Increased complications in patients who test COVID-19 positive after elective surgery and implications for pre and postoperative screening.

BACKGROUND: The COVID-19 pandemic has necessitated the adoption of protocols to minimize risk of periprocedural complications associated with SARS-CoV-2 infection. This typically involves a preoperative symptom screen and nasal swab RT-PCR test for viral RNA. Asymptomatic patients with a negative COVID-19 test are cleared for surgery. However, little is known about the rate of postoperative COVID-19 positivity among elective surgical patients, risk factors for this group and rate of complications. METHODS: This prospective multicenter study included all patients undergoing elective surgery at 170 Veterans Health Administration (VA) hospitals across the United States. Patients were divided into groups based on first positive COVID-19 test within 30 days after surgery (COVID[-/+]), before surgery (COVID[+/-]) or negative throughout (COVID[-/-]). The cumulative incidence, risk factors for and complications of COVID[-/+], were estimated using univariate analysis, exact matching, and multivariable regression. RESULTS: Between March 1 and December 1, 2020 90,093 patients underwent elective surgery. Of these, 60,853 met inclusion criteria, of which 310 (0.5%) were in the COVID[-/+] group. Adjusted multivariable logistic regression identified female sex, end stage renal disease, chronic obstructive pulmonary disease, congestive heart failure, cancer, cirrhosis, and undergoing neurosurgical procedures as risk factors for being in the COVID[-/+] group. After matching on current procedural terminology code and month of procedure, multivariable Poisson regression estimated the complication rate ratio for the COVID[-/+] group vs. COVID[-/-] to be 8.4 (C.I. 4.9-14.4) for pulmonary complications, 3.0 (2.2, 4.1) for major complications, and 2.6 (1.9, 3.4) for any complication. DISCUSSION: Despite preoperative COVID-19 screening, there remains a risk of COVID infection within 30 days after elective surgery. This risk is increased for patients with a high comorbidity burden and those undergoing neurosurgical procedures. Higher intensity preoperative screening and closer postoperative monitoring is warranted in such patients because they have a significantly elevated risk of postoperative complications.

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 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.

SARS-CoV-2 Seroprevalence and Clinical Features of COVID-19 in a German Liver Transplant Recipient Cohort: A Prospective Serosurvey Study.

BACKGROUND: In liver transplant (LT) recipients with severe coronavirus disease 2019 (COVID-19), fatal outcome has been reported in a substantial subset of patients. Whether LT recipients are at increased risk for severe COVID-19 compared with the general population is controversial. Here we report the results of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in a large LT recipient cohort. METHODS: A total of 219 LT recipients were enrolled between May 5, 2020, and August 6, 2020, at the University Hospital Heidelberg. Serum blood samples were collected and tested for anti-SARS-CoV-2 IgG. SARS-CoV-2 RNA was detected in nasopharyngeal swabs using reverse transcription-polymerase chain reaction assays. RESULTS: Taking into account known risk factors of arterial hypertension, obesity, diabetes, or leukopenia, LT recipients a priori represented a high-risk cohort for severe COVID-19 with 101 of 219 (46.1%) presenting with more than 2 risk factors for severe COVID-19. Out of 219 LT recipients, 8 (3.7%) either had a positive test result for nasopharyngeal SARS-CoV-2 RNA or anti-SARS-CoV-2 serum IgG. Five of eight (62.5%) did not show any clinical signs of infection, three of eight (37.5%) had self-limited disease, and none required hospitalization for COVID-19. Two of eight (25%) had known exposure to infected health care staff as the probable source of infection. CONCLUSIONS: In summary, LT recipients showed a SARS-CoV-2 seroconversion rate similar to that of the general population with a substantial percentage of unrecognized infections.

Restarting LDLT During COVID-19: Early Results After Restructuring.

