Faculty Bibliography

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, created an unprecedented need for comprehensive laboratory testing of populations, in order to meet the needs of medical practice and to guide the management and functioning of our society. With the greater New York metropolitan area as an epicenter of this pandemic beginning in March 2020, a consortium of laboratory leaders from the assembled New York academic medical institutions was formed to help identify and solve the challenges of deploying testing. This report brings forward the experience of this consortium, based on the real-world challenges which we encountered in testing patients and in supporting the recovery effort to reestablish the health care workplace. In coordination with the Greater New York Hospital Association and with the public health laboratory of New York State, this consortium communicated with state leadership to help inform public decision-making addressing the crisis. Through the length of the pandemic, the consortium has been a critical mechanism for sharing experience and best practices in dealing with issues including the following: instrument platforms, sample sources, test performance, pre- and post-analytical issues, supply chain, institutional testing capacity, pooled testing, biospecimen science, and research. The consortium also has been a mechanism for staying abreast of state and municipal policies and initiatives, and their impact on institutional and laboratory operations. The experience of this consortium may be of value to current and future laboratory professionals and policy-makers alike, in dealing with major events that impact regional laboratory services.

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epi-demiological parameters. Here, we report the analysis of 864 SARS-CoV-2 sequences from cases in the New York City metropolitan area during the COVID-19 outbreak in Spring 2020. The majority of cases had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that early transmission was most linked to cases from Europe. Our data are consistent with numerous seeds from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of genomic surveillance in addition to traditional epidemiological indicators.

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.

Background: Pneumonia is a leading cause of hospitalization and mortality. Due to the low yield of available diagnostic tests, ATS/IDSA pneumonia guidelines recommend a microbiologic work-up only for hospitalized patients with severe pneumonia.
Method(s): From 5/2019 to 1/2020, we selected adult patients with clinical and radiographic findings highly suggestive of pneumonia. The BioFire FilmArray pneumonia panel was performed on sputum specimens that met quality microbiologic criteria and the results were compared to those of sputum cultures and other tests sent per standard of care. A limit of 105 copies/mL was used for positivity in semi-quantitative bacterial targets. The empiric antimicrobial regimen was reviewed to quantify the potential for antimicrobial optimization.
Result(s): Seventy patients were included in the analysis. Median age was 70 (IQR 53.5-81.75), and the majority (43 patients, 61.4%) were classified as Class IV and V using the pneumonia severity index, indicating severe cases of pneumonia. Sixty-nine patients completed at least a 5-day course for pneumonia and 14.3% died during their hospitalization. The fifteen patients (21.4%) that submitted a sputum culture before the initiation of antimicrobial therapy, had a trend towards a positive sputum culture (60% (9/15) vs 36.4% (20/55)) (p=0.09). The BioFire FilmArray pneumonia Panel increased the number of patients who received a microbiologic diagnosis from 29 (41%) to 59 (84.3%) (p< 0.001). The per isolate analysis revealed significantly more targets detected for Haemophilus influenzae (p=0.002) and Streptococcus pneumoniae (p=0.05). On review of empiric antimicrobial treatment, there was possibility for antimicrobial optimization in 80% of patients, including 9 cases of pathogens (4 MRSA, 3 Legionella pneumophila, 2 CTX-M gram-negative rods) where the pathogens were not covered and another 70 antimicrobials in 49 patients that could be stopped. Flow chart Bacterial Pathogens Detected in Standard of Care Alone Testing and with the Addition of Pneumonia Panel. Potential for Antimicrobial Optimization Using the Pneumonia Panel
Conclusion(s): Incorporation of the pneumonia panel in the diagnostic work-up of patients hospitalized with pneumonia substantially increased the rate of microbiologic diagnosis and had the potential to guide appropriate antimicrobial therapy. Future studies to quantify the effects on clinical outcomes and cost-effectiveness from tailored therapy are needed

