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1.
Hypertension ; 76(5): 1526-1536, 2020 11.
Article in English | MEDLINE | ID: covidwho-2153220

ABSTRACT

ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. Plasma ACE2 exhibited associations with 1011 other plasma proteins. In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.


Subject(s)
Coronavirus Infections/epidemiology , Disease Outbreaks/statistics & numerical data , Disease Progression , Heart Failure/enzymology , Heart Failure/physiopathology , Peptidyl-Dipeptidase A/blood , Pneumonia, Viral/epidemiology , Academic Medical Centers , Analysis of Variance , Angiotensin-Converting Enzyme 2 , Biomarkers/metabolism , COVID-19 , Cohort Studies , Coronavirus Infections/prevention & control , Female , Humans , Linear Models , Male , Middle Aged , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Prognosis , Proportional Hazards Models , Proteomics/methods , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index , United States
2.
JMIR Public Health Surveill ; 7(4): e26330, 2021 04 13.
Article in English | MEDLINE | ID: covidwho-2141310

ABSTRACT

BACKGROUND: The new coronavirus SARS-CoV-2 led to the COVID-19 pandemic starting in January 2020. The Swiss Federal Council prescribed a lockdown of nonessential businesses. Students and employees of higher education institutions had to install home offices and participate in online lectures. OBJECTIVE: The aim of this survey study was to evaluate lifestyle habits, such as physical activity (PA), sitting time, nutritional habits (expressed as median modified Mediterranean Diet Score [mMDS]), alcohol consumption habits, and sleeping behavior during a 2-month period of confinement and social distancing due to the COVID-19 pandemic. Survey participants were students and employees of a Swiss university of applied sciences. METHODS: All students and employees from Bern University of Applied Sciences, Department of Health Professions (ie, nursing, nutrition and dietetics, midwifery, and physiotherapy divisions) were invited to complete an anonymous online survey during the COVID-19 confinement period. Information on the lifestyle dimensions of PA, sitting time, nutritional and alcohol consumption habits, and sleep behavior was gathered using adaptations of validated questionnaires. Frequency analyses and nonparametric statistical methods were used for data analysis. Significance was set at 5% α level of error. RESULTS: Prevalence of non-health-enhancing PA was 37.1%, with participants of the division of physiotherapy showing the lowest prevalence. Prevalence of long sitting time (>8 hours/day) was 36.1%. The median mMDS was 9, where the maximal score was 15, with participants of the division of nutrition and dietetics being more adherent to a Mediterranean diet as compared to the other groups. Prevalence of nonadherence to the Swiss alcohol consumption recommendations was 8.3%. Prevalence of low sleeping quality was 44.7%, while the median sleeping duration was 8 hours, which is considered healthy for adult populations. CONCLUSIONS: In the group analysis, differences in PA, sitting time, and mMDS were observed between different divisions of health professions as well as between Bachelor of Science students, Master of Science students, and employees. Therefore, public health messages regarding healthy lifestyle habits during home confinement should be more group specific. The results of this study may provide support for the implementation of group-specific health promotion interventions at universities in pandemic conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04502108; https://www.clinicaltrials.gov/ct2/show/NCT04502108.


Subject(s)
COVID-19/prevention & control , Exercise/psychology , Faculty/psychology , Feeding Behavior , Quarantine , Sleep , Students/psychology , Adult , COVID-19/epidemiology , Faculty/statistics & numerical data , Female , Humans , Male , Students/statistics & numerical data , Surveys and Questionnaires , Switzerland/epidemiology , Universities , Young Adult
3.
JMIR Public Health Surveill ; 7(4): e25500, 2021 04 07.
Article in English | MEDLINE | ID: covidwho-2141301

