Reduction in risk of death among patients admitted with COVID-19 between first and second epidemic waves in New York City (preprint)

Many regions have experienced successive epidemic waves of COVID-19 since the emergence of SARS-CoV-2 with heterogeneous differences in mortality. Elucidating factors differentially associated with mortality between epidemic waves may inform clinical and public health strategies. We examined clinical and demographic data among patients admitted with COVID-19 during the first (March-June 2020) and second (December 2020-March 2021) epidemic waves at an academic medical center in New York City. Hospitalized patients (N=4631) had lower mortality during the second wave (14%) than the first (23%). Patients in the second wave had a lower 30-day mortality (Hazard Ratio (HR) 0.52, 95% CI 0.44, 0.61) than those in the first wave. The mortality decrease persisted after adjusting for confounders except for the volume of COVID-19 admissions (HR 0.88, 95% CI 0.70, 1.11), a measure of health system strain. Several demographic and clinical patient factors were associated with an increased risk of mortality independent of wave.

Bacterial Pneumonia and Respiratory Culture Utilization among Hospitalized Patients with and without COVID-19 in New York City (preprint)

COVID-19 is associated with prolonged hospitalization and a high risk of intubation, which raises concern for bacterial co-infection and antimicrobial resistance. Previous research has shown a wide range of bacterial pneumonia rates for COVID-19 patients in a variety of clinical and demographic settings, but none have compared hospitalized COVID-19 patients to patients testing negative for SARS-CoV-2 in similar care settings. We performed a retrospective cohort study on hospitalized patients with COVID-19 testing from 10 March 2020 to 31 December 2020. A total of 19,219 patients were included, of which 3,796 tested positive for SARS-CoV-2. We found a 2.6-fold increase (p < 0.001) in respiratory culture ordering in COVID-19 patients. On a per-patient basis, COVID-19 patients were 1.5-fold more likely than non-COVID patients to have abnormal respiratory cultures (46.8% vs. 30.9%, p <0.001), which was primarily driven by patients requiring intubation. Among patients with pneumonia, a significantly higher proportion of COVID-19 patients had ventilator-associated pneumonia (VAP) relative to non-COVID patients (85.7% vs 55.1%, p <0.001), but a lower proportion had community-acquired (12.2% vs 22.1%, p < 0.01) or hospital-acquired pneumonia (2.1% vs. 22.8%, p < 0.001). There was also a significantly higher proportion of respiratory cultures positive for MRSA, K. pneumoniae, and antibiotic-resistant organisms in COVID-19 patients. Increased rates of respiratory culture ordering for COVID-19 patients therefore appear to be clinically justified for patients requiring intubation, but further research is needed to understand how SARS-CoV-2 increases the risk of VAP.

A Novel SARS-CoV-2 Variant of Concern, B.1.526, Identified in New York (preprint)

Recent months have seen surges of SARS-CoV-2 infection across the globe along with considerable viral evolution. Extensive mutations in the spike protein of variants B.1.1.7, B1.351, and P.1 have raised concerns that the efficacy of current vaccines and therapeutic monoclonal antibodies could be threatened. In vitro studies have shown that one mutation, E484K, plays a crucial role in the loss of neutralizing activity of some monoclonal antibodies as well as most convalescent and vaccinee sera against variant B.1.351. In fact, two vaccine trials have recently reported lower protective efficacy in South Africa, where B.1.351 is dominant. To survey for these novel variants in our patient population in New York City, PCR assays were designed to identify viruses with two signature mutations, E484K and N501Y. We observed a steady increase in the detection rate from late December to mid-February, with an alarming rise to 12.3% in the past two weeks. Whole genome sequencing further demonstrated that most of our E484K isolates (n=49/65) fell within a single lineage: NextStrain clade 20C or Pangolin lineage B.1.526. Patients with this novel variant came from diverse neighborhoods in the metropolitan area, and they were on average older and more frequently hospitalized. Phylogenetic analyses of sequences in the database further reveal that this B.1.526 variant is scattered in the Northeast of US, and its unique set of spike mutations may also pose an antigenic challenge for current interventions.