INTRODUCTION: Living-donor liver transplantation (LDLT) has been mostly suspended and deceased-donor living transplantation activity has been considerably reduced because of coronavirus disease 2019 (COVID-19). We modified our protocols and procedures in line with COVID-19 guidelines. Since the restructuring, we have performed 20 LDLTs. Our study reports the outcomes of these cases and demonstrates the feasibility of LDLT during this pandemic. MATERIALS AND METHODS: The changes were influenced by experiences and communications from across the globe. A month-long self-imposed moratorium was spent in restructuring the program and implementing new protocols. Twenty LDLTs were performed between April 18 and September 15 using the new protocols. Our experience includes 2 simultaneous liver-kidney transplants, 1 ABO-incompatible LDLT, and 1 pediatric case (age 11 months). RESULTS: Nineteen patients recovered and 1 patient died. We maintained our postoperative immunosuppression protocol without many changes. Major complications were observed in 30% of recipients but none of the donors. One recipient was infected with COVID-19 during the postoperative period. A donor-recipient couple contracted COVID-19 after discharge from the hospital. All patients recovered from COVID-19 and liver enzymes were unaffected. CONCLUSION: This study represents a microcosm of experience in LDLT during the COVID-19 era. Outcomes of LDLT are not affected by COVID-19 per se, provided that we make necessary changes.

Telemedicine in the Care of Kidney Transplant Recipients With Coronavirus Disease 2019: Case Reports.

Kidney transplant recipients who develop symptoms consistent with coronavirus disease 2019 (COVID-19) are bringing unique challenges to health care professionals. Telemedicine has surged dramatically since the pandemic in effort to maintain patient care and reduce the risk of COVID-19 exposure to patients, health care workers, and the public. Herein we present reports of 3 kidney transplant recipients with COVID-19 who were managed using telemedicine via synchronous video visits integrated with an electronic medical record system, from home to inpatient settings. We demonstrate how telemedicine helped assess, diagnose, triage, and treat patients with COVID-19 while avoiding a visit to an emergency department or outpatient clinic. While there is limited information about the duration of viral shedding for immunosuppressed patients, our findings underscore the importance of using telemedicine in the follow-up care for kidney transplant recipients with COVID-19 who have recovered from symptoms but might have persistently positive nucleic acid tests. Our experience emphasizes the opportunities of telemedicine in the management of kidney transplant recipients with COVID-19 and in the maintenance of uninterrupted follow-up care for such immunosuppressed patients with prolonged viral shedding. Telemedicine may help increase access to care for kidney transplant recipients during and beyond the pandemic as it offers a prompt, safe, and convenient platform in the delivery of care for these patients. Yet, to advance the practice of telemedicine in the field of kidney transplantation, barriers to increasing the widespread implementation of telemedicine should be removed, and research studies are needed to assess the effectiveness of telemedicine in the care of kidney transplant recipients.

T cell and antibody responses to SARS-CoV-2: Experience from a French transplantation and hemodialysis center during the COVID-19 pandemic.

Immunosuppressed organ-transplanted patients are considered at risk for severe forms of COVID-19. Moreover, exaggerated innate and adaptive immune responses might be involved in severe progression of the disease. However, no data on the immune response to SARS-CoV-2 in transplanted patients are currently available. Here, we report the first assessment of antibody and T cell responses to SARS-CoV-2 in 11 kidney-transplanted patients recovered from RT-PCR-confirmed (n = 5) or initially suspected (n = 6) COVID-19. After reduction of immunosuppressive therapy, RT-PCR-confirmed COVID-19 transplant patients were able to mount vigorous antiviral T cell and antibody responses, as efficiently as two nontherapeutically immunosuppressed COVID-19 patients on hemodialysis. By contrast, six RT-PCR-negative patients displayed no antibody response. Among them, three showed very low numbers of SARS-CoV-2-reactive T cells, whereas no T cell response was detected in the other three, potentially ruling out COVID-19 diagnosis. Low levels of T cell reactivity to SARS-CoV-2 were also detected in seronegative healthy controls without known exposure to the virus. These results suggest that during COVID-19, monitoring both T cell and serological immunity might be helpful for the differential diagnosis of COVID-19 but are also needed to evaluate a potential role of antiviral T cells in the development of severe forms of the disease.

Coronavirus Disease 2019 Viremia, Serologies, and Clinical Course in a Case Series of Transplant Recipients.

Here we report a single-center cohort of 6 patients (4 kidney only, and 2 simultaneous liver/kidney transplants) diagnosed with COVID-19 at a median of 1.9 years (range = 0.2-9.3 years) post transplant. Five (of 6) patients required inpatient admission, 2 patients (mortality = 33%) died. Among those with mortality, an increased concentration of inflammatory biomarkers (interleukin-6 and C-reactive protein) was noted with a lack of response to interleukin-6 blockade, remdesivir, and/or convalescent plasma. None of the kidney-only transplants (4/6; 67%) had elevation in plasma donor-derived cell-free DNA above the previously published cut-off of 1%, suggesting absence of significant allo-immune injury. Four (of 5) admitted patients had detectable SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) in blood on samples obtained at/during hospitalization. Of the 4 discharged patients, 2 patients with undetectable virus on repeat nasopharyngeal swabs had seroconversion with positive SARS-CoV-2 IgG formation at 30 to 48 days post infection. One patient had prolonged shedding of virus on nasopharyngeal swab at 28 days post discharge despite lack of symptoms. In this preliminary report, we find that immunocompromised transplant patients had higher rates of RNAemia (67%) than reported in the general population (15%), seeming absence of allo-immune injury despite systemic inflammation, and formation of IgG overtime after recovery from infection.

