Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants.

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.

A COVID-19 Test Triage Tool, Predicting Negative Results and Reducing the Testing Burden on Healthcare Systems During a Pandemic.

Background: Detecting and isolating cases of COVID-19 are amongst the key elements listed by the WHO to reduce transmission. This approach has been reported to reduce those symptomatic with COVID-19 in the population by over 90%. Testing is part of a strategy that will save lives. Testing everyone maybe ideal, but it is not practical. A risk tool based on patient demographics and clinical parameters has the potential to help identify patients most likely to test negative for SARS-CoV-2. If effective it could be used to aide clinical decision making and reduce the testing burden. Methods: At the time of this analysis, a total of 9,516 patients with symptoms suggestive of Covid-19, were assessed and tested at Mount Sinai Institutions in New York. Patient demographics, clinical parameters and test results were collected. A robust prediction pipeline was used to develop a risk tool to predict the likelihood of a positive test for Covid-19. The risk tool was analyzed in a holdout dataset from the cohort and its discriminative ability, calibration and net benefit assessed. Results: Over 48% of those tested in this cohort, had a positive result. The derived model had an AUC of 0.77, provided reliable risk prediction, and demonstrated a superior net benefit than a strategy of testing everybody. When a risk cut-off of 70% was applied, the model had a negative predictive value of 96%. Conclusion: Such a tool could be used to help aide but not replace clinical decision making and conserve vital resources needed to effectively tackle this pandemic.

Humoral response and PCR positivity in patients with COVID-19 in the New York City region, USA: an observational study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The proportion of infected individuals who seroconvert is still an open question. In addition, it has been shown in some individuals that viral genome can be detected up to 3 months after symptom resolution. We investigated both seroconversion and PCR positivity in a large cohort of convalescent serum donors in the New York City (NY, USA) region. METHODS: In this observational study, we ran an outreach programme in the New York City area. We recruited participants via the REDCap (Vanderbilt University, Nashville, TN, USA) online survey response. Individuals with confirmed or suspected SARS-CoV-2 infection were screened via PCR for presence of viral genome and via ELISA for presence of anti-SARS-CoV-2 spike antibodies. One-way ANOVA and Fisher's exact test were used to measure the association of age, gender, symptom duration, and days from symptom onset and resolution with positive antibody results. FINDINGS: Between March 26 and April 10, 2020, we measured SARS-CoV-2 antibody titres in 1343 people. Of the 624 participants with confirmed SARS-CoV-2 infection who had serologies done after 4 weeks, all but three seroconverted to the SARS-CoV-2 spike protein, whereas 269 (37%) of 719 participants with suspected SARS-CoV-2 infection seroconverted. PCR positivity was detected up to 28 days from symptom resolution. INTERPRETATION: Most patients with confirmed COVID-19 seroconvert, potentially providing immunity to reinfection. We also report that in a large proportion of individuals, viral genome can be detected via PCR in the upper respiratory tract for weeks after symptom resolution, but it is unclear whether this signal represents infectious virus. Analysis of our large cohort suggests that most patients with mild COVID-19 seroconvert 4 weeks after illness, and raises questions about the use of PCR to clear positive individuals. FUNDING: None.

Adapting a vascular access service (VAS) to meet the needs of the COVID-19 pandemic.

The novel coronavirus 2019 (COVID-19) pandemic has placed an unprecedented strain on healthcare systems and frontline workers worldwide. The large influx of these high acuity patients has placed pressure on services to modify their operations to meet this increased need. We describe how the Vascular Access Service (VAS) at a New York City academic hospital adopted a team-based approach to efficiently meet increased demand for vascular access devices, while ensuring safety and conserving personal protective equipment.

COVID-19: Staging of a New Disease.

Coronavirus disease 2019 (COVID-19), like cancer, is a complex disease with clinical phases of progression. Initially conceptualized as a respiratory disease, COVID-19 is increasingly recognized as a multi-organ and heterogeneous illness. Disease staging is a method for measuring the progression and severity of an illness using objective clinical and molecular criteria. Integral to cancer staging is "metastasis," defined as the spread of a disease-producing agent, including neoplastic cells and pathogens such as certain viruses, from the primary site to distinct anatomic locations. Staging provides valuable frameworks and benchmarks for clinical decision-making in patient management, improved prognostication, and evidence-based treatment selection.

Introductions and early spread of SARS-CoV-2 in the New York City area.

New York City (NYC) has emerged as one of the epicenters of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. To identify the early transmission events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus that causes coronavirus disease 2019 (COVID-19) in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV-2 genomes indicates multiple, independent, but isolated introductions mainly from Europe and other parts of the United States. Moreover, we found evidence for community transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.