802647

ABSTRACT

In 2019 a total of 756 people died in Germany while registered on the waiting list for an organ transplantation. With 10.8 organ donors/million inhabitants in 2019, Germany belongs to the bottom group in the Eurotransplant foundation as well as worldwide. All political attempts to increase the number of organ donations have so far been unsuccessful. Furthermore, the pandemic triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a further decline in organ donations. Critical care physicians play an important role in the identification of potential doners and are also the main point of contact for relatives; however, multiple uncertainties exist regarding the process of organ donation not only in discussions in the media and society but also among physicians involved in intensive care medicine. Many assumptions and hypotheses, which have been associated with the low number of donors, lack scientific evidence and are discussed in this article.


Subject(s)
COVID-19 , Organ Transplantation , Tissue and Organ Procurement , Critical Care , Humans , SARS-CoV-2 , Tissue Donors
2.
JAMA Netw Open ; 5(4): e226822, 2022 Apr 01.
Article in English | MEDLINE | ID: covidwho-1782543

ABSTRACT

Importance: Recipients of solid organ transplant (SOT) experience decreased immunogenicity after COVID-19 vaccination. Objective: To summarize current evidence on vaccine responses and identify risk factors for diminished humoral immune response in recipients of SOT. Data Sources: A literature search was conducted from existence of database through December 15, 2021, using MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov. Study Selection: Studies reporting humoral immune response of the COVID-19 vaccines in recipients of SOT were reviewed. Data Extraction and Synthesis: Two reviewers independently extracted data from each eligible study. Descriptive statistics and a random-effects model were used. This report was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were analyzed from December 2021 to February 2022. Main Outcomes and Measures: The total numbers of positive immune responses and percentage across each vaccine platform were recorded. Pooled odds ratios (pORs) with 95% CIs were used to calculate the pooled effect estimates of risk factors for poor antibody response. Results: A total of 83 studies were included for the systematic review, and 29 studies were included in the meta-analysis, representing 11 713 recipients of SOT. The weighted mean (range) of total positive humoral response for antispike antibodies after receipt of mRNA COVID-19 vaccine was 10.4% (0%-37.9%) for 1 dose, 44.9% (0%-79.1%) for 2 doses, and 63.1% (49.1%-69.1%) for 3 doses. In 2 studies, 50% of recipients of SOT with no or minimal antibody response after 3 doses of mRNA COVID-19 vaccine mounted an antibody response after a fourth dose. Among the factors associated with poor antibody response were older age (mean [SE] age difference between responders and nonresponders, 3.94 [1.1] years), deceased donor status (pOR, 0.66 [95% CI, 0.53-0.83]; I2 = 0%), antimetabolite use (pOR, 0.21 [95% CI, 0.14-0.29]; I2 = 70%), recent rituximab exposure (pOR, 0.21 [95% CI, 0.07-0.61]; I2 = 0%), and recent antithymocyte globulin exposure (pOR, 0.32 [95% CI, 0.15-0.71]; I2 = 0%). Conclusions and Relevance: In this systematic review and meta-analysis, the rates of positive antibody response in solid organ transplant recipients remained low despite multiple doses of mRNA vaccines. These findings suggest that more efforts are needed to modulate the risk factors associated with reduced humoral responses and to study monoclonal antibody prophylaxis among recipients of SOT who are at high risk of diminished humoral response.


Subject(s)
COVID-19 , Organ Transplantation , COVID-19/prevention & control , COVID-19 Vaccines , Child, Preschool , Humans , Immunity, Humoral , RNA, Messenger , Risk Factors , SARS-CoV-2
3.
Exp Clin Transplant ; 20(Suppl 1): 10-16, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1780228

ABSTRACT

Coronavirus disease (COVID-19) has engulfed the whole world, and India has been the second worst-hit nation. Organ transplant services were halted in both the public and private care sectors of India, with public care sectors more adversely affected. Deceased donations were disproportionately more affected, with unfavorable rates at the peak of the pandemic. Mortality outcomes of COVID-19 among different organ transplant recipients in India have been lower compared with the Western world, with younger age and less comorbidities among Indian populations partly responsible for the lower mortality. Mortality and graft loss were mostly associated with older age and those with chronic graft dysfunction. During the pandemic, invasive fungal infections, like mucormycosis, have been reported, illustrating the need for multidisciplinary management. The Indian transplant societies have formulated and timely revised guidelines for transplantation in the COVID-19 era. Living donor transplants (both liver and kidney) after recovery from COVID-19 were both first described in India, providing a guiding tool for the world. Follow-up reports of recovered solid-organ transplant recipients have also been reported in Indian studies, showing reassuring long-term outcomes. Data of breakthrough COVID-19 cases after vaccination among both transplant recipients and waitlist candidates and research in vaccine efficacy for solid-organ transplant recipients is still underway. We suggest continuing and intensifying research activities for a better plan and strategy in case of a future pandemic.