ABSTRACT

BACKGROUND: The COVID-19 pandemic, caused by a novel coronavirus termed SARS-CoV-2, has spread quickly worldwide. Convalescent plasma (CP) obtained from patients following recovery from COVID-19 infection and development of antibodies against the virus is an attractive option for either prophylactic or therapeutic treatment, since antibodies may have direct or indirect antiviral activities and immunotherapy has proven effective in principle and in many clinical reports. OBJECTIVE: We seek to characterize the latest advances and evidence in the use of CP for COVID-19 through a systematic review and quantitative analysis, identify knowledge gaps in this setting, and offer recommendations and directives for future research. METHODS: PubMed, Web of Science, and Embase were continuously searched for studies assessing the use of CP for COVID-19, including clinical studies, commentaries, reviews, guidelines or protocols, and in vitro testing of CP antibodies. The screening process and data extraction were performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality appraisal of all clinical studies was conducted using a universal tool independent of study designs. A meta-analysis of case-control and randomized controlled trials (RCTs) was conducted using a random-effects model. RESULTS: Substantial literature has been published covering various aspects of CP therapy for COVID-19. Of the references included in this review, a total of 243 eligible studies including 64 clinical studies, 79 commentary articles, 46 reviews, 19 guidance and protocols, and 35 in vitro testing of CP antibodies matched the criteria. Positive results have been mostly observed so far when using CP for the treatment of COVID-19. There were remarkable heterogeneities in the CP therapy with respect to patient demographics, donor antibody titers, and time and dose of CP administration. The studies assessing the safety of CP treatment reported low incidence of adverse events. Most clinical studies, in particular case reports and case series, had poor quality. Only 1 RCT was of high quality. Randomized and nonrandomized data were found in 2 and 11 studies, respectively, and were included for meta-analysis, suggesting that CP could reduce mortality and increase viral clearance. Despite promising pilot studies, the benefits of CP treatment can only be clearly established through carefully designed RCTs. CONCLUSIONS: There is developing support for CP therapy, particularly for patients who are critically ill or mechanically ventilated and resistant to antivirals and supportive care. These studies provide important lessons that should inform the planning of well-designed RCTs to generate more robust knowledge for the efficacy of CP in patients with COVID-19. Future research is necessary to fill the knowledge gap regarding prevention and treatment for patients with COVID-19 with CP while other therapeutics are being developed.


Subject(s)
COVID-19/therapy , Coronavirus Infections , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Humans , Immunization, Passive
4.
JMIR Public Health Surveill ; 7(4): e21468, 2021 04 19.
Article in English | MEDLINE | ID: covidwho-2141284

ABSTRACT

BACKGROUND: The major medical and social challenge of the 21st century is COVID-19, caused by the novel coronavirus SARS-CoV-2. Critical issues include the rate at which the coronavirus spreads and the effect of quarantine measures and population vaccination on this rate. Knowledge of the laws of the spread of COVID-19 will enable assessment of the effectiveness and reasonableness of the quarantine measures used, as well as determination of the necessary level of vaccination needed to overcome this crisis. OBJECTIVE: This study aims to establish the laws of the spread of COVID-19 and to use them to develop a mathematical model to predict changes in the number of active cases over time, possible human losses, and the rate of recovery of patients, to make informed decisions about the number of necessary beds in hospitals, the introduction and type of quarantine measures, and the required threshold of vaccination of the population. METHODS: This study analyzed the onset of COVID-19 spread in countries such as China, Italy, Spain, the United States, the United Kingdom, Japan, France, and Germany based on publicly available statistical data. The change in the number of COVID-19 cases, deaths, and recovered persons over time was examined, considering the possible introduction of quarantine measures and isolation of infected people in these countries. Based on the data, the virus transmissibility and the average duration of the disease at different stages were evaluated, and a model based on the principle of recursion was developed. Its key features are the separation of active (nonisolated) infected persons into a distinct category and the prediction of their number based on the average duration of the disease in the inactive phase and the concentration of these persons in the population in the preceding days. RESULTS: Specific values for SARS-CoV-2 transmissibility and COVID-19 duration were estimated for different countries. In China, the viral transmissibility was 3.12 before quarantine measures were implemented and 0.36 after these measures were lifted. For the other countries, the viral transmissibility was 2.28-2.76 initially, and it then decreased to 0.87-1.29 as a result of quarantine measures. Therefore, it can be expected that the spread of SARS-CoV-2 will be suppressed if 56%-64% of the total population becomes vaccinated or survives COVID-19. CONCLUSIONS: The quarantine measures adopted in most countries are too weak compared to those previously used in China. Therefore, it is not expected that the spread of COVID-19 will stop and the disease will cease to exist naturally or owing to quarantine measures. Active vaccination of the population is needed to prevent the spread of COVID-19. Furthermore, the required specific percentage of vaccinated individuals depends on the magnitude of viral transmissibility, which can be evaluated using the proposed model and statistical data for the country of interest.


