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1.
J Immunotoxicol ; 18(1): 23-29, 2021 12.
Article in English | MEDLINE | ID: covidwho-1593522

ABSTRACT

The coronavirus SARS-CoV-2 of 2019 (COVID-19) causes a pandemic that has been diagnosed in more than 70 million people worldwide. Mild-to-moderate COVID-19 symptoms include coughing, fever, myalgia, shortness of breath, and acute inflammatory lung injury (ALI). In contrast, acute respiratory distress syndrome (ARDS) and respiratory failure occur in patients diagnosed with severe COVID-19. ARDS is mediated, at least in part, by a dysregulated inflammatory response due to excessive levels of circulating cytokines, a condition known as the "cytokine-storm syndrome." Currently, there are FDA-approved therapies that attenuate the dysregulated inflammation that occurs in COVID-19 patients, such as dexamethasone or other corticosteroids and IL-6 inhibitors, including sarilumab, tocilizumab, and siltuximab. However, the efficacy of these treatments have been shown to be inconsistent. Compounds that activate the vagus nerve-mediated cholinergic anti-inflammatory reflex, such as the α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuate ARDS/inflammatory lung injury by decreasing the extracellular levels of high mobility group box-1 (HMGB1) in the airways and the circulation. It is possible that HMGB1 may be an important mediator of the "cytokine-storm syndrome." Notably, high plasma levels of HMGB1 have been reported in patients diagnosed with severe COVID-19, and there is a significant negative correlation between HMGB1 plasma levels and clinical outcomes. Nicotine can activate the cholinergic anti-inflammatory reflex, which attenuates the up-regulation and the excessive release of pro-inflammatory cytokines/chemokines. Therefore, we hypothesize that low molecular weight compounds that activate the cholinergic anti-inflammatory reflex, such as nicotine or GTS-21, may represent a potential therapeutic approach to attenuate the dysregulated inflammatory responses in patients with severe COVID-19.


Subject(s)
Benzylidene Compounds/pharmacology , COVID-19/drug therapy , Cholinergic Agents/pharmacology , Inflammation/drug therapy , Nicotine/metabolism , Pyridines/pharmacology , SARS-CoV-2/physiology , Tobacco Use Disorder/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Cigarette Smoking/adverse effects , Dexamethasone/therapeutic use , HMGB1 Protein/blood , Humans , Pandemics , alpha7 Nicotinic Acetylcholine Receptor/agonists
2.
Crit Care Med ; 49(7): 1149-1158, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1494026

ABSTRACT

OBJECTIVES: Circulating nucleosomes and their component histones have been implicated as pathogenic in sepsis and acute respiratory distress syndrome in adults. However, their role in pediatric acute respiratory distress syndrome is unknown. DESIGN: We performed a prospective cohort study in children with acute respiratory distress syndrome, with plasma collection within 24 hours of acute respiratory distress syndrome onset. We associated nucleosome levels with severity of acute respiratory distress syndrome and with nonpulmonary organ failures and tested for association of nucleosomes with PICU mortality and ventilator-free days at 28 days in univariate and multivariable analyses. We also performed proteomics of DNA-bound plasma proteins in a matched case-control study of septic children with and without acute respiratory distress syndrome in order to identify specific histone proteins elevated in acute respiratory distress syndrome. SETTING: Large academic tertiary-care PICU. PATIENTS: Intubated children meeting Berlin criteria for acute respiratory distress syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We enrolled 333 children with acute respiratory distress syndrome, with 69 nonsurvivors (21%). Plasma nucleosomes were correlated with acute respiratory distress syndrome severity and with the number of nonpulmonary organ failures at acute respiratory distress syndrome onset. Nucleosomes were higher (p < 0.001) in nonsurvivors (0.40 [interquartile range, 0.20-0.71] arbitrary units) relative to survivors (0.10 [interquartile range, 0.04-0.25] arbitrary units). Nucleosomes were associated with PICU mortality in multivariable analysis (adjusted odds ratio 1.84 per 1 sd increase; 95% CI, 1.38-2.45; p < 0.001). Nucleosomes were also associated with a lower probability of being extubated alive by day 28 after multivariable adjustment (adjusted subdistribution hazard ratio, 0.74; 95% CI, 0.63-0.88; p = 0.001). Proteomic analysis demonstrated higher levels of the core nucleosome histones H2A, H2B, H3, and H4 in septic children with acute respiratory distress syndrome, relative to septic children without acute respiratory distress syndrome. CONCLUSIONS: Plasma nucleosomes are associated with acute respiratory distress syndrome severity, nonpulmonary organ failures, and worse outcomes in pediatric acute respiratory distress syndrome.


