Faculty Bibliography

BACKGROUND:Transplant recipients with HIV may have worse outcomes with coronavirus disease 2019 (COVID-19) due to impaired T-cell function coupled with immunosuppressive drugs. Alternatively, immunosuppression might reduce inflammatory complications and/or antiretrovirals could be protective. METHODS:Prospective reporting of all cases of SARS-CoV-2 infection was required within the HOPE in Action Multicenter Consortium, a cohort of kidney and liver transplant recipients with HIV who have received organs from donors with and without HIV at 32 transplant centers in the United States. RESULTS:Between March 20, 2020 and September 25, 2020, there were 11 COVID-19 cases among 291 kidney and liver recipients with HIV (4%). In those with COVID-19, median age was 59 y, 10 were male, 8 were kidney recipients, and 5 had donors with HIV. A higher proportion of recipients with COVID-19 compared with the overall HOPE in the Action cohort were Hispanic (55% versus 12%) and received transplants in New York City (73% versus 34%, P < 0.05). Most (10/11, 91%) were hospitalized. High-level oxygen support was required in 7 and intensive care in 5; 1 participant opted for palliative care instead of transfer to the intensive care unit. HIV RNA was undetectable in all. Median absolute lymphocyte count was 0.3 × 103 cells/μL. Median CD4 pre-COVID-19 was 298 cells/μL, declining to <200 cells/μl in 6/7 with measurements on admission. Treatment included high-dose steroids (n = 6), tocilizumab (n = 3), remdesivir (n = 2), and convalescent plasma (n = 2). Four patients (36%) died. CONCLUSIONS:Within a national prospective cohort of kidney and liver transplant recipients with HIV, we report high mortality from COVID-19.

Solid organ transplant (SOT) candidates and recipients are at risk of significant morbidity and mortality from infection, including those circulating in the community from unexpected outbreaks. In late 2018-summer of 2019, a measles outbreak occurred in the New York City area, with a total of 649 cases reported. We developed a systematic three-part approach to address measles risk in our adult SOT program through: 1) identification of non-immune adults living in outbreak ZIP codes, 2) education focused on risk reduction for patients from outbreak ZIP codes and 3) risk reduction for non-immune patients. All waitlisted or previously transplanted patients residing in outbreak areas received a measles patient education handout. The electronic medical record of patients born in or after 1957 was reviewed for serologic evidence of measles immunity. Measles immunity testing was performed in patients without documentation of immunity. Patients who tested non-immune were offered MMR vaccination or intravenous immunoglobulin depending on their transplant phase and risk profile. Thus, we demonstrate successful implementation of a systematic risk assessment during a large measles outbreak to identify and protect at-risk SOT patients. As vaccine hesitancy persists, our strategies may be increasingly relevant to transplant centers and those caring for immunocompromised patients.

The COVID-19 pandemic affected transplant center activity in areas with high number of cases such as New York City and prompted reevaluation of patients awaiting organ transplant diagnosed with SARS-CoV-2 infection. To resume safe transplantation at our center, we found it necessary to (1) identify transplant candidates with possible exposure to or history of COVID-19 infection, (2) outline a clinical and laboratory assessment to determine adequate clinical recovery from COVID-19 for transplantation, and (3) determine whether the possibility of perioperative COVID-19 transmission from the patient to staff would pose unacceptable risk. Here, we describe our center's approach to proceeding with transplantation in a SARS-CoV-2 seropositive living donor kidney transplant recipient and describe early posttransplant outcomes.

Background: Studies to date indicate that most adults develop IgG antibody to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within 6 weeks of COVID-19 symptom onset. The seroconversion rate of solid organ transplant recipients (SOTR) following COVID-19 is unknown. Elucidation of humoral immune responses following COVID-19 in SOTR may inform risk of reinfection and the development of safe and effective vaccines for immunocompromised hosts.
Method(s): We assessed the frequency of SARS-CoV-2 IgG detection among adult SOTR diagnosed with COVID-19 by nasopharyngeal PCR assays between 3/1/2020 and 6/5/2020. SARS-CoV-2 IgG was detected in serum using the Abbott IgG assay at the manufacturer's recommended cut-off. Our primary objective was the frequency of SARS-CoV-2 IgG seropositivity after COVID-19. A secondary objective was to identify clinical factors associated with seroconversion. The mean age and nadir absolute lymphocyte count (ALC) were calculated between seropositive and negative SOTR and compared by Student's t-test.
Result(s): Among 93 SOTR diagnosed with COVID-19, 19 died before SARSCoV- 2 IgG testing could be performed, and 18 had testing pending as of abstract submission. 56 SOTR (44 kidney, 5 heart, 4 liver, 1 lung, and 1 heart-kidney recipients) completed testing and were included in the analysis. Median age was 58 years (IQR 49.5-67), and all received maintenance immunosuppression at the time of COVID-19 diagnosis with median nadir ALC during illness of 400 (IQR 200-600). SARS-CoV-2 IgG testing was performed at a median of 60 days (IQR 50-70) from symptom onset, the shortest interval being 16 days. 47 out of 56 SOTR tested positive for SARS-CoV-2 IgG. The likelihood of seroconversion was not different between those who were tested at < or >= 60 days from symptom onset (p=0.26), nor did it vary significantly by age (p =0.59), gender (p=0.53) or nadir ALC (p =0.28).
Conclusion(s): 83% of evaluated SOTR with COVID-19 disease had detectable SARS-CoV-2 IgG in serum at a median of 60 days after symptom onset. Studies are ongoing to identify variables associated with poor antibody response among the nearly 20% of SOTR in this cohort who failed to seroconvert. The significance of seroconversion on risk of reinfection and vaccine immunogenicity remains to be determined

