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1.
Elife ; 92020 08 17.
Article in English | MEDLINE | ID: covidwho-2155739

ABSTRACT

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVIDpos) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVIDneg) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVIDneg patients at the time of diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVIDpos patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVIDpos patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.


Subject(s)
Betacoronavirus/isolation & purification , Blood Coagulation Disorders/diagnosis , Blood Coagulation Tests , Blood Coagulation , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Aged , Betacoronavirus/pathogenicity , Biomarkers/blood , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/virology , COVID-19 , COVID-19 Testing , Coronavirus Infections/blood , Coronavirus Infections/virology , Disease Progression , Female , Fibrinogen/metabolism , Host Microbial Interactions , Humans , Leukocyte Count , Longitudinal Studies , Male , Middle Aged , Pandemics , Platelet Count , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , SARS-CoV-2 , Time Factors
2.
Mayo Clin Proc Innov Qual Outcomes ; 6(6): 605-617, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2131838

ABSTRACT

Objective: To estimate rates and identify factors associated with asymptomatic COVID-19 in the population of Olmsted County during the prevaccination era. Patients and Methods: We screened first responders (n=191) and Olmsted County employees (n=564) for antibodies to SARS-CoV-2 from November 1, 2020 to February 28, 2021 to estimate seroprevalence and asymptomatic infection. Second, we retrieved all polymerase chain reaction (PCR)-confirmed COVID-19 diagnoses in Olmsted County from March 2020 through January 2021, abstracted symptom information, estimated rates of asymptomatic infection and examined related factors. Results: Twenty (10.5%; 95% CI, 6.9%-15.6%) first responders and 38 (6.7%; 95% CI, 5.0%-9.1%) county employees had positive antibodies; an additional 5 (2.6%) and 10 (1.8%) had prior positive PCR tests per self-report or medical record, but no antibodies detected. Of persons with symptom information, 4 of 20 (20%; 95% CI, 3.0%-37.0%) first responders and 10 of 39 (26%; 95% CI, 12.6%-40.0%) county employees were asymptomatic. Of 6020 positive PCR tests in Olmsted County with symptom information between March 1, 2020, and January 31, 2021, 6% (n=385; 95% CI, 5.8%-7.1%) were asymptomatic. Factors associated with asymptomatic disease included age (0-18 years [odds ratio {OR}, 2.3; 95% CI, 1.7-3.1] and >65 years [OR, 1.40; 95% CI, 1.0-2.0] compared with ages 19-44 years), body mass index (overweight [OR, 0.58; 95% CI, 0.44-0.77] or obese [OR, 0.48; 95% CI, 0.57-0.62] compared with normal or underweight) and tests after November 20, 2020 ([OR, 1.35; 95% CI, 1.13-1.71] compared with prior dates). Conclusion: Asymptomatic rates in Olmsted County before COVID-19 vaccine rollout ranged from 6% to 25%, and younger age, normal weight, and later tests dates were associated with asymptomatic infection.

3.
Mayo Clinic proceedings. Innovations, quality & outcomes ; 2022.
Article in English | EuropePMC | ID: covidwho-2073911

ABSTRACT

Objective To estimate rates and identify factors associated with asymptomatic COVID-19 in the population of Olmsted County during the pre-vaccination era. Patients and Methods We screened first responders (N=191) and Olmsted County employees (N=564) for antibodies to SARS-CoV-2 from November 2020 to February 2021 to estimate seroprevalence and asymptomatic infection. Second, we retrieved all PCR confirmed COVID-19 diagnoses in Olmsted County from March 2020 through January 2021, ed symptom information, estimated rates of asymptomatic infection and examined related factors. Results Twenty (10.5%;95%CI: 6.9%-15.6%) first responders and thirty-eight (6.7%;95% CI: 5.0%-9.1%) county employees had positive antibodies;an additional 5 (2.6%) and 10 (1.8%) had prior positive PCR tests per self-report or medical record, but no antibodies detected. Of persons with symptom information, 4/20, (20%, 95% CI: 3.0%-37.0%) of first responders and 10/39 (26%, 95% CI: 12.6%-40.0%) county employees, were asymptomatic. Of 6,020 positive PCR tests in Olmsted County with symptom information between March 1, 2020, and January 31, 2021, 6% (n=385;95% CI: 5.8%-7.1%) were asymptomatic. Factors associated with asymptomatic disease included age [0-18 years (OR=2.3, 95% CI: 1.7-3.1) and 65+ years (OR=1.40, 95% CI: 1.0-2.0) compared to ages 19-44 years], body-mass-index [overweight OR=0.58, 95% CI: 0.44-0.77) or obese (OR=0.48, 95% CI: 0.57-0.62) compared to normal or underweight] and tests after November 20, 2020 [(OR=1.35;95% CI: 1.13-1.71) compared to prior dates]. Conclusion Asymptomatic rates in Olmsted County prior to vaccine rollout ranged from 6-25%, and younger age, normal weight, and later tests dates were associated with asymptomatic infection.