Background: SARS-CoV-2, the cause of COVID-19 pneumonia, is associated with heterogenous presentations ranging from asymptomatic infection to severe respiratory failure. We explored the association of SARS-CoV-2 genomic load as a risk factor for adverse patient outcomes.
Method(s): We included adult patients admitted to the hospital with clinical and radiographic findings of pneumonia and a confirmatory polymerase chain reaction (PCR) test of SARS-CoV-2 within 24 hours of admission. We segregated patients into 3 genomic load status groups: low (Cycle threshold (Ct) >=35) intermediate (25< Ct< 35) and high (Ct <=25) using real-time PCR. The primary outcome was a composite outcome of death, intubation and/or use of extracorporeal membrane oxygenation. Secondary outcomes included severity of pneumonia on admission, as measured by the Pneumonia Severity Index (PSI). Sensitivity analyses were performed to include Acute Respiratory Distress Syndrome (ARDS) in the composite outcome and varying Ct classification breakpoints.
Result(s): Of 457 patients positive for SARS-CoV-2 assay from March 31st to April 10th 2020, 316 met inclusion criteria and were included in the final analysis. Included patients were followed for a median of 25 days (IQR 21-28). High genomic load at presentation was associated with higher Charlson Comorbidity Index scores (p=0.005), transplant recipient status (p< 0.001) and duration of illness less than 7 days (p=0.005). Importantly, patients with high genomic load were more likely to reach the primary endpoint (p=0.001), and had higher PSI scores on admission (p=0.03). In multivariate analysis, high genomic load remained an independent predictor of primary outcome. Results remained significant in sensitivity analyses.
Conclusion(s): High genomic load of SARS-CoV-2 in nasopharyngeal samples at the time of admission is independently associated with mortality and intubation. This finding should prompt further research on the role of viral load as a clinical predictor and possible modifiable risk factor for adverse outcomes as treatment strategies evolve in this global pandemic. (Table Presented)

Background: The Infectious Diseases Society of America has identified the potential use of SARS-CoV-2 genomic load for prognostication purposes as a key research question.
Method(s): We designed a retrospective cohort study that included adult patients with COVID-19 pneumonia who had at least 2 positive nasopharyngeal tests at least 24 hours apart to study the correlation between the change in the genomic load of SARS-CoV-2 in nasopharyngeal samples, as reflected by the Cycle threshold (Ct) value of the real-time Polymerase Chain Reaction (PCR) assay, with change in clinical status. The Sequential Organ Failure Assessment (SOFA) score was used as a surrogate for patients' clinical status. A linear mixed-effects regression analysis was performed.
Result(s): Among 457 patients who presented to the emergency department between 3/31/2020- 4/10/2020, we identified 42 patients who met the inclusion criteria. The median initial SOFA score was 2 (IQR 2-3). 20 out of 42 patients had a lower SOFA score on their subsequent tests. We identified a statistically significant inverse correlation between the change in SOFA score and change in the Ct value with a decrease in SOFA score by 0.05 (SE 0.02; p < 0.05) for an increase in Ct values by 1. This correlation was independent of the duration of symptoms.
Conclusion(s): Our findings suggest that an increasing Ct value in sequential tests may be of prognostic value for patients diagnosed with COVID-19 pneumonia. Before repeat testing can be recommended routinely in clinical practice as a predictor of disease outcomes, prospective studies with a standardized interval between repeat tests should confirm our findings. (Table Presented)

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 236 SARS-CoV2 sequences from cases in the New York City metropolitan area during the initial stages of the 2020 COVID-19 outbreak. The majority of cases throughout the region had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that the majority were most related to cases from Europe. Our data are consistent with numerous seed transmissions from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of real-time genomic surveillance in addition to traditional epidemiological indicators.

The recent emergence of the SARS-CoV-2 pandemic has posed formidable challenges for clinical laboratories seeking reliable laboratory diagnostic confirmation. The swift advance of the crisis in the United States has led to Emergency Use Authorization (EUA) facilitating the availability of molecular diagnostic assays without the more rigorous examination to which tests are normally subjected prior to FDA approval. Our laboratory currently uses two real time RT-PCR platforms, the Roche Cobas SARS-CoV2 and the Cepheid Xpert Xpress SARS-CoV-2. Both platforms demonstrate comparable performance; however, the run times for each assay are 3.5 hours and 45 minutes, respectively. In search for a platform with shorter turnaround time, we sought to evaluate the recently released Abbott ID NOW COVID-19 assay which is capable of producing positive results in as little as 5 minutes. We present here the results of comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media and comparisons between Abbott ID NOW COVID-19 and Cepheid Xpert Xpress SARS-CoV-2 using nasopharyngeal swabs transported in viral transport media for Cepheid and dry nasal swabs for Abbott ID NOW. Regardless of method of collection and sample type, Abbott ID NOW COVID-19 had negative results in a third of the samples that tested positive by Cepheid Xpert Xpress when using nasopharyngeal swabs in viral transport media and 45% when using dry nasal swabs.