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.

Early report from the Pediatric Heart Transplant Society on COVID-19 infections in pediatric heart transplant candidates and recipients.

BACKGROUND: Reports focused on adult heart transplant (HTx) recipients with COVID-19 suggest an increased risk of severe disease, however; it is unclear if this holds true for pediatric HTx patients, given the typically milder course of illness in children in general with COVID-19. We sought to rapidly implement a system for multi-center data collection on pediatric HTx candidates and recipients, with the aim of describing the patient population and infection related outcomes. METHODS: The Pediatric Heart Transplant Society (PHTS) is a multi-center collaboration that seeks to improve the outcomes of children who are listed and undergo HTx. The society consists of pediatric HTx centers in North America (n = 53), UK (n = 2), and Brazil (n = 1). In response to the pandemic, PHTS developed a web-based platform to collect COVID-19 specific data on pediatric HTx candidates and recipients. Non-PHTS centers were also invited to submit data. Data fields included pre-and post-HTx patient characteristics, presumed versus documented infection, need for hospitalization (including ICU and ventilator use), treatments administered, and 30-day outcome (resolution, death, sequelae, and or unresolved) RESULTS: Data collection was initiated on 4/30/20. As of 03/15/21 there were 225 patients [19 pre-HTx and 206 post-HTx, median age 14 years (IQR 7, 18)] reported from 41 centers. Hospitalization occurred in 42% (n = 8) of the pre-HTx and 21% (n=43) of the post-HTx patients. Among the patients listed for HTx, 21% (n = 4) required ICU and 10.5% (n = 2) were mechanically ventilated. Among post-HTx patients, 7% (n = 14) required ICU and 1% (n = 3) were mechanically ventilated. At 30 days, the majority of patients had resolution of symptoms (94.7% pre-HTx, 95.6% post-HTx). One death was reported in a post-HTx patient prior to 30 days from onset of COVID-19 illness. CONCLUSIONS: These data demonstrate the ability to rapidly adapt the PHTS data collection infrastructure in response to a novel infection and represent the first known multi-center report of characteristics and early outcomes for patients listed and following pediatric HTx with COVID-19. Hospitalization appears to be more common for both candidates and recipients due to COVID-19 than for the general pediatric population though stays were short and mortality minimal.

COVID-19 in Lung Transplant Recipients: 2 Cases With Acute Respiratory Distress Syndrome Successfully Treated With High-Dose Corticosteroids.

Acute respiratory distress syndrome remains the main cause of death among people with COVID-19. Although many immunomodulatory and antiviral drug therapies have been tested, the only effective therapy against severe COVID-19 pneumonia among the general population is a regimen of high-dose corticosteroids for cases of severe associated inflammation. In solid-organ transplant recipients with long-term immunosuppression, data on disease presentation and evolution are scarce, and the benefit of high-dose corticosteroids remains uncertain for cases of severe COVID-19 pneumonia. Here, we report 2 cases of COVID-19-related acute respiratory distress syndrome that occurred in lung transplant recipients in March and April 2020, respectively. Both cases of acute respiratory distress syndrome occurred in patients with long-term azithromycin treatment prescribed to prevent chronic allograft dysfunction. Acute respiratory distress syndrome was associated with severe inflammation and was cured after early administration of high-dose corticosteroids in both cases, with progressive and complete resolution of lung lesions evidenced on thoracic computed tomography scan. Our findings support the benefit of early high-dose corticosteroids in COVID-19-related acute respiratory distress syndrome with hyperinflammation in patients with long-term immunosuppression such as lung transplant recipients.

Operating-Room Procedures Do Not Increase Risk of COVID-19 Infection.

BACKGROUND AND OBJECTIVES: Operating-room procedures canceled due to the COVID-19 pandemic depleted hospital revenue and potentially worsened patient outcomes through disease progression. Despite safeguards to resume elective procedures, patients remain apprehensive of contracting COVID-19 during hospitalization and recovery. We investigated symptomatic COVID-19 infection in patients undergoing operating-room procedures during the spring 2020 outbreak in Fairfield County, CT, a heavily affected New York Metropolitan area. METHODS: We retrospectively analyzed 419 operating-room patients in Danbury and Norwalk Hospitals between 3/16/20 and 5/19/20. COVID-19 infection was assessed through test results or documented well-being within 2 weeks postdischarge. Variables studied were procedure classification, length of stay, and discharge disposition. Postprocedural COVID-19 infection was analyzed using binomial tests comparing rates to state-mandated infection data. RESULTS: Six patients developed COVID-19 after 212 urgent-elective and 207 emergent procedures. Overall postprocedural infection risk was equivalent to community infection risk (P > .05). No infections occurred in 1-2 day stays or urgent-elective procedures with discharge home (both P < .05). Discharges home reduced the risk to one-sixth of community spread (P = .03). Risk of infection doubled in hospitalizations > 5 days (P = .05) and quadrupled in discharges to extended care facilities (P = .01). DISCUSSION: Operating-room procedures did not increase the risk of symptomatic COVID-19 infection during an outbreak. Urgent-elective and emergent procedures during further outbreaks appear safe when anticipating short stays with discharges home. When anticipating prolonged hospitalization or discharges to facilities, appropriate delay of urgent-elective procedures may minimize risk of infection.

