COVID-19 in solid organ transplant: A multi-center cohort study
BACKGROUND:The COVID-19 pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well-described. METHODS:We performed a multi-center cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. RESULTS:Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (IQR 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had â‰¥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [aOR 3.0, 95%CI 1.7-5.5, p<0.001], congestive heart failure [aOR 3.2, 95%CI 1.4-7.0, p=0.004], chronic lung disease [aOR 2.5, 95%CI 1.2-5.2, p=0.018], obesity [aOR 1.9, 95% CI 1.0-3.4, p=0.039]) and presenting findings (lymphopenia [aOR 1.9, 95%CI 1.1-3.5, p=0.033], abnormal chest imaging [aOR 2.9, 95%CI 1.1-7.5, p=0.027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. CONCLUSIONS:Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.
SARS-CoV-2 antibody responses in solid organ transplant recipients
Antibody responses among immunocompromised solid organ transplant recipients (SOT) infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) may be diminished compared to the general population and have not been fully characterized. We conducted a cohort study at our transplant center to investigate the rate of seroconversion for SARS-CoV-2 IgG antibodies among SOT recipients who were diagnosed with Coronavirus disease 2019 (COVID-19) and underwent serum SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) testing. The 61 patients who were included in the final analysis underwent initial SARS-CoV-2 IgG testing at a median of 62 days (Interquartile range 55.0-75.0) from symptom onset. Note that, 51 of 61 patients (83.6%) had positive SARS-CoV-2 IgG results, whereas 10 (16.4%) had negative IgG results. Six (60%) out of 10 seronegative patients underwent serial IgG testing and remained seronegative up to 17Â weeks post-diagnosis. Use of belatacept in maintenance immunosuppression was significantly associated with negative IgG antibodies to SARS-CoV-2 both in univariate and multivariate analyses (Odds ratio 0.04, pÂ =Â .01). In conclusion, the majority of organ transplant recipients with COVID-19 in our study developed SARS-CoV-2 antibodies. Further longitudinal studies of the durability and immunologic role of these IgG responses and the factors associated with lack of seroconversion are needed.
Clinical signs predictive of covid-19 mortality among transplant recipients [Meeting Abstract]
Purpose: The presentation of Coronavirus disease 2019 (COVID-19) ranges from mild illness to severe respiratory failure. Disease progression may differ in immunocompromised patients and immunocompetent hosts. Therefore, we aim to characterize COVID-19 clinical presentation and outcomes in solid organ transplant recipients (SOTRs) to identify initial clinical factors that may predict COVID-19 associated mortality.
Method(s): We prospectively reviewed baseline demographic and clinical characteristics among adult kidney, pancreas, liver, heart and lung transplant recipients diagnosed with COVID-19 between March 1, 2020 and May 5, 2020 at our transplant center in New York City. A series of chi-square and Fisher's exact tests were conducted to investigate the relationship between several predictor variables (baseline characteristics, symptoms at presentation, and baseline immunosuppression regimen) and 30-day mortality.
Result(s): 73 SOTRs (53 kidney, 8 liver, 7 heart, 3 lung, 2 heart/kidney) with SARSCoV-2 PCR-confirmed COVID-19 were included in the final analysis. Median age was 59 years (IQR 54-68) and 34.2% were female. Median time since transplant was 21 months (IQR 13-46.5). All patients were on baseline immunosuppresion as shown in table 1. The majority of patients were diagnosed in the Emergency Department. Most common presenting symptoms were cough (68.5%), gastrointestinal symptoms (54.8%) and dyspnea (45.2%) with median of 5 days from symptom onset to hospitalization. All patients had elevated inflammatory markers at time of diagnosis (median CRP 54 mg/L, median ferritin 704 ng/mL, median procalcitonin 0.11 ng/mL, median D-dimer 311 ng/mL). 84.1% of patients required supplemental oxygen, including intubation in 19.7%. 13 of 63 (21%) hospitalized patients died. Dyspnea on presentation was the only baseline or presenting patient factor found to be predictive of death (p =.004). When stratified by initial chest X-ray findings, dyspnea combined with abnormal chest X-ray predicted mortality (p=.021) while dyspnea with normal chest X-ray did not.
