A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients.

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.

Difference between SARS-CoV-2, seasonal coronavirus, influenza, and respiratory syncytial virus infection in solid organ transplant recipients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been raging since the end of 2019 and has shown worse outcomes in solid organ transplant (SOT) recipients. The clinical differences as well as outcomes between respiratory viruses have not been well defined in this population. METHODS: This is a retrospective cohort study of adult SOT recipients with nasopharyngeal swab or bronchoalveolar lavage PCR positive for either SARS-CoV-2, seasonal coronavirus, respiratory syncytial virus (RSV) or influenza virus from January 2017 to October 2020. The follow up period was 3 months. Clinical characteristics and outcomes were evaluated. RESULTS: A total of 377 recipients including 157 SARS-CoV-2, 70 seasonal coronavirus, 50 RSV and 100 influenza infections were identified. The most common transplanted organ was kidney 224/377 (59.4%). Lower respiratory tract infection (LRTI) was found in 210/377 (55.7%) and the risk factors identified with multivariable analysis were SARS-CoV-2 infection, steroid use, and older age. Co- and secondary infections were seen in 77/377 (20.4%) recipients with bacterial pathogens as dominant. Hospital admission was seen in 266/377 (67.7%) recipients without significant statistical difference among viruses, however, ICU admission, mechanical ventilation and mortality were higher with SARS-CoV-2 infection. In the multivariable model, the risk factors for mortality were SARS-CoV-2 infection and older age. CONCLUSIONS: We found higher incidence of ICU admission, mechanical ventilation, and mortality among SARS-CoV-2 infected recipients. Older age was found to be the risk factor for lower respiratory tract infection and mortality for SARS-CoV-2, coronaviruses, RSV and influenza virus groups.

Is the Omicron variant truly less virulent in solid organ transplant recipients?

Solid organ transplant (SOT) recipients are at high risk for severe disease with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Emerging variants of concern have disproportionately affected this population. Data on severity and outcomes with the Omicron variant in SOT recipients are limited. Thus we conducted this single-center, retrospective cohort study of SOT recipients diagnosed with SARS-CoV-2 infection from December 18, 2021 to January 18, 2022, when prevalence of the Omicron variant was more than 80%-95% in the community. Univariate and multivariate logistic regression analysis was performed to identify risk factors for hospital admission. We identified 166 SOT patients: 112 (67.5%) kidney, 22 (13.3%) liver, 10 (6.0%) lung, seven (4.2%) heart, and 15 (9.0%) combined transplants. SARS-CoV-2 vaccine series was completed in 59 (35.5%) recipients. Ninety-nine (59.6%) and 13 (7.8%) recipients received casirivimab/imdevimab and sotrovimab, respectively. Fifty-three (32%) recipients required hospital admission, of which 19 (35.8%) required intensive care unit level of care. Median follow-up was 50 (interquartile range, 25-59) days, with mortality reported in six (3.6%) patients. Risk factors identified for hospital admission were African American race (p < .001, odds ratio [OR] 4.00, 95% confidence interval [CI] 1.84-8.70), history of coronary artery disease (p = .031, OR 3.50, 95% CI 1.12-10.87), and maintenance immunosuppression with corticosteroids (p = .048, OR 2.00, 95% CI 1.01-4.00). In conclusion, contrary to that in the general population, we found a higher hospital admission rate in SOT recipients with omicron variant infection. Further studies to investigate the efficacy of newer treatments are necessary, even as outcomes continue to improve.

Personal Protective Equipment for Liver Transplant in SARS-CoV-2 Polymerase Chain Reaction-Positive Convalescing Recipients.

Personal protective equipment (PPE) comes in several variations, and is the principal safety gear during the COVID-19 pandemic. Unfortunately, the user is severely impacted by its serious nonergonomic features. What PPE is appropriate for labor-intensive cases, like liver transplant (LT), remains unknown. We describe our experience with 2 types of PPE used during 2 separate LT performed in COVID-19 positive recipients. We conclude that for the safety of both health care workers and patients, hospitals should designate a few PPE kits for labor-intensive surgical procedures. These kits should include powered air-purifying respirators, or a similar loose-fitting powered air hood.

Delayed mortality among solid organ transplant recipients hospitalized for COVID-19.

INTRODUCTION: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined. METHODS: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90. RESULTS: Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p =<0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p<0.001] and body mass index ≥ 30 kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61]. CONCLUSIONS: In SOT recipients hospitalized for COVID-19, >20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment.

