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  • 1
    In: Autophagy, Informa UK Limited, Vol. 12, No. 1 ( 2016-01-02), p. 1-222
    Type of Medium: Online Resource
    ISSN: 1554-8627 , 1554-8635
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2016
    detail.hit.zdb_id: 2262043-6
    SSG: 12
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  • 2
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S24-S25
    Abstract: The long-term health effects after SARS-CoV-2 infection remain poorly understood. We evaluated health and healthcare usage after SARS-CoV-2 infection via surveys and longitudinal electronic medical record (EMR) review within the Military Health System (MHS). Methods We studied MHS beneficiaries enrolled in the Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) cohort from March to December 2020. COVID-19 illness symptom severity and duration were derived from surveys initiated in late 2020. In addition, multi-year healthcare encounter history before and after onset of COVID-19 symptoms was collected from the MHS EMR. Odds of organ-system clinical diagnoses within the 3 months pre- and post-symptom onset were calculated using generalized linear models, controlling for age, sex, and race, and including participant as a random effect. Results 1,015 participants were included who were SARS-CoV-2 positive, symptomatic, and had 3-month follow-up data available in the EMR (Table 1). 625 of these participants had survey data collected more than 28 days post-symptom onset, among whom 17% and 6% reported persistent symptoms at 28-84 days, and 85+ days, respectively. 9.6% had not resumed normal activities by one month. The most frequently reported symptoms persisting beyond 28 days were dyspnea, loss of smell and/or taste, fatigue, and exercise intolerance (Figure 1A). When compared with the period 61 to 90 days prior to symptom onset, the first month post-symptom onset period was associated with increases of pulmonary (aOR = 57, 95% CI 28-112), renal (aOR = 29, 95% CI 10-84), cardiovascular (aOR = 7, 95% CI 5-11), and neurological diagnoses (aOR = 3, 95% CI 2-4) (Figures 1B and 1C). Cardiovascular disease diagnoses remained elevated through 3 months (aOR = 2, 95% CI 1-3). Table 1. Characteristics of SARS-CoV-2+ EPICC participants, and illness duration among those with 28+ days post-symptom onset survey data collection. Figure 1 Fig1A. Symptoms reported by EPICC participants with illnesses longer than 28 days; 1B. Percent of participants with organ system specific diagnoses on each day, 90 days pre- and post-symptom onset; 1C. Odds of organ system specific diagnoses within each month, +/- 3 months of symptom onset, were calculated using generalized linear models, controlling for age, sex, and race and included participants as a random effect. Odds shown are relative to the earliest period included in the model, 61-90 days before onset. Conclusion In this MHS cohort, a significant proportion of participants had persistent symptoms and cardiovascular disease diagnoses 3 months after COVID-19 illness onset. These findings emphasize the long-term morbidity of COVID-19 and the importance of mitigating SARS-CoV-2 infections. Further analyses will evaluate demographic, clinical, and biomarker predictors of medium-to-long term organ-specific post-acute sequelae. Disclosures Simon Pollett, MBBS, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work)) Ryan C. Maves, MD, EMD Serono (Advisor or Review Panel member)Heron Therapeutics (Advisor or Review Panel member) David A. Lindholm, MD, American Board of Internal Medicine (Individual(s) Involved: Self): Member of Auxiliary R & D Infectious Disease Item-Writer Task Force. No financial support received. No exam questions will be disclosed ., Other Financial or Material Support
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
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  • 3
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S325-S326
    Abstract: Approximately 10-20% of patients with critical COVID-19 harbor neutralizing autoantibodies (auto-Abs) that target type I interferons (IFN), a family of cytokines that induce critical innate immune defense mechanisms upon viral infection. Studies to date indicate that these auto-Abs are mostly detected in men over age 65. Methods We screened for type I IFN serum auto-Abs in sera collected & lt; 21 days post-symptom onset in a subset of 103 COVID-19 inpatients and 24 outpatients drawn from a large prospective cohort study of SARS-CoV-2 infected patients enrolled across U.S. Military Treatment Facilities. The mean age of this n = 127 subset of study participants was 55.2 years (SD = 15.2 years, range 7.7 – 86.2 years), and 86/127 (67.7%) were male. Results Among those hospitalized 49/103 (47.6%) had severe COVID-19 (required at least high flow oxygen), and nine subjects died. We detected neutralizing auto-Abs against IFN-α, IFN-ω, or both, in four inpatients (3.9%, 8.2% of severe cases), with no auto-Abs detected in outpatients. Three of these patients were white males over the age of 62, all with multiple comorbidities; two of whom died and the third