Conclusion(s): Presenting symptoms of dyspnea and radiographic signs of pneumonia on initial imaging predicted mortality among SOTRs with COVID-19 in our cohort. These findings can inform allocation of limited resources in COVID-19 management, including the triage and timing of COVID-19 directed therapies early in the illness course among different patient populations
Prevalence of Strongyloidiasis Among Cardiothoracic Organ Transplant Candidates in a Non-Endemic Region; A Single Center Experience with Universal Screening
Disseminated strongyloidiasis and hyperinfection syndrome can cause significant morbidity and mortality after transplantation. Screening and treatment prior to transplantation can reduce or prevent this disease. Targeted screening of transplant candidates, based on assessed risk, fails to identify all who would benefit. We implemented universal serology-based screening for Strongyloides at our transplant center, located in a non-endemic area. Of 200 transplant candidates who were evaluated for cardiothoracic transplant from January 2018 to June 2019, 169 were screened serologically and 21 (12.4%) were seropositive. Among seropositive patients, 57% reported travel to an endemic region, 38% were born outside the USA, 38% had eosinophilia, 5% had history of gram-negative bacteremia. We estimate that universal screening for strongyloidiasis could identify an average of 17 additional candidates for preventive treatment for every 200 transplant candidates.
COVID-19 Impact on Heart Organ Transplantation - New Insights from a Single-Center Experience [Meeting Abstract]
Purpose: During the COVID 19- pandemic, there is no consensus on management strategies for treating infected heart transplant patients. The outcomes of these patients vary by institution. We report our center experience and management strategies to date.
Method(s): All patients who received heart transplantation, from January 4th 2018 to September 25th 2020 and were diagnosed with SARS-CoV-2 were included and full chart review was performed.
Result(s): There were 113 heart transplants at our institution by September 2020. A total of 13 (12%) patients were infected with SARS-CoV-2: 9 (69%) isolated heart, 3 heart -kidney (23%) and 1 heat- lung (8%). The median (IQR) time from transplant to diagnosis was 10 (5-16) months. The mean age was 57 years and 50% were male; 50% were of Hispanic ethnicity. The main presenting symptoms were fever (43%), cough (86%) and SOB (43%). Chest x-ray was abnormal in all patients. We evaluated all patients and 79% were hospitalized and 21% were closely monitored as outpatients. None of our patients were hospitalized at outside institutions. Two (14%) required intubation and none required V-V ECMO support. The immunotherapy was modified in all patients: MMF and prednisone were discontinued, tacrolimus dose was reduced. COVID19 treatment was: 71% received hydroxychloroquine, 50% azithromycin, 15% remdesevir, 7% convalescent plasma. All hospitalized patients received anticoagulation. One patient had 2R/3A rejection within 30 days prior to diagnosis. Graft function was maintained in all patients with median LVEF% 65 (59-65%) except one patient who had received thymoglobulin 2 weeks prior to COVID 19 infection (LVEF 30%). The patient had a prolonged intubation but ultimately recovered and was discharged from the hospital. The one death (7.1%) was a heart - kidney recipient who concomitantly presented with pseudomonas sepsis and severe neutropenia. The remaining patients have all been discharged home.
Conclusion(s): We present our single center experience in managing COVID 19 infected heart transplant patients. We implemented uniform management strategies by incorporating aggressive reduction of immunosuppression, frequent scheduled contacts with infected outpatients and making sure all infected patients requiring hospitalization were treated at a transplant center.
Measles Outbreak Risk Assessment for Transplant Candidates and Recipients
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.
Healthcare resource use among solid organ transplant recipients hospitalized with COVID-19 [Letter]
Remdesivir for the Treatment of Covid-19 - Final Report
BACKGROUND:Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS:We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS:A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS:Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).
Post-COVID-19 inflammatory syndrome manifesting as refractory status epilepticus
There have been multiple descriptions of seizures during the acute infectious period in patients with COVID-19. However, there have been no reports of status epilepticus after recovery from COVID-19 infection. Herein, we discuss a patient with refractory status epilepticus 6 weeks after initial infection with COVID-19. Extensive workup demonstrated elevated inflammatory markers, recurrence of a positive nasopharyngeal SARS-CoV-2 polymerase chain reaction, and hippocampal atrophy. Postinfectious inflammation may have triggered refractory status epilepticus in a manner similar to the multisystemic inflammatory syndrome observed in children after COVID-19.
COVID-19 antibody responses in solid organ transplant recipients [Meeting Abstract]
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