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1.
Cell Rep Med ; 3(2): 100529, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1649941

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant emerged in November 2021 and consists of several mutations within the spike. We use serum from mRNA-vaccinated individuals to measure neutralization activity against omicron in a live-virus assay. At 2-4 weeks after a primary series of vaccinations, we observe a 30-fold reduction in neutralizing activity against omicron. Six months after the initial two-vaccine doses, sera from naive vaccinated subjects show no neutralizing activity against omicron. In contrast, COVID-19-recovered individuals 6 months after receiving the primary series of vaccinations show a 22-fold reduction, with the majority of the subjects retaining neutralizing antibody responses. In naive individuals following a booster shot (third dose), we observe a 14-fold reduction in neutralizing activity against omicron, and over 90% of subjects show neutralizing activity. These findings show that a third dose is required to provide robust neutralizing antibody responses against the omicron variant.


Subject(s)
/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Vaccination/methods , Adult , Aged , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/virology , Chlorocebus aethiops , Cohort Studies , Female , Humans , Immunization, Secondary/methods , Male , Middle Aged , Mutation , Neutralization Tests , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vero Cells , Young Adult
4.
Open forum infectious diseases ; 8(Suppl 1):755-755, 2021.
Article in English | EuropePMC | ID: covidwho-1564902

ABSTRACT

Background A significant burden of disease exists for adults infected with influenza (flu) and SARS-CoV-2, which causes COVID-19. However, data are limited comparing outcomes between hospitalized adults infected with these viruses. Methods Over the course of 3 consecutive winter respiratory viral seasons, adults ≥ 50 years of age admitted with acute respiratory tract infections (ARI) and adults of any age with COPD or CHF-related admissions were enrolled from 2 Atlanta area hospitals. For the 2018-19 and 2019-20 seasons, participants were approached in the hospital. If the participant enrolled, nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected and tested using BioFire® FilmArray® respiratory panel. Due to the COVID-19 pandemic in 2020-21 and limitations involving participant contact, only NP standard of care (SOC) swabs were collected. A comprehensive medical chart review was completed for each subject which encompassed data on their hospitalization, past medical history, and vaccination history. Co-infected patients were excluded from the analyses. Results Of the eligible participants, 118 were flu positive (three RSV-influenza co-infections were excluded) and 527 were COVID-19 positive. Median age was lower for the flu cohort at 62 (IQR 56-71) than those with COVID-19 (67, IQR 59-77) (p < 0.0001). Length of stay (LOS) was shorter in flu-infected patients (median 3 d, IQR 2-6), but was longer for COVID-19 patients (median 5 d, IQR 3-10). ICU admission occurred in 20% of those with flu, and among those admitted to the ICU mechanical ventilation (MV) occurred in 12.5%. ICU admission and MV was significantly higher for those with COVID-19, with 28% of patients admitted to the ICU and 47% of those requiring MV. Among patients with COVID-19, 8.9% died. This was significantly higher than that of flu (3.4%) (p=0.008). Hospital discharge occurred more frequently to a nursing home or LTCF with COVID-19 (10.3%) than with flu (0%) (p< 0.0001). Table 1. Breakdown of age, hospitalization course, and discharge disposition for participants diagnosed with influenza or COVID-19 during hospitalization. Conclusion COVID-19 resulted in a longer hospital admission, a greater chance of ICU admission and MV as compared to flu. Additionally, COVID-19 participants had a high rate of discharge to a nursing home/LTCF and a significantly higher risk of death. While the clinical course was not as severe as COVID-19, influenza contributed a significant burden. Disclosures David L. Swerdlow, MD, Pfizer Vaccines (Employee) Robin Hubler, MS, Pfizer Inc. (Employee) Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Meissa Vaccines (Other Financial or Material Support, Co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.) Larry Anderson, MD, ADVI (Consultant)Bavarian Nordic (Consultant)Novavax (Consultant)Phizer (Grant/Research Support, Scientific Research Study Investigator)Sciogen (Research Grant or Support) Nadine Rouphael, MD, pfizer, sanofi, lily, quidel, merck (Grant/Research Support) Nadine Rouphael, MD, Lilly (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support;Merck (Individual(s) Involved: Self): Emory study PI, Grant/Research Support;Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant;Pfizer (Individual(s) Involved: Self): Grant/Research Support, I conduct as co-PI the RSV PFIZER study at Emory;Quidel (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support;Sanofi Pasteur (Individual(s) Involved: Self): Chair phase 3 COVID vaccine, Grant/Research Support Evan J. Anderson, MD, GSK (Scientific Research Study Investigator)Janssen (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)Kentucky Bioprocessing, Inc (Advisor or Review Panel m mber)MedImmune (Scientific Research Study Investigator)Medscape (Consultant)Merck (Scientific Research Study Investigator)Micron (Scientific Research Study Investigator)PaxVax (Scientific Research Study Investigator)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Scientific Research Study Investigator)

