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2.
JCI Insight ; 2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1637818

ABSTRACT

Why Multisystem Inflammatory Syndrome in Children (MIS-C) develops after SARS-CoV-2 infection in a subset of children is unknown. We hypothesized that aberrant virus52 specific T-cell responses contribute to MIS-C pathogenesis. We quantified SARS-CoV-2 reactive T-cells, serologic responses against major viral proteins, and cytokine responses from plasma and peripheral blood mononuclear cells in children with convalescent COVID-19, acute MIS-C, and healthy controls. Children with MIS-C had significantly lower virus-specific CD4+ and CD8+ T-cell responses to major SARS-CoV-2 antigens compared with children convalescing from COVID-19. Further, T-cell responses in participants with MIS-C were similar to or lower than those in healthy controls. Serologic responses against spike receptor binding domain (RBD), full-length spike, and nucleocapsid were similar among convalescent COVID-19 and MIS-C, suggesting functional B cell responses. Cytokine profiling demonstrated predominant Th1 polarization of CD4+ T-cells from children with convalescent COVID-19 and MIS-C, although cytokine production was reduced in MIS-C. Our findings support a role for constrained induction of anti-SARS-CoV-2-specific T-cells in the pathogenesis of MIS-C.

3.
Pediatrics ; 149(1):1-12, 2022.
Article in English | Academic Search Complete | ID: covidwho-1602637

ABSTRACT

OBJECTIVES: Describe population-based rates and risk factors for pediatric severe coronavirus disease 2019 (COVID-19) (ie, ICU admission, invasive mechanical ventilation, or death). METHODS: During March 2020 to May 2021, the COVID-19-Associated Hospitalization Surveillance Network identified 3106 children hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection in 14 states. Among 2293 children primarily admitted for COVID-19, multivariable generalized estimating equations generated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) of the associations between demographic and medical characteristics ed from patient electronic medical records and severe COVID-19. We calculated age-adjusted cumulative population-based rates of severe COVID-19 among all children. RESULTS: Approximately 30% of hospitalized children had severe COVID-19;0.5% died during hospitalization. Among hospitalized children aged <2 years, chronic lung disease (aRR: 2.2;95% CI: 1.1-4.3), neurologic disorders (aRR: 2.0;95% CI: 1.5-2.6), cardiovascular disease (aRR: 1.7;95% CI: 1.2-2.3), prematurity (aRR: 1.6;95% CI: 1.1-2.2), and airway abnormality (aRR: 1.6;95% CI: 1.1-2.2) were associated with severe COVID-19. Among hospitalized children aged 2 to 17 years, feeding tube dependence (aRR: 2.0;95% CI: 1.5-2.5), diabetes mellitus (aRR: 1.9;95% CI: 1.6-2.3) and obesity (aRR: 1.2;95% CI: 1.0-1.4) were associated with severe COVID-19. Severe COVID-19 occurred among 12.0 per 100 000 children overall and was highest among infants, Hispanic children, and non-Hispanic Black children. CONCLUSIONS: Results identify children at potentially higher risk of severe COVID-19 who may benefit from prevention efforts, including vaccination. Rates establish a baseline for monitoring changes in pediatric illness severity after increased availability of COVID-19 vaccines and the emergence of new variants. [ FROM AUTHOR] Copyright of Pediatrics is the property of American Academy of Pediatrics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

6.
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)

7.
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)

8.
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)

