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1.
arxiv; 2023.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2308.11173v1

ABSTRACT

This paper examines the effectiveness of several forecasting methods for predicting inflation, focusing on aggregating disaggregated forecasts - also known in the literature as the bottom-up approach. Taking the Brazilian case as an application, we consider different disaggregation levels for inflation and employ a range of traditional time series techniques as well as linear and nonlinear machine learning (ML) models to deal with a larger number of predictors. For many forecast horizons, the aggregation of disaggregated forecasts performs just as well survey-based expectations and models that generate forecasts using the aggregate directly. Overall, ML methods outperform traditional time series models in predictive accuracy, with outstanding performance in forecasting disaggregates. Our results reinforce the benefits of using models in a data-rich environment for inflation forecasting, including aggregating disaggregated forecasts from ML techniques, mainly during volatile periods. Starting from the COVID-19 pandemic, the random forest model based on both aggregate and disaggregated inflation achieves remarkable predictive performance at intermediate and longer horizons.


Subject(s)
COVID-19
2.
BMC Musculoskelet Disord ; 24(1): 466, 2023 Jun 07.
Article in English | MEDLINE | ID: covidwho-20233788

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, people with low back pain (LBP) might have avoided seeking care for their pain. We aimed to investigate how the COVID-19 pandemic has affected LBP care seeking behavior among adults. METHODS: Data from four assessments of the PAMPA cohort were analyzed. Participants who reported experiencing LBP during wave one both before and during social restrictions (n = 1,753 and n = 1,712, respectively), wave two (n = 2,009), and wave three (n = 2,482) were included. We asked participants about sociodemographic, behavioral, and health factors and outcomes related to LBP. Poisson regression analyses were conducted, and data are presented as prevalence ratios (PR) and respective 95% confidence interval (95%CI). RESULTS: Overall, care seeking behavior decreased by half in the first months of restrictions, from 51.5% to 25.2%. Although there was an increase in care seeking behavior observed in the other two assessments (nearly 10 and 16 months after restrictions), it was insufficient to reach pre-pandemic levels. In the first months of restrictions, a similar scenario was observed for specific care, such as general practitioner and exercise professional care, with proportions of pre-pandemic levels reached after 10 and 16 months. Women were more likely to seek care for LBP 10 and 16 months after restrictions (PR 1.30 95%CI 1.11; 1.52, PR 1.22 95%CI 1.06; 1.39, respectively). Also, those participants who worked, were physically active, and reported pain-related disability and high pain levels were more likely to seek care at all time points assessed. CONCLUSION: Overall, care-seeking behavior for LBP significantly decreased in the first months of restrictions and increased in the following months; however, this behavior remained lower than pre-pandemic levels.


Subject(s)
COVID-19 , Low Back Pain , Adult , Humans , Female , Low Back Pain/diagnosis , Low Back Pain/epidemiology , Low Back Pain/therapy , Pandemics , Brazil/epidemiology , COVID-19/epidemiology , Patient Acceptance of Health Care
3.
J Mol Model ; 29(6): 183, 2023 May 22.
Article in English | MEDLINE | ID: covidwho-2325832

ABSTRACT

CONTEXT: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 infection and responsible for millions of victims worldwide, remains a significant threat to public health. Even after the development of vaccines, research interest in the emergence of new variants is still prominent. Currently, the focus is on the search for effective and safe drugs, given the limitations and side effects observed for the synthetic drugs administered so far. In this sense, bioactive natural products that are widely used in the pharmaceutical industry due to their effectiveness and low toxicity have emerged as potential options in the search for safe drugs against COVID-19. Following this line, we screened 10 bioactive compounds derived from cholesterol for molecules capable of interacting with the receptor-binding domain (RBD) of the spike protein from SARS-CoV-2 (SC2Spike), responsible for the virus's invasion of human cells. Rounds of docking followed by molecular dynamics simulations and binding energy calculations enabled the selection of three compounds worth being experimentally evaluated against SARS-CoV-2. METHODS: The 3D structures of the cholesterol derivatives were prepared and optimized using the Spartan 08 software with the semi-empirical method PM3. They were then exported to the Molegro Virtual Docking (MVD®) software, where they were docked onto the RBD of a 3D structure of the SC2Spike protein that was imported from the Protein Data Bank (PDB). The best poses obtained from MVD® were subjected to rounds of molecular dynamics simulations using the GROMACS software, with the OPLS/AA force field. Frames from the MD simulation trajectories were used to calculate the ligand's free binding energies using the molecular mechanics - Poisson-Boltzmann surface area (MM-PBSA) method. All results were analyzed using the xmgrace and Visual Molecular Dynamics (VMD) software.


Subject(s)
Biological Products , COVID-19 , Humans , SARS-CoV-2 , Biological Products/pharmacology , Molecular Dynamics Simulation , Databases, Protein , Molecular Docking Simulation , Antiviral Agents/pharmacology
4.
Motriz (Online) ; 27: e10200200, 2021.
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-2292910

ABSTRACT

Abstract The COVID-19 pandemic had an impact in several areas, and in scientific research was not different. Researchers are working from their homes since research facilities and universities were closed, and face-to-face interaction where limited to stop the virus spread. This brought a lot of changes in observational studies, especially in epidemiology research. Since most studies are being conducted through internet-based assessments, researchers are facing different challenges regarding data collection and participants recruitment, for example. In this paper, we share some of the challenges faced in a population-based study conducted in Southern Brazil, as well as possible alternatives to help researchers to overcome these issues.


