Bryan Andrew Stevens

All Publications

• High Frequency of SARS-CoV-2 RNAemia and Association With Severe Disease. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Hogan, C. A., Stevens, B. A., Sahoo, M. K., Huang, C., Garamani, N., Gombar, S., Yamamoto, F., Murugesan, K., Kurzer, J., Zehnder, J., Pinsky, B. A. 2020

  Abstract

  BACKGROUND: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in blood, also known as RNAemia, has been reported, but its prognostic implications are poorly understood. This study aimed to determine the frequency of SARS-CoV-2 RNA in plasma and its association with coronavirus disease 2019 (COVID-19) clinical severity.METHODS: An analytical cross-sectional study was performed in a single-center tertiary care institution and included consecutive inpatients and outpatients with confirmed COVID-19. The prevalence of SARS CoV-2 RNAemia and the strength of its association with clinical severity variables were examined and included intensive care unit (ICU) admission, invasive mechanical ventilation, and 30-day all-cause mortality.RESULTS: Paired nasopharyngeal and plasma samples were included from 85 patients. The median age was 55 years, and individuals with RNAemia were older than those with undetectable SARS-CoV-2 RNA in plasma (63 vs 50 years; P = .04). Comorbidities were frequent including obesity (37.6%), hypertension (30.6%), and diabetes mellitus (22.4%). RNAemia was detected in 28/85 (32.9%) of patients, including 22/28 (78.6%) who required hospitalization. In models adjusted for age, RNAemia was detected more frequently in individuals who developed severe disease including ICU admission (32.1 vs 14.0%; P = .04) and invasive mechanical ventilation (21.4% vs 3.5%; P = .02). All 4 deaths occurred in individuals with detectable RNAemia. An additional 121 plasma samples from 28 individuals with RNAemia were assessed longitudinally, and RNA was detected for a maximum duration of 10 days.CONCLUSIONS: This study demonstrated a high proportion of SARS-CoV-2 RNAemia, and an association between RNAemia and clinical severity suggesting the potential utility of plasma viral testing as a prognostic indicator for COVID-19.

  View details for DOI 10.1093/cid/ciaa1054

  View details for PubMedID 32965474

• Five-minute point-of-care testing for SARS-CoV-2: Not there yet. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology Hogan, C. A., Sahoo, M. K., Huang, C., Garamani, N., Stevens, B., Zehnder, J., Pinsky, B. A. 2020; 128: 104410

  View details for DOI 10.1016/j.jcv.2020.104410

  View details for PubMedID 32403009

• Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome. Science immunology Röltgen, K., Powell, A. E., Wirz, O. F., Stevens, B. A., Hogan, C. A., Najeeb, J., Hunter, M., Wang, H., Sahoo, M. K., Huang, C., Yamamoto, F., Manohar, M., Manalac, J., Otrelo-Cardoso, A. R., Pham, T. D., Rustagi, A., Rogers, A. J., Shah, N. H., Blish, C. A., Cochran, J. R., Jardetzky, T. S., Zehnder, J. L., Wang, T. T., Narasimhan, B., Gombar, S., Tibshirani, R., Nadeau, K. C., Kim, P. S., Pinsky, B. A., Boyd, S. D. 2020; 5 (54)

  Abstract

  SARS-CoV-2-specific antibodies, particularly those preventing viral spike receptor binding domain (RBD) interaction with host angiotensin-converting enzyme 2 (ACE2) receptor, can neutralize the virus. It is, however, unknown which features of the serological response may affect clinical outcomes of COVID-19 patients. We analyzed 983 longitudinal plasma samples from 79 hospitalized COVID-19 patients and 175 SARS-CoV-2-infected outpatients and asymptomatic individuals. Within this cohort, 25 patients died of their illness. Higher ratios of IgG antibodies targeting S1 or RBD domains of spike compared to nucleocapsid antigen were seen in outpatients who had mild illness versus severely ill patients. Plasma antibody increases correlated with decreases in viral RNAemia, but antibody responses in acute illness were insufficient to predict inpatient outcomes. Pseudovirus neutralization assays and a scalable ELISA measuring antibodies blocking RBD-ACE2 interaction were well correlated with patient IgG titers to RBD. Outpatient and asymptomatic individuals' SARS-CoV-2 antibodies, including IgG, progressively decreased during observation up to five months post-infection.