Subject(s)
COVID-19/transmission , Models, Theoretical , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Global Health , Humans , Quarantine/legislation & jurisprudence
5.
Nature ; 593(7857): 136-141, 2021 05.
Article in English | MEDLINE | ID: covidwho-2114170

ABSTRACT

Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, Synthetic/immunology , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/isolation & purification , Antibodies, Neutralizing/isolation & purification , Antibodies, Viral/isolation & purification , COVID-19/metabolism , COVID-19/virology , Female , HEK293 Cells , Humans , Immune Evasion/genetics , Immune Evasion/immunology , Immunization, Passive , Male , Middle Aged , Models, Molecular , Mutation , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Vaccines, Synthetic/administration & dosage
6.
Ann Intern Med ; 173(4): 268-277, 2020 08 18.
Article in English | MEDLINE | ID: covidwho-2110835

ABSTRACT

BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19-positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. RESULTS: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.


Subject(s)
Autopsy/methods , Coronavirus Infections/mortality , Pneumonia, Viral/mortality , Pulmonary Embolism/mortality , Venous Thromboembolism/mortality , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Cause of Death , Female , Germany/epidemiology , Humans , Male , Middle Aged , Pandemics , Prospective Studies , SARS-CoV-2 , Tomography, X-Ray Computed
7.
Psychiatr Danub ; 32(1): 32-35, 2020.
Article in English | MEDLINE | ID: covidwho-2100749

ABSTRACT

The increase in organisms transference and infectious pandemics across the globe have been accelerated by an increase in travel, international exchange and global changes in earth's climate. COVID-19, a virus caused by the novel coronavirus that was initially identified on December 2019, in Wuhan city of China is currently affecting 146 territories, states and countries raising distress, panic and increasing anxiety in individuals exposed to the (actual or supposed) peril of the virus across the globe. Fundamentally, these concerns ascend with all infections, including those of flu and other agents, and the same worldwide safeguards are compulsory and suggested for protection and the prevention of further diffusion. However, media has underlined COVID-19 as rather an exclusive threat, which has added to panic and stress in masses which can lead to several mental health issues like anxiety, obsessive compulsive disorder and post-traumatic stress disorder which should be contained immediately in its initial phases.


Subject(s)
Coronavirus Infections/psychology , Global Health , Mental Health , Pandemics , Pneumonia, Viral/psychology , Stress, Psychological , Betacoronavirus , COVID-19 , China , Humans , Mass Media , SARS-CoV-2 , Stress Disorders, Post-Traumatic
8.
Scand J Trauma Resusc Emerg Med ; 28(1): 66, 2020 Jul 13.
Article in English | MEDLINE | ID: covidwho-2098371