Subject(s)
Histones/blood , Nucleosomes/metabolism , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/mortality , Adolescent , Airway Extubation , Case-Control Studies , Child , Child, Preschool , DNA/blood , Female , Hospital Mortality , Humans , Intensive Care Units, Pediatric , Male , Multiple Organ Failure/mortality , Prognosis , Prospective Studies , Proteomics , Respiration, Artificial , Respiratory Distress Syndrome/complications , Sepsis/blood , Sepsis/complications , Severity of Illness Index , Survival Rate
3.
Clin Infect Dis ; 73(3): e699-e709, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1387800

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary. METHODS: We present 6 months of data from a longitudinal seroprevalence study of 3276 UK healthcare workers (HCWs). Serial measurements of SARS-CoV-2 anti-nucleocapsid and anti-spike IgG were obtained. Interval censored survival analysis was used to investigate the duration of detectable responses. Additionally, Bayesian mixed linear models were used to investigate anti-nucleocapsid waning. RESULTS: Anti-spike IgG levels remained stably detected after a positive result, for example, in 94% (95% credibility interval [CrI] 91-96%) of HCWs at 180 days. Anti-nucleocapsid IgG levels rose to a peak at 24 (95% CrI 19-31) days post first polymerase chain reaction (PCR)-positive test, before beginning to fall. Considering 452 anti-nucleocapsid seropositive HCWs over a median of 121 days from their maximum positive IgG titer, the mean estimated antibody half-life was 85 (95% CrI 81-90) days. Higher maximum observed anti-nucleocapsid titers were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity, and prior self-reported symptoms were independently associated with higher maximum anti-nucleocapsid levels and increasing age and a positive PCR test undertaken for symptoms with longer anti-nucleocapsid half-lives. CONCLUSIONS: SARS-CoV-2 anti-nucleocapsid antibodies wane within months and fall faster in younger adults and those without symptoms. However, anti-spike IgG remains stably detected. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Viral , Antibody Formation , Bayes Theorem , Health Personnel , Humans , Immunoglobulin G , Seroepidemiologic Studies
4.
Lancet ; 397(10286): 1711-1724, 2021 05 08.
Article in English | MEDLINE | ID: covidwho-1301056

ABSTRACT

BACKGROUND: COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England. METHODS: We conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region. FINDINGS: Of 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 [95% CI 1·07-1·09]), Black group (1·08 [1·06-1·09]), and mixed ethnicity group (1·04 [1·02-1·05]) and was decreased in the other ethnicity group (0·77 [0·76-0·78]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 [1·94-2·04]), Black group (1·69 [1·62-1·77]), mixed ethnicity group (1·49 [1·39-1·59]), and other ethnicity group (1·20 [1·14-1·28]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 [1·41-1·55], Black group 1·78 [1·67-1·90], mixed ethnicity group 1·63 [1·45-1·83], other ethnicity group 1·54 [1·41-1·69]), COVID-19-related ICU admission (2·18 [1·92-2·48], 3·12 [2·65-3·67], 2·96 [2·26-3·87], 3·18 [2·58-3·93]), and death (1·26 [1·15-1·37], 1·51 [1·31-1·71], 1·41 [1·11-1·81], 1·22 [1·00-1·48]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories. INTERPRETATION: Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination. FUNDING: Medical Research Council.


Subject(s)
COVID-19/ethnology , Ethnicity/statistics & numerical data , Hospitalization/statistics & numerical data , Intensive Care Units/statistics & numerical data , Patient Admission/statistics & numerical data , Adult , COVID-19/epidemiology , COVID-19/mortality , Cohort Studies , England , Humans , Observational Studies as Topic , Survival Analysis
5.
MMWR Morb Mortal Wkly Rep ; 70(24): 879-887, 2021 Jun 18.
Article in English | MEDLINE | ID: covidwho-1278792

ABSTRACT

Early during the COVID-19 pandemic, nearly two thirds of unpaid caregivers of adults reported adverse mental or behavioral health symptoms, compared with approximately one third of noncaregivers† (1). In addition, 27% of parents of children aged <18 years reported that their mental health had worsened during the pandemic (2). To examine mental health during the COVID-19 pandemic among U.S. adults on the basis of their classification as having a parenting role (i.e., unpaid persons caring for children and adolescents aged <18 years, referred to as children in this report) or being an unpaid caregiver of adults (i.e., persons caring for adults aged ≥18 years),§ CDC analyzed data from cross-sectional surveys that were administered during December 2020 and February-March 2021 for The COVID-19 Outbreak Public Evaluation (COPE) Initiative.¶ Respondents were categorized as parents only, caregivers of adults only, parents-caregivers (persons in both roles), or nonparents/noncaregivers (persons in neither role). Adjusted odds ratios (aORs) for any adverse mental health symptoms, particularly suicidal ideation, were higher among all respondents who were parents, caregivers of adults, or both compared with respondents who were nonparents/noncaregivers and were highest among persons in both roles (parents-caregivers) (any adverse mental health symptoms: aOR = 5.1, 95% confidence interval [CI] = 4.1-6.2; serious suicidal ideation: aOR = 8.2, 95% CI = 6.5-10.4). These findings highlight that parents and caregivers, especially those balancing roles both as parents and caregivers, experienced higher levels of adverse mental health symptoms during the COVID-19 pandemic than adults without these responsibilities. Caregivers who had someone to rely on for support had lower odds of experiencing any adverse mental health symptoms. Additional measures are needed to improve mental health among parents, caregivers, and parents-caregivers.