Cycle Thresholds Among Solid Organ Transplant Recipients Testing Positive for SARS-CoV-2.

BACKGROUND: The optimal duration of transmission-based precautions among immunocompromised patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. METHODS: Retrospective review of patients with solid organ transplant with positive SARS-CoV-2 polymerase chain reaction result from nasopharyngeal specimens admitted to the hospital between March 13, 2020 and May 15, 2020. RESULTS: Twenty-one percent of solid organ transplant recipients with positive SARS-CoV-2 polymerase chain reaction detected ≥20 d after symptom onset (or after first positive test among asymptomatic individuals) had a low cycle threshold (ie, high viral load). The majority of these patients were asymptomatic or symptomatically improved. CONCLUSIONS: Solid organ transplant recipients may have prolonged high viral burden of SARS-CoV-2. Further data are needed to understand whether cycle threshold data can help inform strategies for prevention of healthcare-associated transmission of SARS-CoV-2 and for appropriate discontinuation of transmission-based precautions.

Immunogenicity of BNT162b2 mRNA COVID-19 vaccine and SARS-CoV-2 infection in lung transplant recipients.

The immunogenicity of the novel mRNA COVID-19 vaccine in immunocompromised lung transplant recipients is still unknown. We compared the antibody response after the first and second doses of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) with the response after natural SARS-CoV-2 infection in lung transplant recipients. None of the vaccinees tested after two doses of the mRNA BNT162b2 vaccine developed anti-SARS-CoV-2 IgG, while 85% patients presented an antibody response after SARS-CoV-2 infection. The absence of antibody response to vaccination led us to investigate the cellular response in a subset of patients. We detected SARS-CoV-2 specific T-cells in 4 out of 12 tested patients. Some patients therefore might have clinical benefit from the vaccine despite an absent antibody response. These results contrast with the excellent antibody response in immunocompetent individuals observed in mRNA BNT162b2 trials and indicate an urgent need to identify the best vaccine type and scheme for immunocompromised transplanted patients.

BNT162b2 vaccination in heart transplant recipients: Clinical experience and antibody response.

BACKGROUND: Data on the safety and efficacy of SARS-CoV-2 vaccines in immunocompromised populations are sparse. METHODS: We conducted a prospective study of 77 heart transplant (HT) recipients vaccinated with two doses of BNT162b2 vaccine and monitored for adverse events following both doses, the receptor-binding domain (RBD) IgG response, and neutralizing antibodies. RESULTS: BNT162b2 vaccination was associated with a low rate of adverse events, characterized mostly by pain at the injection site. By a mean 41 days post second dose there were no clinical episodes of rejection, as suggested by a troponin leak or allograft dysfunction. At a mean 21 days following the second dose, IgG anti-RBD antibodies were detectable in 14 (18%) HT recipients. Immune sera neutralized SARS-CoV-2 pseudo-virus in 8 (57%) of those with IgG anti-RBD antibodies. Immunosuppressive regimen containing mycophenolic acid was associated with lower odds of an antibody response (OR = 0.12, p = 0.042). CONCLUSIONS: Whether a longer time-frame for observation of an antibody response is required after vaccination in immunosuppressed individuals remains unknown.

Mucormycosis after Coronavirus disease 2019 infection in a heart transplant recipient - Case report and review of literature.