9.
Ann Intern Med ; 174(10): 1409-1419, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1515633

ABSTRACT

BACKGROUND: The COVID-19 pandemic has caused substantial morbidity and mortality. OBJECTIVE: To describe monthly clinical trends among adults hospitalized with COVID-19. DESIGN: Pooled cross-sectional study. SETTING: 99 counties in 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET). PATIENTS: U.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during 1 March to 31 December 2020. MEASUREMENTS: Monthly hospitalizations, intensive care unit (ICU) admissions, and in-hospital death rates per 100 000 persons in the population; monthly trends in weighted percentages of interventions, including ICU admission, mechanical ventilation, and vasopressor use, among an age- and site-stratified random sample of hospitalized case patients. RESULTS: Among 116 743 hospitalized adults with COVID-19, the median age was 62 years, 50.7% were male, and 40.8% were non-Hispanic White. Monthly rates of hospitalization (105.3 per 100 000 persons), ICU admission (20.2 per 100 000 persons), and death (11.7 per 100 000 persons) peaked during December 2020. Rates of all 3 outcomes were highest among adults aged 65 years or older, males, and Hispanic or non-Hispanic Black persons. Among 18 508 sampled hospitalized adults, use of remdesivir and systemic corticosteroids increased from 1.7% and 18.9%, respectively, in March to 53.8% and 74.2%, respectively, in December. Frequency of ICU admission, mechanical ventilation, and vasopressor use decreased from March (37.8%, 27.8%, and 22.7%, respectively) to December (20.5%, 12.3%, and 12.8%, respectively); use of noninvasive respiratory support increased from March to December. LIMITATION: COVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country. CONCLUSION: Rates of COVID-19-associated hospitalization, ICU admission, and death were highest in December 2020, corresponding with the third peak of the U.S. pandemic. The frequency of intensive interventions for management of hospitalized patients decreased over time. These data provide a longitudinal assessment of clinical trends among adults hospitalized with COVID-19 before widespread implementation of COVID-19 vaccines. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.


Subject(s)
COVID-19/therapy , Hospitalization/trends , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Age Distribution , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/ethnology , COVID-19/mortality , Critical Care/trends , Cross-Sectional Studies , Female , Humans , Intensive Care Units/trends , Length of Stay/trends , Male , Middle Aged , Pandemics , Respiration, Artificial/trends , SARS-CoV-2 , United States/epidemiology , Vasoconstrictor Agents/therapeutic use , Young Adult
10.
Lancet Infect Dis ; 21(5): 581-582, 2021 05.
Article in English | MEDLINE | ID: covidwho-1510472
11.
MMWR Morb Mortal Wkly Rep ; 70(43): 1513-1519, 2021 Oct 29.
Article in English | MEDLINE | ID: covidwho-1498053

ABSTRACT

In mid-June 2021, B.1.671.2 (Delta) became the predominant variant of SARS-CoV-2, the virus that causes COVID-19, circulating in the United States. As of July 2021, the Delta variant was responsible for nearly all new SARS-CoV-2 infections in the United States.* The Delta variant is more transmissible than previously circulating SARS-CoV-2 variants (1); however, whether it causes more severe disease in adults has been uncertain. Data from the CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system for COVID-19-associated hospitalizations, were used to examine trends in severe outcomes in adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 during periods before (January-June 2021) and during (July-August 2021) Delta variant predominance. COVID-19-associated hospitalization rates among all adults declined during January-June 2021 (pre-Delta period), before increasing during July-August 2021 (Delta period). Among sampled nonpregnant hospitalized COVID-19 patients with completed medical record abstraction and a discharge disposition during the pre-Delta period, the proportion of patients who were admitted to an intensive care unit (ICU), received invasive mechanical ventilation (IMV), or died while hospitalized did not significantly change from the pre-Delta period to the Delta period. The proportion of hospitalized COVID-19 patients who were aged 18-49 years significantly increased, from 24.7% (95% confidence interval [CI] = 23.2%-26.3%) of all hospitalizations in the pre-Delta period, to 35.8% (95% CI = 32.1%-39.5%, p<0.01) during the Delta period. When examined by vaccination status, 71.8% of COVID-19-associated hospitalizations in the Delta period were in unvaccinated adults. Adults aged 18-49 years accounted for 43.6% (95% CI = 39.1%-48.2%) of all hospitalizations among unvaccinated adults during the Delta period. No difference was observed in ICU admission, receipt of IMV, or in-hospital death among nonpregnant hospitalized adults between the pre-Delta and Delta periods. However, the proportion of unvaccinated adults aged 18-49 years hospitalized with COVID-19 has increased as the Delta variant has become more predominant. Lower vaccination coverage in this age group likely contributed to the increase in hospitalized patients during the Delta period. COVID-19 vaccination is critical for all eligible adults, including those aged <50 years who have relatively low vaccination rates compared with older adults.