Subject(s)
COVID-19/psychology , Caregivers/psychology , Mental Disorders/epidemiology , Parents/psychology , Adolescent , Adult , Aged , COVID-19/epidemiology , Caregivers/economics , Caregivers/statistics & numerical data , Female , Health Surveys , Humans , Male , Middle Aged , United States/epidemiology , Young Adult
6.
Cell Rep Med ; 2(7): 100327, 2021 07 20.
Article in English | MEDLINE | ID: covidwho-1275765

ABSTRACT

Severe COVID-19 appears rare in children. This is unexpected, especially in young infants, who are vulnerable to severe disease caused by other respiratory viruses. We evaluate convalescent immune responses in 4 infants under 3 months old with confirmed COVID-19 who presented with mild febrile illness, alongside their parents, and adult controls recovered from confirmed COVID-19. Although not statistically significant, compared to seropositive adults, infants have high serum levels of IgG and IgA to SARS-CoV-2 spike protein, with a corresponding functional ability to block SARS-CoV-2 cellular entry. Infants also exhibit robust saliva anti-spike IgG and IgA responses. Spike-specific IFN-γ production by infant peripheral blood mononuclear cells appears restrained, but the frequency of spike-specific IFN-γ- and/or TNF-α-producing T cells is comparable between infants and adults. On principal-component analysis, infant immune responses appear distinct from their parents. Robust functional antibody responses alongside restrained IFN-γ production may help protect infants from severe COVID-19.


Subject(s)
Antibody Formation , COVID-19/immunology , Interferon-gamma/metabolism , Spike Glycoprotein, Coronavirus/immunology , Adult , Female , Humans , Immunoglobulin A , Immunoglobulin G , Infant , Infant, Newborn , Interferon-gamma/immunology , Leukocytes, Mononuclear/metabolism , Male , Young Adult
7.
Diabetol Metab Syndr ; 13(1): 63, 2021 Jun 11.
Article in English | MEDLINE | ID: covidwho-1266502

ABSTRACT

BACKGROUND: The COVID-19 pandemic is a global public health emergency, which presents wide-ranging negative impacts on individuals with diabetes. To examine psychosocial well-being and diabetes outcomes in individuals with type 1 diabetes during the COVID-19 pandemic, and investigate how these factors vary in different countries. METHODS: Between April and June 2020 we employed a cross national comparative research study in the United States (US), Brazil, and Iran to collect data from 1788 adults with type 1 diabetes using web-based survey. Study participants answered questions relevant to diabetes distress, diabetes burnout, depressive symptoms, COVID-19 related changes, and socio-demographic characteristics. They also reported their last Hemoglobin A1c (HbA1c) and daily Time-in-Range (TiR) blood glucose. We analyzed data using comparative tests (Chi-square, Kruskal-Wallis and McNemar test), logistic and linear regression adjusted for fixed effects. RESULTS: There were significant changes prior and during the pandemic regarding access to diabetes care, diabetes supplies and medications, healthy food and safe places to exercise in all countries (p < 0.05). Participants in Iran experienced higher levels of diabetes distress (57.1%), diabetes burnout (50%), and depressive symptoms (60.9%), followed by Brazil and US (p < 0.0001). US participants reported better glycemic control (HbA1c = 6.97%, T1R = 69.64%) compared to Brazil (HbA1c = 7.94%, T1R = 51.95%) and Iran (HbA1c = 7.47%, T1R = 51.53%) (p < 0.0001). There were also significant relationships between psychosocial well-being, diabetes outcomes, socio-demographic data, and COVID-19 related challenges in overall sample (p < 0.05). CONCLUSIONS: Regardless of differences among US, Brazil, and Iran, our findings revealed that different countries may experience similar challenges related to the COVID-19 pandemic which can impact negatively diabetes outcomes and psychosocial well-being in individuals with type 1 diabetes. Countries need to consider modifiable variables associated with poor diabetes outcomes and sub optimal psychosocial well-being and target vulnerable population using significant socio-demographic variables.

8.
Virol J ; 18(1): 117, 2021 06 04.
Article in English | MEDLINE | ID: covidwho-1259206

ABSTRACT

BACKGROUND: To date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. We determined the levels of inflammatory cytokines in patients with COVID-19 and their relationships with ARDS and extrapulmonary MOD. METHODS: The clinical and laboratory data of 94 COVID-19 patients with and without ARDS were analyzed. The levels of inflammatory cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α [TNF-α]) were measured on days 1, 3, and 5 following admission. Seventeen healthy volunteers were recruited as controls. Correlations in the levels of inflammatory cytokines with clinical and laboratory variables were analyzed, furthermore, we also explored the relationships of different cytokines with ARDS and extrapulmonary MOD. RESULTS: The ARDS group had higher serum levels of all 4 inflammatory cytokines than the controls, and these levels steadily increased after admission. The ARDS group also had higher levels of IL-6, IL-8, and IL-10 than the non-ARDS group, and the levels of these cytokines correlated significantly with coagulation parameters and disseminated intravascular coagulation (DIC). The levels of IL-6 and TNF-α correlated with the levels of creatinine and urea nitrogen, and were also higher in ARDS patients with acute kidney injury (AKI). All 4 inflammatory cytokines had negative correlations with PaO2/FiO2. IL-6, IL-8, and TNF-α had positive correlations with the APACHE-II score. Relative to survivors, non-survivors had higher levels of IL-6 and IL-10 at admission, and increasing levels over time. CONCLUSIONS: The cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients. The levels of IL-6, IL-8, and IL-10 correlated with DIC, and the levels of IL-6 and TNF-α were associated with AKI. Relative to survivors, patients who died within 28 days had increased levels of IL-6 and IL-10.