ABSTRACT

BACKGROUND: There is a need for validated clinical risk scores to identify patients at risk of severe disease and to guide decision-making during the covid-19 pandemic. The National Early Warning Score 2 (NEWS2) is widely used in emergency medicine, but so far, no studies have evaluated its use in patients with covid-19. We aimed to study the performance of NEWS2 and compare commonly used clinical risk stratification tools at admission to predict risk of severe disease and in-hospital mortality in patients with covid-19. METHODS: This was a prospective cohort study in a public non-university general hospital in the Oslo area, Norway, including a cohort of all 66 patients hospitalised with confirmed SARS-CoV-2 infection from the start of the pandemic; 13 who died during hospital stay and 53 who were discharged alive. Data were collected consecutively from March 9th to April 27th 2020. The main outcome was the ability of the NEWS2 score and other clinical risk scores at emergency department admission to predict severe disease and in-hospital mortality in covid-19 patients. We calculated sensitivity and specificity with 95% confidence intervals (CIs) for NEWS2 scores ≥5 and ≥ 6, quick Sequential Organ Failure Assessment (qSOFA) score ≥ 2, ≥2 Systemic Inflammatory Response Syndrome (SIRS) criteria, and CRB-65 score ≥ 2. Areas under the curve (AUCs) for the clinical risk scores were compared using DeLong's test. RESULTS: In total, 66 patients (mean age 67.9 years) were included. Of these, 23% developed severe disease. In-hospital mortality was 20%. Tachypnoea, hypoxemia and confusion at admission were more common in patients developing severe disease. A NEWS2 score ≥ 6 at admission predicted severe disease with 80.0% sensitivity and 84.3% specificity (Area Under the Curve (AUC) 0.822, 95% CI 0.690-0.953). NEWS2 was superior to qSOFA score ≥ 2 (AUC 0.624, 95% CI 0.446-0.810, p < 0.05) and other clinical risk scores for this purpose. CONCLUSION: NEWS2 score at hospital admission predicted severe disease and in-hospital mortality, and was superior to other widely used clinical risk scores in patients with covid-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Early Warning Score , Hospital Mortality , Patient Admission , Pneumonia, Viral/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19 , Cohort Studies , Female , Humans , Male , Middle Aged , Norway/epidemiology , Pandemics , Risk Assessment , SARS-CoV-2 , Sensitivity and Specificity , Severity of Illness Index
9.
J Mol Struct ; 1229: 129489, 2021 Apr 05.
Article in English | MEDLINE | ID: covidwho-2095816

ABSTRACT

The COVID-19 pandemic, caused by SARS CoV-2, is responsible for millions of death worldwide. No approved/proper therapeutics is currently available which can effectively combat this outbreak. Several attempts have been undertaken in the search of effective drugs to control the spread of SARS CoV-2 infection. The main protease (Mpro), key component for the cleavage of the viral polyprotein, is considered to be one of the important drug targets for treating COVID-19. Various phytochemicals, including polyphenols and alkaloids, have been proposed as potent inhibitors of Mpro. The alkaloids from leaf extracts of Justicia adhatoda have also been reported to possess anti-viral activity. But whether these alkaloids exhibit any inhibitory effect on SARS CoV-2 Mpro is far from clear. To explore this in detail, we have adopted computational approaches. Justicia adhatoda alkaloids possessing proper drug-likeness properties and two anti-HIV drugs (lopinavir and darunavir; having binding affinity -7.3 to -7.4 kcal/mol) were docked against SARS CoV-2 Mpro to study their binding properties. Only one alkaloid (anisotine) had interaction with both the catalytic residues (His41 and Cys145) of Mpro and exhibited good binding affinity (-7.9 kcal/mol). Molecular dynamic simulations (100 ns) revealed that Mpro-anisotine complex is more stable, conformationally less fluctuated; slightly less compact and marginally expanded than Mpro-darunavir/lopinavir complex. Even the number of intermolecular H-bonds and MM-GBSA analysis suggested that anisotine is a more potent Mpro inhibitor than the two previously recommended antiviral drugs (lopinavir and darunavir) and may evolve as a promising anti-COVID-19 drug if proven in animal experiments and on patients.