Subject(s)
COVID-19/therapy , COVID-19/virology , Hospitalization/statistics & numerical data , SARS-CoV-2/isolation & purification , Severity of Illness Index , Adolescent , Adult , Aged , COVID-19/diagnosis , COVID-19/epidemiology , Female , Humans , Laboratories , Male , Middle Aged , SARS-CoV-2/genetics , United States/epidemiology , Young Adult
12.
Pediatrics ; 2021 Dec 22.
Article in English | MEDLINE | ID: covidwho-1484903

ABSTRACT

OBJECTIVES: Describe population-based rates and risk factors for severe coronavirus disease 2019 (COVID-19) (ie, ICU admission, invasive mechanical ventilation, or death) among hospitalized children. METHODS: During March 2020 to May 2021, the COVID-19-Associated Hospitalization Surveillance Network identified 3106 children hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection in 14 states. Among 2293 children primarily admitted for COVID-19, multivariable generalized estimating equations generated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) of the associations between demographic and medical characteristics abstracted from medical records and severe COVID-19. We calculated age-adjusted cumulative population-based rates of severe COVID-19 among all children. RESULTS: Approximately 30% of hospitalized children had severe COVID-19; 0.5% died during hospitalization. Among hospitalized children aged <2 years, chronic lung disease (aRR: 2.2; 95% CI: 1.1-4.3), neurologic disorders (aRR: 2.0; 95% CI: 1.5‒2.6), cardiovascular disease (aRR: 1.7; 95% CI: 1.2‒2.3), prematurity (aRR: 1.6; 95% CI: 1.1‒2.2), and airway abnormality (aRR: 1.6; 95% CI: 1.1‒2.2) were associated with severe COVID-19. Among hospitalized children aged 2 to 17 years, feeding tube dependence (aRR: 2.0; 95% CI: 1.5‒2.5), diabetes mellitus (aRR: 1.9; 95% CI: 1.6‒2.3) and obesity (aRR: 1.2; 95% CI: 1.0‒1.4) were associated with severe COVID-19. Severe COVID-19 occurred among 12.0 per 100 000 children overall and was highest among infants, Hispanic children, and non-Hispanic Black children. CONCLUSIONS: Results identify children at potentially higher risk of severe COVID-19 who may benefit from prevention efforts, including vaccination. Rates establish a baseline for monitoring changes in pediatric illness severity after increased availability of COVID-19 vaccines and the emergence of new variants.