Subject(s)
COVID-19/blood , Cytokine Release Syndrome/blood , Cytokines/blood , Respiratory Distress Syndrome/blood , Acute Kidney Injury/diagnosis , Aged , Blood Urea Nitrogen , COVID-19/pathology , Creatinine/blood , Cytokine Release Syndrome/diagnosis , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/pathology , Female , Humans , Interleukin-10/blood , Interleukin-6/blood , Interleukin-8/blood , Male , Respiratory Distress Syndrome/pathology , Retrospective Studies , SARS-CoV-2 , Tumor Necrosis Factor-alpha/blood
9.
Int J Neuropsychopharmacol ; 24(11): 859-866, 2021 11 12.
Article in English | MEDLINE | ID: covidwho-1254714

ABSTRACT

BACKGROUND: COVID-19 lockdown measures have caused severe disruptions to work and education and prevented people from engaging in many rewarding activities. Cannabis users may be especially vulnerable, having been previously shown to have higher levels of apathy and anhedonia than non-users. METHODS: In this survey study, we measured apathy and anhedonia, before and after lockdown measures were implemented, in n = 256 adult and n = 200 adolescent cannabis users and n = 170 adult and n = 172 adolescent controls. Scores on the Apathy Evaluation Scale (AES) and Snaith-Hamilton Pleasure Scale (SHAPS) were investigated with mixed-measures ANCOVA, with factors user group, age group, and time, controlling for depression, anxiety, and other drug use. RESULTS: Adolescent cannabis users had significantly higher SHAPS scores before lockdown, indicative of greater anhedonia, compared with adolescent controls (P = .03, η p2 = .013). Contrastingly, adult users had significantly lower scores on both the SHAPS (P < .001, η p2 = .030) and AES (P < .001, η p2 = .048) after lockdown compared with adult controls. Scores on both scales increased during lockdown across groups, and this increase was significantly smaller for cannabis users (AES: P = .001, η p2 = .014; SHAPS: P = .01, η p2 = .008). Exploratory analyses revealed that dependent cannabis users had significantly higher scores overall (AES: P < .001, η p2 = .037; SHAPS: P < .001, η p2 = .029) and a larger increase in scores (AES: P = .04, η p2 =.010; SHAPS: P = .04, η p2 = .010), compared with non-dependent users. CONCLUSIONS: Our results suggest that adolescents and adults have differential associations between cannabis use as well as apathy and anhedonia. Within users, dependence may be associated with higher levels of apathy and anhedonia regardless of age and a greater increase in levels during the COVID-19 lockdown.


Subject(s)
Anhedonia , Apathy , COVID-19 , Marijuana Abuse/psychology , Marijuana Smoking/psychology , Adolescent , Adult , Age Factors , Case-Control Studies , Female , Humans , Male , Surveys and Questionnaires , Young Adult
10.
Arch Cardiovasc Dis ; 114(5): 426-433, 2021 May.
Article in English | MEDLINE | ID: covidwho-1240132

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been characterized by high transmission rates and high mortality in adults with predisposing factors, including age>70 years, obesity, diabetes, systemic hypertension and other underlying diseases. During the second week of viral pneumonia, acute respiratory distress syndrome can occur and carries high mortality. Unlike most common respiratory viruses, children seem to be less susceptible to SARS-CoV-2 infection, and generally develop mild disease with low mortality. However, clusters of severe shock associated with high levels of cardiac biomarkers and unusual vasoplegia requiring inotropes, vasopressors and volume loading have recently been described. Both the clinical symptoms (i.e. high and persistent fever, gastrointestinal disorders, skin rash, conjunctival injection and dry cracked lips) and the biological signs (e.g. elevated C-reactive protein/procalcitonin and high levels of ferritinaemia) mimicked Kawasaki disease. In most cases, intravenous immunoglobin therapy improved cardiac function and led to full recovery within a few days. Adjunctive steroid therapy and sometimes biotherapy (e.g. anti-interleukin 1Ra and anti-interleukin 6 monoclonal antibodies) were often necessary. Although almost all children fully recovered within a week, some of them later developed coronary artery dilation or aneurysm. Thus, a new "multisystem inflammatory syndrome in children" related to SARS-CoV-2 has recently been described. Similarities with Kawasaki disease and the physiopathology of this syndrome still need further exploration.