  View details for DOI 10.1126/sciimmunol.abe0240

  View details for PubMedID 33288645

• Human B Cell Clonal Expansion and Convergent Antibody Responses to SARS-CoV-2. Cell host & microbe Nielsen, S. C., Yang, F., Jackson, K. J., Hoh, R. A., Röltgen, K., Jean, G. H., Stevens, B. A., Lee, J. Y., Rustagi, A., Rogers, A. J., Powell, A. E., Hunter, M., Najeeb, J., Otrelo-Cardoso, A. R., Yost, K. E., Daniel, B., Nadeau, K. C., Chang, H. Y., Satpathy, A. T., Jardetzky, T. S., Kim, P. S., Wang, T. T., Pinsky, B. A., Blish, C. A., Boyd, S. D. 2020

  Abstract

  B cells are critical for the production of antibodies and protective immunity to viruses. Here we show that patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) display early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify convergence of antibody sequences across SARS-CoV-2-infected patients, highlighting stereotyped naive responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and SARS-CoV.

  View details for DOI 10.1016/j.chom.2020.09.002

  View details for PubMedID 32941787

• Comparison of the Panther Fusion and a laboratory-developed test targeting the envelope gene for detection of SARS-CoV-2. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology Hogan, C. A., Sahoo, M. K., Huang, C., Garamani, N., Stevens, B., Zehnder, J., Pinsky, B. A. 2020; 127: 104383

  Abstract

  Numerous nucleic acid amplification assays have recently received emergency use authorization (EUA) for the diagnosis of SARS-CoV-2 infection, and there is a need to assess their test performance relative to one another.The aim of this study was to compare the test performance of the Hologic Panther Fusion SARS-CoV-2 assay targeting two regions of open reading frame 1ab (ORF1ab) to a high complexity molecular-based, laboratory-developed EUA from Stanford Health Care (SHC) targeting the SARS-CoV-2 envelope (E) gene.We performed a diagnostic comparison study by testing nasopharyngeal samples on the two assays. Assay agreement was assessed by overall percent agreement and Cohen's kappa coefficient.A total of 184 nasopharyngeal samples were tested using the two assays, of which 180 showed valid results and were included for the comparative analysis. Overall percent agreement between the assays was 98.3 % (95 % confidence interval (CI) 95.2-99.7) and kappa coefficient was 0.97 (95 % CI 0.93-1.0). One sample was detected on the SHC laboratory developed test (LDT) and not on the Panther Fusion, and had a Ct of 35.9. Conversely, 2 samples were detected on the Panther Fusion and not on the LDT, and had Ct values of 37.2 and 36.6.The Panther Fusion SARS-CoV-2 assay and the SHC LDT perform similarly on clinical nasopharyngeal swab specimens. Other considerations, including reagent availability, turnaround time, labor requirements, cost and instrument throughput should guide the decision of which assay to perform.

  View details for DOI 10.1016/j.jcv.2020.104383

  View details for PubMedID 32353760

• Comparison of the Accula SARS-CoV-2 Test with a Laboratory-Developed Assay for Detection of SARS-CoV-2 RNA in Clinical Nasopharyngeal Specimens. Journal of clinical microbiology Hogan, C. A., Garamani, N., Lee, A. S., Tung, J. K., Sahoo, M. K., Huang, C., Stevens, B., Zehnder, J., Pinsky, B. A. 2020