Subject(s)
COVID-19 , Organ Transplantation , COVID-19/epidemiology , Humans , Organ Transplantation/adverse effects , Pandemics , SARS-CoV-2 , Treatment Outcome
5.
Am J Transplant ; 22 Suppl 2: 519-552, 2022 03.
Article in English | MEDLINE | ID: covidwho-1735847

ABSTRACT

SRTR uses data collected by OPTN to calculate metrics such as donation rate, organ yield, and rate of organs recovered for transplant but not transplanted. In 2020, there were 12,588 deceased donors, an increase from 11,870 in 2019; this number has been increasing since 2010. The number of deceased donor transplants increased to 33,303 in 2020, from 32,313 in 2019; this number has been increasing since 2012. The increase may be due in part to the rising number of deaths of young people amid the ongoing opioid epidemic. The number of organs transplanted included 18,410 kidneys, 962 pancreata, 8350 livers, 91 intestines, 3722 hearts, and 2463 lungs. Compared with 2019, transplants of all organs except pancreata and lung transplants increased in 2020, which is remarkable despite the pandemic caused by the SARS-CoV2 virus. In 2020, 4870 kidneys, 294 pancreata, 861 livers, 3 intestines, 39 hearts, and 115 lungs were discarded. The number of discards was similar to that of the previous year. In 2019, 4,324 kidneys, 346 pancreata, 867 livers, 5 intestines, 31 hearts, and 148 lungs were discarded. These numbers suggest an opportunity to increase numbers of transplants by reducing discards. Despite the pandemic, there was no dramatic increase in number of discards and an increase in total number of donors and transplants.


Subject(s)
COVID-19 , Organ Transplantation , Tissue Donors/statistics & numerical data , Tissue and Organ Procurement , Adolescent , COVID-19/epidemiology , Humans , Organ Transplantation/standards , Organ Transplantation/statistics & numerical data , Registries , SARS-CoV-2 , Tissue Donors/classification , Tissue and Organ Procurement/statistics & numerical data , Tissue and Organ Procurement/trends
7.
Transplantation ; 106(4): 693-695, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1722758
10.
Pol Arch Intern Med ; 132(2)2022 11 28.
Article in English | MEDLINE | ID: covidwho-1716308

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has disproportionately affected patients who have undergone solid organ transplantation (SOT). OBJECTIVES: We aimed to assess a cohort of transplant recipients who developed COVID­19, with a focus on immunosuppressive regimen, blood tacrolimus levels, clinical course, and patient and graft outcomes. PATIENTS AND METHODS: During the first 12 months of the pandemic, we identified ambulatory SOT recipients, including kidney, liver, and heart transplant recipients, diagnosed with SARS­CoV­2 infection. Baseline and follow­up data on graft function, immunosuppression, and patient and graft outcomes were assessed. RESULTS: Of the 2091 ambulatory patients, we identified 201 transplant recipients (9.6%) with SARS­CoV­2 infection (kidney transplant, n = 112; heart transplant, n = 56; liver transplant, n = 33). Patients after recent kidney (during 2015-2020) or heart (during 2020) transplant were significantly more often diagnosed with COVID ­19 than patients with a longer time since transplant. Additionally, blood trough tacrolimus levels measured during or shortly after COVID­19 in 23 kidney graft recipients were significantly increased by a median of 76.1% (interquartile range, 47.4%-109.4%) relative to predose trough levels. However, liver function parameters were not elevated, necessitating a tacrolimus dose reduction in 73.9% of the patients. CONCLUSIONS: In our study, kidney transplant recipients showed significant disturbances of tacrolimus metabolism, which may account for kidney function worsening during COVID­19. Moreover, infection was more common in patients with recent kidney or heart transplant, which suggests that the level of immunosuppression may affect morbidity related to SARS­CoV­2 infection.