Subject(s)
COVID-19/complications , Mucocutaneous Lymph Node Syndrome/diagnosis , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/diagnosis , Adolescent , Biomarkers , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/etiology , Child , Diagnosis, Differential , Disease Susceptibility , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Length of Stay/statistics & numerical data , Male , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/physiopathology , Shock, Cardiogenic/etiology , Shock, Cardiogenic/therapy , Shock, Septic/diagnosis , Symptom Assessment , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/etiology
11.
Ann Behav Med ; 55(7): 677-685, 2021 06 28.
Article in English | MEDLINE | ID: covidwho-1228422

ABSTRACT

BACKGROUND AND PURPOSE: Virus mitigation strategies such as adhering to stay-at-home orders, practicing social distancing, and engaging in personal protective behaviors are central to slowing the spread of COVID-19. This population-based cohort study sought to identify sociodemographic characteristics and Health Belief Model factors that are associated with nonadherence to COVID-19 mitigation strategies with the goal of informing public health messaging campaigns. METHODS: An online population-based survey was distributed via social media over an 8-week period from April 13, 2020, to June 8, 2020. RESULTS: Data were derived from 2,222 adults (57% female; 40% racial/ethnic minorities). Univariate analyses revealed that men, younger aged (18-30 years) and unmarried adults, and noncollege educated individuals had lower levels of perceived threat, control, and knowledge about COVID-19 (p ≤ .001). Multivariable linear regression models further revealed that male gender was significantly associated with reporting lower levels of adherence to COVID-19 mitigation strategies (p < .001), and that higher levels of perceived threat, perceived control, and knowledge about how to keep oneself and others safe from COVID-19 were significantly associated with reporting higher levels of adherence to COVID-19 mitigation strategies (p < .01). CONCLUSIONS: Findings suggest that public health appeals that target men, emphasize individual risk, and provide clear, consistent guidance on what individuals can do to decrease their risk for COVID-19 may be effective in motivating increased mitigation adherence.


Subject(s)
COVID-19/prevention & control , Communicable Disease Control , Guideline Adherence , Health Belief Model , Adolescent , Adult , Age Factors , Aged , Educational Status , Female , Health Knowledge, Attitudes, Practice , Humans , Linear Models , Male , Marital Status , Middle Aged , SARS-CoV-2 , Sex Factors , Surveys and Questionnaires , United States , Young Adult
12.
Disabil Health J ; 14(4): 101110, 2021 10.
Article in English | MEDLINE | ID: covidwho-1198685

ABSTRACT

BACKGROUND: Evidence from previous public health emergencies indicates that adults with disabilities have higher risk for morbidity (physical and mental) and mortality than adults without disabilities. OBJECTIVE: To provide estimates of mental health indicators and stressors for US adults by disability status during April and May 2020, shortly following the emergence of the COVID-19 pandemic. METHODS: We analyzed data from Porter Novelli View 360 opt-in Internet panel survey conducted during the weeks of April 20th and May 18th, 2020 among 1004 English-speaking adults aged ≥18 years without and with disabilities (serious difficulty with hearing, vision, cognition, or mobility; any difficulty with self-care or independent living). Weighted logistic regression was used to test for significant differences between calculated prevalence estimates at the P ≤ .05 level. RESULTS: One in four adults reported any disability. Adults with any disability were significantly more likely than adults without disability to report current depressive symptoms, frequent mental distress, suicidal ideation, and COVID-19-related initiated or increased substance use (all p values < .0001). Adults with disabilities also reported significantly higher levels of stressors, such as access to health care services (p < .0001), difficulty caring for their own (or another's) chronic condition (p < .0001), emotional or physical abuse from others (p < .001), and not having enough food (p < .01). CONCLUSIONS: The disproportionately high levels of poor mental health indicators among adults with disabilities as compared to those without highlight the importance of delivering timely mental health screening and treatment/intervention during and after the COVID-19 pandemic to persons with disabilities.


Subject(s)
COVID-19 , Disabled Persons , Adolescent , Adult , Cross-Sectional Studies , Humans , Mental Health , Pandemics , SARS-CoV-2
13.
Rev Esp Geriatr Gerontol ; 55(5): 272-278, 2020.
Article in Spanish | MEDLINE | ID: covidwho-1196758

ABSTRACT

OBJECTIVES: To analyze differences by age group in anxiety, depression, loneliness and comorbid anxiety and depression in young people, middle aged adults and older adults during the lock-down period at home due to the COVID-19 pandemic, and to explore the association between negative self-perceptions of aging and psychological symptoms controlling by age group. METHOD: Participants are 1501 people (age range 18 to 88 years). Anxiety, sadness, loneliness and self-perceptions of aging were assessed. The sample was divided according to the age group and quartiles (lower, intermediate levels, and higher) of anxiety, sadness, loneliness and self-perceptions of aging. RESULTS: Older adults reported lower levels of anxiety and sadness than middle aged adults, and middle aged adults reported lower levels than younger participants. Middle aged adults reported the lowest loneliness, followed by older adults and younger participants. For each age group, those with more negative self-perceptions of aging reported higher anxiety, sadness and loneliness. More comorbid anxiety and sadness was found in younger adults and less in older adults; more depressed participants in the middle aged group, and more older adults and less younger participants were found in the group with the lowest levels of anxiety and sadness. For all the age groups, participants with high levels of comorbid anxiety and sadness are those who report the highest scores in negative self-perceptions of aging. CONCLUSIONS: Older adults reported lower psychological anxiety, sadness and loneliness than the other age groups. Having negative self-perceptions of aging damage psychological health irrespective of the chronological age.