11.
Curr Opin Psychiatry ; 34(3): 203-210, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-2078019

ABSTRACT

PURPOSE OF REVIEW: The coronavirus disease 19 (COVID-19) pandemic is having a critical impact on healthcare systems across the world, as well as on mental health in the general population; however, evidence regarding the impact of the COVID-19 pandemic on people living with schizophrenia and on the onset of psychotic symptoms is currently emerging. RECENT FINDINGS: People living with schizophrenia are at an increased risk of COVID-19 and present worse COVID-19-related outcomes, including mortality. They show low levels of information and of concern regarding the possibility of contagion and infection but presented substantially stable levels of psychotic symptoms and even increased subjective well being during the pandemic. SARS-CoV-2, as well as the prolonged social isolation and the spread of misinformation, appear to be responsible in some cases for the onset of psychotic symptoms. SUMMARY: Clinicians should inform and educate their patients on the risks related to SARS-CoV-2 infection and COVID-19 and on the precautions that they should adopt to avoid contagion. Particular attention should be devoted to maintaining the continuity of care, especially in frail patients. Telemedicine might represent a valid support, but face-to-face visits in some cases remain essential. The hypothesis of a direct role of viral infection on the onset of psychotic disorders is currently debated, as viral involvement of central nervous system appears to be rather infrequent in COVID-19.


Subject(s)
COVID-19 , Continuity of Patient Care , Psychotic Disorders , Schizophrenia , Telemedicine , COVID-19/prevention & control , Humans , Psychotic Disorders/therapy , Schizophrenia/therapy
12.
J Am Heart Assoc ; 9(22): e017364, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-2064368

ABSTRACT

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes the angiotensin-converting enzyme-2 (ACE-2) receptor to enter human cells. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARB) are associated with ACE-2 upregulation. We hypothesized that antecedent use of ACEI/ARB may be associated with mortality in coronavirus disease 2019 (COVID-19). Methods and Results We used the Coracle registry, which contains data of patients hospitalized with COVID-19 in 4 regions of Italy, and restricted analyses to those ≥50 years of age. The primary outcome was in-hospital mortality. Among these 781 patients, 133 (17.0%) used an ARB and 171 (21.9%) used an ACEI. While neither sex nor smoking status differed by user groups, patients on ACEI/ARB were older and more likely to have hypertension, diabetes mellitus, and congestive heart failure. The overall mortality rate was 15.1% (118/781) and increased with age (PTrend<0.0001). The crude odds ratios (ORs) for death for ACEI users and ARB users were 0.98, 95% CI, 0.60-1.60, P=0.9333, and 1.13, 95% CI, 0.67-1.91, P=0.6385, respectively. After adjusting for age, hypertension, diabetes mellitus, and congestive heart failure, antecedent ACEI administration was associated with reduced mortality (OR, 0.55; 95% CI, 0.31-0.98, P=0.0436); a similar, but weaker trend was observed for ARB administration (OR, 0.58; 95% CI, 0.32-1.07, P=0.0796). Conclusions In those aged ≥50 years hospitalized with COVID-19, antecedent use of ACEI was independently associated with reduced risk of inpatient death. Our findings suggest a protective role of renin-angiotensin-aldosterone system inhibition in patients with high cardiovascular risk affected by COVID-19.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/therapy , Hospitalization , Age Factors , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Female , Hospital Mortality , Humans , Italy , Male , Middle Aged , Protective Factors , Registries , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
13.
Pathologe ; 42(Suppl 1): 89-97, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1971686