  Abstract

  Background: Several point-of-care (POC) molecular tests have received emergency use authorization (EUA) from the Food and Drug Administration (FDA) for diagnosis of SARS-CoV-2. The test performance characteristics of the Accula (Mesa Biotech) SARS-CoV-2 POC test need to be evaluated to inform its optimal use.Objectives: The aim of this study was to assess test performance of the Accula SARS-CoV-2 test.Study design: The performance of the Accula test was assessed by comparing results of 100 nasopharyngeal swab samples previously characterized by the Stanford Health Care EUA laboratory-developed test (SHC-LDT) targeting the envelope (E) gene. Assay concordance was assessed by overall percent agreement, positive percent agreement (PPA), negative percent agreement (NPA), and Cohen's kappa coefficient.Results: Overall percent agreement between the assays was 84.0% (95% confidence interval [CI] 75.3 to 90.6%), PPA was 68.0% (95% CI 53.3 to 80.5%) and the kappa coefficient was 0.68 (95% CI 0.54 to 0.82). Sixteen specimens detected by the SHC-LDT were not detected by the Accula test, and showed low viral load burden with a median cycle threshold value of 37.7. NPA was 100% (95% CI 94.2 to 100%).Conclusion: Compared to the SHC-LDT, the Accula SARS-CoV-2 test showed excellent negative agreement. However, positive agreement was low for samples with low viral load. The false negative rate of the Accula POC test calls for a more thorough evaluation of POC test performance characteristics in clinical settings, and for confirmatory testing in individuals with moderate to high pre-test probability of SARS-CoV-2 who test negative on Accula.

  View details for DOI 10.1128/JCM.01072-20

  View details for PubMedID 32461285

• Occurrence and Timing of Subsequent SARS-CoV-2 RT-PCR Positivity Among Initially Negative Patients. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Long, D. R., Gombar, S., Hogan, C. A., Greninger, A. L., Shah, V. O., Bryson-Cahn, C., Stevens, B., Rustagi, A., Jerome, K. R., Kong, C. S., Zehnder, J., Shah, N. H., Weiss, N. S., Pinsky, B. A., Sunshine, J. 2020

  Abstract

  Using data for 20,912 patients from two large academic health systems, we analyzed the frequency of SARS-CoV-2 RT-PCR test-discordance among individuals initially testing negative by nasopharyngeal swab who were retested on clinical grounds within 7 days. The frequency of subsequent positivity within this window was 3.5% and similar across institutions.

  View details for DOI 10.1093/cid/ciaa722

  View details for PubMedID 32506118

• Assessment of Sensitivity and Specificity of Patient-Collected Lower Nasal Specimens for Sudden Acute Respiratory Syndrome Coronavirus 2 Testing. JAMA network open Altamirano, J., Govindarajan, P., Blomkalns, A. L., Kushner, L. E., Stevens, B. A., Pinsky, B. A., Maldonado, Y. 2020; 3 (6): e2012005

  View details for DOI 10.1001/jamanetworkopen.2020.12005

  View details for PubMedID 32530469

• Simultaneous Coccidioidomycosis and Phaeohyphomycosis in a Kidney Transplant Recipient: A Case Report and Literature Review. Transplant infectious disease : an official journal of the Transplantation Society Puing, A. G., Couture-Cossette, A., Wang, A. X., Zygourakis, C. C., Cheng, X., Stevens, B. A., Banaei, N., Novoa, R. A., Ho, D. Y., Subramanian, A. 2020: e13365

  Abstract

  Advances in solid organ transplantation have improved the survival of end-stage organ disease at the expense of an increased risk for opportunistic infections. Unusual clinical presentations and the possibility of concurrent infections make diagnosing invasive fungal infection (IFI) more difficult. Here we present a case of simultaneous vertebral infection caused by Coccidioides immitis-posadasii and subcutaneous phaeohyphomycosis due to Nigrograna mackinnonii in a kidney transplant recipient. The diagnosis of both infections required invasive procedures to obtain tissue and a high index of suspicion that more than one IFI could be present. A multidisciplinary team approach for the management of immunocompromised patients with suspected or diagnosed IFI is warranted.

