Early plasma angiopoietin-2 is prognostic for ARDS and mortality among critically ill patients with sepsis.

Angiopoietin-2 (Ang-2) is associated with vascular endothelial injury and permeability in the acute respiratory distress syndrome (ARDS) and sepsis. Elevated circulating Ang-2 levels may identify critically ill patients with distinct pathobiology amenable to targeted therapy. We hypothesized that plasma Ang-2 measured shortly after hospitalization among patients with sepsis would be associated with the development of ARDS and poor clinical outcomes. To test this hypothesis, we measured plasma Ang-2 in a cohort of 757 patients with sepsis, including 267 with ARDS, enrolled in the emergency department or early in their ICU course before the COVID-19 pandemic. Multivariable models were used to test the association of Ang-2 with the development of ARDS and 30-day morality. We found that early plasma Ang-2 in sepsis was associated with higher baseline severity of illness, the development of ARDS, and mortality risk. The association between Ang-2 and mortality was strongest among patients with ARDS and sepsis as compared to those with sepsis alone (OR 1.81 vs. 1.52 per log Ang-2 increase). These findings might inform models testing patient risk prediction and strengthen the evidence for Ang-2 as an appealing biomarker for patient selection for novel therapeutic agents to target vascular injury in sepsis and ARDS.

Building a thriving academic hospitalist workforce: A rapid qualitative analysis identifying key areas of focus in the field.

BACKGROUND: The hospitalist workforce has been at the forefront of the pandemic and has been stretched in both clinical and nonclinical domains. We aimed to understand current and future workforce concerns, as well as strategies to cultivate a thriving hospital medicine workforce. DESIGN, SETTING, AND PARTICIPANTS: We conducted qualitative, semistructured focus groups with practicing hospitalists via video conferencing (Zoom). Utilizing components from the Brainwriting Premortem Approach, attendees were split into small focus groups and listed their thoughts about workforce issues that hospitalists may encounter in the next 3 years, identifying the highest priority workforce issues for the hospital medicine community. Each small group discussed the most pressing workforce issues. These ideas were then shared across the entire group and ranked. We used rapid qualitative analysis to guide a structured exploration of themes and subthemes. RESULTS: Five focus groups were held with 18 participants from 13 academic institutions. We identified five key areas: (1) support for workforce wellness; (2) staffing and pipeline development to maintain an adequate workforce to match clinical growth; (3) scope of work, including how hospitalist work is defined and whether the clinical skillset should be expanded; (4) commitment to the academic mission in the setting of rapid and unpredictable clinical growth; and (5) alignment between the duties of hospitalists and resources of hospitals. Hospitalists voiced numerous concerns about the future of our workforce. Several domains were identified as high-priority areas of focus to address current and future challenges.

Practical Applications of Rapid Qualitative Analysis for Operations, Quality Improvement, and Research in Dynamically Changing Hospital Environments.

BACKGROUND: Health care systems are in a constant state of change. As such, methods to quickly acquire and analyze data are essential to effectively evaluate current processes and improvement projects. Rapid qualitative analysis offers an expeditious approach to evaluate complex, dynamic, and time-sensitive issues. METHODS: We used rapid data acquisition and qualitative methods to assess six real-world problems the hospitalist field faced during the COVID-19 pandemic. We iteratively modified and applied a six-step framework for conducting rapid qualitative analysis, including determining if rapid methods are appropriate, creating a team, selecting a data collection approach, data analysis, and synthesis and dissemination. Virtual platforms were used for focus groups and interviews; templated summaries and matrix analyses were then applied to allow for rapid qualitative analyses. RESULTS: We conducted six projects using rapid data acquisition and rapid qualitative analysis from December 4, 2020, to January 14, 2022, each of which included 23 to 33 participants. One project involved participants from a single institution; the remainder included participants from 15 to 24 institutions. These projects led to the refinement of an adapted rapid qualitative method for evaluation of hospitalist-driven operational, research, and quality improvement efforts. We describe how we used these methods and disseminated our results. We also discuss situations for which rapid qualitative methods are well-suited and strengths and weaknesses of the methods. CONCLUSION: Rapid qualitative methods paired with rapid data acquisition can be employed for prompt turnaround assessments of quality, operational, and research projects in complex health care environments. Although rapid qualitative analysis is not meant to replace more traditional qualitative methods, it may be appropriate in certain situations. Application of a framework to guide projects using a rapid qualitative approach can help provide structure to the analysis and instill confidence in the findings.

Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19.