requiring high flow oxygen therapy. The fourth patient was a 36-year-old Hispanic female with a history of obesity who required mechanical ventilation during her admission for COVID-19. Conclusion These findings support the association between type I IFN auto-antibody production and life-threatening COVID-19. With further validation, reliable high-throughput screening for type I IFN auto-Abs may inform diagnosis, pathogenesis and treatment strategies for COVID-19, particularly in older males. Our finding of type I IFN auto-Ab production in a younger female prompts further study of this autoimmune phenotype in a broader population. Disclosures David A. Lindholm, MD, American Board of Internal Medicine (Individual(s) Involved: Self): Member of Auxiliary R & D Infectious Disease Item-Writer Task Force. No financial support received. No exam questions will be disclosed ., Other Financial or Material Support David Tribble, M.D., DrPH, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work)) Simon Pollett, MBBS, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work))
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
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  • 4
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S273-S273
    Abstract: The risk factors of venous thromboembolism (VTE) in COVID-19 warrant further study. We leveraged a cohort in the Military Health System (MHS) to identify clinical and virological predictors of incident deep venous thrombosis (DVT), pulmonary embolism (PE), and other VTE within 90-days after COVID-19 onset. Methods PCR or serologically-confirmed SARS-CoV-2 infected MHS beneficiaries were enrolled via nine military treatment facilities (MTF) through April 2021. Case characteristics were derived from interview and review of the electronic medical record (EMR) through one-year follow-up in outpatients and inpatients. qPCR was performed on upper respiratory swab specimens collected post-enrollment to estimate SARS-CoV-2 viral load. The frequency of incident DVT, PE, or other VTE by 90-days post-COVID-19 onset were ascertained by ICD-10 code. Correlates of 90-day VTE were determined through multivariate logistic regression, including age and sampling-time-adjusted log10-SARS-CoV-2 GE/reaction as a priori predictors in addition to other demographic and clinical covariates which were selected through stepwise regression. Results 1473 participants with SARS-CoV-2 infection were enrolled through April 2021. 21% of study participants were inpatients; the mean age was 41 years (SD = 17.0 years). The median Charlson Comorbidity Index score was 0 (IQR = 0 - 1, range = 0 - 13). 27 (1.8%) had a prior history of VTE. Mean maximum viral load observed was 1.65 x 107 genome equivalents/reaction. 36 (2.4%) of all SARS-CoV-2 cases (including inpatients and outpatients), 29 (9.5%) of COVID-19 inpatients, and 7 (0.6%) of outpatients received an ICD-10 diagnosis of any VTE within 90 days after COVID-19 onset. Logistic regression identified hospitalization (aOR = 11.1, p = 0.003) and prior VTE (aOR = 6.2 , p = 0.009) as independent predictors of VTE within 90 days of symptom onset. Neither age (aOR = 1.0, p = 0.50), other demographic covariates, other comorbidities, nor SARS-CoV-2 viral load (aOR = 1.1, p = 0.60) were associated with 90-day VTE. Conclusion VTE was relatively frequent in this MHS cohort. SARS-CoV-2 viral load did not increase the odds of 90-day VTE. Rather, being hospitalized for SARS-CoV-2 and prior VTE history remained the strongest predictors of this complication. Disclosures Simon Pollett, MBBS, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work)) Ryan C. Maves, MD, EMD Serono (Advisor or Review Panel member)Heron Therapeutics (Advisor or Review Panel member) David A. Lindholm, MD, American Board of Internal Medicine (Individual(s) Involved: Self): Member of Auxiliary R & D Infectious Disease Item-Writer Task Force. No financial support received. No exam questions will be disclosed ., Other Financial or Material Support David Tribble, M.D., DrPH, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work))
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
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  • 5
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S331-S332
    Abstract: The novel coronavirus disease 2019 (COVID-19) pandemic remains a global challenge. Accurate COVID-19 prognosis remains an important aspect of clinical management. While many prognostic systems have been proposed, most are derived from analyses of individual symptoms or biomarkers. Here, we take a machine learning approach to first identify discrete clusters of early stage-symptoms which may delineate groups with distinct symptom phenotypes. We then sought to identify whether these groups correlate with subsequent disease severity. Methods The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal cohort study with data and biospecimens collected from nine military treatment facilities over 1 year of follow-up. Demographic and clinical characteristics were measured with interviews and electronic medical record review. Early symptoms by