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  • 1
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    Impact of coinfection status and comorbidity on disease severity in adult emergency department patients with influenza B
    Wiley ; 2022
    In:  Influenza and Other Respiratory Viruses Vol. 16, No. 2 ( 2022-03), p. 236-246
    Details
    In: Influenza and Other Respiratory Viruses, Wiley, Vol. 16, No. 2 ( 2022-03), p. 236-246
    Abstract: Influenza B accounts for approximately one fourth of the seasonal influenza burden. However, research on the importance of influenza B has received less attention compared to influenza A. We sought to describe the association of both coinfections and comorbidities with disease severity among adults presenting to emergency departments (ED) with influenza B. Methods Nasopharyngeal samples from patients found to be influenza B positive in four US and three Taiwanese ED over four consecutive influenza seasons (2014–2018) were tested for coinfections with the ePlex RP RUO panel. Multivariable logistic regressions were fitted to model adjusted odds ratios (aOR) for two severity outcomes separately: hospitalization and pneumonia diagnosis. Adjusting for demographic factors, underlying health conditions, and the National Early Warning Score (NEWS), we estimated the association of upper respiratory coinfections and comorbidity with disease severity (including hospitalization or pneumonia). Results Amongst all influenza B positive individuals ( n  = 446), presence of another upper respiratory pathogen was associated with an increased likelihood of hospitalization (aOR = 2.99 [95% confidence interval (95% CI): 1.14–7.85, p  = 0.026]) and pneumonia (aOR = 2.27 [95% CI: 1.25–4.09, p  = 0.007]). Chronic lung diseases (CLD) were the strongest predictor for hospitalization (aOR = 3.43 [95% CI: 2.98–3.95, p   〈  0.001]), but not for pneumonia (aOR = 1.73 [95% CI: 0.80–3.78, p  = 0.166]). Conclusion Amongst ED patients infected with influenza B, the presence of other upper respiratory pathogens was independently associated with both hospitalization and pneumonia; presence of CLD was also associated with hospitalization. These findings may be informative for ED clinician's in managing patients infected with influenza B.
    Type of Medium: Online Resource
    ISSN: 1750-2640 , 1750-2659
    URL: Issue
    URL: Article
    DOI: 10.1111/irv.v16.2
    DOI: 10.1111/irv.12907
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2272349-3
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  • 2
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    Evolution of Influenza A H3N2 viruses in two consecutive seasons of genomic Surveillance, 2021-2023
    Oxford University Press (OUP) ; 2023
    In:  Open Forum Infectious Diseases
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP)
    Abstract: The circulation and the genomic evolution of influenza A H3N2 viruses during the 2021/2022 and 2022/2023 seasons were studied and associated with infection outcomes. Methods Remnant influenza A positive samples following standard of care testing from patients across the Johns Hopkins Health System (JHHS) were used for the study. Samples were randomly selected for whole viral genome sequencing. The sequence-based pEpitope model was used to estimate the predicted vaccine efficacy (pVE) for circulating H3N2 viruses. Clinical data were collected and associated with viral genomic data. Results A total of 121,683 respiratory specimens were tested for influenza at JHHS between September 1st, 2021, and December 31st, 2022. Among them, 6,071 (4.99%) tested positive for influenza A. Out of these, 805 samples were randomly selected for sequencing, with HA segments characterized for 610 samples. Among the characterized samples, 581 were H3N2 (95.2%). Phylogenetic analysis of HA segments revealed the exclusive circulation of H3N2 viruses with HA segments of the 3C.2a1b.2a.2 clade. Analysis of a total of 445 complete H3N2 genomes revealed reassortments; 200 out of 227 of the 2022/2023 season genomes (88.1%) were found to have reassorted with clade 3C.2a1b.1a. The pVE was estimated to be -42.53% for the 2021/2022 season and 30.27% for the 2022/2023 season. No differences in clinical presentations or admissions were observed between the two seasons. Conclusions The increased numbers of cases and genomic diversity of influenza A H3N2 during the 2022/2023 season were not associated with a change in disease severity compared to the previous influenza season.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofad577
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2757767-3
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  • 3
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    Monocyte distribution width as a pragmatic screen for SARS-CoV-2 or influenza infection
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-12-13)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-12-13)