Subject(s)
Aging/psychology , Anxiety/complications , Anxiety/psychology , Coronavirus Infections , Depression/complications , Depression/psychology , Loneliness/psychology , Pandemics , Pneumonia, Viral , Quarantine/psychology , Sadness/psychology , Self Concept , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Anxiety/epidemiology , COVID-19 , Coronavirus Infections/epidemiology , Depression/epidemiology , Humans , Middle Aged , Pneumonia, Viral/epidemiology , Young Adult
14.
Heliyon ; 7(4): e06873, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1193326

ABSTRACT

Little is known about the immediate psychological impacts of the national lockdown implemented during the COVID-19 pandemic on the general population in Arab countries like Jordan. The aim of this study was to assess the levels of depression, coping skills, and quality of life and their correlates among a sample of Jordanian adults aged ≥18 years during the COVID-19 lockdown implemented in Jordan. A quantitative, descriptive, correlational, cross-sectional design was conducted using an anonymous online self-report survey to collect data on participants' demographics, depression, coping skills, and quality of life. This study included a total of 511 participants aged 18-65 years (mean = 30, SD = 10.6), most of whom were female (n = 333, 65.2%). About 65% (n = 332) of the participants were found to be suffering from depressive symptoms and 32% (n = 163) of them had moderate to severe depression levels. Religion, acceptance, and planning were the most frequently reported coping skills. The mean total quality of life score among all of the participants was 73.21 (SD = 16.17). Female participants had significantly higher levels of depression and lower levels of quality of life than male participants. Further, age was not found to be significantly correlated with depression, coping skills, or total quality of life scores. Depression scores were significantly positively correlated with coping skills and negatively correlated with total quality of life scores. No significant correlation was found between coping skills scores and total quality of life scores in this study. Being employed, holding an undergraduate degree, having chronic physical problems, and having mental health problems were found to be significantly associated with higher levels of depression. Holding a graduate degree, being a student, having military health insurance, not having mental health problems, and being a non-smoker were found to be significantly associated with lower coping skills scores. Being female, being educated to high school level or below, having mental health problems, and having family history of chronic physical problems were found to be significantly associated with lower total quality of life scores. This study provides valuable information on the psychological impacts of the national lockdown during the initial outbreak of the COVID-19 pandemic on Jordanian adults. This information may help in the development of appropriate psychological interventions aimed at improving mental health and quality of life among at-risk groups during the COVID-19 pandemic.

15.
Autism ; 25(7): 2140-2145, 2021 10.
Article in English | MEDLINE | ID: covidwho-1181065

ABSTRACT

LAY ABSTRACT: This study used data collected from 275 adults in the United States with autism spectrum disorder both before the pandemic and then 10 weeks into the pandemic to assess COVID-19-related distress and its impact. Two-thirds of those surveyed reported some type of distress related to the pandemic (i.e. difficulty coping or negative impact on emotional and mental health). While there were no changes in depressive and anxiety symptoms from prior to COVID-19 to 10 week later in the group as a whole, self-reported distress predicted increases in both anxiety and depression across the two timepoints. Furthermore, adults with higher levels of anxiety prior to the pandemic were more likely to report distress, and women were more likely to report a negative impact of the pandemic on their emotional and mental health. Findings highlight the importance of monitoring with adults with autism spectrum disorder to assess their need for mental health support, and providing ongoing support to those who already experience anxiety even before the pandemic.


Subject(s)
Autism Spectrum Disorder , COVID-19 , Adult , Anxiety/epidemiology , Autism Spectrum Disorder/epidemiology , Depression/epidemiology , Female , Humans , SARS-CoV-2 , United States/epidemiology
16.
Infect Dis Ther ; 10(2): 1045-1054, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1171566