A Less Restrictive Policy for Liver Transplantation in Coronavirus Disease 2019 Positive Patients, Based Upon Cycle Threshold Values.

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.

Changing trends in mortality among solid organ transplant recipients hospitalized for COVID-19 during the course of the pandemic.

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.

[Factors associated with the incidence and mortality from COVID-19 in the autonomous communities of Spain]. / Factores asociados a la incidencia y la mortalidad por COVID-19 en las comunidades autónomas.

OBJECTIVE: Analyze the evolution of the epidemic of COVID-19 after the alarm state and identify factors associated with the differences between the autonomous communities. METHOD: Ecological study that used epidemiological, demographic, environmental and variables on the structure of health services as explanatory variables. The analysis period was from March 15th (the start of the alarm state) until April 22nd, 2020. Incidence and mortality rates were the main response variables. The magnitude of the associations has been estimated using the Spearman correlation coefficient and multiple regression analysis. RESULTS: Incidence and mortality rates at the time of decree of alarm status are associated with current incidence, mortality and hospital demand rates. Higher mean temperatures are significantly associated with a lower current incidence of COVID-19 in the autonomous communities. Likewise, a higher proportion of older people in nursing homes is significantly associated with a higher current mortality in the autonomous communities. CONCLUSION: It is possible to predict the evolution of the epidemic through the analysis of incidence and mortality. Lower temperatures and the proportion of older people in residences are factors associated with a worse prognosis. These parameters must be considered in decisions about the timing and intensity of the implementation of containment measures. In this sense, strengthening epidemiological surveillance is essential to improve predictions.

When is it safe to perform abdominal transplantation in patients with prior SARS-CoV-2 infection: A case series.

BACKGROUND: The Coronavirus disease 2019(COVID-19) pandemic has negatively impacted worldwide organ transplantation. However, there is limited information on recipients transplanted after SARS-CoV-2 infection. A full understanding of this scenario is required, as transplantation is a life-saving procedure and COVID-19 remains an ongoing threat. METHODS: Abdominal organ transplant recipients diagnosed with COVID-19 prior to transplantation were identified by chart review and clinical data were collected. The primary outcome was the transplant outcome including graft loss, rejection and death, and reactivation of infection post-transplant. RESULTS: We identified 14 patients who received abdominal organ transplants after symptomatic PCR confirmed SARS-CoV-2 infection; four patients had a positive PCR at the time of admission for transplantation. The median time of follow-up was 79 (22-190) days. One recipient with negative PCR before transplant tested positive 9 days after transplant. One of 14 transplanted patients developed disseminated mold infection and died 86 days after transplant. During the follow-up, only one patient developed rejection; thirteen patients had favorable graft outcomes. CONCLUSIONS: We were able to perform abdominal transplantation for patients with COVID-19 before transplant, even with positive PCR at the time of transplant. Larger studies are needed to determine the time to safe transplant after SARS-CoV-2 infection.

COVID-19 in hospitalized lung and non-lung solid organ transplant recipients: A comparative analysis from a multicenter study.

Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p = .02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p = .032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0-2.6, p = .04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0-11.3, p = .05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality.

Social determinants of health and COVID-19 infection in Brazil: an analysis of the pandemic