    Abstract: Monocyte distribution width (MDW) is a novel marker of monocyte activation, which is known to occur in the immune response to viral pathogens. Our objective was to determine the performance of MDW and other leukocyte parameters as screening tests for SARS-CoV-2 and influenza infection. This was a prospective cohort analysis of adult patients who underwent complete blood count (CBC) and SARS-CoV-2 or influenza testing in an Emergency Department (ED) between January 2020 and July 2021. The primary outcome was SARS-CoV-2 or influenza infection. Secondary outcomes were measures of severity of illness including inpatient hospitalization, critical care admission, hospital lengths of stay and mortality. Descriptive statistics and test performance measures were evaluated for monocyte percentage, MDW, white blood cell (WBC) count, and neutrophil to lymphocyte ratio (NLR). 3,425 ED patient visits were included. SARS-CoV-2 testing was performed during 1,922 visits with a positivity rate of 5.4%; influenza testing was performed during 2,090 with a positivity rate of 2.3%. MDW was elevated in patients with SARS-Cov-2 (median 23.0U; IQR 20.5–25.1) or influenza (median 24.1U; IQR 22.0–26.9) infection, as compared to those without (18.9U; IQR 17.4–20.7 and 19.1U; 17.4–21, respectively, P   〈  0.001). Monocyte percentage, WBC and NLR values were within normal range in patients testing positive for either virus. MDW identified SARS-CoV-2 and influenza positive patients with an area under the curve (AUC) of 0.83 (95% CI 0.79–0.86) and 0.83 (95% CI 0.77–0.88), respectively. At the accepted cut-off value of 20U for MDW, sensitivities were 83.7% (95% CI 76.5–90.8%) for SARS-CoV-2 and 89.6% (95% CI 80.9–98.2%) for influenza, compared to sensitivities below 45% for monocyte percentage, WBC and NLR. MDW negative predictive values were 98.6% (95% CI 98.0–99.3%) and 99.6% (95% CI 99.3–100.0%) respectively for SARS-CoV-2 and influenza. Monocyte Distribution Width (MDW), available as part of a routine complete blood count (CBC) with differential, may be a useful indicator of SARS-CoV-2 or influenza infection.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-24978-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 4
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    Uptake of public health measures and vaccine acceptance during the COVID-19 pandemic in rural Zambia
    Informa UK Limited ; 2022
    In:  Human Vaccines & Immunotherapeutics Vol. 18, No. 7 ( 2022-12-30)
    Details
    In: Human Vaccines & Immunotherapeutics, Informa UK Limited, Vol. 18, No. 7 ( 2022-12-30)
    Type of Medium: Online Resource
    ISSN: 2164-5515 , 2164-554X
    URL: Article
    DOI: 10.1080/21645515.2022.2153538
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2022
    detail.hit.zdb_id: 2664177-X
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  • 5
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    Differential Cytokine Signatures of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Influenza Infection Highlight Key Differences in Pathobiology
    Oxford University Press (OUP) ; 2022
    In:  Clinical Infectious Diseases Vol. 74, No. 2 ( 2022-01-29), p. 254-262
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 74, No. 2 ( 2022-01-29), p. 254-262
    Abstract: Several inflammatory cytokines are upregulated in severe coronavirus disease 2019 (COVID-19). We compared cytokines in COVID-19 versus influenza to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19, we examined the relationship of BMI to cytokines associated with severe disease. Methods Thirty-seven cytokines and chemokines were measured in plasma from 135 patients with COVID-19, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was used to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was used to identify cytokines that mediate the effect of BMI and age on disease severity. Results Interleukin-18 (IL-18), IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) were significantly increased in COVID-19 versus influenza patients, whereas granulocyte macrophage colony-stimulating factor, interferon-γ (IFN-γ), IFN-λ1, IL-10, IL-15, and monocyte chemoattractant protein 2 were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18, IL-6, and TNF-α were elevated in severe COVID-19, but not in severe influenza. Random forest analysis identified high IL-6 and low IFN-λ1 levels as the most distinct between severe COVID-19 and severe influenza. Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity. Conclusions These findings point to activation of fundamentally different innate immune pathways in severe acute respiratory syndrome coronavirus 2 and influenza infection, and emphasize drivers of severe COVID-19 to focus both mechanistic and therapeutic investigations.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciab376
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2002229-3
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  • 6
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    The Influenza B Virus Victoria and Yamagata Lineages Display Distinct Cell Tropism and Infection-Induced Host Gene Expression in Human Nasal Epithelial Cell Cultures
    MDPI AG ; 2023
    In:  Viruses Vol. 15, No. 9 ( 2023-09-20), p. 1956-
    Details
    In: Viruses, MDPI AG, Vol. 15, No. 9 ( 2023-09-20), p. 1956-