Heart transplant recipients with confirmed 2019 novel coronavirus infection: The Detroit experience.

A chronic immunosuppressed state as in solid organ transplant recipients is a reported risk factor for the novel 2019 coronavirus infection. Patients with a history of orthotopic heart transplant (OHT) at a tertiary care transplant center in Detroit, Michigan were retrospectively reviewed from March until May 2020. Clinical parameters and outcomes of 5 OHT recipients and one combined heart-lung recipient with confirmed SARS-CoV-2 were obtained. The cohort was predominately African American males with median age of 59 years (interquartile range, 48.25-73.25). All patients were classified as having mild-moderate disease; none required intubation or ICU admission with no deaths. The most common presenting symptoms were fever and shortness of breath 83% (n = 5), followed by cough and chills 67% (n = 4). All admitted patients (n = 5) received hydroxychloroquine and 3 received high-dose steroids. Antimetabolites were held for 2 patients (33.3%). The calcineurin inhibitor trough goal was decreased in only 1 patient; 3 other patients, without change in goal, required calcineurin inhibitor dosage reduction. Two patients requiring readmission presented 7 and 23 days after initial symptoms onset. In conclusion, our experience with OHT patients infected by the SARS-CoV-2 virus did not have an elevated risk of severe infection. Impact of modifying immunosuppression remains unclear.

Awareness and Impact of Non-pharmaceutical Interventions During Coronavirus Disease 2019 Pandemic in Renal Transplant Recipients.

The concerns generated by coronavirus disease 2019 (COVID-19) pandemic are having profound impact on solid organ transplantation (SOT). Non-pharmaceutical interventions (NPI) are currently the only measures available to contain COVID-19 in the general population and in more vulnerable recipients of any organ transplant. In this cross-sectional case control study from a patient survey undertaken in 2 transplant centers (TxC) in the Kingdom of Saudi Arabia and Italy, we aimed to appraise awareness of the NPI implemented by respective these governments. We have also evaluated the impact of COVID-19 on our kidney transplant (KT) recipients and a control group of kidney living donors (KLD). In our series, there were zero cases of COVID-19 among 111 KT recipients and 70 KLD of the control group. Demography, transplant type, immunosuppression regimes, and, importantly, the different COVID-19 prevalence in the 2 regions of the TxC did not appear to influence incidence of COVID-19 in our KT recipients. The absence of COVID-19 cases in our series was unexpected. Our findings suggest that awareness of NPI is associated with a successful containment of COVID-19 in vulnerable, immunosuppressed KT recipients.

The COVID-19 pandemic: A community approach.

An unprecedented global pandemic caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has quickly overwhelmed the health care systems worldwide. While there is an absence of consensus among the community in how to manage solid organ transplant recipients and donors, a platform provided by the American Society of Transplantation online community "Outstanding Questions in Transplantation," hosted a collaborative multicenter, multinational discussions to share knowledge in a rapidly evolving global situation. Here, we present a summary of the discussion in addition to the latest published literature.

Liver transplant immunosuppression during the covid-19 pandemic. / Inmunosupresión en el trasplante hepático en la era covid-19.

SARS-CoV-2 infection has produced a pandemic with serious consequences for our health care system. Although liver transplant patients represent only a minority of the population, the hepatologists who follow these patients have tried to coordinate efforts to produce a protocol the management of immunosuppression during SARS-CoV-2 infection. Although there are no solid studies to support general recommendations, experiences with other viral infections (hepatitis C, cytomegalovirus) suggest that management of immunosuppression without mycophenolate mofetil or m-Tor inhibitors (drugs that are also associated with leukopenia and lymphopenia) may be beneficial. It is also important to pay attention to possible drug interactions, especially in the case of tacrolimus, with some of the treatments with antiviral effect given in the context of COVID 19 (lopinavir/ritonavir, azithromycin). Finally, the immunosuppressive effect of immunomodulating drugs (tocilizumab and similar) administered to patients with severe lung disease should be taken into account. The mechanisms of action of the different immunosuppressive drugs are reviewed in this article, as well as their potential effect on SARS-CoV-2 infection, and suggests guidelines for the management of immunosuppression.