BACKGROUND: Studies quantifying SARS-CoV-2 have focused on upper respiratory tract or plasma viral RNA with inconsistent association with clinical outcomes. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 nucleocapsid antigen (N-antigen) concentration and both markers of host response and clinical outcomes. METHODS: SARS-CoV-2 N-antigen concentrations were measured in the first study plasma sample (D0), collected within 72 h of hospital admission, from 256 subjects admitted between March 2020 and August 2021 in a prospective observational cohort of hospitalized patients with COVID-19. The rank correlations between plasma N-antigen and plasma biomarkers of tissue damage, coagulation, and inflammation were assessed. Multiple ordinal regression was used to test the association between enrollment N-antigen plasma concentration and the primary outcome of clinical deterioration at one week as measured by a modified World Health Organization (WHO) ordinal scale. Multiple logistic regression was used to test the association between enrollment plasma N-antigen concentration and the secondary outcomes of ICU admission, mechanical ventilation at 28 days, and death at 28 days. The prognostic discrimination of an externally derived "high antigen" cutoff of N-antigen ≥ 1000 pg/mL was also tested. RESULTS: N-antigen on D0 was detectable in 84% of study participants. Plasma N-antigen levels significantly correlated with RAGE (r = 0.61), IL-10 (r = 0.59), and IP-10 (r = 0.59, adjusted p = 0.01 for all correlations). For the primary outcome of clinical status at one week, each 500 pg/mL increase in plasma N-antigen level was associated with an adjusted OR of 1.05 (95% CI 1.03-1.08) for worse WHO ordinal status. D0 plasma N-antigen ≥ 1000 pg/mL was 77% sensitive and 59% specific (AUROC 0.68) with a positive predictive value of 23% and a negative predictive value of 93% for a worse WHO ordinal scale at day 7 compared to baseline. D0 N-antigen concentration was independently associated with ICU admission and 28-day mechanical ventilation, but not with death at 28 days. CONCLUSIONS: Plasma N-antigen levels are readily measured and provide important insight into the pathogenesis and prognosis of COVID-19. The measurement of N-antigen levels early in-hospital course may improve risk stratification, especially for identifying patients who are unlikely to progress to severe disease.

Mass cytometry reveals a conserved immune trajectory of recovery in hospitalized COVID-19 patients.

While studies have elucidated many pathophysiological elements of COVID-19, little is known about immunological changes during COVID-19 resolution. We analyzed immune cells and phosphorylated signaling states at single-cell resolution from longitudinal blood samples of patients hospitalized with COVID-19, pneumonia and/or sepsis, and healthy individuals by mass cytometry. COVID-19 patients showed distinct immune compositions and an early, coordinated, and elevated immune cell signaling profile associated with early hospital discharge. Intra-patient longitudinal analysis revealed changes in myeloid and T cell frequencies and a reduction in immune cell signaling across cell types that accompanied disease resolution and discharge. These changes, together with increases in regulatory T cells and reduced signaling in basophils, also accompanied recovery from respiratory failure and were associated with better outcomes at time of admission. Therefore, although patients have heterogeneous immunological baselines and highly variable disease courses, a core immunological trajectory exists that defines recovery from severe SARS-CoV-2 infection.

Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: results from the IMPACC study (preprint)

Background: Better understanding of the association between characteristics of patients hospital-ized with coronavirus disease 2019 (COVID-19) and outcome is needed to further improve upon patient management. Methods: Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) is a prospective, observational study of 1,164 patients from 20 hospitals across the United States. Disease severi-ty was assessed using a 7-point ordinal scale based on degree of respiratory illness. Patients were prospectively surveyed for 1 year after discharge for post-acute sequalae of COVID-19 (PASC) through quarterly surveys. Demographics, comorbidities, radiographic findings, clinical laboratory values, SARS-CoV-2 PCR and serology were captured over a 28-day period. Multi-variable logistic regression was performed. Findings: The median age was 59 years (interquartile range [IQR] 20); 711 (61%) were men; overall mortality was 14%, and 228 (20%) required invasive mechanical ventilation. Unsuper-vised clustering of ordinal score over time revealed distinct disease course trajectories. Risk fac-tors associated with prolonged hospitalization or death by day 28 included age [≥] 65 years (odds ratio [OR], 2.01; 95% CI 1.28-3.17), Hispanic ethnicity (OR, 1.71; 95% CI 1.13-2.57), elevated baseline creatinine (OR 2.80; 95% CI 1.63- 4.80) or troponin (OR 1.89; 95% 1.03-3.47), baseline lymphopenia (OR 2.19; 95% CI 1.61-2.97), presence of infiltrate by chest imaging (OR 3.16; 95% CI 1.96-5.10), and high SARS-CoV2 viral load (OR 1.53; 95% CI 1.17-2.00). Fatal cases had the lowest ratio of SARS-CoV-2 antibody to viral load levels compared to other trajectories over time (p=0.001). 589 survivors (51%) completed at least one survey at follow-up with 305 (52%) hav-ing at least one symptom consistent with PASC, most commonly dyspnea (56% among symp-tomatic patients). Female sex was the only associated risk factor for PASC. Interpretation: Integration of PCR cycle threshold, and antibody values with demographics, comorbidities, and laboratory/radiographic findings identified risk factors for 28-day outcome severity, though only female sex was associated with PASC. Longitudinal clinical phenotyping offers important insights, and provides a framework for immunophenotyping for acute and long COVID-19. Funding: NIH