    Abstract: Understanding Influenza B virus infections is of critical importance in our efforts to control severe influenza and influenza-related diseases. Until 2020, two genetic lineages of influenza B virus—Yamagata and Victoria—circulated in the population. These lineages are antigenically distinct, but the differences in virus replication or the induction of host cell responses after infection have not been carefully studied. Recent IBV clinical isolates of both lineages were obtained from influenza surveillance efforts of the Johns Hopkins Center of Excellence in Influenza Research and Response and characterized in vitro. B/Victoria and B/Yamagata clinical isolates were recognized less efficiently by serum from influenza-vaccinated individuals in comparison to the vaccine strains. B/Victoria lineages formed smaller plaques on MDCK cells compared to B/Yamagata, but infectious virus production in primary human nasal epithelial cell (hNEC) cultures showed no differences. While ciliated epithelial cells were the dominant cell type infected by both lineages, B/Victoria lineages had a slight preference for MUC5AC-positive cells, and B/Yamagata lineages infected more basal cells. Finally, while both lineages induced a strong interferon response 48 h after infection of hNEC cultures, the B/Victoria lineages showed a much stronger induction of interferon-related signaling pathways compared to B/Yamagata. This demonstrates that the two influenza B virus lineages differ not only in their antigenic structure but also in their ability to induce host innate immune responses.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v15091956
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2516098-9
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  • 7
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    Facility-based surveillance for influenza and respiratory syncytial virus in rural Zambia
    Springer Science and Business Media LLC ; 2021
    In:  BMC Infectious Diseases Vol. 21, No. 1 ( 2021-12)
    Details
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: While southern Africa experiences among the highest mortality rates from respiratory infections, the burden of influenza and respiratory syncytial virus (RSV) in rural areas is poorly understood. Methods We implemented facility-based surveillance in Macha, Zambia. Outpatients and inpatients presenting with influenza-like illness (ILI) underwent testing for influenza A, influenza B, and RSV and were prospectively followed for 3 to 5 weeks to assess clinical course. Log-binomial models assessed correlates of infection and clinical severity. Results Between December 2018 and December 2019, 17% of all outpatients presented with ILI and 16% of inpatients were admitted with an acute respiratory complaint. Influenza viruses and RSV were detected in 17% and 11% of outpatient participants with ILI, and 23% and 16% of inpatient participants with ILI, respectively. Influenza (July–September) and RSV (January-April) prevalence peaks were temporally distinct. RSV (relative risk [RR]: 1.78; 95% confidence interval [CI] 1.51–2.11), but not influenza, infection was associated with severe disease among patients with ILI. Underweight patients with ILI were more likely to be infected with influenza A (prevalence ratio [PR]: 1.72; 95% CI 1.04–2.87) and to have severe influenza A infections (RR: 2.49; 95% CI 1.57–3.93). Conclusions Populations in rural Zambia bear a sizeable burden of viral respiratory infections and severe disease. The epidemiology of infections in this rural area differs from that reported from urban areas in Zambia.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    URL: Article
    DOI: 10.1186/s12879-021-06677-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041550-3
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  • 8
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    Anti-PF4 antibodies associated with disease severity in COVID-19
    Proceedings of the National Academy of Sciences ; 2022
    In:  Proceedings of the National Academy of Sciences Vol. 119, No. 47 ( 2022-11-22)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 47 ( 2022-11-22)
    Abstract: Severe COVID-19 is characterized by a prothrombotic state associated with thrombocytopenia, with microvascular thrombosis being almost invariably present in the lung and other organs at postmortem examination. We evaluated the presence of antibodies to platelet factor 4 (PF4)–polyanion complexes using a clinically validated immunoassay in 100 hospitalized patients with COVID-19 with moderate or severe disease (World Health Organization score, 4 to 10), 25 patients with acute COVID-19 visiting the emergency department, and 65 convalescent individuals. Anti-PF4 antibodies were detected in 95 of 100 hospitalized patients with COVID-19 (95.0%) irrespective of prior heparin treatment, with a mean optical density value of 0.871 ± 0.405 SD (range, 0.177 to 2.706). In contrast, patients hospitalized for severe acute respiratory disease unrelated to COVID-19 had markedly lower levels of the antibodies. In a high proportion of patients with COVID-19, levels of all three immunoglobulin (Ig) isotypes tested (IgG, IgM, and IgA) were simultaneously elevated. Antibody levels were higher in male than in female patients and higher in African Americans and Hispanics than in White patients. Anti-PF4 antibody levels were correlated with the maximum disease severity score and with significant reductions in circulating platelet counts during hospitalization. In individuals convalescent from COVID-19, the antibody levels returned to near-normal values. Sera from patients with COVID-19 induced higher levels of platelet activation than did sera from healthy blood donors, but the results were not correlated with the levels of anti-PF4 antibodies. These results demonstrate that the vast majority of patients with severe COVID-19 develop anti-PF4 antibodies, which may play a role in the clinical complications of COVID-19.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2213361119