ABSTRACT

BACKGROUND: A dysregulated immune response is considered one of the major factors leading to severe COVID-19. Previously described mechanisms include the development of a cytokine storm, missing immunoglobulin class switch, antibody-mediated enhancement, and aberrant antigen presentation. OBJECTIVES: To understand the heterogeneity of immune response in COVID-19, a thorough investigation of histomorphological patterns in regional lymph nodes was performed. MATERIALS AND METHODS: Lymph nodes from the cervical, mediastinal, and hilar regions were extracted from autopsies of patients with lethal COVID-19 (n = 20). Histomorphological characteristics, SARS-CoV­2 qRT-PCR, and gene expression profiling on common genes involved in immunologic response were analyzed. RESULTS: Lymph nodes displayed moderate to severe capillary stasis and edema, an increased presence of extrafollicular plasmablasts, mild to moderate plasmacytosis, a dominant population of CD8+ T­cells, and CD11c/CD68+ histiocytosis with hemophagocytic activity. Out of 20 cases, 18 presented with hypoplastic or missing germinal centers with a decrease of follicular dendritic cells and follicular T­helper cells. A positive viral load was detected by qRT-PCR in 14 of 20 cases, yet immunohistochemistry for SARS-CoV-2 N-antigen revealed positivity in sinus histiocytes of only one case. Gene expression analysis revealed an increased expression of STAT1, CD163, granzyme B, CD8A, MZB1, and PAK1, as well as CXCL9. CONCLUSIONS: Taken together, our findings imply a dysregulated immune response in lethal COVID-19. The absence/hypoplasia of germinal centers and increased presence of plasmablasts implies a transient B­cell response, implying an impaired development of long-term immunity against SARS-CoV­2 in such occasions.


Subject(s)
COVID-19 , CD8-Positive T-Lymphocytes , Humans , Lung , Lymph Nodes , SARS-CoV-2
14.
Clin Exp Rheumatol ; 39(3): 676-687, 2021.
Article in English | MEDLINE | ID: covidwho-1970080

ABSTRACT

Systemic autoimmune diseases (SAD) are a heterogeneous group of diseases with a common aetiopathogenic basis affecting all ages characterised by a systemic phenotypic expression with a wide range of severity and outcomes that often require immunosuppressive therapies, leaving patients at high risk of infection. Knowledge of the impact of COVID-19 in patients with SAD is limited because most are included in studies carried out in patients with autoimmune and rheumatic diseases (mainly inflammatory arthritis). Most studies supported an increased risk of SARS-Cov-2 infection in patients with AD and SAD. Although case-control studies reported no significant differences in the rate of poor outcomes between patients with and without AD, large population-based studies analysing baseline risk factors reported a 2-3 times higher rate of poor outcomes in patients with AD, especially in those with SAD. Individual risk factors associated with poor outcomes included gender male, older age, and underlying comorbidities and therapies (glucocorticoids, sulfasalazine, immunosuppressants and rituximab). Patients with SAD had less favourable COVID-19 outcomes than those with inflammatory arthritis, possibly due to a differentiated underlying therapeutic approach (glucocorticoids, immunosuppressants and B-cell depleting agents for most SAD, anti-cytokine therapies and JAK inhibitors for inflammatory arthritis). Despite the limited evidence, most studies suggest that patients with SAD have an increased risk of a worse evolution of SARS-CoV-2 infection, including a greater risk of hospitalisation/ICU admission and worse survival rates and, therefore, should be considered a high-risk group for COVID-19.


Subject(s)
Autoimmune Diseases , COVID-19 , Rheumatic Diseases , Aged , Autoimmune Diseases/diagnosis , Autoimmune Diseases/drug therapy , Autoimmune Diseases/epidemiology , Glucocorticoids/therapeutic use , Humans , Male , SARS-CoV-2
15.
Curr Opin Anaesthesiol ; 34(2): 187-198, 2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1956585