Mucormycosis is an invasive fungal infection (IFI) due to several species of saprophytic fungi, occurring in patients with underlying co-morbidities (including organ transplantation). During the ongoing Coronavirus disease 2019 (COVID-19) pandemic, there have been increasing reports of bacterial and fungal co-infections occurring in COVID-19 patients, including COVID-19 associated pulmonary aspergillosis (CAPA). We describe a case of mucormycosis occurring after COVID-19, in an individual who received a recent heart transplant for severe heart failure. Two months after heart transplant, our patient developed upper respiratory and systemic symptoms and was diagnosed with COVID-19. He was managed with convalescent plasma therapy and supportive care. Approximately three months after COVID-19 diagnosis, he developed cutaneous mucormycosis at an old intravascular device site. He underwent extensive surgical interventions, combined with broad-spectrum antifungal therapy. Despite the aggressive therapeutic measures, he died after a prolonged hospital stay. In this case report, we also review the prior well-reported cases of mucormycosis occurring in COVID-19 patients and discuss potential mechanisms by which COVID-19 may predispose to IFIs. Similar to CAPA, mucormycosis with COVID-19 may need to be evaluated as an emerging disease association. Clinicians should be vigilant to evaluate for invasive fungal infections such as mucormycosis in patients with COVID-19 infection.

Clinical Outcomes of 2019 COVID-19 Positive Patients Who Underwent Surgery: A New York City Experience.

BACKGROUND: The coronavirus disease 2019 (COVID-19) global pandemic has led to a halt in elective surgeries throughout the United States and many other countries throughout the world. Early reports suggest that COVID-19 patients undergoing surgery have an increased risk of requiring intensive care unit (ICU) admission and overall mortality. MATERIALS AND METHODS: A retrospective review was performed of all COVID-19, positive with polymerase chain reaction confirmation, patients who had surgery between February 17, 2020 and April 26, 2020 at a major New York City hospital. Clinical characteristics and outcomes including ICU admission, ventilator requirement, and mortality were analyzed. RESULTS: Thirty-nine COVID-19 surgical patients were identified. Mean age was 53.9 y, and there were more men than women in the cohort (56.4% versus 43.6%). Twenty-two patients (56.4%) had a confirmed positive COVID-19 test preoperatively, and the remainder tested positive after their procedure. The majority (59%) of patients had an American Society of Anesthesiologists (ASA) class of 3 or higher. Postoperatively, 7 patients (17.9%) required ICU level care with a mean length of stay of 7.7 d. There were 4 deaths (10.3%) in this patient population, all of which occurred in patients who were ASA class 3 or 4. CONCLUSIONS: This study represents the largest study to date, that objectively analyzes the outcomes of COVID-19 positive patients who underwent surgery. Overall, ICU admission rates and mortality are similar to reported rates in the literature for nonsurgical COVID-19 patients. Notably, in COVID-19 patients with ASA 1 or 2, there was a 0% mortality rate in the postoperative period.

Effect of Calcineurin Inhibitors and Mammalian Target of Rapamycin Inhibitors on the Course of COVID-19 in Kidney Transplant Recipients.

Coronavirus disease 19 (COVID-19) has been an ongoing pandemic since December 2019. Unfortunately, kidney transplant recipients are a high-risk group during the disease course, and scientific data are still limited in this patient group. Beyond the dosage of immunosuppressive drugs, pharmacological immunosuppression may also alter the infection response in the COVID-19 course. The effects of immunosuppressive agents on the development and process of infection should not be decided only by determining how potent they are and how much they suppress the immune system; it is also thought that the direct effect of the virus, increased oxidative stress, and cytokine storm play a role in the pathogenesis of COVID-19 disease. There are data about immunosuppressive drugs like calcineurin inhibitors (CNI) or mammalian target of rapamycin inhibitors (mTORi) therapy related to their beneficial effects during any infection course. Limited data suggest that the use of CNI or mTORi may have beneficial effects on the process. In this hypothetical review, the probable impacts of CNI and mTORi on the pathogenesis of the COVID-19 were investigated.

COVID-19 Pneumonia on Post-Operative Day 2 after Esophagectomy: Performing Esophago-Gastric Junction Cancer Surgery during the SARS-Cov-2 Second Wave.

The coronavirus disease 2019 (COVID-19) pandemic has had a substantial impact on the provision of medical healthcare. Due to an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) transmission, elective surgical treatment has been suspended in many centers. The effects of COVID-19 in the early post-operative period after esophagectomy remains unknown. In this report, we present three cases of patients diagnosed with esophago-gastric junction cancer who were scheduled for elective esophagectomy with a curative intention during second wave of COVID-19 pandemic in a single high-volume tertiary center. Despite all available safety measures, one of the patients developed COVID-19 pneumonia on post-operative day two, leading to an impaired respiratory function and increased pleural fluid collection from the chest tube, resulting in a prolonged time of hospital stay. Finding a good balance between the COVID-19-related perioperative risks and consequences of delaying surgical treatment in patients diagnosed with esophago-gastric cancer is a challenge. In order to achieve the best possible outcome, care must be taken to ensure availability of necessary treatment options and to reduce the risk of SARS-Cov-2 transmission perioperatively.