Subject(s)
COVID-19 , Organ Transplantation , Humans , Immunosuppressive Agents/adverse effects , Organ Transplantation/adverse effects , Pandemics , SARS-CoV-2 , Transplant Recipients
11.
Transpl Infect Dis ; 24(2): e13788, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1709062

ABSTRACT

BACKGROUND: Clinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in solid organ transplant recipients (SOTRs) is not well documented despite multiple studies demonstrating sub-optimal immunogenicity. METHODS: We reviewed medical records of eligible SOTRs at a single center to assess vaccination status and identify cases of symptomatic COVID-19 from January 1 to August 12, 2021. We developed a Cox proportional hazards model using the date of vaccination and time since transplantation as a time-varying covariate with age and gender as potential time-invariant confounders. Survival curves were created using the parameters estimated from the Cox model. RESULTS: Among 1904 SOTRs, 1362 were fully vaccinated (96% received mRNA vaccines) and 542 were either unvaccinated (n = 470) or partially vaccinated (n = 72). There were 115 cases of COVID-19, of which 12 occurred in fully vaccinated individuals. Cox regression with the date of vaccination and time since transplantation as the time-varying co-variates showed that after baseline adjustment for age and sex, being fully vaccinated had a significantly lower hazard for COVID-19, hazard ratio (HR) = 0.29 and 95% confidence interval ([CI] 0.09, 0.91). CONCLUSION: We found that 2-dose mRNA COVID-19 vaccination was protective of symptomatic COVID-19 in vaccinated versus unvaccinated SOTRs. TWEET: COVID-19 vaccination was associated with a significantly lower hazard for symptomatic COVID-19 (HR 0.29; 95% CI 0.09, 0.91) among 1904 SOT recipients at a single center from January 1 to August 12, 2021.


Subject(s)
COVID-19 , Organ Transplantation , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Organ Transplantation/adverse effects , SARS-CoV-2 , Transplant Recipients , Vaccination
12.
Transplantation ; 105(7): 1405-1422, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1706459

ABSTRACT

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has raised concerns for programs overseeing donation and transplantation of cells, tissues, and organs (CTO) that this virus might be transmissible by transfusion or transplantation. Transplant recipients are considered particularly vulnerable to pathogens because of immunosuppression, and SARS-CoV-2 is likely to generate complications if contracted. Several signs and symptoms observed in COVID-19 positive patients reflect damage to multiple organs and tissues, raising the possibility of extrapulmonary SARS-CoV-2 infections and risk of transmission. At the beginning of the pandemic, a consensus has emerged not to consider COVID-19 positive patients as potential living or deceased donors, resulting in a global decrease in transplantation procedures. Medical decision-making at the time of organ allocation must consider safely alongside the survival advantages offered by transplantation. To address the risk of transmission by transplantation, this review summarizes the published cases of transplantation of cells or organs from donors infected with SARS-CoV-2 until January 2021 and assesses the current state of knowledge for the detection of this virus in different biologic specimens, cells, tissues, and organs. Evidence collected to date raises the possibility of SARS-CoV-2 infection and replication in some CTO, which makes it impossible to exclude transmission through transplantation. However, most studies focused on evaluating transmission under laboratory conditions with inconsistent findings, rendering the comparison of results difficult. Improved standardization of donors and CTO screening practices, along with a systematic follow-up of transplant recipients could facilitate the assessment of SARS-CoV-2 transmission risk by transplantation.


Subject(s)
COVID-19/transmission , Donor Selection/methods , Hematopoietic Stem Cell Transplantation/adverse effects , Organ Transplantation/adverse effects , Postoperative Complications/etiology , SARS-CoV-2/isolation & purification , COVID-19/diagnosis , COVID-19/prevention & control , COVID-19/virology , Humans , Postoperative Complications/diagnosis , Postoperative Complications/prevention & control , Risk
13.
Eur J Med Res ; 27(1): 23, 2022 Feb 12.
Article in English | MEDLINE | ID: covidwho-1703609