4.
Sci Immunol ; 7(71): eabo1303, 2022 05 20.
Article in English | MEDLINE | ID: covidwho-1759271

ABSTRACT

Durable T cell responses to SARS-CoV-2 antigens after infection or vaccination improve immune-mediated viral clearance. To date, population-based surveys of COVID-19 adaptive immunity have focused on testing for IgG antibodies that bind spike protein and/or neutralize the virus. Deployment of existing methods for measuring T cell immunity could provide a more complete profile of immune status, informing public health policies and interventions.


Subject(s)
COVID-19 , Antibodies, Viral , Humans , Public Health , SARS-CoV-2 , T-Lymphocytes
5.
J Med Internet Res ; 23(9): e30157, 2021 09 28.
Article in English | MEDLINE | ID: covidwho-1443978

ABSTRACT

BACKGROUND: COVID-19 is caused by the SARS-CoV-2 virus and has strikingly heterogeneous clinical manifestations, with most individuals contracting mild disease but a substantial minority experiencing fulminant cardiopulmonary symptoms or death. The clinical covariates and the laboratory tests performed on a patient provide robust statistics to guide clinical treatment. Deep learning approaches on a data set of this nature enable patient stratification and provide methods to guide clinical treatment. OBJECTIVE: Here, we report on the development and prospective validation of a state-of-the-art machine learning model to provide mortality prediction shortly after confirmation of SARS-CoV-2 infection in the Mayo Clinic patient population. METHODS: We retrospectively constructed one of the largest reported and most geographically diverse laboratory information system and electronic health record of COVID-19 data sets in the published literature, which included 11,807 patients residing in 41 states of the United States of America and treated at medical sites across 5 states in 3 time zones. Traditional machine learning models were evaluated independently as well as in a stacked learner approach by using AutoGluon, and various recurrent neural network architectures were considered. The traditional machine learning models were implemented using the AutoGluon-Tabular framework, whereas the recurrent neural networks utilized the TensorFlow Keras framework. We trained these models to operate solely using routine laboratory measurements and clinical covariates available within 72 hours of a patient's first positive COVID-19 nucleic acid test result. RESULTS: The GRU-D recurrent neural network achieved peak cross-validation performance with 0.938 (SE 0.004) as the area under the receiver operating characteristic (AUROC) curve. This model retained strong performance by reducing the follow-up time to 12 hours (0.916 [SE 0.005] AUROC), and the leave-one-out feature importance analysis indicated that the most independently valuable features were age, Charlson comorbidity index, minimum oxygen saturation, fibrinogen level, and serum iron level. In the prospective testing cohort, this model provided an AUROC of 0.901 and a statistically significant difference in survival (P<.001, hazard ratio for those predicted to survive, 95% CI 0.043-0.106). CONCLUSIONS: Our deep learning approach using GRU-D provides an alert system to flag mortality for COVID-19-positive patients by using clinical covariates and laboratory values within a 72-hour window after the first positive nucleic acid test result.


Subject(s)
COVID-19 , Clinical Laboratory Information Systems , Deep Learning , Algorithms , Electronic Health Records , Humans , Retrospective Studies , SARS-CoV-2
6.
iScience ; 24(7): 102780, 2021 Jul 23.
Article in English | MEDLINE | ID: covidwho-1284160

ABSTRACT

Patients with COVID-19 can experience symptoms and complications after viral clearance. It is important to identify clinical features of patients who are likely to experience these prolonged effects. We conducted a retrospective study to compare longitudinal laboratory test measurements (hemoglobin, hematocrit, estimated glomerular filtration rate, serum creatinine, and blood urea nitrogen) in patients rehospitalized after PCR-confirmed SARS-CoV-2 clearance (n = 104) versus patients not rehospitalized after viral clearance (n = 278). Rehospitalized patients had lower median hemoglobin levels in the year prior to COVID-19 diagnosis (Cohen's D = -0.50; p = 1.2 × 10-3) and during their active SARS-CoV-2 infection (Cohen's D = -0.71; p = 4.6 × 10-8). Rehospitalized patients were also more likely to be diagnosed with moderate or severe anemia during their active infection (Odds Ratio = 4.07; p = 4.99 × 10-9). These findings suggest that anemia-related laboratory tests should be considered in risk stratification algorithms for patients with COVID-19.

