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1.
Curr Psychol ; : 1-4, 2021 Feb 20.
Article in English | MEDLINE | ID: covidwho-1525625

ABSTRACT

The current pandemic of the coronavirus disease 2019 (COVID-19) has negatively impacted medical workers' mental health in many countries including Japan. Although research identified poor mental health of medical workers in COVID-19, protective factors for their mental health remain to be appraised. Accordingly, this study aimed to investigate relationships between mental health problems, loneliness, hope and self-compassion among Japanese medical workers, and compare with the general population. Online self-report measures regarding those four constructs were completed by 142 medical workers and 138 individuals in the general population. T-tests and multiple regression analysis were performed. Medical workers had higher levels of mental health problems and loneliness, and lower levels of hope and self-compassion than the general population. Loneliness was the strongest predictor of mental health problems in the medical workers. Findings suggest that Japanese medical workplaces may benefit from targeting workplace loneliness to prevent mental health problems among the medical staff.

2.
J Clin Med ; 10(8)2021 Apr 13.
Article in English | MEDLINE | ID: covidwho-1526835

ABSTRACT

BACKGROUND: In coronavirus disease 2019 (COVID-19) patients, increases in high-sensitive cardiac troponin T (hs-cTnT) have been reported to be associated with worse outcomes. In the critically ill, the prognostic value of hs-cTnT, however, remains to be assessed given that most previous studies have involved a case mix of non- and severely ill COVID-19 patients. METHODS: We conducted, from March to May 2020, in three French intensive care units (ICUs), a multicenter retrospective cohort study to assess in-hospital mortality predictability of hs-cTnT levels in COVID-19 patients. RESULTS: 111 laboratory-confirmed COVID-19 patients (68% of male, median age 67 (58-75) years old) were included. At ICU admission, the median Charlson Index, Simplified Acute Physiology Score II, and PaO2/FiO2 were at 3 (2-5), 37 (27-48), and 140 (98-154), respectively, and the median hs-cTnT serum levels were at 16.0 (10.1-31.9) ng/L. Seventy-five patients (68%) were mechanically ventilated, 41 (37%) were treated with norepinephrine, and 17 (15%) underwent renal replacement therapy. In-hospital mortality was 29% (32/111) and was independently associated with lower PaO2/FiO2 and higher hs-cTnT serum levels. CONCLUSIONS: At ICU admission, besides PaO2/FiO2, hs-cTnT levels may allow early risk stratification and triage in critically ill COVID-19 patients.

3.
Clin Transl Immunology ; 10(4): e1271, 2021.
Article in English | MEDLINE | ID: covidwho-1525427

ABSTRACT

Objectives: Emerging evidence of dysregulation of the myeloid cell compartment urges investigations on neutrophil characteristics in coronavirus disease 2019 (COVID-19). We isolated neutrophils from the blood of COVID-19 patients receiving general ward care and from patients hospitalised at intensive care units (ICUs) to explore the kinetics of circulating neutrophils and factors important for neutrophil migration and activation. Methods: Multicolour flow cytometry was exploited for the analysis of neutrophil differentiation and activation markers. Multiplex and ELISA technologies were used for the quantification of protease, protease inhibitor, chemokine and cytokine concentrations in plasma. Neutrophil polarisation responses were evaluated microscopically. Gelatinolytic and metalloproteinase activity in plasma was determined using a fluorogenic substrate. Co-culturing healthy donor neutrophils with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) allowed us to investigate viral replication in neutrophils. Results: Upon ICU admission, patients displayed high plasma concentrations of granulocyte-colony-stimulating factor (G-CSF) and the chemokine CXCL8, accompanied by emergency myelopoiesis as illustrated by high levels of circulating CD10-, immature neutrophils with reduced CXCR2 and C5aR expression. Neutrophil elastase and non-metalloproteinase-derived gelatinolytic activity were increased in plasma from ICU patients. Significantly higher levels of circulating tissue inhibitor of metalloproteinase 1 (TIMP-1) in patients at ICU admission yielded decreased total MMP proteolytic activity in blood. COVID-19 neutrophils were hyper-responsive to CXCL8 and CXCL12 in shape change assays. Finally, SARS-CoV-2 failed to replicate inside human neutrophils. Conclusion: Our study provides detailed insights into the kinetics of neutrophil phenotype and function in severe COVID-19 patients, and supports the concept of an increased neutrophil activation state in the circulation.

