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3.
Exp Clin Transplant ; 20(Suppl 1): 10-16, 2022 03.
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.
Transplantation ; 106(4): 693-695, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1722758
6.
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
8.
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
9.
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
10.
Clin Microbiol Infect ; 28(6): 779-784, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1693762

ABSTRACT

BACKGROUND: The COVID-19 pandemic has influenced the field of solid organ transplantation (SOT) in many ways. COVID-19 has led to programmatic impacts and changes in donor and recipient selection. Several studies have evaluated the course, optimal treatment, and prevention of COVID-19 in SOT recipients. OBJECTIVES: To review the literature on COVID-19 in SOT recipients. SOURCES: PubMed, Web of Science, and Google Scholar were searched. The search was restricted to articles published between January 1, 2019 and December 1, 2021. CONTENT: The COVID-19 pandemic initially led to a decreased volume of solid organ transplants. However, transplant volumes at most centres have rebounded. Donor selection remains an incompletely defined issue. Several reports suggest that donor-derived SARS-CoV-2 infections occur only in lung transplant recipients and that other organs from SARS-CoV-2 PCR-positive donors could potentially be safely used. However, these data are limited to case series. Transplantation for end-stage lung disease after COVID-19 infection is increasingly common and has been performed with acceptable outcomes. In acute COVID-19 in a transplant candidate, transplantation should be delayed when feasible. After adjustment, mortality after COVID-19 appear similar in SOT recipients compared to the general population, with notable increased use of antiviral and anti-inflammatory treatment options. Prevention of COVID-19 is key in SOT recipients. Vaccination of SOT recipients and anyone who is in contact with SOT recipients is one of the cornerstones of prevention. Nonpharmacological interventions such as face coverings, hand hygiene, and physical distancing remain ever important as well. IMPLICATIONS: The COVID-19 pandemic continues to have an important impact on SOT candidates and recipients. Prevention of infection is the most important measure and requires careful attention to approaches to vaccination and messaging of the ongoing need for face coverings, physical distancing, and hand hygiene.


Subject(s)
COVID-19 , Organ Transplantation , COVID-19/epidemiology , Humans , Organ Transplantation/adverse effects , Pandemics/prevention & control , SARS-CoV-2 , Transplant Recipients
13.
Kidney Int ; 101(5): 1027-1038, 2022 05.
Article in English | MEDLINE | ID: covidwho-1665243

ABSTRACT

Long-term adaptive immune memory has been reported among immunocompetent individuals up to eight months following SARS-CoV-2 infection. However, limited data is available in convalescent patients with a solid organ transplant. To investigate this, we performed a thorough evaluation of adaptive immune memory at different compartments (serological, memory B cells and cytokine [IFN-γ, IL-2, IFN-γ/IL12 and IL-21] producing T cells) specific to SARS-CoV-2 by ELISA and FluoroSpot-based assays in 102 convalescent patients (53 with a solid organ transplants (38 kidney, 5 liver, 5 lung and 5 heart transplant) and 49 immunocompetent controls) with different clinical COVID-19 severity (severe, mild and asymptomatic) beyond six months after infection. While similar detectable memory responses at different immune compartments were detected between those with a solid organ transplant and immunocompetent individuals, these responses were predominantly driven by distinct COVID-19 clinical severities (97.6%, 80.5% and 42.1%, all significantly different, were seropositive; 84% vs 75% vs 35.7%, all significantly different, showed IgG-producing memory B cells and 82.5%, 86.9% and 31.6%, displayed IFN-γ producing T cells; in severe, mild and asymptomatic convalescent patients, respectively). Notably, patients with a solid organ transplant with longer time after transplantation did more likely show detectable long-lasting immune memory, regardless of COVID-19 severity. Thus, our study shows that patients with a solid organ transplant are capable of maintaining long-lasting peripheral immune memory after COVID-19 infection; mainly determined by the degree of infection severity.