7.
Mayo Clin Proc ; 96(5): 1165-1174, 2021 05.
Article in English | MEDLINE | ID: covidwho-1157598

ABSTRACT

OBJECTIVE: To estimate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in health care personnel. METHODS: The Mayo Clinic Serology Screening Program was created to provide a voluntary, two-stage testing program for SARS-CoV-2 antibodies to health care personnel. The first stage used a dried blood spot screening test initiated on June 15, 2020. Those participants identified as reactive were advised to have confirmatory testing via a venipuncture. Venipuncture results through August 8, 2020, were considered. Consent and authorization for testing was required to participate in the screening program. This report, which was conducted under an institutional review board-approved protocol, only includes employees who have further authorized their records for use in research. RESULTS: A total of 81,113 health care personnel were eligible for the program, and of these 29,606 participated in the screening program. A total of 4284 (14.5%) of the dried blood spot test results were "reactive" and warranted confirmatory testing. Confirmatory testing was completed on 4094 (95.6%) of the screen reactive with an overall seroprevalence rate of 0.60% (95% CI, 0.52% to 0.69%). Significant variation in seroprevalence was observed by region of the country and age group. CONCLUSION: The seroprevalence for SARS-CoV-2 antibodies through August 8, 2020, was found to be lower than previously reported in other health care organizations. There was an observation that seroprevalence may be associated with community disease burden.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19 , Disease Transmission, Infectious/statistics & numerical data , Health Personnel/statistics & numerical data , SARS-CoV-2 , Academic Medical Centers , Adult , COVID-19/blood , COVID-19/epidemiology , COVID-19/therapy , COVID-19 Serological Testing/methods , COVID-19 Serological Testing/statistics & numerical data , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Public Health/methods , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies , Spatio-Temporal Analysis , United States/epidemiology
8.
Cell Death Discov ; 7(1): 55, 2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1135657

ABSTRACT

Intensive care unit (ICU) admissions and mortality in severe COVID-19 patients are driven by "cytokine storms" and acute respiratory distress syndrome (ARDS). Interim clinical trial results suggest that the corticosteroid dexamethasone displays better 28-day survival in severe COVID-19 patients requiring ventilation or oxygen. In this study, 10 out of 16 patients (62.5%) that had an average plasma IL-6 value over 10 pg/mL post administration of corticosteroids also had worse outcomes (i.e., ICU stay >15 days or death), compared to 8 out of 41 patients (19.5%) who did not receive corticosteroids (p-value = 0.0024). Given this potential association between post-corticosteroid IL-6 levels and COVID-19 severity, we hypothesized that the glucocorticoid receptor (GR or NR3C1) may be coupled to IL-6 expression in specific cell types that govern cytokine release syndrome (CRS). Examining single-cell RNA-seq data from BALF of severe COVID-19 patients and nearly 2 million cells from a pan-tissue scan shows that alveolar macrophages, smooth muscle cells, and endothelial cells co-express NR3C1 and IL-6, motivating future studies on the links between the regulation of NR3C1 function and IL-6 levels.