4.
J Am Soc Nephrol ; 32(2): 448-458, 2021 02.
Article in English | MEDLINE | ID: covidwho-1496669

ABSTRACT

BACKGROUND: Fine particulate matter (PM2.5) is an important environmental risk factor for cardiopulmonary diseases. However, the association between PM2.5 and risk of CKD remains under-recognized, especially in regions with high levels of PM2.5, such as China. METHODS: To explore the association between long-term exposure to ambient PM2.5 and CKD prevalence in China, we used data from the China National Survey of CKD, which included a representative sample of 47,204 adults. We estimated annual exposure to PM2.5 before the survey date at each participant's address, using a validated, satellite-based, spatiotemporal model with a 10 km×10 km resolution. Participants with eGFR <60 ml/min per 1.73 m2 or albuminuria were defined as having CKD. We used a logistic regression model to estimate the association and analyzed the influence of potential modifiers. RESULTS: The 2-year mean PM2.5 concentration was 57.4 µg/m3, with a range from 31.3 to 87.5 µg/m3. An increase of 10 µg/m3 in PM2.5 was positively associated with CKD prevalence (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.22 to 1.35) and albuminuria (OR, 1.39; 95% CI, 1.32 to 1.47). Effect modification indicated these associations were significantly stronger in urban areas compared with rural areas, in males compared with females, in participants aged <65 years compared with participants aged ≥65 years, and in participants without comorbid diseases compared with those with comorbidities. CONCLUSIONS: These findings regarding the relationship between long-term exposure to high ambient PM2.5 levels and CKD in the general Chinese population provide important evidence for policy makers and public health practices to reduce the CKD risk posed by this pollutant.


Subject(s)
Air Pollution/adverse effects , Albuminuria/epidemiology , Environmental Exposure/adverse effects , Particulate Matter/adverse effects , Renal Insufficiency, Chronic/epidemiology , Adult , Aged , Albuminuria/diagnosis , China , Female , Glomerular Filtration Rate , Humans , Logistic Models , Male , Middle Aged , Prevalence , Renal Insufficiency, Chronic/diagnosis , Risk Factors , Surveys and Questionnaires , Time Factors
5.
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
6.
J Athl Train ; 2021 May 26.
Article in English | MEDLINE | ID: covidwho-1478191

ABSTRACT

The COVID-19 pandemic has created a unique challenge for sports medicine staffs as they are attempting to safely transition elite athletes into sport participation after a COVID-19 infection. Athletes must isolate for a period of time after testing positive for COVID-19 to prevent the spread of the virus within a community. After an isolation period, a battery of cardiac tests must be given to assess whether or not an athlete is ready to begin a reconditioning protocol. A return-to-play plan should be established to safely re-integrate high-level athletes into strength and conditioning, sport-specific drill work, and contact drill work. Elite athletes should also be gradually eased back into full training loads in order to avoid increases in orthopedic injuries after a prolonged absence from training.