ABSTRACT

PURPOSE OF REVIEW: Hospitalizations for COVID-19 dramatically increase with age. This is likely because of increases in fragility across biological repair systems and a weakened immune system, including loss of the cardiorenal protective arm of the renin--angiotensin system (RAS), composed of angiotensin-converting enzyme-2 (ACE2)/angiotensin-(1--7) [Ang-(1--7)] and its actions through the Mas receptor. The purpose of this review is to explore how cardiac ACE2 changes with age, cardiac diseases, comorbid conditions and pharmaceutical regimens in order to shed light on a potential hormonal unbalance facilitating SARs-CoV-2 vulnerabilities in older adults. RECENT FINDINGS: Increased ACE2 gene expression has been reported in human hearts with myocardial infarction, cardiac remodeling and heart failure. We also found ACE2 mRNA in atrial appendage tissue from cardiac surgical patients to be positively associated with age, elevated by certain comorbid conditions (e.g. COPD and previous stroke) and increased in conjunction with patients' chronic use of antithrombotic agents and thiazide diuretics but not drugs that block the renin--angiotensin system. SUMMARY: Cardiac ACE2 may have bifunctional roles in COVID-19 as ACE2 not only mediates cellular susceptibility to SARS-CoV-2 infection but also protects the heart via the ACE2/Ang-(1--7) pathway. Linking tissue ACE2 from cardiac surgery patients to their comorbid conditions and medical regimens provides a unique latform to address the influence that altered expression of the ACE2/Ang-(1-7)/Mas receptor axis might have on SARs-CoV-2 vulnerability in older adults.


Subject(s)
Atrial Appendage , COVID-19 , Cardiac Surgical Procedures , Aged , Aging , Angiotensin-Converting Enzyme 2 , Angiotensins , Atrial Appendage/surgery , Humans , SARS-CoV-2
16.
Front Psychol ; 11: 594837, 2020.
Article in English | MEDLINE | ID: covidwho-1933808

ABSTRACT

Unemployed benefit recipients are stigmatized and generally perceived negatively in terms of their personality characteristics and employability. The COVID19 economic shock led to rapid public policy responses across the globe to lessen the impact of mass unemployment, potentially shifting community perceptions of individuals who are out of work and rely on government income support. We used a repeated cross-sections design to study change in stigma tied to unemployment and benefit receipt in a pre-existing pre-COVID19 sample (n = 260) and a sample collected during COVID19 pandemic (n = 670) by using a vignette-based experiment. Participants rated attributes of characters who were described as being employed, working poor, unemployed or receiving unemployment benefits. The results show that compared to employed characters, unemployed characters were rated substantially less favorably at both time points on their employability and personality traits. The difference in perceptions of the employed and unemployed was, however, attenuated during COVID19 with benefit recipients perceived as more employable and more Conscientious than pre-pandemic. These results add to knowledge about the determinants of welfare stigma highlighting the impact of the global economic and health crisis on perception of others.

17.
Lancet Respir Med ; 9(5): 533-544, 2021 05.
Article in English | MEDLINE | ID: covidwho-1931217

ABSTRACT

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Cough/etiology , Inflammation/etiology , Nervous System Diseases/etiology , Neuroimmunomodulation , Cough/physiopathology , Humans , Inflammation/physiopathology , Nervous System Diseases/physiopathology , SARS-CoV-2 , Syndrome
18.
Sleep Med ; 91: 185-188, 2022 03.
Article in English | MEDLINE | ID: covidwho-1907780

ABSTRACT

OBJECTIVE: This study investigates insomnia among employees in occupations critical to the functioning of society (e.g health, education, welfare and emergency services) during the COVID-19 pandemic. Many of these workers experience higher job pressure and increased risk of infection due to their work. It is crucial to investigate which factors that can contribute to insomnia in these important sectors. METHODS: Data was collected using an online survey administered in June 2020. The questionnaire measured demographic variables, sleep, stress, psychosocial factors and health concerns (i.e worrying about health consequences related to the pandemic). The sample in the present study consisted of 1327 (76% females) employees in organizations with societal critical functions. RESULTS: The employees reported higher levels of insomnia symptoms compared to normative data collected before the pandemic. Health concerns specifically related to COVID-19 had the strongest association to insomnia, followed by work stress. Job demands (i.e workload, time pressure and overtime) had merely a weak association to insomnia. CONCLUSION: Worrying about consequences the pandemic can have on your own health and the health of your family or colleagues have a stronger negative impact on sleep than work pressure during the COVID-19 pandemic. Impaired sleep can have detrimental effects on performance and health, and a stronger focus on preventing insomnia as a mean of sustaining critical societal functions both during and after the pandemic is warranted. Organizations should consider interventions aimed at reducing health concerns among their employees during the COVID-19 pandemic.