  View details for DOI 10.1111/tid.13365

  View details for PubMedID 32533741

• Comparison of a laboratory-developed test targeting the envelope gene with three nucleic acid amplification tests for detection of SARS-CoV-2. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology Bulterys, P. L., Garamani, N., Stevens, B., Sahoo, M. K., Huang, C., Hogan, C. A., Zehnder, J., Pinsky, B. A. 2020; 129: 104427

  Abstract

  Numerous nucleic acid amplification tests, including real-time, reverse transcription PCR (rRT-PCR) and isothermal amplification methods, have been developed to detect SARS-CoV-2 RNA, including many that have received emergency use authorization (EUA). There is a need to assess their test performance relative to one another.The aim of this study was to compare the test performance of a high complexity laboratory-developed rRT-PCR EUA from Stanford Health Care (SHC) targeting the SARS-CoV-2 envelope (E) gene with other tests: the Atila isothermal amplification assay targeting the nucleocapsid (N) gene and open reading frame 1ab (ORF1ab), the Altona E and spike (S) multiplex, real-time RT-PCR, and the US Centers for Disease Control and Prevention (CDC) N1 and N2 rRT-PCRs.A diagnostic comparison study was performed by testing nasopharyngeal samples from persons under investigation for coronavirus disease 2019 (COVID-19). Assay performance was assessed by percent agreement and Cohen's kappa coefficient.Positive percent agreement with the SHC EUA reference assay was 82.8 % (95 % confidence interval (CI) 65.0 to 92.9) for Atila, 86.7 % (95 % CI 69.7 to 95.3) for the Altona E and S targets, and 86.7 % (95 % CI 69.7 to 95.3) and 90.0 % (95 % CI 73.6 to 97.3), for the CDC N1 and N2 targets, respectively. All assays demonstrated 100 % negative percent agreement. Kappa coefficients ranged from 0.86 to 0.92, indicating excellent agreement.Performance was comparable among the SARS-CoV-2 nucleic acid amplification methods tested, with a limited number of discrepancies observed in specimens with low viral loads.

  View details for DOI 10.1016/j.jcv.2020.104427

  View details for PubMedID 32535398

  View details for PubMedCentralID PMC7207111

• Comparison of a Point-of-Care Assay and a High-Complexity Assay for Detection of SARS-CoV-2 RNA. The journal of applied laboratory medicine Stevens, B., Hogan, C. A., Sahoo, M. K., Huang, C., Garamani, N., Zehnder, J., Kurzer, J., Pinsky, B. A. 2020

  Abstract

  Numerous nucleic acid amplification assays utilizing different target genes of the SARS-CoV-2 genome have received emergency use authorization (EUA) by the United States Food and Drug Administration (FDA). Limited data are available comparing the test performance characteristics of these assays.A diagnostic comparison study was performed to evaluate the performance of the Cepheid Xpert Xpress SARS-CoV-2 assay compared to the Hologic Panther Fusion SARS-CoV-2 assay using clinical nasopharyngeal specimens. Agreement between the two assays was assessed by overall, positive, and negative percent agreement and Cohen's kappa coefficient.A total of 104 (54 positive and 50 negative) clinical nasopharyngeal samples were tested by both assays. Using the Panther Fusion as a reference standard, the Xpert demonstrated an overall agreement of 99.0% (95% confidence interval (CI): 94.8 - 100), positive percent agreement of 98.1% (95% CI: 90.1 - 100), and a negative percent agreement of 100% (95% CI: 94.2 - 100). The kappa coefficient was 0.98 (95% CI: 0.94 - 1.0). One sample positive by the Panther Fusion with a cycle threshold (Ct) of 38.6 was found to be reproducibly negative by the Xpert assay.The Cepheid Xpert Xpress SARS-CoV-2 assay provides test performance comparable to the Hologic Panther Fusion SARS-CoV-2 assay while offering laboratories rapid, on-demand testing capacity.

  View details for DOI 10.1093/jalm/jfaa135

  View details for PubMedID 32761092