7.
Arthritis Rheumatol ; 73(11): 1976-1985, 2021 11.
Article in English | MEDLINE | ID: covidwho-1432359

ABSTRACT

OBJECTIVE: The clinical relevance of antiphospholipid antibodies (aPLs) in COVID-19 is controversial. This study was undertaken to investigate the prevalence and prognostic value of conventional and nonconventional aPLs in patients with COVID-19. METHODS: This was a multicenter, prospective observational study in a French cohort of patients hospitalized with suspected COVID-19. RESULTS: Two hundred forty-nine patients were hospitalized with suspected COVID-19, in whom COVID-19 was confirmed in 154 and not confirmed in 95. We found a significant increase in lupus anticoagulant (LAC) positivity among patients with COVID-19 compared to patients without COVID-19 (60.9% versus 23.7%; P < 0.001), while prevalence of conventional aPLs (IgG and IgM anti-ß2 -glycoprotein I and IgG and IgM anticardiolipin isotypes) and nonconventional aPLs (IgA isotype of anticardiolipin, IgA isotype of anti-ß2 -glycoprotein I, IgG and IgM isotypes of anti-phosphatidylserine/prothrombin, and IgG and IgM isotypes of antiprothrombin) was low in both groups. Patients with COVID-19 who were positive for LAC, as compared to patients with COVID-19 who were negative for LAC, had higher levels of fibrinogen (median 6.0 gm/liter [interquartile range 5.0-7.0] versus 5.3 gm/liter [interquartile range 4.3-6.4]; P = 0.028) and C-reactive protein (CRP) (median 115.5 mg/liter [interquartile range 66.0-204.8] versus 91.8 mg/liter [interquartile range 27.0-155.1]; P = 0.019). Univariate analysis did not show any association between LAC positivity and higher risks of venous thromboembolism (VTE) (odds ratio 1.02 [95% confidence interval 0.44-2.43], P = 0.95) or in-hospital mortality (odds ratio 1.80 [95% confidence interval 0.70-5.05], P = 0.24). With and without adjustment for CRP level, age, and sex, Kaplan-Meier survival curves according to LAC positivity confirmed the absence of an association with VTE or in-hospital mortality (unadjusted P = 0.64 and P = 0.26, respectively; adjusted hazard ratio 1.13 [95% confidence interval 0.48-2.60] and 1.80 [95% confidence interval 0.67-5.01], respectively). CONCLUSION: Patients with COVID-19 have an increased prevalence of LAC positivity associated with biologic markers of inflammation. However, LAC positivity at the time of hospital admission is not associated with VTE risk and/or in-hospital mortality.


Subject(s)
COVID-19/complications , Lupus Coagulation Inhibitor/blood , Venous Thromboembolism/etiology , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/mortality , Female , Hospital Mortality , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Risk Factors , Survival Rate , Venous Thromboembolism/blood
8.
AACE Clin Case Rep ; 7(5): 288-292, 2021.
Article in English | MEDLINE | ID: covidwho-1397116

ABSTRACT

Objective: During the ongoing coronavirus disease 2019 pandemic, procalcitonin (PCT) levels have proven useful in assisting clinicians to diagnose bacterial superinfection. However, in the absence of signs of infection or at the resolution thereof, inappropriately and persistently high PCT levels may suggest and reveal the presence of other pathologies. We report a patient with severe acute respiratory syndrome coronavirus 2 pneumonia with initially elevated PCT levels that persisted during recovery, prompting the diagnosis of medullary thyroid carcinoma (MTC). Methods: A 43-year-old man presented with a 2-day history of fever, sneezing, sore throat, and dry cough. His PCT was 94 ng/mL (normal value, 0.00-0.10 ng/mL), and he was positive for severe acute respiratory syndrome coronavirus 2 RNA. Results: Empirical antibiotic therapy was administered for 7 days, but despite a clinical improvement, serum PCT remained high (84 ng/mL). Serum calcitonin (CTN) was 2120 pg/mL (normal, ≤12 pg/mL). Cytologic examination of thyroid nodules and CTN measurement of the aspiration needle washout confirmed MTC. The patient underwent total thyroidectomy with bilateral cervical lymph node dissection. Lowered CTN (986 pg/mL) and PCT (16 ng/mL) levels were observed 48 hours after surgery. A close follow-up was planned following the results of RET gene analysis. Conclusion: PCT can be a useful biochemical marker of MTC suspicion in patients with inflammatory conditions and persistently elevated PCT, even after resolution. In our case, high levels of PCT in a patient with coronavirus disease 2019 pneumonia without signs of bacterial infection led to MTC diagnosis.

