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  1. Article ; Online: SARS-CoV-2 infection is associated with self-reported post-acute neuropsychological symptoms within six months of follow-up.

    Andronescu, Liana R / Richard, Stephanie A / Scher, Ann I / Lindholm, David A / Mende, Katrin / Ganesan, Anuradha / Huprikar, Nikhil / Lalani, Tahaniyat / Smith, Alfred / Mody, Rupal M / Jones, Milissa U / Bazan, Samantha E / Colombo, Rhonda E / Colombo, Christopher J / Ewers, Evan / Larson, Derek T / Maves, Ryan C / Berjohn, Catherine M / Maldonado, Carlos J /
    English, Caroline / Sanchez Edwards, Margaret / Rozman, Julia S / Rusiecki, Jennifer / Byrne, Celia / Simons, Mark P / Tribble, David / Burgess, Timothy H / Pollett, Simon D / Agan, Brian K

    PloS one

    2024  Volume 19, Issue 4, Page(s) e0297481

    Abstract: Background: Chronic neuropsychological sequelae following SARS-CoV-2 infection, including depression, anxiety, fatigue, and general cognitive difficulties, are a major public health concern. Given the potential impact of long-term neuropsychological ... ...

    Abstract Background: Chronic neuropsychological sequelae following SARS-CoV-2 infection, including depression, anxiety, fatigue, and general cognitive difficulties, are a major public health concern. Given the potential impact of long-term neuropsychological impairment, it is important to characterize the frequency and predictors of this post-infection phenotype.
    Methods: The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal study assessing the impact of SARS-CoV-2 infection in U.S. Military Healthcare System (MHS) beneficiaries, i.e. those eligible for care in the MHS including active duty servicemembers, dependents, and retirees. Four broad areas of neuropsychological symptoms were assessed cross-sectionally among subjects 1-6 months post-infection/enrollment, including: depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), fatigue (PROMIS® Fatigue 7a), and cognitive function (PROMIS® Cognitive Function 8a and PROMIS® Cognitive Function abilities 8a). Multivariable Poisson regression models compared participants with and without SARS-CoV-2 infection history on these measures, adjusting for sex, ethnicity, active-duty status, age, and months post-first positive or enrollment of questionnaire completion (MPFP/E); models for fatigue and cognitive function were also adjusted for depression and anxiety scores.
    Results: The study population included 2383 participants who completed all five instruments within six MPFP/E, of whom 687 (28.8%) had at least one positive SARS-CoV-2 test. Compared to those who had never tested positive for SARS-CoV-2, the positive group was more likely to meet instrument-based criteria for depression (15.4% vs 10.3%, p<0.001), fatigue (20.1% vs 8.0%, p<0.001), impaired cognitive function (15.7% vs 8.6%, p<0.001), and impaired cognitive function abilities (24.3% vs 16.3%, p<0.001). In multivariable models, SARS-CoV-2 positive participants, assessed at an average of 2.7 months after infection, had increased risk of moderate to severe depression (RR: 1.44, 95% CI 1.12-1.84), fatigue (RR: 2.07, 95% CI 1.62-2.65), impaired cognitive function (RR: 1.64, 95% CI 1.27-2.11), and impaired cognitive function abilities (RR: 1.41, 95% CI 1.15-1.71); MPFP/E was not significant.
    Conclusions: Participants with a history of SARS-CoV-2 infection were up to twice as likely to report cognitive impairment and fatigue as the group without prior SARS-CoV-2 infection. These findings underscore the continued importance of preventing SARS-CoV-2 infection and while time since infection/enrollment was not significant through 6 months of follow-up, this highlights the need for additional research into the long-term impacts of COVID-19 to mitigate and reverse these neuropsychological outcomes.
    MeSH term(s) Humans ; Self Report ; COVID-19/complications ; COVID-19/epidemiology ; SARS-CoV-2 ; Follow-Up Studies ; Longitudinal Studies ; Fatigue/epidemiology ; Fatigue/etiology ; Anxiety Disorders
    Language English
    Publishing date 2024-04-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0297481
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A machine learning approach identifies distinct early-symptom cluster phenotypes which correlate with hospitalization, failure to return to activities, and prolonged COVID-19 symptoms.