organ-domain were measured by FLU-PRO-plus surveys collected for 14 days post-enrollment, with surveys completed a median 14.5 (Interquartile Range, IQR = 13) days post-symptom onset. Using these FLU-PRO-plus responses, we applied principal component analysis followed by unsupervised machine learning algorithm k-means to identify groups with distinct clusters of symptoms. We then fit multivariate logistic regression models to determine how these early-symptom clusters correlated with hospitalization risk after controlling for age, sex, race, and obesity. Results Using SARS-CoV-2 positive participants (n = 1137) from the EPICC cohort (Figure 1), we transformed reported symptoms into domains and identified three groups of participants with distinct clusters of symptoms. Logistic regression demonstrated that cluster-2 was associated with an approximately three-fold increased odds [3.01 (95% CI: 2-4.52); P & lt; 0.001] of hospitalization which remained significant after controlling for other factors [2.97 (95% CI: 1.88-4.69); P & lt; 0.001]. (A) Baseline characteristics of SARS-CoV-2 positive participants. (B) Heatmap comparing FLU-PRO response in each participant. (C) Principal component analysis followed by k-means clustering identified three groups of participants. (D) Crude and adjusted association of identified cluster with hospitalization. Conclusion Our findings have identified three distinct groups with early-symptom phenotypes. With further validation of the clusters’ significance, this tool could be used to improve COVID-19 prognosis in a precision medicine framework and may assist in patient triaging and clinical decision-making. Disclaimer Disclosures David A. Lindholm, MD, American Board of Internal Medicine (Individual(s) Involved: Self): Member of Auxiliary R & D Infectious Disease Item-Writer Task Force. No financial support received. No exam questions will be disclosed ., Other Financial or Material Support Ryan C. Maves, MD, EMD Serono (Advisor or Review Panel member)Heron Therapeutics (Advisor or Review Panel member) Simon Pollett, MBBS, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work))
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
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  • 6
    In: Cell, Elsevier BV, Vol. 181, No. 7 ( 2020-06), p. 1464-1474
    Type of Medium: Online Resource
    ISSN: 0092-8674
    RVK:
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 187009-9
    detail.hit.zdb_id: 2001951-8
    SSG: 12
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  • 7
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. 12 ( 2021-12-01)
    Abstract: We evaluated clinical outcomes, functional burden, and complications 1 month after coronavirus disease 2019 (COVID-19) infection in a prospective US Military Health System (MHS) cohort of active duty, retiree, and dependent populations using serial patient-reported outcome surveys and electronic medical record (EMR) review. Methods MHS beneficiaries presenting at 9 sites across the United States with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test, a COVID-19-like illness, or a high-risk SARS-CoV-2 exposure were eligible for enrollment. Medical history and clinical outcomes were collected through structured interviews and International Classification of Diseases–based EMR review. Risk factors associated with hospitalization were determined by multivariate logistic regression. Results A total of 1202 participants were enrolled. There were 1070 laboratory-confirmed SARS-CoV-2 cases and 132 SARS-CoV-2-negative participants. In the first month post–symptom onset among the SARS-CoV-2-positive cases, there were 212 hospitalizations, 80% requiring oxygen, 20 ICU admissions, and 10 deaths. Risk factors for COVID-19-associated hospitalization included race (increased for Asian, Black, and Hispanic compared with non-Hispanic White), age (age 45–64 and 65+ compared with & lt;45), and obesity (BMI≥30 compared with BMI & lt;30). Over 2% of survey respondents reported the need for supplemental oxygen, and 31% had not returned to normal daily activities at 1 month post–symptom onset. Conclusions Older age, reporting Asian, Black, or Hispanic race/ethnicity, and obesity are associated with SARS-CoV-2 hospitalization. A proportion of acute SARS-CoV-2 infections require long-term oxygen therapy; the impact of SARS-CoV-2 infection on short-term functional status was substantial. A significant number of MHS beneficiaries had not yet returned to normal activities by 1 month.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
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  • 8
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. 12 ( 2021-12-01)