ABSTRACT

BACKGROUND: Immunocompromised (IC) patients are at higher risk of severe SARS-CoV-2 infection, morbidity, and mortality compared to the general population. They should be prioritized for primary prevention through vaccination. This study aimed to evaluate the efficacy of COVID-19 mRNA vaccines in IC patients through a systematic review and meta-analysis approach. METHOD: PubMed-MEDLINE, Scopus, and Web of Science were searched for original articles reporting the immunogenicity of two doses of mRNA COVID-19 vaccines in adult patients with IC condition between June 1, 2020 and September 1, 2021. Meta-analysis was performed using either random or fixed effect according to the heterogeneity of the studies. Subgroup analysis was performed to identify potential sources of heterogeneity. RESULTS: A total of 26 studies on 3207 IC patients and 1726 healthy individuals were included. The risk of seroconversion in IC patients was 48% lower than those in controls (RR = 0.52 [0.42, 0.65]). IC patients with autoimmune conditions were 54%, and patients with malignancy were 42% more likely to have positive seroconversion than transplant recipients (P < 0.01). Subgroup meta-analysis based on the type of malignancy, revealed significantly higher proportion of positive seroconversion in solid organ compared to hematologic malignancies (RR = 0.88 [0.85, 0.92] vs. 0.61 [0.44, 0.86], P = 0.03). Subgroup meta-analysis based on type of transplantation (kidney vs. others) showed no statistically significant between-group difference of seroconversion (P = 0.55). CONCLUSIONS: IC patients, especially transplant recipients, developed lower immunogenicity with two-dose of COVID-19 mRNA vaccines. Among patients with IC, those with autoimmune conditions and solid organ malignancies are mostly benefited from COVID-19 vaccination. Findings from this meta-analysis could aid healthcare policymakers in making decisions regarding the importance of the booster dose or more strict personal protections in the IC patients.


Subject(s)
COVID-19 Vaccines/immunology , Immunocompromised Host , Vaccines, Synthetic/immunology , /immunology , Autoimmune Diseases/immunology , COVID-19 Vaccines/therapeutic use , Case-Control Studies , Humans , Neoplasms/immunology , Organ Transplantation , Vaccines, Synthetic/therapeutic use , /therapeutic use
14.
J Infect Public Health ; 15(3): 365-372, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1693249

ABSTRACT

BACKGROUND: Although many studies have reported cases of COVID-19 infection in transplant recipients, most of them only involve a small number of patients and narrow geographic areas. This study aims to investigate the clinical characteristics, morbidity, severity, and mortality of COVID-19 infection among solid organ transplant (SOT) recipients by meta-analysis. METHOD: We performed a literature search using the databases PubMed, Web of Science, and Google Scholar as of November 26, 2020. We included randomized controlled trials and cohort studies, excluding case reports and small case series (n < 10). The pooled incidence proportion and 95% confidence intervals (CI) were used to estimate the combined results of forty-seven studies were included for the meta-analysis. Heterogeneity was assessed using I2. Freeman-Tukey double arcsine transformation was used to stabilize the specific rate variance. Publication bias was using Egger's test. RESULTS: The morbidity rate of COVID-19 in SOT recipients was 2.10% [95% CI 1.35-3.01], and the proportion of severe infection was 22.46% [95% CI 15.74-29.90]. The mortality rate was 17.38% [95% CI 13.72-21.34]. In the analysis by transplanted organ, the proportion of patients with severe infection was highest in recipients of two or more transplants 48.85% [95% CI 11.88-86.38]. The mortality rate was highest in lung transplant recipients 25.12% [95% CI 16.94-34.00]. The most common symptoms of COVID-19 in SOT recipients were fever (73.39%), cough (58.90%), and respiratory symptoms (45.77%). CONCLUSION: SOT was a risk factor for worse COVID-19 outcomes, although the morbidity of COVID-19 in SOT recipients was not markedly higher than the general population. These results may change when our understanding of the disease progress.


Subject(s)
COVID-19 , Organ Transplantation , Transplant Recipients , COVID-19/complications , COVID-19/epidemiology , COVID-19/mortality , Humans , Morbidity , Risk Factors , SARS-CoV-2
15.
J Infect Dis ; 225(3): 374-384, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1672205

ABSTRACT

BACKGROUND: The underlying immunologic deficiencies enabling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection are currently unknown. We describe deep longitudinal immune profiling of a transplant recipient hospitalized twice for coronavirus disease 2019 (COVID-19). METHODS: A 66-year-old male renal transplant recipient was hospitalized with COVID-19 March 2020 then readmitted to the hospital with COVID-19 233 days after initial diagnosis. Virologic and immunologic investigations were performed on samples from the primary and secondary infections. RESULTS: Whole viral genome sequencing and phylogenetic analysis revealed that viruses causing both infections were caused by distinct genetic lineages without evidence of immune escape mutations. Longitudinal comparison of cellular and humoral responses during primary SARS-CoV-2 infection revealed that this patient responded to the primary infection with low neutralization titer anti-SARS-CoV-2 antibodies that were likely present at the time of reinfection. CONCLUSIONS: The development of neutralizing antibodies and humoral memory responses in this patient failed to confer protection against reinfection, suggesting that they were below a neutralizing titer threshold or that additional factors may be required for efficient prevention of SARS-CoV-2 reinfection. Development of poorly neutralizing antibodies may have been due to profound and relatively specific reduction in naive CD4 T-cell pools. Seropositivity alone may not be a perfect correlate of protection in immunocompromised patients.


