Should VV ECMO be considered as treatment option in COVID-19 infection after kidney transplant? A word of caution.

Several reports have shown that hospitalized kidney transplant recipients (KTR) had high mortality rates when infected with COVID-19. Extracorporeal Membrane Oxygenation (ECMO) has been shown to be an option for refractory respiratory failure in COVID-19 patients with variable rates of recovery. The outcome of ECMO in respiratory failure is highly related to cohort investigated and patient selection. Over a 10-month period in the height of COVID-19 pandemic 5 KTR patients were placed on ECMO with none of the patients surviving to discharge. All patients experienced multisystem organ failure (MSOF) and hematologic pathology while on ECMO. We concluded that COVID-19 in KTR patients presents with a refractory MSOF that is not well supported with ECMO in a traditional approach. Future work is needed to determine how to best support refractory respiratory failure in KTR patients with COVID-19.

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.

Reinfection with SARS-CoV-2 in solid-organ transplant recipients: Incidence density and convalescent immunity prior to reinfection.

BACKGROUND: Long-term protective immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains poorly characterized, particularly in solid organ transplant (SOT) patients. METHOD: We determined the incidence density of SARS-CoV-2 reinfection in a cohort of adult SOT recipients initially infected between March 1st, 2020 and March 30th, 2021 and included those with initial infection before or after transplantation. Incidence density was the total cases divided by total days after initial diagnosis with active graft. RESULTS: Of 210 infected recipients, five (2.4%) developed reinfection, including two who had received full mRNA vaccination, but none developed hypoxia. The incidence density for reinfection was 9.4 (95% confidence interval [CI] 3.9-22.6) and for primary infection the density was 9.1 (95% CI 7.9-10.5) cases/100,000 patient days. Two recipients had immunity evaluated in the weeks prior to reinfection, by measuring immunoglobulin-G (IgG) antibody titer to the SARS-CoV-2 receptor binding domain and virus-specific CD4+ and CD8+ T-cell reactivity following stimulation with SARS-CoV-2 peptide pools. Both mounted virus specific CD4 T-cell responses prior to reinfection (1.19% and 0.28% of total CD4 T cells) and both had reactive IgG testing (1.30 and 4.99 signal/cut off ratio). CONCLUSIONS: This suggests that SOT recipients infected with SARS-CoV-2 remain at high risk for reinfection even after generating cellular and humoral immune responses.

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.

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.

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.

Deceased donor kidney transplant in a 70-year-old Jehovah's Witness patient: to transplant or not to transplant-a case report.

While Jehovah's Witness (JW) patients refuse transfusions of blood or blood products, they are willing to accept renal allograft transplantation. We describe here a case of what we believe is the oldest (a 70-year-old) JW candidate to undergo a deceased donor kidney transplant reported in the literature. Prior to transplantation, discussions ensued amongst the multidisciplinary transplant team, weighing the potential benefits vs. risks of performing a kidney transplant on this patient due to her refusal (due to religion) to accept any blood transfusions or blood products combined with her advanced age and having longstanding insulin-dependent, type 2 diabetes mellitus with extensive peripheral vascular disease. Preoperatively, we believed that the odds were in favor of performing the kidney transplant safely without the need for any blood product usage. However, her post-operative course was complicated by severe anemia, which developed by post-transplant day 4. The anemia incapacitated the patient's physical and psychological state, creating medical, social and financial burdens on the patient, family, medical team and hospital. Both family and patient grew concerned about her overall condition. Blood transfusion was offered in order to improve her weakness and shortness of breath that developed due to the severe anemia, but the patient (along with her family) refused such treatment. During the 17 days of hospitalization, it was a continuous struggle between the transplant team, patient, and family for her to continue with the recovery process; at times we had even considered that performing the transplant had been a mistake. While organ transplantation can be performed safely in Jehovah's Witnesses, there are multiple factors seen in this particular case that warrant analyzing: (I) the potential use of stricter transplant exclusionary criteria, given the recipient's advanced age and preexisting co-morbidities, which likely increased her risk of developing severe anemia post-operatively, and (II) the recipient's emotional/psychological post-operative state of high anxiety, which developed while she was experiencing the severe anemia; in hindsight, her anxiety level may have been reduced if we had offered daily post-operative psychological counseling sessions. While the patient's allograft is currently doing well, we probably did not have strict enough criteria for proper selection of a JW candidate for kidney transplantation.

COVID-19 in solid organ transplant recipients: A systematic review and meta-analysis of current literature.

Severe acute respiratory virus syndrome 2 (SARS-CoV-2) has led to a worldwide pandemic. Early studies in solid organ transplant (SOT) recipients suggested a wide variety of presentations, however, there remains a paucity of robust data in this population. We conducted a systematic review and meta-analysis of SOT recipients with SARS-CoV-2 infection from January 1st t October 9th, 2020. Pooled incidence of symptoms, treatments and outcomes were assessed. Two hundred and fifteen studies were included for systematic review and 60 for meta-analysis. We identified 2,772 unique SOT recipients including 1,500 kidney, 505 liver, 141 heart and 97 lung. Most common presenting symptoms were fever and cough in 70.2% and 63.8% respectively. Majority (81%) required hospital admission. Immunosuppressive medications, especially antimetabolites, were decreased in 76.2%. Hydroxychloroquine and interleukin six antagonists were administered in59.5% and 14.9% respectively, while only few patients received remdesivir and convalescent plasma. Intensive care unit admission was 29% from amongst hospitalized patients. Only few studies reported secondary infections. Overall mortality was 18.6%. Our analysis shows a high incidence of hospital admission in SOT recipients with SARS-CoV-2 infection. As management of SARS-CoV-2 continues to evolve, long-term outcomes among SOT recipients should be assessed in future studies.

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.