Adaptability on Shifting Ground: a Rapid Qualitative Assessment of Multi-institutional Inpatient Surge Planning and Workforce Deployment During the COVID-19 Pandemic.

BACKGROUND: During the initial wave of COVID-19 hospitalizations, care delivery and workforce adaptations were rapidly implemented. In response to subsequent surges of patients, institutions have deployed, modified, and/or discontinued their workforce plans. OBJECTIVE: Using rapid qualitative methods, we sought to explore hospitalists' experiences with workforce deployment, types of clinicians deployed, and challenges encountered with subsequent iterations of surge planning during the COVID-19 pandemic across a collaborative of hospital medicine groups. APPROACH: Using rapid qualitative methods, focus groups were conducted in partnership with the Hospital Medicine Reengineering Network (HOMERuN). We interviewed physicians, advanced practice providers (APP), and physician researchers about (1) ongoing adaptations to the workforce as a result of the COVID-19 pandemic, (2) current struggles with workforce planning, and (3) evolution of workforce planning. KEY RESULTS: We conducted five focus groups with 33 individuals from 24 institutions, representing 52% of HOMERuN sites. A variety of adaptations was described by participants, some common across institutions and others specific to the institution's location and context. Adaptations implemented shifted from the first waves of COVID patients to subsequent waves. Three global themes also emerged: (1) adaptability and comfort with dynamic change, (2) the importance of the unique hospitalist skillset for effective surge planning and redeployment, and (3) the lack of universal solutions. CONCLUSIONS: Hospital workforce adaptations to the COVID pandemic continued to evolve. While few approaches were universally effective in managing surges of patients, and successful adaptations were highly context dependent, the ability to navigate a complex system, adaptability, and comfort in a chaotic, dynamic environment were themes considered most critical to successful surge management. However, resource constraints and sustained high workload levels raised issues of burnout.

A conserved immune trajectory of recovery in hospitalized COVID-19 patients (preprint)

Many studies have provided insights into the immune response to COVID-19; however, little is known about the immunological changes and immune signaling occurring during COVID-19 resolution. Individual heterogeneity and variable disease resolution timelines obscure unifying immune characteristics. Here, we collected and profiled >200 longitudinal peripheral blood samples from patients hospitalized with COVID-19, with other respiratory infections, and healthy individuals, using mass cytometry to measure immune cells and signaling states at single cell resolution. COVID-19 patients showed a unique immune composition and an early, coordinated and elevated immune cell signaling profile, which correlated with early hospital discharge. Intra-patient time course analysis tied to clinically relevant events of recovery revealed a conserved set of immunological processes that accompany, and are unique to, disease resolution and discharge. This immunological process, together with additional changes in CD4 regulatory T cells and basophils, accompanies recovery from respiratory failure and is associated with better clinical outcomes at the time of admission. Our work elucidates the biological timeline of immune recovery from COVID-19 and provides insights into the fundamental processes of COVID-19 resolution in hospitalized patients.

Increased rates of secondary bacterial infections, including Enterococcus bacteremia, in patients hospitalized with coronavirus disease 2019 (COVID-19).