9.
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
10.
J Am Pharm Assoc (2003) ; 61(6): 703-708, 2021.
Article in English | MEDLINE | ID: covidwho-1376017

ABSTRACT

BACKGROUND: Student pharmacists and faculty exhibit high levels of stress, independent of the current coronavirus 2019 pandemic, and their path toward wellness, including a reduction in stress and anxiety, is of the utmost importance. Yoga and meditation are proven interventions to reduce stress and anxiety and increase wellness. Yin yoga is an adaptable, quiet practice ideal for those lacking previous yoga experience, flexibility, and time. OBJECTIVE: To evaluate the impact of a 6-week yin yoga and meditation intervention on College of Pharmacy faculty and students' stress perception, anxiety levels, and mindfulness skills. METHODS: Faculty and students participated in a 6-week pilot program comprising a once-weekly yin yoga class followed by guided meditation. Yin yoga was selected for its quiet meditative style. Participants completed a pre- and postquestionnaire at 6 weeks and 3 and 6 months to evaluate potential changes in perceived stress scores, anxiety scores, and mindfulness skills. The questionnaire was composed of 3 self-reporting tools: Beck Anxiety Inventory (BAI), Perceived Stress Scale, and the Five Facet Mindfulness Questionnaire. RESULTS: Twenty participants, 12 students and 8 faculty (ages 18-66 years), completed the study. Anxiety and stress scores decreased, and mindfulness increased at 6 weeks, 3 months and 6 months, with all changes reaching statistical significance. No participants reported being in the "high" category of anxiety after intervention using BAI categorical data, although this finding was not statistically significant. CONCLUSION: Faculty and students demonstrated a reduction in stress and anxiety levels and an increase in mindfulness after a 6-week yin yoga and meditation program. Outcomes suggest that inclusion of an adaptable, meditative practice, which may easily be replicated at home, for as little as once per week for 6 weeks may reduce stress and anxiety and increase mindfulness long term. Creating a culture of wellness should be a priority for all Colleges of Pharmacy.


Subject(s)
Meditation , Mindfulness , Yoga , Adolescent , Adult , Aged , Faculty, Pharmacy , Humans , Middle Aged , Stress, Psychological/prevention & control , Students , Young Adult
11.
J Med Virol ; 93(9): 5416-5424, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363679

ABSTRACT

The kinetics of IgG antibodies after coronavirus disease 2019 (COVID-19) remain poorly understood. We investigated factors influencing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody levels and time to seronegativation during the follow-up of severe and critically ill patients. We retrospectively reviewed serological evaluations drawn during the follow-up of severe or critical laboratory-proven COVID-19 patients hospitalized at a large academic hospital. Specific IgG titers were measured using a chemiluminescent assay targeting anti-spike and anti-nucleocapsid protein IgG. The influence of time, demographic factors, clinical and paraclinical characteristics, and COVID-19 therapeutics on IgG levels were assessed through linear regression using a mixed-effect model, and delay until IgG negativation through a Weibull regression model. The cohort included 116 patients with a total of 154 IgG measurements drawn at a median of 79 days after diagnosis. IgG antibodies were increased with age (p = 0.005) and decreased significantly over time (p = 0.0002). Using elapsed time and age as covariates, we demonstrated higher IgG levels in patients with a higher body mass index (BMI) (p = 0.0026) and lower IgG levels in immunocompromised patients (p = 0.032). A high BMI was further found to delay and immunodeficiency to hasten significantly seronegativation, whereas no significant effect was observed with corticosteroids. These data highlight the waning over time of IgG antibodies after severe or critical COVID-19. Age, BMI, and immunosuppression also appear to influence the IgG kinetics, while short-term corticotherapy does not. Those data improve the understanding of SARS-CoV-2 serology while further research should determine the determinants of long-term seroprotection.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunocompromised Host , Immunoglobulin G/blood , Respiratory Insufficiency/immunology , SARS-CoV-2/immunology , Adrenal Cortex Hormones/therapeutic use , Aged , Body Mass Index , COVID-19/blood , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Serological Testing , Convalescence , Female , Humans , Hydroxychloroquine/therapeutic use , Male , Middle Aged , Respiratory Insufficiency/blood , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/drug therapy , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index , Time Factors
12.
J Headache Pain ; 22(1): 51, 2021 Jun 04.
Article in English | MEDLINE | ID: covidwho-1346199