ABSTRACT

INTRODUCTION: Terminal complement amplification is hypothesized to be a key contributor to the clinical manifestations of severe coronavirus disease 2019 (COVID-19). Ravulizumab, a humanized monoclonal antibody that binds with high affinity to complement protein C5 and inhibits terminal complement activation, is being evaluated as a treatment for COVID-19-related severe pneumonia, acute lung injury, and acute respiratory distress syndrome in an ongoing phase 3 randomized controlled trial (ALXN1210-COV-305). To address the overactivation of terminal complement in severe COVID-19 compared to the diseases in which ravulizumab is currently approved, a modified dosing regimen was adopted. This analysis evaluates preliminary pharmacokinetic/pharmacodynamic data to confirm the modified dosing regimen. METHODS: Weight-based ravulizumab doses were administered on days 1, 5, 10, and 15. Serum levels of ravulizumab and free C5 were measured before and after administration of ravulizumab and any time on day 22. Free C5 levels < 0.5 µg/mL indicate complete C5 inhibition. The pharmacokinetic target was defined as ravulizumab concentrations at the end of the dosing interval > 175 µg/mL, the concentration above which C5 is completely inhibited. RESULTS: Twenty-two patients were included in this evaluation. At baseline, mean C5 concentration was 240 ± 67 µg/mL. In all patients and at all individual timepoints after the first dose was administered, ravulizumab concentrations remained > 175 µg/mL and free C5 concentrations remained < 0.5 µg/mL. CONCLUSION: High levels of baseline C5 observed in patients with severe COVID-19 contribute to the growing body of evidence that suggests this disease is marked by amplification of terminal complement activation. Data from this preliminary pharmacokinetic/pharmacodynamic evaluation of 22 patients with severe COVID-19 show that the modified ravulizumab dosing regimen achieved immediate and complete terminal complement inhibition, which can be sustained for up to 22 days. These data support the continued use of this dosage regimen in the ongoing phase 3 study. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04369469.


While many people have no or mild COVID-19 symptoms, a small number of people become very sick and require hospitalization in intensive care units. One part of their immune system, known as complement, overreacts and attacks the lungs and other organs. Researchers are looking for a way to keep the immune system from attacking the body instead of protecting it. Ravulizumab is a medication currently used to do this in other diseases. Ravulizumab is being studied to see if it can reduce the destructive and deadly effects of the coronavirus infection. In this evaluation, ravulizumab effectively reduced complement in patients with severe COVID-19.

17.
JCI Insight ; 6(9)2021 05 10.
Article in English | MEDLINE | ID: covidwho-1171263

ABSTRACT

BACKGROUNDCoronavirus disease 2019 (COVID-19) is more benign in children compared with adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more robust early innate immune response to SARS coronavirus 2 (SARS-CoV-2) protects against severe disease.METHODSClinical outcomes, SARS-CoV-2 viral copies, and cellular gene expression were compared in nasopharyngeal swabs obtained at the time of presentation to the emergency department from 12 children and 27 adults using bulk RNA sequencing and quantitative reverse-transcription PCR. Total protein, cytokines, and anti-SARS-CoV-2 IgG and IgA were quantified in nasal fluid.RESULTSSARS-CoV-2 copies, angiotensin-converting enzyme 2, and TMPRSS2 gene expression were similar in children and adults, but children displayed higher expression of genes associated with IFN signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1ß protein were detected in nasal fluid in children versus adults. Children also expressed higher levels of genes associated with immune cells, whereas expression of those associated with epithelial cells did not differ in children versus adults. Anti-SARS-CoV-2 IgA and IgG were detected at similar levels in nasal fluid from both groups. None of the children required supplemental oxygen, whereas 7 adults did (P = 0.03); 4 adults died.CONCLUSIONThese findings provide direct evidence of a more vigorous early mucosal immune response in children compared with adults and suggest that this contributes to favorable clinical outcomes.FUNDINGNIH grants R01 AI134367, UL1 TR002556, T32 AI007501, T32GM007288, P30 AI124414; an Albert Einstein College of Medicine Dean's COVID-19 Pilot Research Award; and the Eric J. Heyer, MD, PhD Translational Research Pilot Project Award.


Subject(s)
COVID-19/immunology , Immunity, Mucosal , SARS-CoV-2 , Adult , Aged , Antibodies, Viral/metabolism , COVID-19/genetics , Child , Child, Preschool , Cytokines/metabolism , Female , Humans , Immunity, Innate/genetics , Immunity, Mucosal/genetics , Infant , Male , Middle Aged , Nasal Mucosa/immunology , Pandemics , SARS-CoV-2/immunology , Transcriptome
18.
New Microbes New Infect ; 41: 100876, 2021 May.
Article in English | MEDLINE | ID: covidwho-1157635

ABSTRACT

Coronavirus disease 2019 (COVID-19) has spread worldwide and become an emerging life-threatening pandemic disease since 2019. This study aimed to evaluate the basic knowledge, awareness, personal hygiene and healthy practices regarding COVID-19 during its outbreak among the Palestinian population in the Gaza Strip. It is a cross-sectional survey carried out between July and August 2020 and included 458 participants, aged 18 years or older, belonging to the five Gaza Strip governorates, Palestine, with a variety of socio-economic status. Sociodemographic data and data on COVID-19 knowledge, awareness, personal hygiene and healthy practices were collected via email and social media applications (WhatsApp and Facebook) from the study participants. Statistical analyses were performed using Vr 22 of the SPSS software. Overall, the mean ± SD age of the participants was 26.5 ± 4.2 years. Our findings showed that most of the Gazan adults had very good knowledge regarding COVID-19 in terms of host sources, causative agents, incubation period, symptoms, transmission, treatment and prevention. Additionally, most of the participants had a high level of personal hygiene and healthy practices during the COVID-19 outbreak, where personal hygiene and healthy practices against COVID-19 was 77.4%. Furthermore, a higher educational level did not affect the quality of personal hygiene and healthy practice behaviours during the COVID-19 outbreak. Although most of the Gazans had good knowledge regarding the healthy practices, a significant percentage of the population did not practice the hygiene protocol. Despite the majority of the Gazan population having very good knowledge regarding COVID-19 and a high level of personal hygiene and healthy practices during the COVID-19 outbreak, a small proportion require education about avoiding physical contact and maintaining social distancing with others during the pandemic.