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2022
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 9
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    Respiratory viruses in rural Zambia before and during the COVID ‐19 pandemic
    Wiley ; 2022
    In:  Tropical Medicine & International Health Vol. 27, No. 7 ( 2022-07), p. 647-654
    Details
    In: Tropical Medicine & International Health, Wiley, Vol. 27, No. 7 ( 2022-07), p. 647-654
    Abstract: With the emergence of the COVID‐19 pandemic, restrictions were implemented globally to control the virus. Data on respiratory pathogens in sub‐Saharan Africa during the COVID‐19 pandemic are scarce. This analysis was conducted to evaluate patterns of respiratory pathogens in rural Zambia before and during the first year of the pandemic. Methods Surveillance was established in December 2018 at Macha Hospital in southern Zambia. Patients with respiratory symptoms in the outpatient and inpatient clinics were recruited. Nasopharyngeal samples were collected and tested for respiratory pathogens. The prevalence of respiratory symptoms and pathogens was evaluated and compared in the first (December 10, 2018–December 9, 2019) and second (December 10, 2019–November 30, 2020) years of surveillance. Results Outpatient visits and admissions for respiratory illness significantly decreased from the first to second year, especially among children. SARS‐CoV‐2 was not detected from any participants in Year 2. Among outpatients and inpatients with respiratory symptoms, the prevalence of respiratory syncytial virus and influenza viruses decreased from the first to second year. In contrast, the prevalence of rhinovirus/enterovirus, metapneumovirus and parainfluenza virus increased. Conclusions The epidemiology of respiratory viruses in rural Zambia changed during the first year of the COVID‐19 pandemic, suggesting that public health interventions may have had an impact on the introduction and circulation of respiratory pathogens in this area.
    Type of Medium: Online Resource
    ISSN: 1360-2276 , 1365-3156
    URL: Issue
    URL: Article
    DOI: 10.1111/tmi.v27.7
    DOI: 10.1111/tmi.13781
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2018112-7
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  • 10
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    Distinct Cytokine and Chemokine Dysregulation in Hospitalized Children With Acute Coronavirus Disease 2019 and Multisystem Inflammatory Syndrome With Similar Levels of Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 Shedding
    Oxford University Press (OUP) ; 2021
    In:  The Journal of Infectious Diseases Vol. 224, No. 4 ( 2021-08-16), p. 606-615
    Details
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 224, No. 4 ( 2021-08-16), p. 606-615
    Abstract: Multisystem inflammatory syndrome in children (MIS-C) is a severe clinical phenotype of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that remains poorly understood. Methods Hospitalized children & lt;18 years of age with suspected coronavirus disease 2019 (COVID-19) (N = 53) were recruited into a prospective cohort study; 32 had confirmed COVID-19, with 16 meeting the US Centers for Disease Control criteria for MIS-C. Differences in nasopharyngeal viral ribonucleic acid (RNA) levels, SARS-CoV-2 seropositivity, and cytokine/chemokine profiles were examined, including after adjustments for age and sex. Results The median ages for those with and without MIS-C were 8.7 years (interquartile range [IQR], 5.5–13.9) and 2.2 years (IQR, 1.1–10.5), respectively (P = .18), and nasopharyngeal levels of SARS-CoV-2 RNA did not differ significantly between the 2 groups (median 63 848.25 copies/mL versus 307.1 copies/mL, P = .66); 75% of those with MIS-C were antibody positive compared with 44% without (P = .026). Levels of 14 of 37 cytokines/chemokines (interleukin [IL] -1RA, IL-2RA, IL-6, IL-8, tumor necrosis factor-α, IL-10, IL-15, IL-18, monocyte chemoattractant protein [MCP]-1, IP-10, macrophage-inflammatory protein [MIP] -1α, MCP-2, MIP-1β, eotaxin) were significantly higher in children with MIS-C compared to those without, irrespective of age or sex (false discovery rate & lt;0.05; P & lt; .05). Conclusions The distinct pattern of heightened cytokine/chemokine dysregulation observed with MIS-C, compared with acute COVID-19, occurs across the pediatric age spectrum and with similar levels of nasopharyngeal SARS-CoV-2 RNA.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Article
    DOI: 10.1093/infdis/jiab285
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1473843-0
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