    Epsi, Nusrat J / Powers, John H / Lindholm, David A / Mende, Katrin / Malloy, Allison / Ganesan, Anuradha / Huprikar, Nikhil / Lalani, Tahaniyat / Smith, Alfred / Mody, Rupal M / Jones, Milissa U / Bazan, Samantha E / Colombo, Rhonda E / Colombo, Christopher J / Ewers, Evan C / Larson, Derek T / Berjohn, Catherine M / Maldonado, Carlos J / Blair, Paul W /
    Chenoweth, Josh / Saunders, David L / Livezey, Jeffrey / Maves, Ryan C / Sanchez Edwards, Margaret / Rozman, Julia S / Simons, Mark P / Tribble, David R / Agan, Brian K / Burgess, Timothy H / Pollett, Simon D

    PloS one

    2023  Volume 18, Issue 2, Page(s) e0281272

    Abstract: Background: Accurate COVID-19 prognosis is a critical aspect of acute and long-term clinical management. We identified discrete clusters of early stage-symptoms which may delineate groups with distinct disease severity phenotypes, including risk of ... ...

    Abstract Background: Accurate COVID-19 prognosis is a critical aspect of acute and long-term clinical management. We identified discrete clusters of early stage-symptoms which may delineate groups with distinct disease severity phenotypes, including risk of developing long-term symptoms and associated inflammatory profiles.
    Methods: 1,273 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative symptom scores (FLU-PRO Plus) were included in this analysis. We employed machine-learning approaches to identify symptom clusters and compared risk of hospitalization, long-term symptoms, as well as peak CRP and IL-6 concentrations.
    Results: We identified three distinct clusters of participants based on their FLU-PRO Plus symptoms: cluster 1 ("Nasal cluster") is highly correlated with reporting runny/stuffy nose and sneezing, cluster 2 ("Sensory cluster") is highly correlated with loss of smell or taste, and cluster 3 ("Respiratory/Systemic cluster") is highly correlated with the respiratory (cough, trouble breathing, among others) and systemic (body aches, chills, among others) domain symptoms. Participants in the Respiratory/Systemic cluster were twice as likely as those in the Nasal cluster to have been hospitalized, and 1.5 times as likely to report that they had not returned-to-activities, which remained significant after controlling for confounding covariates (P < 0.01). Respiratory/Systemic and Sensory clusters were more likely to have symptoms at six-months post-symptom-onset (P = 0.03). We observed higher peak CRP and IL-6 in the Respiratory/Systemic cluster (P < 0.01).
    Conclusions: We identified early symptom profiles potentially associated with hospitalization, return-to-activities, long-term symptoms, and inflammatory profiles. These findings may assist in patient prognosis, including prediction of long COVID risk.
    MeSH term(s) Humans ; COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; Interleukin-6 ; Phenotype ; Hospitalization ; Machine Learning
    Chemical Substances Interleukin-6
    Language English
    Publishing date 2023-02-09
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0281272
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Immune and behavioral correlates of protection against symptomatic post-vaccination SARS-CoV-2 infection.