Subject(s)
COVID-19 , Reinfection , Transplant Recipients , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Humans , Male , Organ Transplantation , Phylogeny , Reinfection/immunology , Reinfection/virology , SARS-CoV-2/genetics
17.
Immun Inflamm Dis ; 10(3): e587, 2022 03.
Article in English | MEDLINE | ID: covidwho-1625924

ABSTRACT

BACKGROUND: Tocilizumab was studied to reduce cytokine syndrome in patients with severe COVID-19 pneumonia in solid organ transplant (SOT) recipients with conflicting results. We aim to study the early use of tocilizumab in SOT with COVID-19 pneumonia on low flow oxygen. METHODS: This is a retrospective cohort study that was conducted in two transplant centers in Saudi Arabia among 46 SOT with COVID-19 comparing 21 patients who received tocilizumab to 25 patients who received standard of care. Their clinical characteristics and outcomes were described. RESULTS: Compared to patients who received standard of care, patients in the tocilizumab group were older (60.2 ± 12.8 vs. 48.6 ± 12.3, p = .003), had higher ferritin (862.1 ± 919.1 vs. 414 ± 447.3, p = .025) and C-reactive protein (CRP) (85 ± 83.1 vs. 42.9 ± 57.3, p = .012). More patients in the tocilizumab group required high flow oxygen (38.1% vs. 8.0%, p = .028) compared to patients on standard of care. There were no differences in mortality or mechanical ventilation requirement. Hospital stay was significantly shorter in the tocilizumab group than the standard of care group (9.6 ± 7.4 vs. 20.7 ± 11.7, p < .001). CONCLUSIONS: Early use of tocilizumab in SOT was associated with a shorter hospital stay. There was no difference in mortality rate and the requirement for mechanical ventilation in both groups.


Subject(s)
COVID-19 , Organ Transplantation , Antibodies, Monoclonal, Humanized , COVID-19/drug therapy , Humans , Retrospective Studies , SARS-CoV-2 , Saudi Arabia/epidemiology
19.
J Infect Dis ; 224(11): 1849-1860, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1612585

ABSTRACT

T-cell immunity associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination in solid organ transplant recipients (SOTRs) is poorly understood. To address this, we measured T-cell responses in 50 SOTRs with prior SARS-CoV-2 infection. The majority of patients mounted SARS-CoV-2-specific CD4+ T-cell responses against spike (S), nucleocapsid, and membrane proteins; CD8+ T-cell responses were generated to a lesser extent. CD4+ T-cell responses correlated with antibody levels. Severity of disease and mycophenolate dose were moderately associated with lower proportions of antigen-specific T cells. Relative to nontransplant controls, SOTRs had perturbations in both total and antigen-specific T cells, including higher frequencies of total PD-1+ CD4+ T cells. Vaccinated SOTRs (n = 55) mounted significantly lower proportions of S-specific polyfunctional CD4+ T cells after 2 doses, relative to unvaccinated SOTRs with prior coronavirus disease 2019. Together, these results suggest that SOTRs generate robust T-cell responses following natural infection that correlate with disease severity but generate comparatively lower T-cell responses following mRNA vaccination.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , T-Lymphocytes/immunology , Transplant Recipients , Humans , Immunity, Cellular , Organ Transplantation , SARS-CoV-2 , Vaccination
20.
Am J Transplant ; 22(4): 1253-1260, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1583700

ABSTRACT

Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralization. A third SARS-CoV-2 vaccine dose increased median total anti-spike (1.6-fold), pseudoneutralization against VOCs (2.5-fold vs. Delta), and neutralizing antibodies (1.4-fold against Delta). However, neutralization activity was significantly lower than healthy controls (p < .001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination compared to 100% for controls. Correlation with nAb was seen at anti-spike IgG >4 Log10 (AU/ml) on the Euroimmun ELISA and >4 Log10 (AU/ml) on the MSD research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.


Subject(s)
COVID-19 , Organ Transplantation , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Organ Transplantation/adverse effects , SARS-CoV-2 , Transplant Recipients , Vaccines, Synthetic
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