    Abstract: The inFLUenza Patient-Reported Outcome Plus (FLU-PRO Plus) is a patient-reported outcome data collection instrument assessing symptoms of viral respiratory tract infections across 8 body systems. This study evaluated the measurement properties of FLU-PRO Plus in a study enrolling individuals with coronavirus disease 2019 (COVID-19). Methods Data from a prospective cohort study (EPICC) in US Military Health System beneficiaries evaluated for COVID-19 was utilized. Adults with symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with FLU-PRO Plus survey information within 1 week of symptom onset were included. Reliability of FLU-PRO Plus was estimated using intraclass correlation coefficient (ICC; 2 days’ reproducibility). Known-groups validity was assessed using patient global assessment (PGA) of disease severity. Patient report of return to usual health was used to assess responsiveness (day 1–6/7). Results Two hundred twenty-six SARS-CoV-2–positive participants were included in the analysis. Reliability among those who reported no change in their symptoms from one day to the next was high for most domains (ICC range, 0.68–0.94 for day 1 to day 2). Construct validity was demonstrated by moderate to high correlation between the PGA rating of disease severity and domain and total scores (eg, total scores correlation: 0.69 [influenza-like illness severity], 0.69 [interference in daily activities] , and –0.58 [physical health]). In addition, FLU-PRO Plus demonstrated good known-groups validity, with increasing domain and total scores observed with increasing severity ratings. Conclusions FLU-PRO Plus performs well in measuring signs and symptoms in SARS-CoV-2 infection with excellent construct validity, known-groups validity, and responsiveness to change. Standardized data collection instruments facilitate meta-analyses, vaccine effectiveness studies, and other COVID-19 research activities.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2757767-3
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  • 9
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 224, No. 9 ( 2021-11-16), p. 1462-1472
    Abstract: The mechanisms underlying the association between obesity and coronavirus disease 2019 (COVID-19) severity remain unclear. After verifying that obesity was a correlate of severe COVID-19 in US Military Health System (MHS) beneficiaries, we compared immunological and virological phenotypes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in both obese and nonobese participants. Methods COVID-19–infected MHS beneficiaries were enrolled, and anthropometric, clinical, and demographic data were collected. We compared the SARS-CoV-2 peak IgG humoral response and reverse-transcription polymerase chain reaction viral load in obese and nonobese patients, stratified by hospitalization, utilizing logistic regression models. Results Data from 511 COVID-19 patients were analyzed, among whom 24% were obese and 14% severely obese. Obesity was independently associated with hospitalization (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI] , 1.15–3.18) and need for oxygen therapy (aOR, 3.39; 95% CI, 1.61–7.11). In outpatients, severely obese had a log10 (1.89) higher nucleocapsid (N1) genome equivalents (GE)/reaction and log10 (2.62) higher N2 GE/reaction than nonobese (P = 0.03 and P & lt; .001, respectively). We noted a correlation between body mass index and peak anti-spike protein IgG in inpatients and outpatients (coefficient = 5.48, P & lt; .001). Conclusions Obesity is a strong correlate of COVID-19 severity in MHS beneficiaries. These findings offer new pathophysiological insights into the relationship between obesity and COVID-19 severity.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1473843-0
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  • 10
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. 3 ( 2022-03-01)
    Abstract: Nasopharyngeal (NP) swabs are the standard for SARS-CoV-2 diagnosis. If less invasive alternatives to NP swabs (eg, oropharyngeal [OP] or nasal swabs [NS] ) are comparably sensitive, the use of these techniques may be preferable in terms of comfort, convenience, and safety. Methods This study compared the detection of SARS-CoV-2 in swab samples collected on the same day among participants with at least one positive PCR test. Results Overall, 755 participants had at least one set of paired swabs. Concordance between NP and other swab types was 75% (NS), 72% (OP), 54% (rectal swabs [RS]), and 78% (NS/OP combined). Kappa values were moderate for the NS, OP, and NS/OP comparisons (0.50, 0.45, and 0.54, respectively). Highest sensitivity relative to NP (0.87) was observed with a combination of NS/OP tests (positive if either NS or OP was positive). Sensitivity of the non-NP swab types was hig hest in the first week postsymptom onset and decreased thereafter. Similarly, virus RNA quantity was highest in the NP swabs as compared with NS, OP, and RS within two weeks postsymptom onset. OP and NS performance decreased as virus RNA quantity decreased. No differences were noted between NS specimens collected at home or in clinic. Conclusions NP swabs detected more SARS-CoV-2 cases than non-NP swabs, and the sensitivity of the non-NP swabs decreased with time postsymptom onset. While other swabs may be simpler to collect, NP swabs present the best chance of detecting SARS-CoV-2 RNA, which is essential for clinical care as well as genomic surveillance.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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