ABSTRACT Objective: To analyze the influence of socioeconomic, demographic, epidemiological factors, and the health system structure in the evolution of the COVID-19 pandemic in Brazil. Methods: Ecological study with variables extracted from databases, having the incidence and mortality by COVID-19 until August 23, 2020, in Brazilian states, as response variables. The magnitude of the associations was estimated using Spearman's correlation coefficient and multiple regression analysis. Results: In the Brazilian states, 59.8% of variation in the incidence of COVID-19 was justified by income inequality, significant home densification, and higher mortality. In the case of mortality, those same variables explained 57.9% of the country's variations in federal units. Conclusion: Our results indicate that socioeconomic factors influenced the evolution and impact of COVID-19 in Brazil. Thus, we suggest comprehensive actions to ensure economic conditions and strengthening of health networks for populations with socioeconomic vulnerability. RESUMEN Objetivo: Analizar la influencia de factores socioeconómicos, demográficos, epidemiológicos y estructura del sistema de salud en la evolución del COVID-19 en Brasil. Métodos: Estudio ecológico con variables extraídas de bancos de datos, teniendo la incidencia y mortalidad por COVID-19 hasta 23 de agosto de 2020, en estados brasileños, como variables respuesta. Las relaciones han estimadas usando el coeficiente de correlación de Spearman y análisis de regresión múltiple. Resultados: En los estados brasileños, 59,8% de la variación de la incidencia de COVID-19 ha justificada por la desigualdad de renta, mayor densificación domiciliar y mayor letalidad. En la mortalidad, esas mismas variables explicaron 57,9% de las variaciones encontradas en las Unidades Federativas del país. Conclusión: Nuestros resultados indican que factores socioeconómicos influenciaron la evolución e impacto de COVID-19 en Brasil. Así, sugerimos acciones abarcadoras para garantizar condiciones económicas y el fortalecimiento de las redes de salud para poblaciones con vulnerabilidad socioeconómica. RESUMO Objetivo: Analisar a influência de fatores socioeconômicos, demográficos, epidemiológicos e da estrutura do sistema de saúde na evolução da pandemia da COVID-19 no Brasil. Métodos: Estudo ecológico com variáveis extraídas de bancos de dados, tendo a incidência e mortalidade por COVID 19 até 23 de agosto de 2020, nos estados brasileiros, como variáveis-resposta. A magnitude das associações foi estimada usando o coeficiente de correlação de Spearman e análise de regressão múltipla. Resultados: Nos estados brasileiros, 59,8% da variação da incidência de COVID-19 foi justificada pela desigualdade de renda, maior adensamento domiciliar e maior letalidade. No caso da mortalidade, essas mesmas variáveis explicaram 57,9% das variações encontradas nas Unidades Federativas do país. Conclusão: Nossos resultados indicam que fatores socioeconômicos influenciaram a evolução e impacto da COVID-19 no Brasil. Dessa forma, sugerimos ações abrangentes a fim de garantir condições econômicas e o fortalecimento das redes de saúde para populações com vulnerabilidade socioeconômica.

Social determinants of health and COVID-19 infection in Brazil: an analysis of the pandemic.

OBJECTIVE: To analyze the influence of socioeconomic, demographic, epidemiological factors, and the health system structure in the evolution of the COVID-19 pandemic in Brazil. METHODS: Ecological study with variables extracted from databases, having the incidence and mortality by COVID-19 until August 23, 2020, in Brazilian states, as response variables. The magnitude of the associations was estimated using Spearman's correlation coefficient and multiple regression analysis. RESULTS: In the Brazilian states, 59.8% of variation in the incidence of COVID-19 was justified by income inequality, significant home densification, and higher mortality. In the case of mortality, those same variables explained 57.9% of the country's variations in federal units. CONCLUSION: Our results indicate that socioeconomic factors influenced the evolution and impact of COVID-19 in Brazil. Thus, we suggest comprehensive actions to ensure economic conditions and strengthening of health networks for populations with socioeconomic vulnerability.

Kidney transplantation during coronavirus 2019 pandemic at a large hospital in Miami.

BACKGROUND: Coronavirus 2019 (COVID-19) pandemic has resulted in more than 350 000 deaths worldwide. The number of kidney transplants has declined during the pandemic. We describe our deceased donor kidney transplantation (DDKT) experience during the pandemic. METHODS: A retrospective study was conducted to evaluate the safety of DDKT during the COVID-19 pandemic. Multiple preventive measures were implemented. Adult patients that underwent DDKT from 3/1/20 to 4/30/20 were included. COVID-19 clinical manifestations from donors and recipients, and post-transplant outcomes (COVID-19 infections, readmissions, allograft rejection, and mortality) were obtained. The kidney transplant (KT) recipients were followed until 5/31/20. RESULTS: Seventy-six patients received kidneys from 57 donors. Fever, dyspnea, and cough were reported in 1, 2, and 1 donor, respectively. Thirty-eight (66.6%) donors were tested for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) prior to donation (mainly by nasopharyngeal or bronchoalveolar lavage polymerase chain reaction [PCR]) and 36 (47.3%) KT recipients were tested at the time of DDKT by nasopharyngeal PCR; all of these were negative. Our recipients were followed for a median of 63 (range: 33-91) days. A total of 42 (55.3%) recipients were tested post-transplant for SARS-CoV2 by nasopharyngeal PCR including 12 patients that became symptomatic; all tests were negative except for one that was inconclusive, but it was repeated and came back negative. Forty (52.6%) KT recipients were readmitted, and 7 (9.2%) had biopsy-proven rejection during the follow-up. None of the KT recipients transplanted during this period died. CONCLUSIONS: Our cohort demonstrated that DDKT can be safely performed during the COVID-19 pandemic when preventive measures are implemented.