    Goguet, Emilie / Olsen, Cara H / Meyer, William A / Ansari, Sara / Powers, John H / Conner, Tonia L / Coggins, Si'Ana A / Wang, Wei / Wang, Richard / Illinik, Luca / Sanchez Edwards, Margaret / Jackson-Thompson, Belinda M / Hollis-Perry, Monique / Wang, Gregory / Alcorta, Yolanda / Wong, Mimi A / Saunders, David / Mohammed, Roshila / Balogun, Bolatito /
    Kobi, Priscilla / Kosh, Lakeesha / Bishop-Lilly, Kimberly / Cer, Regina Z / Arnold, Catherine E / Voegtly, Logan J / Fitzpatrick, Maren / Luquette, Andrea E / Malagon, Francisco / Ortega, Orlando / Parmelee, Edward / Davies, Julian / Lindrose, Alyssa R / Haines-Hull, Hannah / Moser, Matthew S / Samuels, Emily C / Rekedal, Marana S / Graydon, Elizabeth K / Malloy, Allison M W / Tribble, David R / Burgess, Timothy H / Campbell, Wesley / Robinson, Sara / Broder, Christopher C / O'Connell, Robert J / Weiss, Carol D / Pollett, Simon / Laing, Eric D / Mitre, Edward

    Frontiers in immunology

    2024  Volume 15, Page(s) 1287504

    Abstract: Introduction: We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine inzfections (PVI) acquired during the first Omicron wave in the United States.: Methods: Serum and saliva samples from 176 vaccinated adults ... ...

    Abstract Introduction: We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine inzfections (PVI) acquired during the first Omicron wave in the United States.
    Methods: Serum and saliva samples from 176 vaccinated adults were collected from October to December of 2021, immediately before the Omicron wave, and assessed for SARS-CoV-2 Spike-specific IgG and IgA binding antibodies (bAb). Sera were also assessed for bAb using commercial assays, and for neutralization activity against several SARS-CoV-2 variants. PVI duration and severity, as well as risk and precautionary behaviors, were assessed by questionnaires.
    Results: Serum anti-Spike IgG levels assessed by research assay, neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against PVIs after multivariable regression analysis. Commercial assays did not perform as well as research assay, likely due to their lower dynamic range.
    Discussion: In the 32 participants that developed PVI, anti-Spike IgG bAbs correlated with lower disease severity and shorter duration of illness.
    MeSH term(s) Adult ; Humans ; COVID-19/prevention & control ; SARS-CoV-2 ; COVID-19 Vaccines ; Antibodies, Viral ; Immunoglobulin G
    Chemical Substances COVID-19 Vaccines ; Antibodies, Viral ; Immunoglobulin G
    Language English
    Publishing date 2024-03-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2024.1287504
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Cellular interferon-gamma and interleukin-2 responses to SARS-CoV-2 structural proteins are broader and higher in those vaccinated after SARS-CoV-2 infection compared to vaccinees without prior SARS-CoV-2 infection.

    Sedegah, Martha / Porter, Chad / Goguet, Emilie / Ganeshan, Harini / Belmonte, Maria / Huang, Jun / Belmonte, Arnel / Inoue, Sandra / Acheampong, Neda / Malloy, Allison M W / Hollis-Perry, Monique / Jackson-Thompson, Belinda / Ramsey, Kathy F / Alcorta, Yolanda / Maiolatesi, Santina E / Wang, Gregory / Reyes, Anatolio E / Illinik, Luca / Sanchez-Edwards, Margaret /
    Burgess, Timothy H / Broder, Christopher C / Laing, Eric D / Pollett, Simon D / Villasante, Eileen / Mitre, Edward / Hollingdale, Michael R

    PloS one

    2022  Volume 17, Issue 10, Page(s) e0276241

    Abstract: Class I- and Class II-restricted epitopes have been identified across the SARS-CoV-2 structural proteome. Vaccine-induced and post-infection SARS-CoV-2 T-cell responses are associated with COVID-19 recovery and protection, but the precise role of T-cell ... ...

