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1.
Cell Host Microbe ; 2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2082311

ABSTRACT

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

2.
Open Forum Infect Dis ; 9(7): ofac314, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2051508

ABSTRACT

Background: There is limited information on the functional consequences of coronavirus disease 2019 (COVID-19) vaccine side effects. To support patient counseling and public health messaging, we describe the risk and correlates of COVID-19 vaccine side effects sufficient to prevent work or usual activities and/or lead to medical care ("severe" side effects). Methods: The EPICC study is a longitudinal cohort study of Military Healthcare System beneficiaries including active duty service members, dependents, and retirees. We studied 2789 adults who were vaccinated between December 2020 and December 2021. Results: Severe side effects were most common with the Ad26.COV2.S (Janssen/Johnson and Johnson) vaccine, followed by mRNA-1273 (Moderna) then BNT162b2 (Pfizer/BioNTech). Severe side effects were more common after the second than first dose (11% vs 4%; P < .001). First (but not second) dose side effects were more common in those with vs without prior severe acute respiratory syndrome coronavirus 2 infection (9% vs 2%; adjusted odds ratio [aOR], 5.84; 95% CI, 3.8-9.1), particularly if the prior illness was severe or critical (13% vs 2%; aOR, 10.57; 95% CI, 5.5-20.1) or resulted in inpatient care (17% vs 2%; aOR, 19.3; 95% CI, 5.1-72.5). Side effects were more common in women than men but not otherwise related to demographic factors. Conclusions: Vaccine side effects sufficient to prevent usual activities were more common after the second than first dose and varied by vaccine type. First dose side effects were more likely in those with a history of COVID-19-particularly if that prior illness was severe or associated with inpatient care. These findings may assist clinicians and patients by providing a real-world evaluation of the likelihood of experiencing impactful postvaccine symptoms.

3.
Open Forum Infect Dis ; 9(7): ofac275, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1961127

ABSTRACT

Background: Patient-reported outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are an important measure of the full burden of coronavirus disease (COVID). Here, we examine how (1) infecting genotype and COVID-19 vaccination correlate with inFLUenza Patient-Reported Outcome (FLU-PRO) Plus score, including by symptom domains, and (2) FLU-PRO Plus scores predict return to usual activities and health. Methods: The epidemiology, immunology, and clinical characteristics of pandemic infectious diseases (EPICC) study was implemented to describe the short- and long-term consequences of SARS-CoV-2 infection in a longitudinal, observational cohort. Multivariable linear regression models were run with FLU-PRO Plus scores as the outcome variable, and multivariable Cox proportional hazards models evaluated effects of FLU-PRO Plus scores on return to usual health or activities. Results: Among the 764 participants included in this analysis, 63% were 18-44 years old, 40% were female, and 51% were White. Being fully vaccinated was associated with lower total scores (ß = -0.39; 95% CI, -0.57 to -0.21). The Delta variant was associated with higher total scores (ß = 0.25; 95% CI, 0.05 to 0.45). Participants with higher FLU-PRO Plus scores were less likely to report returning to usual health and activities (health: hazard ratio [HR], 0.46; 95% CI, 0.37 to 0.57; activities: HR, 0.56; 95% CI, 0.47 to 0.67). Fully vaccinated participants were more likely to report returning to usual activities (HR, 1.24; 95% CI, 1.04 to 1.48). Conclusions: Full SARS-CoV-2 vaccination is associated with decreased severity of patient-reported symptoms across multiple domains, which in turn is likely to be associated with earlier return to usual activities. In addition, infection with the Delta variant was associated with higher FLU-PRO Plus scores than previous variants, even after controlling for vaccination status.

4.
Open forum infectious diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1940240

ABSTRACT

Background There is limited information on the functional consequences of COVID-19 vaccine side effects. To support patient counseling and public health messaging, we describe the risk and correlates of COVID-19 vaccine side effects sufficient to prevent work or usual activities and/or lead to medical care (“severe” side effects). Methods The EPICC study is a longitudinal cohort study of Military Healthcare System beneficiaries including active duty service members, dependents, and retirees. We studied 2,789 adults who were vaccinated between December 2020 and December 2021. Results Severe side effects were most common with the Ad26.COV2.S-(Janssen/Johnson and Johnson) vaccine followed by mRNA-1273-(Moderna) then BNT162b2-(Pfizer/BioNTech). Severe side effects were more common after the second than first dose (11% vs 4%, p < 0.001). First (but not second) dose side effects were more common in those with versus without prior SARS-CoV-2 infection (9% vs 2%, adjusted odds ratio (aOR) = 5.84[3.8-9.1]), particularly if the prior illness was severe or critical (13% vs 2%, aOR = 10.57[5.5-20.1]) or resulted in inpatient care (17% vs 2%, aOR = 19.3[5.1-72.5]). Side effects were more common in women than men but not otherwise related to demographic factors. Conclusions Vaccine side effects sufficient to prevent usual activities were more common after the second than first dose and varied by vaccine type. First dose side effects were more likely in those with a history of COVID-19 – particularly if that prior illness was severe or associated with inpatient care. These findings may assist clinicians and patients by providing a real-world evaluation of the likelihood of experiencing impactful post-vaccine symptoms.