ABSTRACT

BACKGROUND: The presence of headache during the acute phase of COVID-19 could be associated with the innate response and the cytokine release. We aim to compare the cytokine and interleukin profile in hospitalized COVID-19 patients at the moment of admission with and without headache during the course of the disease. METHODS: An observational analytic study with a case control design was performed. Hospitalized patients from a tertiary hospital with confirmed COVID-19 disease were included. Patients were classified into the headache or the control group depending on whether they presented headache not better accounted for by another headache disorder other than acute headache attributed to systemic viral infection. Several demographic and clinical variables were studies in both groups. We determined the plasmatic levels of 45 different cytokines and interleukins from the first hospitalization plasma extraction in both groups. RESULTS: One hundred and four patients were included in the study, aged 67.4 (12.8), 43.3% female. Among them, 29 (27.9%) had headache. Patients with headache were younger (61.8 vs. 69.5 years, p = 0.005) and had higher frequency of fever (96.6 vs. 78.7%, p = 0.036) and anosmia (48.3% vs. 22.7%, p = 0.016). In the comparison of the crude median values of cytokines, many cytokines were different between both groups. In the comparison of the central and dispersion parameters between the two groups, GROa, IL-10, IL1RA, IL-21, IL-22 remained statistically significant. After adjusting the values for age, sex, baseline situation and COVID-19 severity, IL-10 remained statistically significant (3.3 vs. 2.2 ng/dL, p = 0.042), with a trend towards significance in IL-23 (11.9 vs. 8.6 ng/dL, p = 0.082) and PIGF1 (1621.8 vs. 110.6 ng/dL, p = 0.071). CONCLUSIONS: The higher levels of IL-10 -an anti-inflammatory cytokine- found in our sample in patients with headache may be explained as a counteract of cytokine release, reflecting a more intense immune response in these patients.


Subject(s)
COVID-19 , Cytokines , Case-Control Studies , Female , Headache/complications , Humans , Interleukins , Male , SARS-CoV-2
13.
JCI Insight ; 6(14)2021 07 22.
Article in English | MEDLINE | ID: covidwho-1341362

ABSTRACT

BACKGROUNDThe fungal cell wall constituent 1,3-ß-d-glucan (BDG) is a pathogen-associated molecular pattern that can stimulate innate immunity. We hypothesized that BDG from colonizing fungi in critically ill patients may translocate into the systemic circulation and be associated with host inflammation and outcomes.METHODSWe enrolled 453 mechanically ventilated patients with acute respiratory failure (ARF) without invasive fungal infection and measured BDG, innate immunity, and epithelial permeability biomarkers in serially collected plasma samples.RESULTSCompared with healthy controls, patients with ARF had significantly higher BDG levels (median [IQR], 26 pg/mL [15-49 pg/mL], P < 0.001), whereas patients with ARF with high BDG levels (≥40 pg/mL, 31%) had higher odds for assignment to the prognostically adverse hyperinflammatory subphenotype (OR [CI], 2.88 [1.83-4.54], P < 0.001). Baseline BDG levels were predictive of fewer ventilator-free days and worse 30-day survival (adjusted P < 0.05). Integrative analyses of fungal colonization and epithelial barrier disruption suggested that BDG may translocate from either the lung or gut compartment. We validated the associations between plasma BDG and host inflammatory responses in 97 hospitalized patients with COVID-19.CONCLUSIONBDG measurements offered prognostic information in critically ill patients without fungal infections. Further research in the mechanisms of translocation and innate immunity recognition and stimulation may offer new therapeutic opportunities in critical illness.FUNDINGUniversity of Pittsburgh Clinical and Translational Science Institute, COVID-19 Pilot Award and NIH grants (K23 HL139987, U01 HL098962, P01 HL114453, R01 HL097376, K24 HL123342, U01 HL137159, R01 LM012087, K08HK144820, F32 HL142172, K23 GM122069).