13.
JAMA Netw Open ; 4(10): e2130479, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1482074

ABSTRACT

Importance: Racial and ethnic minority groups are disproportionately affected by COVID-19. Objectives: To evaluate whether rates of severe COVID-19, defined as hospitalization, intensive care unit (ICU) admission, or in-hospital death, are higher among racial and ethnic minority groups compared with non-Hispanic White persons. Design, Setting, and Participants: This cross-sectional study included 99 counties within 14 US states participating in the COVID-19-Associated Hospitalization Surveillance Network. Participants were persons of all ages hospitalized with COVID-19 from March 1, 2020, to February 28, 2021. Exposures: Laboratory-confirmed COVID-19-associated hospitalization, defined as a positive SARS-CoV-2 test within 14 days prior to or during hospitalization. Main Outcomes and Measures: Cumulative age-adjusted rates (per 100 000 population) of hospitalization, ICU admission, and death by race and ethnicity. Rate ratios (RR) were calculated for each racial and ethnic group compared with White persons. Results: Among 153 692 patients with COVID-19-associated hospitalizations, 143 342 (93.3%) with information on race and ethnicity were included in the analysis. Of these, 105 421 (73.5%) were 50 years or older, 72 159 (50.3%) were male, 28 762 (20.1%) were Hispanic or Latino, 2056 (1.4%) were non-Hispanic American Indian or Alaska Native, 7737 (5.4%) were non-Hispanic Asian or Pacific Islander, 40 806 (28.5%) were non-Hispanic Black, and 63 981 (44.6%) were White. Compared with White persons, American Indian or Alaska Native, Latino, Black, and Asian or Pacific Islander persons were more likely to have higher cumulative age-adjusted rates of hospitalization, ICU admission, and death as follows: American Indian or Alaska Native (hospitalization: RR, 3.70; 95% CI, 3.54-3.87; ICU admission: RR, 6.49; 95% CI, 6.01-7.01; death: RR, 7.19; 95% CI, 6.47-7.99); Latino (hospitalization: RR, 3.06; 95% CI, 3.01-3.10; ICU admission: RR, 4.20; 95% CI, 4.08-4.33; death: RR, 3.85; 95% CI, 3.68-4.01); Black (hospitalization: RR, 2.85; 95% CI, 2.81-2.89; ICU admission: RR, 3.17; 95% CI, 3.09-3.26; death: RR, 2.58; 95% CI, 2.48-2.69); and Asian or Pacific Islander (hospitalization: RR, 1.03; 95% CI, 1.01-1.06; ICU admission: RR, 1.91; 95% CI, 1.83-1.98; death: RR, 1.64; 95% CI, 1.55-1.74). Conclusions and Relevance: In this cross-sectional analysis, American Indian or Alaska Native, Latino, Black, and Asian or Pacific Islander persons were more likely than White persons to have a COVID-19-associated hospitalization, ICU admission, or in-hospital death during the first year of the US COVID-19 pandemic. Equitable access to COVID-19 preventive measures, including vaccination, is needed to minimize the gap in racial and ethnic disparities of severe COVID-19.


Subject(s)
COVID-19/ethnology , Health Status Disparities , Hospital Mortality , Hospitalization/statistics & numerical data , Intensive Care Units/statistics & numerical data , Adult , Age Distribution , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2 , United States/epidemiology
14.
Nat Immunol ; 22(11): 1452-1464, 2021 11.
Article in English | MEDLINE | ID: covidwho-1454797

ABSTRACT

There is limited understanding of the viral antibody fingerprint following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children. Herein, SARS-CoV-2 proteome-wide immunoprofiling of children with mild/moderate or severe coronavirus disease 2019 (COVID-19) versus multisystem inflammatory syndrome in children versus hospitalized control patients revealed differential cytokine responses, IgM/IgG/IgA epitope diversity, antibody binding and avidity. Apart from spike and nucleocapsid, IgG/IgA recognized epitopes in nonstructural protein (NSP) 2, NSP3, NSP12-NSP14 and open reading frame (ORF) 3a-ORF9. Peptides representing epitopes in NSP12, ORF3a and ORF8 demonstrated SARS-CoV-2 serodiagnosis. Antibody-binding kinetics with 24 SARS-CoV-2 proteins revealed antibody parameters that distinguish children with mild/moderate versus severe COVID-19 or multisystem inflammatory syndrome in children. Antibody avidity to prefusion spike correlated with decreased illness severity and served as a clinical disease indicator. The fusion peptide and heptad repeat 2 region induced SARS-CoV-2-neutralizing antibodies in rabbits. Thus, we identified SARS-CoV-2 antibody signatures in children associated with disease severity and delineate promising serodiagnostic and virus neutralization targets. These findings might guide the design of serodiagnostic assays, prognostic algorithms, therapeutics and vaccines in this important but understudied population.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/complications , COVID-19/immunology , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/immunology , Adolescent , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , COVID-19/diagnosis , Child , Child, Preschool , Disease Progression , Epitopes/metabolism , Female , Hospitalization , Humans , Immunity, Humoral , Immunoglobulin A/metabolism , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Male , Prognosis , Proteome , Severity of Illness Index , Systemic Inflammatory Response Syndrome/diagnosis
15.
MMWR Morb Mortal Wkly Rep ; 70(36): 1255-1260, 2021 Sep 10.
Article in English | MEDLINE | ID: covidwho-1441397