COVID-19 in Kidney Transplant Patients From a Large UK Transplant Center: Exploring Risk Factors for Disease Severity.

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised concern for the health of immunocompromised individuals, who are potentially at higher risk of more severe infection and poorer outcomes. As a large London transplant center serving a diverse patient population, we report the outcomes of SARS-CoV-2 infection in our cohort of 2848 kidney and/or pancreas transplant patients. METHODS: Data were obtained retrospectively for all transplant patients who attended hospital during the peak of the pandemic and had a positive nasopharyngeal SARS-CoV-2 test. RESULTS: Sixty-six patients were found to be positive for SARS-CoV-2. Twenty percent were treated as outpatients, 59% were admitted to the general ward, and 21% required intensive care. Treatment consisted of reduced immunosuppression, antibiotics for pneumonia or sepsis, and other supportive treatments. Within our cohort, 12 patients died (18%), with an overall mortality of 0.4%. Predictive risk factors for COVID-19 severity were explored. CONCLUSIONS: Severe disease was associated with lower hemoglobin prior to COVID-19 diagnosis and lower lymphocyte count at the time of diagnosis but not age, sex, ethnicity, or preexisting comorbidities. Lower glomerular filtration rate and higher C-reactive protein were associated with more severe disease. Despite no use of hydroxychloroquine, azithromycin, antiviral, or immunomodulatory medications, our mortality rate (kidney and pancreas transplant patients) is similar to current international rates.

Experiences and Short-Term Outcomes of Kidney Transplantation During the Coronavirus Disease 2019 Pandemic From a Medium-Volume Transplantation and Superregional Coronavirus Disease 2019 Treatment Center.

INTRODUCTION: The coronavirus, which first appeared in 2019, developed into a pandemic during 2020. It remains unclear to what extent the pandemic endangers the safety of kidney transplantation programs. In this study, we evaluated the short-term outcomes of our patients receiving a kidney transplant during the first phase and compared them with patients who received a kidney transplant immediately before the coronavirus pandemic. MATERIALS AND METHODS: Our retrospective study includes 34 kidney transplant recipients between October 1, 2019, and April 30, 2020. Nineteen patients from the phase immediately prior to the first coronavirus wave (pre-corona group), and 15 patients from the phase of the first coronavirus wave (corona group) were studied. We retrospectively evaluated demographic data, postoperative short-term outcomes and complications, immunosuppression regime, coronavirus infection status, and behavior during the first phase of the pandemic. RESULTS: There were no differences between the 2 groups regarding short-term outcomes and postoperative complications or in immunosuppressive medication. After the introduction of intensified hygienic conditions and routine swabs prior to transplantation, no nosocomial SARS-CoV-2 infections occurred. In the outpatient setting, none of the patients developed a SARS-CoV-2 infection. The majority of patients performed voluntary quarantine. CONCLUSIONS: The short-term outcomes after kidney transplantation during the first phase of the coronavirus pandemic were comparable to pre-pandemic patients, and no SARS-CoV-2-associated death or transplant failure occurred in our small cohort. We considered patient compliance with hygiene and self-isolation measures very high. Nevertheless, in further phases of the pandemic, the continuation of the living kidney donation program must be critically evaluated.

Is elective cancer surgery feasible during the lock-down period of the COVID-19 pandemic? Analysis of a single institutional experience of 404 consecutive patients.

BACKGROUND: We aimed to assess the feasibility and short-term clinical outcomes of surgical procedures for cancer at an institution using a coronavirus disease 2019 (COVID-19)-free surgical pathway during the peak phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. MATERIALS AND METHODS: This was a single-center study, including cancer patients from all surgical departments, who underwent elective surgical procedures during the first peak phase between March 10 and June 30, 2020. The primary outcomes were the rate of postoperative SARS-CoV-2 infection and 30-day pulmonary or non-pulmonary related morbidity and mortality associated with SARS-CoV-2 disease. RESULTS: Four hundred and four cancer patients fulfilling inclusion criteria were analyzed. The rate of patients who underwent open and minimally invasive procedures was 61.9% and 38.1%, respectively. Only one (0.2%) patient died during the study period due to postoperative SARS-CoV2 infection because of acute respiratory distress syndrome. The overall non-SARS-CoV2 related 30-day morbidity and mortality rates were 19.3% and 1.7%, respectively; whereas the overall SARS-CoV2 related 30-day morbidity and mortality rates were 0.2% and 0.2%, respectively. CONCLUSIONS: Under strict institutional policies and measures to establish a COVID-19-free surgical pathway, elective and emergency cancer operations can be performed with acceptable perioperative and postoperative morbidity and mortality.

Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) infection has led to the reorganization of hospital care in several countries. The objective was to report the postoperative mortality after elective digestive resections in a nationwide cohort during the lockdown period. METHODS: This analytic study was performed using a national billing database (the Programme de Médicalisation des Systèmes d'Informations). Patients who underwent elective digestive resections were divided in 2 groups: the lockdown group defined by hospital admissions between March 17 and May 11, 2020; and the control group, defined by hospital admissions during the corresponding period in 2019. Groups were matched on propensity score, geographical region, and surgical procedure. The primary outcome was the postoperative mortality. RESULTS: The overall population included 15,217 patients: 9,325 patients in the control group and 5,892 in the lockdown group. The overall surgical activity was decreased by 37% during the lockdown period. The overall in-hospital mortality during the hospital stay was 2.7%. After matching and adjustment, no difference in mortality between groups was reported (OR = 1.05; 95% CI: 0.83-1.34; P = .669). An asymptomatic COVID-19 infection was a risk factor for a 2-fold increased mortality, whereas a symptomatic COVID-19 infection was associated with a 10-fold increased mortality. CONCLUSION: Despite a considerable reduction in the surgical activity for elective digestive resections during the lockdown period, mortality remained stable on a nationwide scale in COVID-free patients. These findings support that systematic COVID-19 screening should be advocated before elective gastrointestinal surgery and that all efforts should be made to maintain elective surgical resection for cancer during the second wave in COVID-free patients.

A Recipient and Donor Both Have COVID-19 Disease. Should We Perform a Liver Transplant?

Coronavirus 2019 (COVID-19) is a new infectious disease that continues to spread globally. There is growing concern about donor-induced transmission of Coronavirus 2 (SARS -CoV-2). For liver transplantation, the COVID-19 PCR test is routine, in addition to epidemiological history and clinical and radiological examination 24-48 h before surgery. One of the liver transplant candidates was found to be infected with COVID-19, as well as the planned donor candidate. Since COVID-19 will be a high-risk operation for both the recipient and the donor, the operation was postponed by giving medical treatment. After the treatment and quarantine process was over, the patient and the donor then had a negative COVID-19 PCR test and the patient received a living donor liver transplant. We present a case of donor and recipient who initially both tested positive for COVID-19. This liver transplantation scenario has not previously been reported in the literature.

Is Kidney Transplantation From a COVID-19-Positive Deceased Donor Safe for the Recipient?

INTRODUCTION: In recent months, the number of kidney transplants from deceased donors has declined significantly. One of the reasons is the possibility of infection of the recipient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Determining the risk of transmission of coronavirus disease 2019 (COVID-19) with a donor organ is very important for developing a kidney transplantation policy during a pandemic. MATERIALS AND METHOD: We present cases of kidney transplantation from COVID-19-positive deceased donors to 2 dialysis patients 49 and 45 years old. One of them was on hemodialysis for 28 months; the other received continuous ambulatory peritoneal dialysis (CAPD). Both patients received only basic immunosuppression, including tacrolimus, methylprednisolone, and mycophenolic acid. No antilymphocyte agents were used for induction therapy. RESULTS: Cold ischemia time was 22 and 21 hours, respectively. One recipient had delayed graft function with increasing of urine output on day 8; another had immediate function. Both patients had no febrile and no other symptoms of acute respiratory disease during their hospital stay. No abnormalities on the chest x-ray were seen. No serum anti-SARS-CoV-2 IgM and IgG were detected before and during 6 weeks after surgery. Repeated nasopharyngeal swabs real-time reverse transcription polymerase chain reaction (rRT-PCR) were negative during the period. Both recipients were discharged 5 weeks after surgery with serum creatinine levels of 122 and 91 mcmol/L, respectively. CONCLUSION: Today we have no evidence of the possibility of transmission of COVID-19 from a SARS-CoV-2 positive donor to a kidney recipient. We also have no reason to suspect kidney damage by COVID-19 in a deceased donor at normal serum creatinine level.