Subject(s)
COVID-19 , Candida , Immunity, Innate/immunology , Respiration, Artificial , beta-Glucans/blood , Biomarkers/blood , COVID-19/immunology , COVID-19/therapy , Candida/immunology , Candida/isolation & purification , Capillary Permeability/immunology , Critical Illness/therapy , Female , Gastrointestinal Microbiome/immunology , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Respiration, Artificial/adverse effects , Respiration, Artificial/methods , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Respiratory System/immunology , Respiratory System/microbiology , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
14.
Sci Rep ; 11(1): 11886, 2021 06 04.
Article in English | MEDLINE | ID: covidwho-1341009

ABSTRACT

The cholinergic system has been proposed as a potential regulator of COVID-19-induced hypercytokinemia. We investigated whole-blood expression of cholinergic system members and correlated it with COVID-19 severity. Patients with confirmed SARS-CoV-2 infection and healthy aged-matched controls were included in this non-interventional study. A whole blood sample was drawn between 9-11 days after symptoms onset, and peripheral leukocyte phenotyping, cytokines measurement, RNA expression and plasma viral load were determined. Additionally, whole-blood expression of native alpha-7 nicotinic subunit and its negative dominant duplicate (CHRFAM7A), choline acetyltransferase and acetylcholine esterase (AchE) were determined. Thirty-seven patients with COVID-19 (10 moderate, 11 severe and 16 with critical disease) and 14 controls were included. Expression of CHRFAM7A was significantly lower in critical COVID-19 patients compared to controls. COVID-19 patients not expressing CHRFAM7A had higher levels of CRP, more extended pulmonary lesions and displayed more pronounced lymphopenia. COVID-19 patients without CHRFAM7A expression also showed increased TNF pathway expression in whole blood. AchE was also expressed in 30 COVID-19 patients and in all controls. COVID-19-induced hypercytokinemia is associated with decreased expression of the pro-inflammatory dominant negative duplicate CHRFAM7A. Expression of this duplicate might be considered before targeting the cholinergic system in COVID-19 with nicotine.


Subject(s)
Acetylcholine/immunology , COVID-19/immunology , Inflammation/immunology , SARS-CoV-2/immunology , alpha7 Nicotinic Acetylcholine Receptor/immunology , Adult , Aged , COVID-19/genetics , Down-Regulation , Female , Humans , Inflammation/genetics , Male , Middle Aged , alpha7 Nicotinic Acetylcholine Receptor/genetics
15.
Nature ; 588(7837): 315-320, 2020 12.
Article in English | MEDLINE | ID: covidwho-1337122

ABSTRACT

There is increasing evidence that coronavirus disease 2019 (COVID-19) produces more severe symptoms and higher mortality among men than among women1-5. However, whether immune responses against severe acute respiratory syndrome coronavirus (SARS-CoV-2) differ between sexes, and whether such differences correlate with the sex difference in the disease course of COVID-19, is currently unknown. Here we examined sex differences in viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines and blood-cell phenotyping in patients with moderate COVID-19 who had not received immunomodulatory medications. Male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. By contrast, female patients had more robust T cell activation than male patients during SARS-CoV-2 infection. Notably, we found that a poor T cell response negatively correlated with patients' age and was associated with worse disease outcome in male patients, but not in female patients. By contrast, higher levels of innate immune cytokines were associated with worse disease progression in female patients, but not in male patients. These findings provide a possible explanation for the observed sex biases in COVID-19, and provide an important basis for the development of a sex-based approach to the treatment and care of male and female patients with COVID-19.