Clinical Performance of SARS-CoV-2 Molecular Testing (preprint)

Molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the gold standard for diagnosis of coronavirus disease 2019 (COVID-19), but the test clinical performance is poorly understood. From 3/10/2020-5/1/2020 NewYork-Presbyterian laboratories performed 27,377 SARS-CoV-2 molecular assays from 22,338 patients. Repeat testing was performed in 3,432 patients, of which 2,413 had negative and 1,019 had positive first day results. Repeat-tested patients were more likely to be older, male, African-American or Hispanic, and to have severe disease. Among the patients with initially negative results, 18.6% became positive upon repeat-testing. Only 58.1% of any-time positive patients had a result of "detected" on the first test. The clinical sensitivity of COVID-19 molecular assays is estimated between 66.2 % and 95.6%, depending on the unknown number of false negative results in single-tested patients. Conversion to a negative result is unlikely to occur before 15 to 20 days after initial testing or 20-30 days after the onset of symptoms, with 50% conversion occurring at 28 days after initial testing. Forty-nine initially-positive patients converted to negative and then back to positive in subsequent days. Conversion from first day negative to positive results increased linearly with each day of testing, reaching 25% probability in 20 days. In summary, our study provides estimates of the clinical performance of SARS-CoV-2 molecular assays and suggests time frames for appropriate repeat testing, namely 15 to 20 days after a positive test and the same or next 2 days after a negative test in a patient with high suspicion for COVID-19.

Bacteremia and Blood Culture Utilization During COVID-19 Surge in New York City (preprint)

A surge of patients with coronavirus disease 2019 (COVID-19) presenting to New York City hospitals in March 2020 led to a sharp increase in the utilization of blood cultures, which overwhelmed the capacity of automated blood culture instruments. We sought to evaluate the utilization and diagnostic yield of blood cultures during the COVID-19 pandemic to determine prevalence and common etiologies of bacteremia, and to inform a diagnostic approach to relieve blood culture overutilization. We performed a retrospective cohort analysis of 88,201 blood cultures from 28,011 patients at a multicenter network of hospitals within New York City to evaluate order volume, positivity rate, time to positivity, and etiologies of positive cultures in COVID-19. Ordering volume increased by 34.8% in the second half of March 2020 compared to the first half of the month. The rate of bacteremia was significantly lower among COVID-19 patients (3.8%) than COVID-19 negative patients (8.0%) and those not tested (7.1%), p < 0.001. COVID-19 patients had a high proportion of organisms reflective of commensal skin microbiota, reducing the bacteremia rate to 1.6% when excluded. More than 98% of all positive cultures were detected within 4 days of incubation. Bloodstream infections are very rare for COVID-19 patients, which supports the judicious use of blood cultures in the absence of compelling evidence for bacterial co-infection. Clear communication with ordering providers is necessary to prevent overutilization of blood cultures during COVID-19 surges, and laboratories should consider shortening the incubation period from 5 days to 4 days to free additional capacity.

Characterization and Clinical Course of 1000 Patients with COVID-19 in New York: retrospective case series (preprint)

Objective: To characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient wards, and intensive care units (ICUs). Design: Retrospective manual medical record review. Setting: NewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC. Participants: The first 1000 consecutive patients with laboratory-confirmed COVID-19. Methods: We identified the first 1000 consecutive patients with a positive RT-SARS-CoV-2 PCR test who first presented to the ED or were hospitalized at NYP/CUIMC between March 1 and April 5, 2020. Patient data was manually abstracted from the electronic medical record. Main outcome measures: We describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. Results: Among the first 1000 patients, 150 were ED patients, 614 were admitted without requiring ICU-level care, and 236 were admitted or transferred to the ICU. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (63.1%). Hospitalized patients, and ICU patients in particular, most commonly had baseline comorbidities including of hypertension, diabetes, and obesity. ICU patients were older, predominantly male (66.9%), and long lengths of stay (median 23 days; IQR 12 to 32 days); 78.0% developed AKI and 35.2% required dialysis. Notably, for patients who required mechanical ventilation, only 4.4% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. As of April 30, 90 patients remained hospitalized and 211 had died in the hospital. Conclusions: Hospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset.

Testing the association between blood type and COVID-19 infection, intubation, and death (preprint)

The rapid global spread of the novel coronavirus SARS-CoV-2 has strained healthcare and testing resources, making the identification and prioritization of individuals most at-risk a critical challenge. Recent evidence suggests blood type may affect risk of severe COVID-19. We used observational healthcare data on 14,112 individuals tested for SARS-CoV-2 with known blood type in the New York Presbyterian (NYP) hospital system to assess the association between ABO and Rh blood types and infection, intubation, and death. We found slightly increased infection prevalence among non-O types. Risk of intubation was decreased among A and increased among AB and B types, compared with type O, while risk of death was increased for type AB and decreased for types A and B. We estimated Rh-negative blood type to have a protective effect for all three outcomes. Our results add to the growing body of evidence suggesting blood type may play a role in COVID-19.