19.
Cytokine ; 143: 155507, 2021 07.
Article in English | MEDLINE | ID: covidwho-1157230

ABSTRACT

AIM: COVID-19 pandemic has caused extensive burden on public life and health care worldwide. This study aimed to assess circulating levels of inflammatory cytokines in adult patients who were hospitalized with COVID-19 and stratified according to age (older or younger than 65 years) aiming to explore associations between these markers of inflammation and comorbidities. METHODS: This was a cross-sectional study of 142 COVID-19 patients consecutively admitted to the University Hospital of the Federal University of São Carlos, from July to October 2020. Sociodemographic data, chronic comorbidities, and baseline NEWS2 and SOFA for clinical deterioration were obtained at hospital admission. Serum levels of inflammatory cytokines were determined by flow cytometry. RESULTS: Older adults with COVID-19 had higher serum levels of IL-6 and IL-10 as compared to those under 65 years of age (p < 0.001 and p = 0.003, respectively). IL-10 was independently associated with age (p = 0.04) and severity of the disease (p = 0.05), whereas serum levels of IL-6 were not directly associated with age (p = 0.5). The comorbidity index seems to be the main responsible for this, being significantly associated with IL-6 levels among those aged 65 and over (p = 0.007), in addition to the severity of the disease. CONCLUSIONS: Higher serum levels of IL-6 and IL-10 are associated with the severity of the disease and a higher comorbidity index among adults aged 65 and over with COVID-19. This should raise awareness of the importance of comorbidity index, rather than age, during risk stratification.


Subject(s)
COVID-19/blood , COVID-19/pathology , Interleukin-10/blood , Interleukin-6/blood , Severity of Illness Index , Adult , Age Factors , Aged , Aged, 80 and over , Aging , Brazil , Comorbidity , Cross-Sectional Studies , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/pathology , Female , Humans , Inflammation/diagnosis , Male , Middle Aged , Risk Factors , SARS-CoV-2/immunology , Young Adult
20.
East Asian Arch Psychiatry ; 31(1): 3-8, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1147318

ABSTRACT

OBJECTIVES: To compare older adults with late-life depression (LLD) and healthy controls in terms of suicidal ideation during the COVID-19 pandemic, and to determine predictors of suicidal ideation. METHODS: Between March and April 2020, old adults diagnosed with major depressive disorder (single or recurrent episode) as defined by the DSM-5 were recruited from psychiatric clinics or inpatient wards, whereas 31 healthy older adults without a history of depression or other psychiatric illnesses were recruited from voluntary organisations or elderly community centres. Their depressive symptoms, perceived severity of the pandemic, perceived time spent on receiving related information, perceived health, levels of loneliness, perceived coping efficacy, suicidal ideation, and the level of symptomatic responses to a specific traumatic stressor in the past week were assessed. RESULTS: In total, 21 men and 43 women aged 61 to 89 years were interviewed through telephone by trained research assistants. Of them, 33 were older adults with LLD (cases) and 31 were healthy older adults (controls). Older people with LLD had a higher level of suicidal ideation than healthy controls, after controlling for the level of depression and medical comorbidity (F (1, 59) = 5.72, p = 0.020). Regression analyses showed that coping efficacy and loneliness accounted for a significant portion of the variance in suicidal ideation, and loneliness significantly predicted the level of stress. Mediation analyses reveal an indirect effect between group and suicidal ideation through coping efficacy (Z = 2.43, p = 0.015). CONCLUSIONS: Older people with LLD are at increased suicidal risk and require timely mental health support. Coping efficacy and loneliness are important predictors for suicidal ideation and stress.


Subject(s)
COVID-19 , Depressive Disorder, Major , Mental Disorders , Noncommunicable Diseases , Suicidal Ideation , Suicide , Adaptation, Psychological , Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/psychology , Case-Control Studies , Depression/diagnosis , Depression/etiology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/psychology , Diagnostic and Statistical Manual of Mental Disorders , Female , Hong Kong/epidemiology , Humans , Loneliness/psychology , Male , Mental Disorders/diagnosis , Mental Disorders/epidemiology , Mental Disorders/psychology , Noncommunicable Diseases/epidemiology , Noncommunicable Diseases/psychology , Psychosocial Support Systems , SARS-CoV-2 , Stress, Psychological/diagnosis , Stress, Psychological/etiology , Suicide/prevention & control , Suicide/psychology
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