Subject(s)
COVID-19/immunology , Cytokines/immunology , Immunity, Innate/immunology , SARS-CoV-2/immunology , Sex Characteristics , T-Lymphocytes/immunology , COVID-19/blood , COVID-19/virology , Chemokines/blood , Chemokines/immunology , Cohort Studies , Cytokines/blood , Disease Progression , Female , Humans , Lymphocyte Activation , Male , Monocytes/immunology , Phenotype , Prognosis , RNA, Viral/analysis , SARS-CoV-2/pathogenicity , Viral Load
16.
Anaesthesiol Intensive Ther ; 53(2): 134-140, 2021.
Article in English | MEDLINE | ID: covidwho-1328217

ABSTRACT

INTRODUCTION: The family response to intensive care unit (ICU) hospitalisation includes development of adverse psychological outcomes such as stress, anxiety or depression. These complications from exposure to critical care are termed post-intensive care syndrome-family (PICS-f). Psychological repercussions of critical illness affect the family member's ability to perform care functions after hospitalisation. MATERIAL AND METHODS: A total of 37 family members of patients hospitalised in an ICU were included. To evaluate the level stress, anxiety, depression and basic hope the standardized questionnaires the Perceived Stress Scale (PSS-10), the Hospital Anxiety and Depression Scale (HADS) and the Basic Hope Inventory (BHI-12) respectively were used. RESULTS: In 33 respondents (89.19%) a high level of stress was identified, and 14 (37.84%) and 12 (32.43%) respondents had severe anxiety and depression, respectively. Higher levels of stress, anxiety and depression were found in spouses and family members living with the patient. Female subjects had a higher level of basic hope (P = 0.026). It was found that perceived stress correlated with anxiety (r = 0.456, P = 0.005) and depression (r = 0.481, P = 0.003). CONCLUSIONS: Most relatives of the patients reported stress, anxiety, depression and low basic hope. Preventive family-centred interventions are needed to minimize the risk of adverse psychological repercussions, including post-intensive care syndrome family.


Subject(s)
Anxiety , Depression , Anxiety/epidemiology , Critical Illness , Depression/epidemiology , Family , Female , Humans , Intensive Care Units , Stress, Psychological/epidemiology
17.
Curr Rheumatol Rev ; 17(3): 318-326, 2021 Aug 30.
Article in English | MEDLINE | ID: covidwho-1328036

ABSTRACT

BACKGROUND: People with rheumatic disease may be at higher risk for more severe course with COVID- 19, and the adverse effects of drugs used to treat rheumatic diseases is a major concern. OBJECTIVE: We conducted this survey to learn about the real impact of COVID-19 pandemic on patients with rheumatic diseases. METHODS: Participants were asked to complete a questionnaire using a telephonic interview conducted by two rheumatologists. Rheumatic disease characteristics, knowledge and attitude toward COVID-19, and impacts of pandemic on rheumatology care and patient's compliance were assessed. RESULTS: We included 307 patients in the survey, and rheumatoid arthris was the main rheumatic disease. Patients had mostly moderate level of knowledge about COVID-19, and patients with higher level of education were more likely to have better knowledge. Participants respected mainly recommended preventive measures. The pandemic and sanitary containment impacted strongly the rheumatology care. Over quarter of patients noted worsening of their rheumatic disease, two-thirds reported postponed or canceled medical apointments and more than three quarters postponed their laboratory tests. Patients with higher disease activity were more likely to have lack of follow-up. Medication change was noted in more than third of cases. It was mostly stopped, and DMARDs were mainly affected. Patients living in rural areas and who had canceled, or postponed their appointments were more likely to change their treatment. CONCLUSION: Our data are useful to better manage rheumatic patients. Physicians are encouraged to renew contact with their patients to insure medication compliance.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Patient Participation , Physician-Patient Relations , Rheumatic Diseases/diagnosis , Rheumatic Diseases/epidemiology , Adult , Aged , Antirheumatic Agents/therapeutic use , COVID-19/drug therapy , Cross-Sectional Studies , Disease Management , Female , Humans , Male , Middle Aged , Pandemics , Patient Participation/trends , Rheumatic Diseases/drug therapy
18.
Nutrients ; 13(4)2021 Apr 20.
Article in English | MEDLINE | ID: covidwho-1325744