    Abstract Class I- and Class II-restricted epitopes have been identified across the SARS-CoV-2 structural proteome. Vaccine-induced and post-infection SARS-CoV-2 T-cell responses are associated with COVID-19 recovery and protection, but the precise role of T-cell responses remains unclear, and how post-infection vaccination ('hybrid immunity') further augments this immunity To accomplish these goals, we studied healthy adult healthcare workers who were (a) uninfected and unvaccinated (n = 12), (b) uninfected and vaccinated with Pfizer-BioNTech BNT162b2 vaccine (2 doses n = 177, one dose n = 1) or Moderna mRNA-1273 vaccine (one dose, n = 1), and (c) previously infected with SARS-CoV-2 and vaccinated (BNT162b2, two doses, n = 6, one dose n = 1; mRNA-1273 two doses, n = 1). Infection status was determined by repeated PCR testing of participants. We used FluoroSpot Interferon-gamma (IFN-γ) and Interleukin-2 (IL-2) assays, using subpools of 15-mer peptides covering the S (10 subpools), N (4 subpools) and M (2 subpools) proteins. Responses were expressed as frequencies (percent positive responders) and magnitudes (spot forming cells/106 cytokine-producing peripheral blood mononuclear cells [PBMCs]). Almost all vaccinated participants with no prior infection exhibited IFN-γ, IL-2 and IFN-γ+IL2 responses to S glycoprotein subpools (89%, 93% and 27%, respectively) mainly directed to the S2 subunit and were more robust than responses to the N or M subpools. However, in previously infected and vaccinated participants IFN-γ, IL-2 and IFN-γ+IL2 responses to S subpools (100%, 100%, 88%) were substantially higher than vaccinated participants with no prior infection and were broader and directed against nine of the 10 S glycoprotein subpools spanning the S1 and S2 subunits, and all the N and M subpools. 50% of uninfected and unvaccinated individuals had IFN-γ but not IL2 or IFN-γ+IL2 responses against one S and one M subpools that were not increased after vaccination of uninfected or SARS-CoV-2-infected participants. Summed IFN-γ, IL-2, and IFN-γ+IL2 responses to S correlated with IgG responses to the S glycoprotein. These studies demonstrated that vaccinations with BNT162b2 or mRNA-1273 results in T cell-specific responses primarily against epitopes in the S2 subunit of the S glycoprotein, and that individuals that are vaccinated after SARS-CoV-2 infection develop broader and greater T cell responses to S1 and S2 subunits as well as the N and M proteins.
    MeSH term(s) Adult ; Humans ; 2019-nCoV Vaccine mRNA-1273 ; Antibodies, Viral ; BNT162 Vaccine ; COVID-19/prevention & control ; Epitopes ; Immunoglobulin G ; Interferon-gamma/immunology ; Interleukin-2/immunology ; Leukocytes, Mononuclear ; Proteome ; SARS-CoV-2 ; Vaccination
    Chemical Substances 2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; Antibodies, Viral ; BNT162 Vaccine ; Epitopes ; Immunoglobulin G ; Interferon-gamma (82115-62-6) ; Interleukin-2 ; Proteome
    Language English
    Publishing date 2022-10-17
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0276241
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Immune and behavioral correlates of protection against symptomatic post-vaccination SARS-CoV-2 infection

    Goguet, Emilie / Olsen, Cara / Meyer, William A / Ansari, Sara / Powers, John H / Conner, Tonia L / Coggins, Si'Ana A / Wang, Wei / Wang, Richard / Illinik, Luca / Sanchez Edwards, Margaret / Jackson-Thompson, Belinda M / Hollis-Perry, Monique / Wang, Gregory / Alcorta, Yolanda / Wong, Mimi A / Saunders, David / Mohammed, Roshila / Balogun, Bolatito /
    Kobi, Priscilla / Kosh, Lakeesha / Bishop-Lilly, Kimberly / Cer, Regina Z / Arnold, Catherine E / Voegtly, Logan J / Fitzpatrick, Maren / Luquette, Andrea E / Malagon, Francisco / Ortega, Orlando / Parmelee, Edward / Davies, Julian / Lindrose, Alyssa R / Haines-Hull, Hannah / Moser, Matthew S / Samuels, Emily C / Tso, Marana S / Graydon, Elizabeth / Malloy, Allison M.W / Tribble, David R / Burgess, Timothy H / Campbell, Wesley / Robinson, Sara / Broder, Christopher C / O'Connell, Robert J / Weiss, Carol D / Pollett, Simon / Laing, Eric D / Mitre, Edward

    medRxiv

    Abstract: Background: We sought to determine immune and behavioral pre-infection correlates of protection against SARS-CoV-2 post-vaccine infections in a joint analysis of epidemiological and immunological cohort data. Methods: Serum and saliva samples from 176 ... ...

