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 ≥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.
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.
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.
f This case series highlights our experience with use of the Fungitell assay for quantifying (1,3)--D-glucan in cerebrospinal fluid during the current U.S. outbreak of fungal meningitis related to contaminated methylprednisolone acetate. This test may prove a useful adjunct in diagnosis and management of exposed patients.(1,3)--D-glucan (BG) is found in cell walls of multiple fungi. Its detection in serum assists in diagnosis of invasive fungal infections (1). Recently, diagnostic challenge has arisen in the fungal meningitis outbreak associated with exposure to contaminated epidural steroid injections (2). Diagnosis in this setting has been established by culture of cerebrospinal fluid (CSF) and/or detection using a pan-fungal PCR assay performed by the Centers for Disease Control (CDC). However, these tests have not always been positive in suspected cases (3). One early study has demonstrated the proof of concept of using CSF BG detection in diagnosis of fungal central nervous system infection in an experimental hematogenous Candida meningoencephalitis model (4). Here we report our experience with CSF BG measurement in 5 individuals from Johns Hopkins Hospital and Indiana University Hospital who were exposed to potentially contaminated drugs. Cases were diagnosed and managed according to CDC guidelines. BG was tested at Beacon Diagnostics Laboratory (East Falmouth, MA) using the Fungitell assay. Information was obtained by chart review with approval from the Johns Hopkins Institutional Review Board.The first case was a 55-year-old woman who developed headaches, blurred vision, and injection site pain 1 week after lumbar epidural injection with potentially contaminated methylprednisolone and was admitted 35 days after symptom onset when the outbreak was recognized. CSF showed 30 white blood cells (WBCs)/mm 3 and normal glucose and protein; no opening pressure was recorded. Intravenous voriconazole was initiated, but symptoms continued despite troughs of 2 to 3 g/ml. Repeat lumbar puncture (LP) showed opening pressure of 42 cm H 2 O, 974 WBC/mm 3 (56% neutrophils, 16% lymphocytes, 21% monocytes), 1,000 red blood cells (RBCs)/mm 3 , normal glucose, and 93 mg/dl protein, with a negative culture. CSF PCR performed by the CDC was negative. With serial LPs for persistent headache and elevated opening pressures and voriconazole increase to maintain troughs of 3 to 5 g/ml, her symptoms resolved. CSF fungal cultures from postinjection days 57, 69, and 73 were negative. CSF BG samples sent on postinjection days 57 and 73 were positive at 2,396 and 701 pg/ml, respectively (Table 1).The second case was a 37-year-old man who underwent lumbar epidural injection with potentially contaminated methylprednisolone and developed a headache several days later. Thirteen days after the injection he started oral voriconazole. His symptoms did not improve, and LP 2 weeks later showed 5 WBCs/mm 3 ( Table 1). PCR performed by the CDC and fungal cultures were negative. Magnetic resonance imaging (MRI) of the brain showed a small intrapa...
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 17 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, p = .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.
Solid organ transplant (SOT) candidates and recipients are at risk of significant morbidity and mortality from infection due to receipt of immunosuppressive medications necessary to mitigate risk of allograft rejection after transplant. 1-4 Infection prevention measures are routinely incorporated into patient care before and after transplantation and include antibiotic prophylaxis, immunizations, and patient education. Transplant professionals must remain aware of regional infectious disease outbreaks and the associated potential risk for patients awaiting transplantation and for patients who have successfully undergone transplantation. The measles (rubeola) virus is the most contagious human pathogen and an important vaccine-preventable cause of morbidity and mortality around the world. 5 No specific treatment exists for measles infection. Complications and long-term sequelae of infection include pneumonia, vision loss. and subacute sclerosing panencephalitis.
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. Methods 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. Results Among 93 SOTR diagnosed with COVID-19, 19 died before SARS-CoV-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 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. Disclosures All Authors: No reported disclosures
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