ABSTRACT

Although COVID-19-associated hospitalizations and deaths have occurred more frequently in adults,† COVID-19 can also lead to severe outcomes in children and adolescents (1,2). Schools are opening for in-person learning, and many prekindergarten children are returning to early care and education programs during a time when the number of COVID-19 cases caused by the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, is increasing.§ Therefore, it is important to monitor indicators of severe COVID-19 among children and adolescents. This analysis uses Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET)¶ data to describe COVID-19-associated hospitalizations among U.S. children and adolescents aged 0-17 years. During March 1, 2020-August 14, 2021, the cumulative incidence of COVID-19-associated hospitalizations was 49.7 per 100,000 children and adolescents. The weekly COVID-19-associated hospitalization rate per 100,000 children and adolescents during the week ending August 14, 2021 (1.4) was nearly five times the rate during the week ending June 26, 2021 (0.3); among children aged 0-4 years, the weekly hospitalization rate during the week ending August 14, 2021, was nearly 10 times that during the week ending June 26, 2021.** During June 20-July 31, 2021, the hospitalization rate among unvaccinated adolescents (aged 12-17 years) was 10.1 times higher than that among fully vaccinated adolescents. Among all hospitalized children and adolescents with COVID-19, the proportions with indicators of severe disease (such as intensive care unit [ICU] admission) after the Delta variant became predominant (June 20-July 31, 2021) were similar to those earlier in the pandemic (March 1, 2020-June 19, 2021). Implementation of preventive measures to reduce transmission and severe outcomes in children is critical, including vaccination of eligible persons, universal mask wearing in schools, recommended mask wearing by persons aged ≥2 years in other indoor public spaces and child care centers,†† and quarantining as recommended after exposure to persons with COVID-19.§§.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Hospitalization/statistics & numerical data , Hospitalization/trends , Adolescent , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Child , Child, Preschool , Humans , Infant , Infant, Newborn , SARS-CoV-2/isolation & purification , Severity of Illness Index , United States/epidemiology , Vaccination/statistics & numerical data
16.
PLoS One ; 16(9): e0257622, 2021.
Article in English | MEDLINE | ID: covidwho-1438350

ABSTRACT

OBJECTIVES: Some studies suggested more COVID-19-associated hospitalizations among racial and ethnic minorities. To inform public health practice, the COVID-19-associated Hospitalization Surveillance Network (COVID-NET) quantified associations between race/ethnicity, census tract socioeconomic indicators, and COVID-19-associated hospitalization rates. METHODS: Using data from COVID-NET population-based surveillance reported during March 1-April 30, 2020 along with socioeconomic and denominator data from the US Census Bureau, we calculated COVID-19-associated hospitalization rates by racial/ethnic and census tract-level socioeconomic strata. RESULTS: Among 16,000 COVID-19-associated hospitalizations, 34.8% occurred among non-Hispanic White (White) persons, 36.3% among non-Hispanic Black (Black) persons, and 18.2% among Hispanic or Latino (Hispanic) persons. Age-adjusted COVID-19-associated hospitalization rate were 151.6 (95% Confidence Interval (CI): 147.1-156.1) in census tracts with >15.2%-83.2% of persons living below the federal poverty level (high-poverty census tracts) and 75.5 (95% CI: 72.9-78.1) in census tracts with 0%-4.9% of persons living below the federal poverty level (low-poverty census tracts). Among White, Black, and Hispanic persons living in high-poverty census tracts, age-adjusted hospitalization rates were 120.3 (95% CI: 112.3-128.2), 252.2 (95% CI: 241.4-263.0), and 341.1 (95% CI: 317.3-365.0), respectively, compared with 58.2 (95% CI: 55.4-61.1), 304.0 (95%: 282.4-325.6), and 540.3 (95% CI: 477.0-603.6), respectively, in low-poverty census tracts. CONCLUSIONS: Overall, COVID-19-associated hospitalization rates were highest in high-poverty census tracts, but rates among Black and Hispanic persons were high regardless of poverty level. Public health practitioners must ensure mitigation measures and vaccination campaigns address needs of racial/ethnic minority groups and people living in high-poverty census tracts.