Subject(s)
COVID-19 , Sleep Initiation and Maintenance Disorders , Anxiety , Female , Humans , Male , Occupations , Pandemics , Sleep Initiation and Maintenance Disorders/epidemiology
19.
Clin Imaging ; 64: 35-42, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1906892

ABSTRACT

As the global pandemic of coronavirus disease-19 (COVID-19) progresses, many physicians in a wide variety of specialties continue to play pivotal roles in diagnosis and management. In radiology, much of the literature to date has focused on chest CT manifestations of COVID-19 (Zhou et al. [1]; Chung et al. [2]). However, due to infection control issues related to patient transport to CT suites, the inefficiencies introduced in CT room decontamination, and lack of CT availability in parts of the world, portable chest radiography (CXR) will likely be the most commonly utilized modality for identification and follow up of lung abnormalities. In fact, the American College of Radiology (ACR) notes that CT decontamination required after scanning COVID-19 patients may disrupt radiological service availability and suggests that portable chest radiography may be considered to minimize the risk of cross-infection (American College of Radiology [3]). Furthermore, in cases of high clinical suspicion for COVID-19, a positive CXR may obviate the need for CT. Additionally, CXR utilization for early disease detection may also play a vital role in areas around the world with limited access to reliable real-time reverse transcription polymerase chain reaction (RT-PCR) COVID testing. The purpose of this pictorial review article is to describe the most common manifestations and patterns of lung abnormality on CXR in COVID-19 in order to equip the medical community in its efforts to combat this pandemic.


Subject(s)
Clinical Laboratory Techniques , Coronavirus Infections , Pandemics , Pneumonia, Viral , Radiography, Thoracic , Betacoronavirus , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Coronavirus , Coronavirus Infections/diagnosis , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/epidemiology , Humans , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/epidemiology , Radiography, Thoracic/instrumentation , SARS-CoV-2 , Tomography, X-Ray Computed , X-Rays
20.
Adv Radiat Oncol ; 7(5): 100667, 2022.
Article in English | MEDLINE | ID: covidwho-1899443

ABSTRACT

Purpose: The COVID-19 pandemic brought several challenges to cancer practice, especially in ensuring continuity of treatment during this period while minimizing the risks of transmission to a vulnerable population. For radiation oncology departments in Brazil, this contingency has become even more complex owing to the significant effect observed in different sectors of society and the large number of COVID-19 cases and deaths. This study estimated the effect of the COVID-19 pandemic on Brazilian radiation oncology departments and the coping measures used in the country. Methods and Materials: The Brazilian Radiotherapy Society developed a questionnaire, with 14 questions, that were sent to all heads of radiation oncology departments in the country between May and June 2020. These data were evaluated regarding cases confirmed and deaths by COVID-19 in epidemiologic week 28, on July 11, 2020. Results: One hundred twenty-six questionnaires from different regions were answered, representing 44% of the country's services. A drop in the number of patients was observed in 61% of services. This drop was observed both in patients from the public and supplementary private health insurance systems. Regarding patients and employees with COVID-19, we observed that services that primarily treat Unified Health System patients reported significantly fewer cases of the disease. About half of the services had collaborators and patients during radiation therapy with a positive diagnosis of COVID-19. Among the coping measures, the services used intensified hygiene and cleanliness practices, interpersonal distancing, restrictions on access to companions, and other changes in daily practice. Conclusions: Thus, there was an important drop in the number of radiation therapy patients in the country during the pandemic, and this effect was similar among the services, regardless of the characteristics of the patients and the departments' coping measures adopted during the pandemic.

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