9.
Mayo Clin Proc ; 96(3): 601-618, 2021 03.
Article in English | MEDLINE | ID: covidwho-988744

ABSTRACT

OBJECTIVE: To report the Mayo Clinic experience with coronavirus disease 2019 (COVID-19) related to patient outcomes. METHODS: We conducted a retrospective chart review of patients with COVID-19 diagnosed between March 1, 2020, and July 31, 2020, at any of the Mayo Clinic sites. We abstracted pertinent comorbid conditions such as age, sex, body mass index, Charlson Comorbidity Index variables, and treatments received. Factors associated with hospitalization and mortality were assessed in univariate and multivariate models. RESULTS: A total of 7891 patients with confirmed COVID-19 infection with research authorization on file received care across the Mayo Clinic sites during the study period. Of these, 7217 patients were adults 18 years or older who were analyzed further. A total of 897 (11.4%) patients required hospitalization, and 354 (4.9%) received care in the intensive care unit (ICU). All hospitalized patients were reviewed by a COVID-19 Treatment Review Panel, and 77.5% (695 of 897) of inpatients received a COVID-19-directed therapy. Overall mortality was 1.2% (94 of 7891), with 7.1% (64 of 897) mortality in hospitalized patients and 11.3% (40 of 354) in patients requiring ICU care. CONCLUSION: Mayo Clinic outcomes of patients with COVID-19 infection in the ICU, hospital, and community compare favorably with those reported nationally. This likely reflects the impact of interprofessional multidisciplinary team evaluation, effective leveraging of clinical trials and available treatments, deployment of remote monitoring tools, and maintenance of adequate operating capacity to not require surge adjustments. These best practices can help guide other health care systems with the continuing response to the COVID-19 pandemic.


Subject(s)
Biomedical Research , COVID-19/therapy , Pandemics , SARS-CoV-2 , Adolescent , COVID-19/epidemiology , Child , Child, Preschool , Female , Follow-Up Studies , Hospitalization/trends , Humans , Infant , Infant, Newborn , Intensive Care Units/statistics & numerical data , Male , Retrospective Studies
10.
Cell Death Discov ; 6(1): 138, 2020 Dec 02.
Article in English | MEDLINE | ID: covidwho-962237

ABSTRACT

Longitudinal characterization of SARS-CoV-2 PCR testing from COVID-19 patient's nasopharynx and its juxtaposition with blood-based IgG-seroconversion diagnostic assays is critical to understanding SARS-CoV-2 infection durations. Here, we retrospectively analyze 851 SARS-CoV-2-positive patients with at least two positive PCR tests and find that 99 of these patients remain SARS-CoV-2-positive after 4 weeks from their initial diagnosis date. For the 851-patient cohort, the mean lower bound of viral RNA shedding was 17.3 days (SD: 7.8), and the mean upper bound of viral RNA shedding from 668 patients transitioning to confirmed PCR-negative status was 22.7 days (SD: 11.8). Among 104 patients with an IgG test result, 90 patients were seropositive to date, with mean upper bound of time to seropositivity from initial diagnosis being 37.8 days (95% CI: 34.3-41.3). Our findings from juxtaposing IgG and PCR tests thus reveal that some SARS-CoV-2-positive patients are non-hospitalized and seropositive, yet actively shed viral RNA (14 of 90 patients). This study emphasizes the need for monitoring viral loads and neutralizing antibody titers in long-term non-hospitalized shedders as a means of characterizing the SARS-CoV-2 infection lifecycle.

11.
Elife ; 92020 07 07.
Article in English | MEDLINE | ID: covidwho-635065

ABSTRACT

Understanding temporal dynamics of COVID-19 symptoms could provide fine-grained resolution to guide clinical decision-making. Here, we use deep neural networks over an institution-wide platform for the augmented curation of clinical notes from 77,167 patients subjected to COVID-19 PCR testing. By contrasting Electronic Health Record (EHR)-derived symptoms of COVID-19-positive (COVIDpos; n = 2,317) versus COVID-19-negative (COVIDneg; n = 74,850) patients for the week preceding the PCR testing date, we identify anosmia/dysgeusia (27.1-fold), fever/chills (2.6-fold), respiratory difficulty (2.2-fold), cough (2.2-fold), myalgia/arthralgia (2-fold), and diarrhea (1.4-fold) as significantly amplified in COVIDpos over COVIDneg patients. The combination of cough and fever/chills has 4.2-fold amplification in COVIDpos patients during the week prior to PCR testing, in addition to anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19. This study introduces an Augmented Intelligence platform for the real-time synthesis of institutional biomedical knowledge. The platform holds tremendous potential for scaling up curation throughput, thus enabling EHR-powered early disease diagnosis.


Subject(s)
Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Adult , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Chills/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Diarrhea/virology , Dysgeusia/virology , Female , Fever/virology , Humans , Male , Middle Aged , Myalgia/virology , Olfaction Disorders/virology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Polymerase Chain Reaction , SARS-CoV-2
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