Subject(s)
COVID-19 , Health Status Disparities , Hospitalization , Minority Groups , SARS-CoV-2 , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19/therapy , Female , Humans , Male , Middle Aged , United States/epidemiology
17.
Exp Biol Med (Maywood) ; : 15353702211046835, 2021 Sep 26.
Article in English | MEDLINE | ID: covidwho-1438228

ABSTRACT

This study sought to evaluate the candidacy of plasma osteopontin (OPN) as a biomarker of COVID-19 severity and multisystem inflammatory condition in children (MIS-C) in children. A retrospective analysis of 26 children (0-21 years of age) admitted to Children's Healthcare of Atlanta with a diagnosis of COVID-19 between March 17 and May 26, 2020 was undertaken. The patients were classified into three categories based on COVID-19 severity levels: asymptomatic or minimally symptomatic (control population, admitted for other non-COVID-19 conditions), mild/moderate, and severe COVID-19. A fourth category of children met the Centers for Disease Control and Prevention's case definition for MIS-C. Residual blood samples were analyzed for OPN, a marker of inflammation using commercial ELISA kits (R&D), and results were correlated with clinical data. This study demonstrates that OPN levels are significantly elevated in children hospitalized with moderate and severe COVID-19 and MIS-C compared to OPN levels in mild/asymptomatic children. Further, OPN differentiated among clinical levels of severity in COVID-19, while other inflammatory markers including maximum erythrocyte sedimentation rate, C-reactive protein and ferritin, minimum lymphocyte and platelet counts, soluble interleukin-2R, and interleukin-6 did not. We conclude OPN is a potential biomarker of COVID-19 severity and MIS-C in children that may have future clinical utility. The specificity and positive predictive value of this marker for COVID-19 and MIS-C are areas for future larger prospective research studies.

18.
N Engl J Med ; 385(19): 1774-1785, 2021 Nov 04.
Article in English | MEDLINE | ID: covidwho-1434206

ABSTRACT

BACKGROUND: At interim analysis in a phase 3, observer-blinded, placebo-controlled clinical trial, the mRNA-1273 vaccine showed 94.1% efficacy in preventing coronavirus disease 2019 (Covid-19). After emergency use of the vaccine was authorized, the protocol was amended to include an open-label phase. Final analyses of efficacy and safety data from the blinded phase of the trial are reported. METHODS: We enrolled volunteers who were at high risk for Covid-19 or its complications; participants were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 µg) or placebo, 28 days apart, at 99 centers across the United States. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The data cutoff date was March 26, 2021. RESULTS: The trial enrolled 30,415 participants; 15,209 were assigned to receive the mRNA-1273 vaccine, and 15,206 to receive placebo. More than 96% of participants received both injections, 2.3% had evidence of SARS-CoV-2 infection at baseline, and the median follow-up was 5.3 months in the blinded phase. Vaccine efficacy in preventing Covid-19 illness was 93.2% (95% confidence interval [CI], 91.0 to 94.8), with 55 confirmed cases in the mRNA-1273 group (9.6 per 1000 person-years; 95% CI, 7.2 to 12.5) and 744 in the placebo group (136.6 per 1000 person-years; 95% CI, 127.0 to 146.8). The efficacy in preventing severe disease was 98.2% (95% CI, 92.8 to 99.6), with 2 cases in the mRNA-1273 group and 106 in the placebo group, and the efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0% (95% CI, 56.6 to 68.5), with 214 cases in the mRNA-1273 group and 498 in the placebo group. Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions. No safety concerns were identified. CONCLUSIONS: The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Adolescent , Adult , Aged , COVID-19/epidemiology , COVID-19 Vaccines/adverse effects , Follow-Up Studies , Humans , Immunization, Secondary , Incidence , Intention to Treat Analysis , Male , Middle Aged , Patient Acuity , Single-Blind Method , Treatment Outcome , Young Adult
19.
Vaccines (Basel) ; 9(9)2021 Sep 21.
Article in English | MEDLINE | ID: covidwho-1430994