5.
Open forum infectious diseases ; 8(Suppl 1):752-753, 2021.
Article in English | EuropePMC | ID: covidwho-1564762

ABSTRACT

Background The burden of Respiratory Syncytial Virus (RSV)-associated hospitalization in adults is incompletely understood. The COVID-19 pandemic has resulted in multiple public health measures (e.g., social distancing, handwashing, masking) to decrease SARS-CoV-2 transmission, which could impact RSV-associated hospitalizations. We sought to compare RSV-associated hospitalizations from 2 pre- and one mid-COVID-19 winter viral respiratory seasons. Methods We conducted an IRB-approved prospective surveillance at two Atlanta-area hospitals during the winter respiratory viral seasons from Oct 2018–Apr 2021 for adults ≥ 50 years of age admitted with acute respiratory infections (ARI) and adults of any age with COPD or CHF-related admissions. Adults were eligible if they were residents of an 8 county region surrounding Atlanta, Georgia. Those with symptoms > 14 days were excluded. Standard of care test results were included. Asymptomatic adults ≥ 50 years of age were enrolled as controls in Seasons 1 and 2. Nasopharyngeal swabs from cases and controls were tested for RSV using BioFire® FilmArray® Respiratory Viral Panel (RVP). We compared the demographic features and outcomes of RSV+ cases and controls. Results RSV was detected in 71/2,728 (2.6%) hospitalized adults with ARI, CHF, or COPD and 4/466 (0.9%) controls. In Season 1, RSV occurred in 5.9% (35/596 patients), in Season 2 3.6% (35/970 patients), but in only 0.09% (1/1,162 patients) in Season 3 (P < 0.001 for both seasons). RSV detection in Season 3 was similar to RSV detection among controls during Seasons 1 and 2 (P=0.6). Median age of cases and controls was 67 years (Table 1). Of cases with RSV 11% were admitted to the ICU and two required mechanical ventilation. The majority of hospitalized patients were discharged home (95.8%) with a median length of hospitalization of three days (IQR 2-7). Table 1. Demographic Features and Outcomes Among RSV-Positive Hospitalized Adults. Conclusion Over 3 seasons, RSV was detected in 2.6% of adults admitted to the hospital with ARI, CHF or COPD. The rate of RSV dramatically declined during the 2020-21 winter respiratory viral season, likely due to public health measures implemented in response to COVID-19. Disclosures David L. Swerdlow, MD, Pfizer Vaccines (Employee) Robin Hubler, MS, Pfizer Inc. (Employee) Larry Anderson, MD, ADVI (Consultant)Bavarian Nordic (Consultant)Novavax (Consultant)Phizer (Grant/Research Support, Scientific Research Study Investigator)Sciogen (Research Grant or Support) Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Meissa Vaccines (Other Financial or Material Support, Co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.) Nadine Rouphael, MD, pfizer, sanofi, lily, quidel, merck (Grant/Research Support) Nadine Rouphael, MD, Lilly (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support;Merck (Individual(s) Involved: Self): Emory study PI, Grant/Research Support;Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant;Pfizer (Individual(s) Involved: Self): Grant/Research Support, I conduct as co-PI the RSV PFIZER study at Emory;Quidel (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support;Sanofi Pasteur (Individual(s) Involved: Self): Chair phase 3 COVID vaccine, Grant/Research Support Evan J. Anderson, MD, GSK (Scientific Research Study Investigator)Janssen (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)Kentucky Bioprocessing, Inc (Advisor or Review Panel member)MedImmune (Scientific Research Study Investigator)Medscape (Consultant)Merck (Scientific Research Study Investigator)Micron (Scientific Research Study Investigator)PaxVax (Scientific Research Study Investigator)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Scientific Research Study Investigator)