ABSTRACT

Stiff person syndrome (SPS) is a rare autoimmune disease characterised by axial stiffness and episodic painful spasms. It is associated with additional autoimmune diseases and cerebellar ataxia. Most patients with SPS have high levels of glutamic acid decarboxylase (GAD) antibodies. The aetiology of SPS remains unclear but autoimmunity is thought to play a major part. We have previously demonstrated overlap between anti-GAD ataxia and gluten sensitivity. We have also demonstrated the beneficial effect of a gluten-free diet (GFD) in patients with anti-GAD ataxia. Here, we describe our experience in the management of 20 patients with SPS. The mean age at symptom onset was 52 years. Additional autoimmune diseases were seen in 15/20. Nineteen of the 20 patients had serological evidence of gluten sensitivity and 6 had coeliac disease. Fourteen of the 15 patients who had brain imaging had evidence of cerebellar involvement. Twelve patients improved on GFD and in seven GFD alone was the only treatment required long term. Twelve patients had immunosuppression but only three remained on such medication. Gluten sensitivity plays an important part in the pathogenesis of SPS and GFD is an effective therapeutic intervention.


Subject(s)
Food Intolerance/complications , Glutens/adverse effects , Stiff-Person Syndrome/complications , Adult , Aged , Female , Food Intolerance/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Stiff-Person Syndrome/diagnostic imaging
19.
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 , Ethnic Groups/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
20.
Int J Clin Pract ; 75(10): e14492, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1297677

ABSTRACT

OBJECTIVES: Isolation precautions are very important for emergency personnel faced with this high risk. This is cross-sectional study carried out to determine the compliance of emergency healthcare personnel with isolation precautions during the COVID-19 pandemic. METHODS: The study was carried out in the Emergency Services department of Erzurum Atatürk University and Erzurum Regional Training and Research Hospital from May 2020 to June 2020. The study population comprised 184 healthcare professionals working in emergency services, and the sample comprised 138 healthcare professionals who agreed to participate in the study. Data were collected using the "Healthcare Professionals Sociodemographic Form" and the "Compliance with Isolation Precautions Scale". Percentage distribution, t test, variance analysis (ANOVA), Mann-Whitney U test and Kruskal-Wallis test were used to analyse the data. Permission to conduct the study was obtained from the ethics committee and the Ministry of Health. RESULTS: Of the participants, 58.7% were male, 37.7% had worked for 1-5 years, 31.2% were nurses and the mean age was 30.78 ± 7.17. Of the participants, 86.2% wanted to receive training on isolation precautions, 87% knew the type of isolation practiced, 81.2% were able to identify suspected patients and 84.1% knew suspected patients were put into isolation. The emergency healthcare personnel's mean score on the isolation precautions compliance scale was determined as 67.63 ± 4.64. CONCLUSION: It was concluded that the emergency healthcare personnel had high levels of knowledge about the COVID-19 pandemic; however, they had an average level of compliance with isolation precautions.


Subject(s)
COVID-19 , Pandemics , Adult , Cross-Sectional Studies , Health Personnel , Humans , Male , Patient Compliance , SARS-CoV-2 , Surveys and Questionnaires , Young Adult
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