Subject(s)
COVID-19 , Organ Transplantation , Antibodies, Viral , Humans , Immunologic Memory , Organ Transplantation/adverse effects , SARS-CoV-2 , Transplant Recipients
15.
Am J Transplant ; 22(4): 1253-1260, 2022 04.
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
16.
Transpl Infect Dis ; 24(2): e13779, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1583253

ABSTRACT

BACKGROUND: Solid organ transplant (SOT) recipients are at increased risk for complications from SARS-CoV-2 infection. Little is known regarding clinical course and outcomes of breakthrough COVID-19 in the fully vaccinated SOT population. We sought to describe our cohort of SOT recipients who developed symptomatic breakthrough COVID-19 after full vaccination. METHODS: We conducted a retrospective review of SOT recipients diagnosed with COVID-19 at least 14 days after completing SARS-CoV-2 vaccination. Patients were analyzed according to those presenting with mild-to-moderate and severe COVID-19, respectively. We described presenting characteristics, COVID-19 therapy, and analyzed outcomes including emergency department (ED) visits, hospitalization, and intensive care unit (ICU) admission. RESULTS: Thirty-five patients met inclusion criteria. These had a mean age of 60.8 years and kidney transplant was the most common SOT type. Five patients presented with severe COVID-19 at diagnosis, all requiring hospitalization without ICU admission. From the 30 patients who presented with mild-to-moderate infection, 28 received casirivimab-imdevimab. Four of these 28 (14.3%) had an ED visit, with one requiring hospital admission (3.4%). No patients required ICU admission. CONCLUSION: Breakthrough COVID-19 may occur in SOT recipients after full vaccination, though they appear to have acceptable outcomes. Anti-spike monoclonal antibody therapy for eligible SOT patients may have mitigated clinical progression and improved the outcomes. Further study with large cohorts is warranted.


Subject(s)
COVID-19 , Organ Transplantation , Antibodies, Monoclonal , Antibodies, Monoclonal, Humanized , COVID-19 Vaccines , Humans , Middle Aged , Organ Transplantation/adverse effects , SARS-CoV-2 , Transplant Recipients , Vaccination
17.
Ann Transplant ; 26: e933152, 2021 Nov 12.
Article in English | MEDLINE | ID: covidwho-1575127

ABSTRACT

BACKGROUND It is unclear whether solid organ transplant (SOT) patients have more severe coronavirus disease 2019 (COVID-19) and worse outcome than the general population. MATERIAL AND METHODS We conducted a case-control study on 32 SOT recipients and 84 non-SOT controls matched for age and sex admitted for confirmed COVID-19. The primary endpoint was in-hospital all-cause mortality rate. Secondary endpoints included severe acute respiratory distress syndrome (ARDS), use of high-flow oxygen therapy, and length of hospital stay. RESULTS The median (IQR) Charlson comorbidity index (CCI) at admission was significantly higher in SOT recipients (6 (3-8) vs 3 (2-4); P<0.01). Fever was less frequent in SOT recipients (78% vs 94%, P=0.01). SOT recipients had a higher median SaO2/FiO2 at admission (452 [443-462] vs 443 [419-452], P<0.01) and reached the worst SaO2/FiO2 value later during hospitalization 15 (10-21) vs 11 (9-14) days, P=0.01). Both groups had a similar severe ARDS rate during hospitalization (33% vs 28%) (p=0.59). There were no significant differences during hospitalization in terms of highest level of respiratory support needed, or length of hospital stay: 8.5 (5.5-21) vs 11.5 (6.5-16.5) days; P=0.34) in SOT recipients when compared to controls. In-hospital all-cause mortality rates were significantly higher in SOT recipients (21.9% vs 4.7%, P<0.01; OR 1.08; 95% CI 0.10-10.98), but among patients who died, median CCI was similar between groups (8 [6-8] vs 7 [6-8]). CONCLUSIONS In our experience, hospitalized SOT recipients for COVID-19 had higher in-hospital mortality compared to non-SOT patients, probably due to the greater number of underlying comorbidities, and not directly related to chronic immunosuppression.