6.
Open forum infectious diseases ; 8(Suppl 1):757-758, 2021.
Article in English | EuropePMC | ID: covidwho-1564711

ABSTRACT

Background Acute respiratory tract infections (ARIs) are a significant cause of morbidity in adults. Influenza is associated with about 490,600 hospitalizations and 34,200 deaths in the US in the 2018-2019 season. The burden of rhinovirus among adults hospitalized with ARI is less well known. We compared the burden of influenza and rhinovirus from 2 consecutive winter respiratory viral seasons in hospitalized adults and healthy controls pre-COVID-19 and one season mid-COVID-19 to determine the impact of rhinovirus as a pathogen. Methods From Oct 2018 to Apr 2021, prospective surveillance of adults ≥50 years old admitted with ARI or COPD/CHF exacerbations at any age was conducted at two Atlanta hospitals. Adults were eligible if they lived within an eight-county region around Atlanta and if their symptom duration was < 14 days. In the seasons from Oct 2018 to Mar 2020, asymptomatic adults ≥50 years old were enrolled as controls. Standard of care test results were included and those enrolled contributed nasopharyngeal swabs that were tested for respiratory pathogens using BioFire® FilmArray® Respiratory Viral Panel (RVP). Results During the first two seasons, 1566 hospitalized adults were enrolled. Rhinovirus was detected in 7.5% (118) and influenza was detected in 7.7% (121). Rhinovirus was also detected in 2.2% of 466 healthy adult controls while influenza was detected in 0%. During Season 3, the peak of the COVID-19 pandemic, influenza declined to 0% of ARI hospitalizations. Rhinovirus also declined (p=0.01) but still accounted for 5.1% of all ARIs screened (Figure 1). Rhinovirus was detected at a greater rate in Season 3 than in asymptomatic controls in the first 2 seasons (p=0.008). In the first two seasons, Influenza was detected in 8.6% (24/276) of those admitted to the ICU. Rhinovirus was detected in 6.1% (17/276) of those admitted to the ICU but declined to 3.1% (8/258) in Season 3. Figure 1. Percent Positive Cases of Influenza and Rhinovirus between Season 1&2 (hospitalized and healthy controls) vs Season 3 (hospitalized) Conclusion Dramatic declines occurred in influenza in adults hospitalized with ARI, CHF, or COPD in Atlanta during the COVID-19 pandemic and with enhanced public health measures. Although rhinovirus declined during the COVID-19 pandemic, it continued to be identified at a rate higher than in historical controls. Additional data are needed to understand the role of rhinovirus in adult ARI, CHF, and COPD exacerbations. Disclosures David L. Swerdlow, MD, Pfizer Vaccines (Employee) Robin Hubler, MS, Pfizer Inc. (Employee) Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Meissa Vaccines (Other Financial or Material Support, Co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.) Larry Anderson, MD, ADVI (Consultant)Bavarian Nordic (Consultant)Novavax (Consultant)Phizer (Grant/Research Support, Scientific Research Study Investigator)Sciogen (Research Grant or Support) Nadine Rouphael, MD, pfizer, sanofi, lily, quidel, merck (Grant/Research Support) Nadine Rouphael, MD, Lilly (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support;Merck (Individual(s) Involved: Self): Emory study PI, Grant/Research Support;Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant;Pfizer (Individual(s) Involved: Self): Grant/Research Support, I conduct as co-PI the RSV PFIZER study at Emory;Quidel (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support;Sanofi Pasteur (Individual(s) Involved: Self): Chair phase 3 COVID vaccine, Grant/Research Support Evan J. Anderson, MD, GSK (Scientific Research Study Investigator)Janssen (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)Kentucky Bioprocessing, Inc (Advisor or Review Panel me ber)MedImmune (Scientific Research Study Investigator)Medscape (Consultant)Merck (Scientific Research Study Investigator)Micron (Scientific Research Study Investigator)PaxVax (Scientific Research Study Investigator)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Scientific Research Study Investigator)

7.
Science ; 369(6508): 1210-1220, 2020 09 04.
Article in English | MEDLINE | ID: covidwho-704393

ABSTRACT

Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators-including EN-RAGE, TNFSF14, and oncostatin M-which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , COVID-19 , Cytokines/blood , DNA, Bacterial/blood , Dendritic Cells/immunology , Dendritic Cells/metabolism , Female , Flow Cytometry , HLA-DR Antigens/analysis , Humans , Immunity , Immunity, Innate , Immunoglobulins/blood , Immunoglobulins/immunology , Inflammation Mediators/blood , Interferon Type I/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Lipopolysaccharides/blood , Male , Myeloid Cells/immunology , Myeloid Cells/metabolism , Pandemics , SARS-CoV-2 , Signal Transduction , Single-Cell Analysis , Systems Biology , TOR Serine-Threonine Kinases/metabolism , Transcription, Genetic , Transcriptome
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