Faculty Bibliography
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Healthcare resource use among solid organ transplant recipients hospitalized with COVID-19 [Letter]
PMID: 33349940
ISSN: 1399-0012
CID: 4735272
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.).
PMID: 32445440
ISSN: 1533-4406
CID: 4637302
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.
PMID: 32944946
ISSN: 1528-1167
CID: 4593452
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
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
EMBASE:634732194
ISSN: 2328-8957
CID: 4841502
Outpatient management of kidney transplant recipients with suspected COVID-19-Single-center experience during the New York City surge
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 14Â 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 48Â 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.
PMID: 32578324
ISSN: 1399-3062
CID: 4514502
Comparison of T2candida assay with blood culture, candida sepsis score and serum beta-d-glucan in diagnosis of candidemia [Meeting Abstract]
Background. Although blood cultures are the clinical diagnostic standard for candidemia, their delay in results and low sensitivity has lead to increasing the use of alternate tests and diagnostic algorithms. The T2Candida magnetic resonance assay (T2C) results in a few hours, but concomitant cultures are also needed. We compared results from the T2C with beta-d-glucan (BDG), blood cultures (BCx) and the Candida Sepsis Score (CSc) in diagnosis and management of candidemia. Methods. This retrospective observational study included patients from July 2017 to December 2018 who had a T2C as well as BCx. Positive (+) and negative (-) results of BCx and BDG within 24 hours (24 h) of T2C were recorded, with clinical data to determine CSc at the time of T2C (recent surgery, severe sepsis, parenteral nutrition, multifocal candida colonization). Results. There were 648 T2Cs done over the study period. Only the first +T2C for patients with multiple T2Cs on admission was included. There were 41 patients with +T2, in which 31 had a 24hBCx. Two patients were of pediatric age. There were 7 neutropenic, 1 post-transplant, and 27 intensive care (ICU) patients. Reasons for ordering T2C included sepsis and persistent fevers. In 18 (44%) patients, antifungals were given prior to the T2C. Eight among 31 24hBCx were positive for concordant Candida spp. (26%). Six of these 8 patients were on antifungal therapy when T2C was sent. Seventeen patients had a 24hBDG, with 7 positive (41%). Overall mean CSc in 27 ICU patients with +T2C was 2.2 +/- 0.8, and 40% of adult non-neutropenic ICU patients had a CSc of 3 or above. A central line was present in 26 patients, and was removed in 16 after +T2. In 213 patients with -T2C who had 24hBCx, only 1 BCx was positive, from a PICC line in a 2-year-old patient. Seven of the 41 patients with +T2C were treated for deep-seated candidiasis with 6 weeks antifungal therapy or longer; others received 1 to 4 weeks. Thirteen patients died while on antifungal therapy. Conclusion. T2Candida was used for diagnosis and management of candidemia in patients who had concomitant blood culture positive in 26%, beta-d-glucan positive in 41%, and ICU Candida sepsis score 3 or above in 40% patients. It did not miss candidemia in adults, compared with blood culture within 24 hours. Positive T2Candida helped expedite source control e.g line removal
EMBASE:630693531
ISSN: 2328-8957
CID: 4295912