    Abstract Background: We sought to determine immune and behavioral pre-infection correlates of protection against SARS-CoV-2 post-vaccine infections in a joint analysis of epidemiological and immunological cohort data. Methods: Serum and saliva samples from 176 BNT162b2-vaccinated adults in the Prospective Assessment of SARS-CoV-2 Seroconversion study were collected between October and December 2021 and assessed for serum and saliva levels of Wuhan-1 wild-type (WT) SARS-CoV-2 Spike (S)-specific IgG and IgA binding antibodies (bAb) using a multiplex microsphere-based immunoassay (MMIA). Serum samples were also assessed for WT receptor binding domain (RBD)-specific bAb by two commercial assays, BA.1 S-specific IgG bAb by MMIA, and neutralization activity against D614G, Delta (B.1.617.2), and Omicron BA.1 and BA.1.1 variants using a lentiviral pseudovirus neutralization assay. After the Fall 2021 visit, participants reported all positive PCR and/or antigen tests for SARS-CoV-2. Duration, severity, and type of symptoms, as well as risk exposures and adherence to precautionary measures, were assessed by questionnaires during the Spring 2022 visit. Results: Thirty-two participants (18.2%) developed symptomatic post-vaccination SARS-CoV-2 infections (PVI) between December 7, 2021 and April 1, 2022. Pre-infection WT (geometric mean (GM) of 3,863 vs 2,736 binding antibody unit [BAU]/ml, uninfected vs PVI, p=0.0098) and BA.1 (GM of 276.9 vs 179.9 arbitrary bAb unit [AU]/ml, uninfected vs PVI, p=0.04) anti-S IgG bAb levels measured by MMIA and neutralizing titers (NT) against BA.1 (GM titer [GMT] of 493.6 vs 286.2, uninfected vs PVI, p=0.0313) and BA.1.1 (GMT of 552.0 vs 302.5, uninfected vs PVI, p=0.021) were significantly higher in individuals that did not develop PVIs. WT anti-S bAb levels greater than 5,000 BAU/ml were associated with > 90% protection against symptomatic PVI. In individuals that developed PVI, WT anti-S IgG bAb levels correlated with lower disease severity scores (ρ= -0.3859, p=0.032) and shorter duration of clinical disease (ρ= -0.5273, p=0.0023). WT anti-RBD bAb levels measured by commercial assays correlated strongly with bAb levels measured by MMIA (ρ=0.8239, p<0.0001 and ρ=0.6929, p<0.0001, Roche and Siemens assays, respectively), but did not reach statistical significance for correlation with protection against PVI. Home risk score, but neither work nor home precautionary measures, correlated strongly with risk of PVI (mean score of 20.77 vs 47.33, uninfected vs PVI respectively, p<0.0001). Conclusions: Anti-S IgG bAb levels (directed against either WT or Omicron BA.1 subvariant) and NTs served as correlates of protection against symptomatic SARS-CoV-2 infection. Anti-S (WT) IgG bAb levels remained a significant correlate of protection against PVIs when adjusting for demography and risk behavior. Results of this study also suggest that commercial assays for anti-S bAb may need to be reformatted to enable detection of higher maximum values for use as predictors of increased susceptibility to SARS-CoV-2 infection.
    Keywords covid19
    Language English
    Publishing date 2023-08-28
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2023.08.25.23294626
    Database COVID19

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