OBJECTIVE: We compared the rates of hospital-onset secondary bacterial infections in patients with coronavirus disease 2019 (COVID-19) with rates in patients with influenza and controls, and we investigated reports of increased incidence of Enterococcus infections in patients with COVID-19. DESIGN: Retrospective cohort study. SETTING: An academic quaternary-care hospital in San Francisco, California. PATIENTS: Patients admitted between October 1, 2019, and October 1, 2020, with a positive SARS-CoV-2 PCR (N = 314) or influenza PCR (N = 82) within 2 weeks of admission were compared with inpatients without positive SARS-CoV-2 or influenza tests during the study period (N = 14,332). METHODS: National Healthcare Safety Network definitions were used to identify infection-related ventilator-associated complications (IVACs), probable ventilator-associated pneumonia (PVAP), bloodstream infections (BSIs), and catheter-associated urinary tract infections (CAUTIs). A multiple logistic regression model was used to control for likely confounders. RESULTS: COVID-19 patients had significantly higher rates of IVAC and PVAP compared to controls, with adjusted odds ratios of 4.7 (95% confidence interval [CI], 1.7-13.9) and 10.4 (95 % CI, 2.1-52.1), respectively. COVID-19 patients had higher incidence of BSI due to Enterococcus but not BSI generally, and whole-genome sequencing of Enterococcus isolates demonstrated that nosocomial transmission did not explain the increased rate. Subanalyses of patients admitted to the intensive care unit and patients who required mechanical ventilation revealed similar findings. CONCLUSIONS: COVID-19 is associated with an increased risk of IVAC, PVAP, and Enterococcus BSI compared with hospitalized controls, which is not fully explained by factors such as immunosuppressive treatments and duration of mechanical ventilation. The mechanism underlying increased rates of Enterococcus BSI in COVID-19 patients requires further investigation.

Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. METHODS: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID-19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). FINDINGS: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. INTERPRETATION: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. FUNDING: Funded by Roche Sequencing Solutions, Inc.

Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS.

The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a "cytokine storm," we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.

Drug and alcohol positivity of traumatically injured patients related to COVID-19 stay-at-home orders.

Background: COVID-19 related stay-at-home (SAH) orders created many economic and social stressors, possibly increasing the risk of drug/alcohol abuse in the community and trauma population.Objectives: Describe changes in alcohol/drug use in traumatically injured patients after SAH orders in California and evaluate demographic or injury pattern changes in alcohol or drug-positive patients.Methods: A retrospective analysis of 11 trauma centers in Southern California (1/1/2020-6/30/2020) was performed. Blood alcohol concentration, urine toxicology results, demographics, and injury characteristics were collected. Patients were grouped based on injury date - before SAH (PRE-SAH), immediately after SAH (POST-SAH), and a historical comparison (3/19/2019-6/30/2019) (CONTROL) - and compared in separate analyses. Groups were compared using chi-square tests for categorical variables and Mann-Whitney U tests for continuous variables.Results: 20,448 trauma patients (13,634 male, 6,814 female) were identified across three time-periods. The POST-SAH group had higher rates of any drug (26.2% vs. 21.6% and 24.7%, OR = 1.26 and 1.08, p < .001 and p = .035), amphetamine (10.4% vs. 7.5% and 9.3%, OR = 1.43 and 1.14, p < .001 and p = .023), tetrahydrocannabinol (THC) (13.8% vs. 11.0% and 11.4%, OR = 1.30 and 1.25, p < .001 and p < .001), and 3,4-methylenedioxy methamphetamine (MDMA) (0.8% vs. 0.4% and 0.2%, OR = 2.02 and 4.97, p = .003 and p < .001) positivity compared to PRE-SAH and CONTROL groups. Alcohol concentration and positivity were similar between groups (p > .05).Conclusion: This Southern California multicenter study demonstrated increased amphetamine, MDMA, and THC positivity in trauma patients after SAH, but no difference in alcohol positivity or blood concentration. Drug prevention strategies should continue to be adapted within and outside of hospitals during a pandemic.

Using Technology to Measure Older Adults' Social Networks for Health and Well-Being: A Scoping Review.

BACKGROUND AND OBJECTIVES: Social networks affect the health and well-being of older adults. Advancements in technology (e.g., digital devices and mHealth) enrich our ability to collect social networks and health data. The purpose of this scoping review was to identify and map the use of technology in measuring older adults' social networks for health and social care. RESEARCH DESIGN AND METHODS: The Joanna Briggs Institute methodology was followed. PubMed (MEDLINE), Sociological Abstracts, SocINDEX, CINAHL, and Web of Science were searched for relevant articles. Conference abstracts and proceedings were searched via Conference Papers Index, the American Sociological Society, and The Gerontological Society of America. Studies published in English from January 2004 to March 2020 that aimed to improve health or social care for older adults and used technology to measure social networks were included. Data were extracted by 2 independent reviewers using an a priori extraction tool. RESULTS: The majority of the 18 reviewed studies were pilot or simulation research conducted in Europe that focused on older adults living in the community. The various types of technologies used can be categorized as environment-based, person-based, and data-based. DISCUSSION AND IMPLICATIONS: Technology facilitates objective and longitudinal data collection on the social interactions and activities of older adults. The use of technology to measure older adults' social networks, however, is primarily in an exploratory phase. Multidisciplinary collaborations are needed to overcome operational, analytical, and implementation challenges. Future studies should leverage technologies for addressing social isolation and care for older adults, especially during the coronavirus disease 2019 pandemic.

COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and may be modified by dexamethasone (preprint)

We performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with ARDS from COVID-19 or other etiologies, or without ARDS. We found no evidence of cytokine storm but instead observed complex host response dysregulation driven by genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone. Compared to other viral ARDS, COVID-19 was characterized by impaired interferon-stimulated gene expression.

Upper airway gene expression reveals suppressed immune responses to SARS-CoV-2 compared with other respiratory viruses.

SARS-CoV-2 infection is characterized by peak viral load in the upper airway prior to or at the time of symptom onset, an unusual feature that has enabled widespread transmission of the virus and precipitated a global pandemic. How SARS-CoV-2 is able to achieve high titer in the absence of symptoms remains unclear. Here, we examine the upper airway host transcriptional response in patients with COVID-19 (n = 93), other viral (n = 41) or non-viral (n = 100) acute respiratory illnesses (ARIs). Compared with other viral ARIs, COVID-19 is characterized by a pronounced interferon response but attenuated activation of other innate immune pathways, including toll-like receptor, interleukin and chemokine signaling. The IL-1 and NLRP3 inflammasome pathways are markedly less responsive to SARS-CoV-2, commensurate with a signature of diminished neutrophil and macrophage recruitment. This pattern resembles previously described distinctions between symptomatic and asymptomatic viral infections and may partly explain the propensity for pre-symptomatic transmission in COVID-19. We further use machine learning to build 27-, 10- and 3-gene classifiers that differentiate COVID-19 from other ARIs with AUROCs of 0.981, 0.954 and 0.885, respectively. Classifier performance is stable across a wide range of viral load, suggesting utility in mitigating false positive or false negative results of direct SARS-CoV-2 tests.

Upper airway gene expression differentiates COVID-19 from other acute respiratory illnesses and reveals suppression of innate immune responses by SARS-CoV-2 (preprint)

We studied the host transcriptional response to SARS-CoV-2 by performing metagenomic sequencing of upper airway samples in 238 patients with COVID-19, other viral or non-viral acute respiratory illnesses (ARIs). Compared to other viral ARIs, COVID-19 was characterized by a diminished innate immune response, with reduced expression of genes involved in toll-like receptor and interleukin signaling, chemokine binding, neutrophil degranulation and interactions with lymphoid cells. Patients with COVID-19 also exhibited significantly reduced proportions of neutrophils and macrophages, and increased proportions of goblet, dendritic and B-cells, compared to other viral ARIs. Using machine learning, we built 26-, 10- and 3-gene classifiers that differentiated COVID-19 from other acute respiratory illnesses with AUCs of 0.980, 0.950 and 0.871, respectively. Classifier performance was stable at low viral loads, suggesting utility in settings where direct detection of viral nucleic acid may be unsuccessful. Taken together, our results illuminate unique aspects of the host transcriptional response to SARS-CoV-2 in comparison to other respiratory viruses and demonstrate the feasibility of COVID-19 diagnostics based on patient gene expression.

Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: a comparison of patients with and without COVID-19 (preprint)

BackgroundEmerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses. MethodsWe examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury). FindingsIn a cohort of 316 patients, 33 (10%) tested positive for SARS-CoV-2; 31 patients, all without COVID-19, tested positive for another respiratory virus (16%). Among patients with additional viral testing, no co-infections with SARS-CoV-2 were identified by PCR or mNGS. Patients with COVID-19 reported longer symptoms duration (median 7 vs. 3 days) and were more likely to report fever (82% vs. 44%) fatigue (85% vs. 50%) and myalgias (61% vs 27%); p<0.001 for all comparisons. Lymphopenia (55% vs 34%, p=0.018) and bilateral opacities on initial chest radiograph (55% vs. 24%, p=0.001) were more common in patients with COVID-19. Patients with COVID-19 were more often hospitalized (79% vs. 56%, p=0.014). Of 186 hospitalized patients, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p<0.001) and were more likely to develop ARDS (23% vs. 3%, p<0.001). Most comorbidities, home medications, signs and symptoms, vital signs, laboratory results, treatment, and outcomes did not differ by COVID-19 status. InterpretationWhile we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. These findings enhance understanding of the clinical characteristics of COVID-19 in comparison to other acute respiratory illnesses.