Follow-up and Management of Kidney Transplant Recipients During the COVID-19 Lockdown: The Experience of an Italian Transplant Center, Including Two Cases of COVID-19 Pneumonia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new infectious disease that emerged in China in late 2019 and is now spreading around the world. Social distancing measures were needed to reduce transmission, and lockdown included restricted access to health care facilities. The impact of COVID-19 on transplant recipients is unknown, but considering their immunosuppression status and associated comorbidities, they should be considered a high-risk population. METHODS: A kidney transplant center in Central Italy implemented a strategy to maintain follow-up of kidney transplant recipients by phone and e-mail during lockdown. Telephone interviews were used to administer a clinical questionnaire to patients, and e-mail was used to receive the results of diagnostic tests conducted in outpatient settings. RESULTS: From March 17 to April 23, 2020, a total of 143 kidney transplant recipients were contacted. Twenty-eight patients needed in-hospital consultation for problems unrelated to COVID-19, 3 of whom needed hospitalization. Eleven patients were managed at home for mild urinary or respiratory diseases, and 1 was referred to the hematologist. We identified 2 suspected cases of COVID-19 infection, and the patients were referred to hospital care. Immunosuppressive therapy was modulated, and intravenous corticosteroids and potentially effective antiviral therapy were administered with a favorable outcome. CONCLUSIONS: In the context of a lockdown, such as that occurring in response to COVID-19, we suggest implementing remote surveillance programs in kidney transplant recipients with the help of any available technology and offering medical consulting and logistic support as needed.

A proposed strategy for management of immunosuppression in heart transplant patients with COVID-19.

There is limited experience in management of orthotopic heart transplant (OHT) patients with COVID-19. In this study, we present our initial experience using a standardized management algorithm. Data collection was performed on OHT patients with COVID-19 after March 10, 2020 (declaration of state of emergency in Massachusetts). Among the 358 OHT patients currently followed at our program, 5 patients (1.4%) tested positive for COVID-19 (median age 50 years [IQR, 49-58], duration post-OHT 21 years [IQR, 6-25], and 4 of 5 [80%] were men). Among the 5 OHT patients, 2 of 5 (20%) had mild disease and had no change in baseline immunosuppression therapy. Two of 5 (20%) had moderate disease and received remdesivir as part of a clinical trial and reduced immunosuppression therapy. One patient (20%) died prior to presenting to the hospital, consistent with 20% case fatality rate. Four patients (80%) are doing well 4 weeks post-discharge. In this small cohort of OHT patients with COVID-19, we report a 1.4% COVID-19 infection rate and 20% case fatality rate. All OHT patients managed under our clinical management algorithm had good short-term outcomes. Further study to estimate the true risk profile of OHT patients and validate the proposed management strategy is warranted.

Attenuated early inflammatory response in solid organ recipients with COVID-19.

Immunosuppression leaves transplanted patients at particular risk for severe acute respiratory syndrome 2 (SARS-CoV-2) infection. The specific features of coronavirus disease 2019 (COVID-19) in immunosuppressed patients are largely unknown and therapeutic experience is lacking. Seven transplanted patients (two liver, three kidneys, one double lung, one heart) admitted to the Ludwig-Maximilians-University Munich because of COVID-19 and tested positive for SARS-CoV-2 were included. The clinical course and the clinical findings were extracted from the medical record. The two liver transplant patients and the heart transplant patient had an uncomplicated course and were discharged after 14, 18, and 12 days, respectively. Two kidney transplant recipients were intubated within 48 hours. One kidney and the lung transplant recipients were required to intubate after 10 and 15 days, respectively. Immunosuppression was adapted in five patients, but continued in all patients. Compared to non-transplanted patients at the ICU (n = 19) the inflammatory response was attenuated in transplanted patients, which was proven by decreased IL-6 blood values. This analysis might provide evidence that continuous immunosuppression is safe and probably beneficial since there was no hyperinflammation evident. Although transplanted patients might be more susceptible to an infection with SARS-CoV-2, their clinical course seems to be similar to immunocompetent patients.