5.
Open forum infectious diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1898163

ABSTRACT

Background Patient reported outcomes of SARS-CoV-2 infection are an important measure of the full burden of COVID. Here, we examine how 1) infecting genotype and COVID-19 vaccination correlate with FLU-PRO Plus score, including by symptom domains, and 2) FLU-PRO Plus scores predict return to usual activities and health. Methods The EPICC study was implemented to describe the short- and long-term consequences of SARS-CoV-2 infection in a longitudinal, observational cohort. Multivariable linear regression models were run with FLU-PRO Plus scores as the outcome variable and multivariable Cox proportional hazards models evaluated effects of FLU-PRO Plus scores on return to usual health or activities. Results Among the 764 participants included in this analysis, 63% were 18-44 years old, 40% were female, and 51% were white. Being fully vaccinated was associated with lower total scores (β=-0.39 (95% confidence interval (CI) -0.57, -0.21)). The Delta variant was associated with higher total scores (β=0.25 (95% CI 0.05, 0.45)). Participants with higher FLU-PRO Plus scores were less likely to report returning to usual health and activities (Health: hazard ratio (HR) 0.46 (95% CI 0.37, 0.57);Activities: HR 0.56 (95% CI 0.47, 0.67)). Fully vaccinated participants were more likely to report returning to usual activities (HR 1.24 (95% CI 1.04, 1.48)). Conclusions Full SARS-CoV-2 vaccination is associated with decreased severity of patient-reported symptoms across multiple domains, which in turn is likely to be associated with earlier return to usual activities. In addition, infection with the Delta variant was associated with higher FLU-PRO Plus scores than previous variants, even after controlling for vaccination status.

6.
Clin Infect Dis ; 2022 May 24.
Article in English | MEDLINE | ID: covidwho-1860831

ABSTRACT

BACKGROUND: Comparing humoral responses in SARS-CoV-2 vaccinees, those with SARS-CoV-2 infection, or combinations of vaccine/infection ('hybrid immunity'), may clarify predictors of vaccine immunogenicity. METHODS: We studied 2660 U.S. Military Health System beneficiaries with a history of SARS-CoV-2 infection-alone (n = 705), vaccination-alone (n = 932), vaccine-after-infection (n = 869), and vaccine-breakthrough-infection (n = 154). Peak anti-spike-IgG responses through 183 days were compared, with adjustment for vaccine product, demography, and comorbidities. We excluded those with evidence of clinical or sub-clinical SARS-CoV-2 reinfection from all groups. RESULTS: Multivariable regression results indicated vaccine-after-infection anti-spike-IgG responses were higher than infection-alone (p < 0.01), regardless of prior infection severity. An increased time between infection and vaccination was associated with a greater post-vaccination IgG response (p < 0.01). Vaccination-alone elicited a greater IgG response, but more rapid waning of IgG (p < 0.01), compared to infection-alone (p < 0.01). BNT162b2 and mRNA-1273 vaccine-receipt was associated with greater IgG responses compared to JNJ-78436735 (p < 0.01), regardless of infection history. Those with vaccine-after-infection or vaccine-breakthrough-infection had a more durable anti-spike-IgG response compared to infection-alone (p < 0.01). CONCLUSIONS: Vaccine-receipt elicited higher anti-spike-IgG responses than infection-alone, although IgG levels waned faster in those vaccinated (compared to infection-alone). Vaccine-after-infection elicits a greater humoral response compared to vaccine or infection alone; and the timing, but not disease severity, of prior infection predicted these post-vaccination IgG responses. While differences between groups were small in magnitude, these results offer insights into vaccine immunogenicity variations that may help inform vaccination timing strategies.

7.
Sci Transl Med ; 14(645): eabn8543, 2022 05 18.
Article in English | MEDLINE | ID: covidwho-1774930

ABSTRACT

The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms about the effectiveness of current medical countermeasures. To address this concern, we measured the neutralization of the Omicron BA.1 variant pseudovirus by postvaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex was associated with the differences in postvaccination antibody responses. We also evaluated 18 clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/therapy , COVID-19 Vaccines , Humans , Immunization, Passive , Vaccination , Vaccines, Synthetic , mRNA Vaccines
8.
Open Forum Infect Dis ; 9(3): ofab623, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1684764

ABSTRACT

BACKGROUND: 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 highest 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.