ABSTRACT

A paucity of data exists evaluating a guardian's intent to vaccinate their child against COVID-19 in the United States. We administered 102 first (April-November 2020) and 45 second (December-January 2020-2021) surveys to guardians of children (<18 years) who had a laboratory-confirmed diagnosis of COVID-19 and assessed their intent to give a COVID-19 vaccine to their child, when one becomes available. The first and second surveys of the same cohort of guardians were conducted before and following the press releases detailing the adult Pfizer-BioNTech and Moderna Phase 3 results. Both surveys included an intent-to-vaccinate question using the subjective language of "if a safe and effective vaccine" became available, and a second question was added to second surveys using the objective language of "would prevent 19 of 20 people from getting disease". When using subjective language, 24 of 45 (53%) guardians endorsed vaccine administration for their children in the first survey, which decreased to 21 (46%) in the second survey. When adding objective language, acceptance of vaccination increased to 31 (69%, p = 0.03). Common reasons for declining vaccination were concerns about adverse effects and/or vaccine safety. Providing additional facts on vaccine efficacy increased vaccine acceptance. Evidence-based strategies are needed to increase pediatric COVID-19 vaccine uptake.

20.
Microbiol Spectr ; 9(2): e0045821, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1398599

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic with over 152 million cases and 3.19 million deaths reported by early May 2021. Understanding the serological response to SARS-CoV-2 is critical to determining the burden of infection and disease (coronavirus disease 2019 [COVID-19]) and transmission dynamics. We developed a capture IgM assay because it should have better sensitivity and specificity than the commonly used indirect assay. Here, we report the development and performance of a capture IgM enzyme-linked immunosorbent assay (ELISA) and a companion indirect IgG ELISA for the spike (S) and nucleocapsid (N) proteins and the receptor-binding domain (RBD) of S. We found that among the IgM ELISAs, the S ELISA was positive in 76% of 55 serum samples from SARS-CoV-2 PCR-positive patients, the RBD ELISA was positive in 55% of samples, and the N ELISA was positive in 15% of samples. The companion indirect IgG ELISAs were positive for S in 89% of the 55 serum samples, RBD in 78%, and N in 85%. While the specificities for IgM RBD, S, and N ELISAs and IgG S and RBD ELISAs were 97% to 100%, the specificity of the N IgG ELISA was lower (89%). RBD-specific IgM antibodies became undetectable by 3 to 6 months, and S IgM reached low levels at 6 months. The corresponding IgG S, RBD, and N antibodies persisted with some decreases in levels over this time period. These capture IgM ELISAs and the companion indirect IgG ELISAs should enhance serologic studies of SARS-CoV-2 infections. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has inflicted tremendous loss of lives, overwhelmed health care systems, and disrupted all aspects of life worldwide since its emergence in Wuhan, China, in December 2019. Detecting current and past infection by PCR or serology is important to understanding and controlling SARS-CoV-2. With increasing prevalence of past infection or vaccination, IgG antibodies are less helpful in diagnosing a current infection. IgM antibodies indicate a more recent infection and can supplement PCR diagnosis. We report an alternative method, capture IgM, to detect serum IgM antibodies, which should be more sensitive and specific than most currently used methods. We describe this capture IgM assay and a companion indirect IgG assay for the SARS-CoV-2 spike (S), nucleocapsid (N), and receptor-binding domain (RBD) proteins. These assays can add value to diagnostic and serologic studies of coronavirus disease 2019 (COVID-19).


Subject(s)
Antibodies, Viral/immunology , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Immunoglobulin M/blood , SARS-CoV-2/immunology , COVID-19/therapy , Coronavirus Nucleocapsid Proteins/immunology , Enzyme-Linked Immunosorbent Assay/methods , Humans , Immunization, Passive , Immunoglobulin G/blood , Phosphoproteins/immunology , Sensitivity and Specificity , Serologic Tests/methods , Spike Glycoprotein, Coronavirus/immunology
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