Subject(s)
COVID-19 , Organ Transplantation , Case-Control Studies , Humans , Organ Transplantation/adverse effects , Retrospective Studies , SARS-CoV-2 , Transplant Recipients
18.
PLoS One ; 16(3): e0247251, 2021.
Article in English | MEDLINE | ID: covidwho-1574883

ABSTRACT

In the context of COVID-19 pandemic, we aimed to analyze the epidemiology, clinical characteristics, risk factors for mortality and impact of COVID-19 on outcomes of solid organ transplant (SOT) recipients compared to a cohort of non transplant patients, evaluating if transplantation could be considered a risk factor for mortality. From March to May 2020, 261 hospitalized patients with COVID-19 pneumonia were evaluated, including 41 SOT recipients. Of these, thirty-two were kidney recipients, 4 liver, 3 heart and 2 combined kidney-liver transplants. Median time from transplantation to COVID-19 diagnosis was 6 years. Thirteen SOT recipients (32%) required Intensive Care Unit (ICU) admission and 5 patients died (12%). Using a propensity score match analysis, we found no significant differences between SOT recipients and non-transplant patients. Older age (OR 1.142; 95% [CI 1.08-1.197]) higher levels of C-reactive protein (OR 3.068; 95% [CI 1.22-7.71]) and levels of serum creatinine on admission (OR 3.048 95% [CI 1.22-7.57]) were associated with higher mortality. The clinical outcomes of SARS-CoV-2 infection in our cohort of SOT recipients appear to be similar to that observed in the non-transplant population. Older age, higher levels of C-reactive protein and serum creatinine were associated with higher mortality, whereas SOT was not associated with worse outcomes.


Subject(s)
COVID-19/complications , Organ Transplantation/mortality , Adult , Aged , Aged, 80 and over , Allografts/physiology , Allografts/virology , COVID-19/epidemiology , COVID-19 Testing , Cohort Studies , Female , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Organ Transplantation/adverse effects , Organ Transplantation/methods , Pandemics , Propensity Score , Risk Factors , SARS-CoV-2/pathogenicity , Spain/epidemiology , Transplant Recipients/statistics & numerical data , Treatment Outcome
19.
Transpl Infect Dis ; 24(2): e13774, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1571111

ABSTRACT

BACKGROUND: Solid organ transplant recipients (SOTR) have diminished humoral immune responses to COVID-19 vaccination and higher rates of COVID-19 vaccine breakthrough infection than the general population. Little is known about COVID-19 disease severity in SOTR with COVID-19 vaccine breakthrough infections. METHODS: Between 4/7/21 and 6/21/21, we requested case reports via the Emerging Infections Network (EIN) listserv of SARS-CoV-2 infection following COVID-19 vaccination in SOTR. Online data collection included patient demographics, dates of COVID-19 vaccine administration, and clinical data related to COVID-19. We performed a descriptive analysis of patient factors and evaluated variables contributing to critical disease or need for hospitalization. RESULTS: Sixty-six cases of SARS-CoV-2 infection after vaccination in SOTR were collected. COVID-19 occurred after the second vaccine dose in 52 (78.8%) cases, of which 43 (82.7%) occurred ≥14 days post-vaccination. There were six deaths, three occurring in fully vaccinated individuals (7.0%, n = 3/43). There was no difference in the percentage of patients who recovered from COVID-19 (70.7% vs. 72.2%, p = .90) among fully and partially vaccinated individuals. We did not identify any differences in hospitalization (60.5% vs. 55.6%, p = .72) or critical disease (20.9% vs. 33.3%, p = .30) among those who were fully versus partially vaccinated. CONCLUSIONS: SOTR vaccinated against COVID-19 can still develop severe, and even critical, COVID-19 disease. Two doses of mRNA COVID-19 vaccine may be insufficient to protect against severe disease and mortality in SOTR. Future studies to define correlates of protection in SOTR are needed.


Subject(s)
COVID-19 , Organ Transplantation , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Organ Transplantation/adverse effects , SARS-CoV-2 , Transplant Recipients , Vaccination
20.
Clin Infect Dis ; 73(11): e4090-e4099, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1561046

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described. METHODS: We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. RESULTS: Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, P < .001], congestive heart failure [aOR 3.2, 95% CI 1.4-7.0, P = .004], chronic lung disease [aOR 2.5, 95% CI 1.2-5.2, P = .018], obesity [aOR 1.9, 95% CI 1.0-3.4, P = .039]) and presenting findings (lymphopenia [aOR 1.9, 95% CI 1.1-3.5, P = .033], abnormal chest imaging [aOR 2.9, 95% CI 1.1-7.5, P = .027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. CONCLUSIONS: Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.


Subject(s)
COVID-19 , Organ Transplantation , Cohort Studies , Humans , Male , Middle Aged , Organ Transplantation/adverse effects , SARS-CoV-2 , Transplant Recipients
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