9.
Open forum infectious diseases ; 8(Suppl 1):S325-S326, 2021.
Article in English | EuropePMC | ID: covidwho-1602651

ABSTRACT

Background 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 < 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))

10.
Open forum infectious diseases ; 8(Suppl 1):S273-S273, 2021.
Article in English | EuropePMC | ID: covidwho-1602411

ABSTRACT

Background 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))

12.
J Infect Dis ; 224(12): 2010-2019, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1574912

ABSTRACT

BACKGROUND: Characterizing the longevity and quality of cellular immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enhances understanding of coronavirus disease 2019 (COVID-19) immunity that influences clinical outcomes. Prior studies suggest SARS-CoV-2-specific T cells are present in peripheral blood 10 months after infection. Analysis of the function, durability, and diversity of cellular response long after natural infection, over a range of ages and disease phenotypes, is needed to identify preventative and therapeutic interventions. METHODS: We identified participants in our multisite longitudinal, prospective cohort study 12 months after SARS-CoV-2 infection representing a range of disease severity. We investigated function, phenotypes, and frequency of T cells specific for SARS-CoV-2 using intracellular cytokine staining and spectral flow cytometry, and compared magnitude of SARS-CoV-2-specific antibodies. RESULTS: SARS-CoV-2-specific antibodies and T cells were detected 12 months postinfection. Severe acute illness was associated with higher frequencies of SARS-CoV-2-specific CD4 T cells and antibodies at 12 months. In contrast, polyfunctional and cytotoxic T cells responsive to SARS-CoV-2 were identified in participants over a wide spectrum of disease severity. CONCLUSIONS: SARS-CoV-2 infection induces polyfunctional memory T cells detectable at 12 months postinfection, with higher frequency noted in those who experienced severe disease.


Subject(s)
COVID-19/immunology , COVID-19/virology , Immunologic Memory , SARS-CoV-2/immunology , T-Lymphocyte Subsets/immunology , Adult , Antibodies, Viral , Antigens, Viral , Biomarkers , COVID-19/diagnosis , COVID-19/epidemiology , Female , Humans , Immunity, Cellular , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Severity of Illness Index , T-Lymphocyte Subsets/metabolism , Time Factors
13.
Open Forum Infect Dis ; 8(12): ofab556, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1575421

ABSTRACT

BACKGROUND: 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 <45), and obesity (BMI≥30 compared with BMI<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.

16.
Open Forum Infect Dis ; 8(12): ofab517, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1570092

ABSTRACT

BACKGROUND: 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.

17.
Open forum infectious diseases ; 8(Suppl 1):S24-S25, 2021.
Article in English | EuropePMC | ID: covidwho-1564722

ABSTRACT

Background 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

18.
Open forum infectious diseases ; 8(Suppl 1):S331-S332, 2021.
Article in English | EuropePMC | ID: covidwho-1564090

ABSTRACT

Background 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 < 0.001] of hospitalization which remained significant after controlling for other factors [2.97 (95% CI: 1.88-4.69);P < 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))

19.
Open Forum Infect Dis ; 8(12): ofab421, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1560588

ABSTRACT

BACKGROUND: Early recognition of high-risk patients with coronavirus disease 2019 (COVID-19) may improve outcomes. Although many predictive scoring systems exist, their complexity may limit utility in COVID-19. We assessed the prognostic performance of the National Early Warning Score (NEWS) and an age-based modification (NEWS+age) among hospitalized COVID-19 patients enrolled in a prospective, multicenter US Military Health System (MHS) observational cohort study. METHODS: Hospitalized adults with confirmed COVID-19 not requiring invasive mechanical ventilation at admission and with a baseline NEWS were included. We analyzed each scoring system's ability to predict key clinical outcomes, including progression to invasive ventilation or death, stratified by baseline severity (low [0-3], medium [4-6], and high [≥7]). RESULTS: Among 184 included participants, those with low baseline NEWS had significantly shorter hospitalizations (P < .01) and lower maximum illness severity (P < .001). Most (80.2%) of low NEWS vs 15.8% of high NEWS participants required no or at most low-flow oxygen supplementation. Low NEWS (≤3) had a negative predictive value of 97.2% for progression to invasive ventilation or death; a high NEWS (≥7) had high specificity (93.1%) but low positive predictive value (42.1%) for such progression. NEWS+age performed similarly to NEWS at predicting invasive ventilation or death (NEWS+age: area under the receiver operating characteristics curve [AUROC], 0.69; 95% CI, 0.65-0.73; NEWS: AUROC, 0.70; 95% CI, 0.66-0.75). CONCLUSIONS: NEWS and NEWS+age showed similar test characteristics in an MHS COVID-19 cohort. Notably, low baseline scores had an excellent negative predictive value. Given their easy applicability, these scoring systems may be useful in resource-limited settings to identify COVID-19 patients who are unlikely to progress to critical illness.

20.
Open Forum Infect Dis ; 8(11): ofab523, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1528172
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