Data describing the clinical progression of coronavirus disease 2019 (COVID-19) in transplant recipients are limited. In New York City during the surge in COVID-19 cases, a systematic approach to monitoring and triaging immunocompromised transplant patients was required in the context of strained healthcare resources, limited outpatient testing, and heightened hospital exposure risks. Public health guidance at the onset of the COVID-19 outbreak recommended outpatient monitoring of mildly symptomatic patients without specific recommendations for special populations such as transplant recipients. We developed and implemented a systematic monitoring algorithm for kidney transplant recipients at our transplant center who reported mild symptoms suggestive of COVID-19. We describe the outcomes of the first 44 patients monitored through this algorithm. A total of 44 kidney transplant recipients thought to be symptomatic for COVID-19 disease were followed for a minimum of 14 days. The majority of mildly symptomatic patients (34/44) had clinical progression of disease and were referred to the emergency department where they all tested PCR positive and required hospitalization. More than half of these patients presented with hypoxia requiring supplemental oxygen, 39% were intubated within 48 hours, and 53% developed acute kidney injury but did not require dialysis. There were 6 deaths. During surge outbreaks, kidney transplant patients with even mild symptoms have a high likelihood of COVID-19 disease and most will worsen requiring hospitalization for supportive measures. Earlier outpatient testing and hospitalization may improve COVID-19 outcomes among transplant recipients.

Study: Infections of the percutaneous lead site remain a frequent and costly complication for patients supported with durable left ventricular assist devices (LVADs). This retrospective analysis compares the use of three different driveline management kits and the occurrence of infection experienced at a single center. The kits used differ based on cleansing solution and adhesive covering. The primary 'green' kit utilizes chlorhexidine for cleaning and a tegaderm as the adhesive component. Patients that experienced peripheral irritation remote from the exit site were switched to the 'yellow' kit, which includes chlorhexidine and bordered gauze. The last kit, the 'blue' kit uses povidone iodine and bordered gauze and is reserved only for those with a chlorhexidine allergy.
Method(s): All patients that were implanted with a durable LVAD device at a single center were included in the analysis. Patient data was extracted that included the following information: occurrence of a driveline infection, which management kit was used, which device was implanted, additional diagnosis of diabetes, presence of a caregiver and other demographics. The sample of patients that experienced driveline site infections was further examined to extract clinically significant influences.
Result(s): Data from 104 patients was included in the analysis. 70 were implanted with the Heartmate II device and 34 with the HVAD. The age range for the population was 23-77. The gender breakdown included 78 males and 26 females. A total of 23 patient infections were appreciated. Statistical analysis of the infected sample showed a higher rate of infections associated with use of the 'blue' kit that contains povidone iodine instead of chlorhexidine. It also was noted that incidence of infection was higher in younger patients and decreased with age. Diabetes, the presence of a caregiver, type of LVAD device and gender did not show statistically significant findings

We represent a group of investigators funded by the National Institutes of Health (R01AI120938, U01AI134591, U01AI138897) to conduct a prospective multicenter study of the landscape of HIV-infected (HIV+) donors and two prospective multicenter trials comparing outcomes between HIV+ recipients of HIV+ and non-HIV+ donor kidneys and livers. These clinical trials are ongoing (NCT02602262, NCT03500315, NCT03734393).

Background. Strongyloidiasis can lead to hyperinfection and dissemination afer transplantation with signifcant morbidity and mortality. Treatment for Strongyloidiasis prior to transplantation can reduce the risk of disseminated infection. Targeted screening based on travel history and country of origin incompletely identifes at-risk patients. Data on universal screening prior to solid-organ (SOT) or hematopoietic stem cell transplantation (HSCT) are limited. We implemented universal serology-based screening for strongyloides at our transplant center, located in a metropolitan non-ndemic area. Methods. We identifed patients screened with serum Strongyloides IgG by ELISA during pre-transplant evaluation for SOT or HSCT from August 1, 2017 to April 25, 2018. We reviewed adherence to the screening recommendation by program type and the medical record of seropositive patients for country of origin, history of eosinophilia (>500 cell/muL), Gram-negative bacteremia, ova and parasite (O&P) examination and treatment. Results. A total of 812 patients were evaluated for transplant during the study period: 484 for kidney, 152 for liver, 12 for liver/kidney transplant, 40 for heart, 24 for lung, and 100 for HSCT. 201 (24.7%) of the 812 patients were screened for Strongyloides; 107 (17%) evaluated for abdominal transplant, 32 (50%) for thoracic transplant, and 62 (60%) for HSCT. Seventeen (8.4%) of 201 patients screened tested positive: nine evaluated for kidney transplant, four for heart, one for liver, and three for HSCT. Nine of 17 patients (53%) were treated with Ivermectin or referred to Infectious Diseases clinic prior to our review. Ten (59%) seropositive patients were from the United States and 70% had no documented travel to endemic areas; six patients were from countries other than the United States; and one from Puerto Rico. Two patients with Strongyloidiasis had eosinophilia, one had history of Klebsiella pneumoniae bac-teremia and one had stool O&P examination. Screening was higher when using an electronic order set (57% vs. 17%). Conclusion. Universal screening for Strongyloidiasis identifed individuals with latent infection who did not have epidemiological or clinical fndings suggestive of Strongyloidiasis. Screening for Strongyloidiasis was higher in transplant programs that incorporated the recommendation into an electronic order set