Candida auris
is an urgent antimicrobial resistance threat due to its global emergence, high mortality, and persistent transmissions. Nearly half of
C. auris
clinical and surveillance cases in the United States are from the New York and New Jersey Metropolitan area.
Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although intrahost evolution has been documented, direct evidence of subsequent transmission and continued stepwise adaptation is lacking. Here we describe sequential persistent SARS-CoV-2 infections in three individuals that led to the emergence, forward transmission, and continued evolution of a new Omicron sublineage, BA.1.23, over an eight-month period. The initially transmitted BA.1.23 variant encoded seven additional amino acid substitutions within the spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), and displayed substantial resistance to neutralization by sera from boosted and/or Omicron BA.1-infected study participants. Subsequent continued BA.1.23 replication resulted in additional substitutions in the spike protein (S254F, N448S, F456L, M458K, F981L, S982L) as well as in five other virus proteins. Our findings demonstrate not only that the Omicron BA.1 lineage can diverge further from its already exceptionally mutated genome but also that patients with persistent infections can transmit these viral variants. Thus, there is, an urgent need to implement strategies to prevent prolonged SARS-CoV-2 replication and to limit the spread of newly emerging, neutralization-resistant variants in vulnerable patients.
Persistent SARS-CoV-2 infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. It has been speculated that the emergence of antigenically diverse SARS-CoV-2 variants such as the Omicron variant may be the result of intra-host viral evolution driven by suboptimal immune responses, which must be followed by forward transmission. However, while intrahost evolution has been documented, to our knowledge no direct evidence of subsequent forward transmission is available to date.
Here we describe the emergence of an Omicron BA.1 sub-lineage with 8 additional amino acid substitutions within the spike (E96D, L167T, R346T, L455W, K458M, A484V, H681R, A688V) in an immune-compromised host along with evidence of 5 forward transmission cases. Our findings show that the Omicron BA.1 lineage can further diverge from its exceptionally mutated genome during prolonged SARS-CoV-2 infection; highlighting an urgent need to employ therapeutic strategies to limit duration of infection and spread in vulnerable patients.
Background
Liver transplantation (LT) is a treatment option for select human immunodeficiency virus (HIV)-infected patients with advanced liver disease. The aim of this study was to describe LT evaluation outcomes in HIV-infected patients.
Methods
All HIV-infected patients referred for their first LT evaluation at the Mount Sinai Medical Center were included in this retrospective, descriptive cohort study. Multivariable logistic regression was used to identify factors independently associated with listing.
Results
From February 2000 and April 2012, 366 patients were evaluated for LT, with 66 (18.0%) listed for LT and 300 (82.0%) not listed. Fifty-one patients (13.9%) died before completing evaluation and 85 (23.2%) were too early for listing. Reasons patients were declined for listing were psychosocial (15.8%), HIV-related (10.4%), loss to follow up (9.6%), surgical/medical (6.0%), liver-related (4.4%), patient choice (3.4%), and financial (1.6%). Listed patients were more likely to have hepatocellular carcinoma (HCC) (43.1% vs. 17.1%; P <0.0001) and less likely to have hepatitis B (6.2% vs. 15.7%; P = 0.04) or a psychiatric history (19.7% vs. 35.2%; P = 0.02) than those not listed. In multivariable analysis, HCC (odds ratio [OR] 5.79; 95% confidence interval 2.97–11.28), MELD at referral (OR 1.06; 1.01–1.11), and hepatitis B (OR 0.26; 0.08–0.79) were associated with listing.
Conclusion
MELD score and HCC were positive predictors of listing in HIV-infected patients referred for LT evaluation and, therefore, timely referrals are vital in these patients. Because MELD is a predictor for death while undergoing an evaluation, a rapid evaluation should be performed in HIV-infected patients with a higher MELD score.
Contact precautions are used to prevent the spread of extended-spectrum β-lactamase (ESBL)–producing organisms in acute-care hospitals, but supporting data are lacking. We discontinued such precautions for ESBL Escherichia coli and Klebsiella spp and found no increased prevalence of these organisms with our change in practice.
Over 3 months, we provided monthly education to internal medicine residents and distributed resources regarding penicillin-allergy history taking. Allergy information in the electronic record was updated more often during the intervention compared to the period before the intervention (16.1% vs 10.9%; P = .02). Education and interdepartmental collaboration have the potential to affect provider behavior.
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