Subject(s)
Social Isolation , Health Care Surveys/methods , COVID-19/epidemiology , Data Collection/supply & distribution
5.
Int J Methods Psychiatr Res ; : e1931, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-2276834

ABSTRACT

OBJECTIVES: We describe the harmonized MRI acquisition and quality assessment of an ongoing global OCD study, with the aim to translate representative, well-powered neuroimaging findings in neuropsychiatric research to worldwide populations. METHODS: We report on T1-weighted structural MRI, resting-state functional MRI, and multi-shell diffusion-weighted imaging of 140 healthy participants (28 per site), two traveling controls, and regular phantom scans. RESULTS: Human image quality measures (IQMs) and outcome measures showed smaller within-site variation than between-site variation. Outcome measures were less variable than IQMs, especially for the traveling controls. Phantom IQMs were stable regarding geometry, SNR, and mean diffusivity, while fMRI fluctuation was more variable between sites. CONCLUSIONS: Variation in IQMs persists, even for an a priori harmonized data acquisition protocol, but after pre-processing they have less of an impact on the outcome measures. Continuous monitoring IQMs per site is valuable to detect potential artifacts and outliers. The inclusion of both cases and healthy participants at each site remains mandatory.

6.
ZDM ; : 1-14, 2022 Sep 06.
Article in English | MEDLINE | ID: covidwho-2236665

ABSTRACT

Research literature on the role of mathematics teachers during the COVID-19 crisis shows that teacher preparation for emergency situations is required. In reporting on this exploratory study, we present and analyse lesson plans created by seven future teachers for mathematics classes during the pandemic. Data were collected between April and October 2021 from 16 four-hour class sessions in a Mathematics Degree Program at a public university in Medellín, Colombia. The notion of Humans-with-Media and the Learning by Expanding theory were used as frameworks to understand what roles prospective mathematics teacher (PMTs) assign to technologies for teaching in pandemic conditions. The PMTs' uses of technology for teaching mathematics during a pandemic were categorized. The results show that technology was used to reorganize and reproduce mathematics teaching practices. This report addresses the impact of technology on the activity system, and we conclude with a discussion of opportunities and limitations of students' conceptions about teaching and technology during a pandemic.

7.
ZDM ; : 1-14, 2022 Sep 20.
Article in English | MEDLINE | ID: covidwho-2229761

ABSTRACT

The global COVID-19 pandemic has provided an opportunity to re-examine the possibility of organising virtual conferences in mathematics education, in which the social needs of participants can also be addressed. In this study we investigated the future impact that this change may have on the format and nature of mathematics education conferences. The study was conducted in two phases. We used an online questionnaire in which we asked participants to give us some input on the issues above. In the second phase of the project, focus group interviews were conducted with international mathematics education researchers. This study is an exploratory study, in which the sample was not developed in a way that could generate comparisons. The aim of the study was to raise possibilities about what may be the future of mathematics education conferences. Findings indicate that although academics are pro-actively thinking about alternative conference formats, the proven value of face-to-face conferences is still very real, showing that it is too early for us to have a clear vision of the future format of academic conferences.

8.
Transplant Cell Ther ; 29(4): 254.e1-254.e9, 2023 04.
Article in English | MEDLINE | ID: covidwho-2181022

ABSTRACT

Toxicities after chimeric antigen receptor T cell (CAR-T) therapy are well known, yet the patient experience during and after CAR-T therapy has not been well described outside of the trial setting. We explored the patient experience after CAR-T therapy to inform the patient-reported outcomes (PRO) measurement approach for the Center for International Blood and Marrow Transplant Research (CIBMTR). We recruited (1) adult patients diagnosed with a hematologic malignancy 14 days to 6 months after receiving a commercial CAR T cell product who had agreed to be contacted by the CIBMTR, (2) caregivers of those patients, and (3) clinical experts in CAR-T therapy. Telephone interviews were conducted following a semistructured guide that included open-ended questions about symptoms and functioning. We conducted a systematic content analysis of each transcript using prespecified codes representing common domains of health, as well as open coding for emergent themes. Forty patients at 29 centers, 15 of their caregivers, and 15 experts from 9 centers participated, representing diversity with respect to age, sex, race/ethnicity, and years in practice (experts). Patients, caregivers, and experts shared largely consistent impressions of the patient experience after CAR-T therapy. Commonly described themes included anxiety, cognitive dysfunction, depression, fatigue, pain, impaired physical function, gastrointestinal symptoms, sexual dysfunction, sleep difficulties, need for support, financial impact, hospitalization, communication with healthcare providers, and the COVID-19 pandemic. Limitations in patients' ability to participate in social roles and activities was the most prevalent theme, found in nearly all interviews. In the setting of CAR-T therapy, a multidimensional approach to PRO measurement is needed that includes physical, mental, and social health, as well as the financial impact of this novel treatment. High-quality existing PRO tools are available to measure these concepts. Results will inform the CIBMTR measurement of PROs after CAR-T therapy and may be applicable to other CAR-T studies that aim to represent patient experiences.


Subject(s)
COVID-19 , Receptors, Chimeric Antigen , Adult , Humans , Pandemics , COVID-19/epidemiology , Patient Reported Outcome Measures , Anxiety
9.
BMC Public Health ; 23(1): 44, 2023 01 06.
Article in English | MEDLINE | ID: covidwho-2196187

ABSTRACT

BACKGROUND: To evaluate the short-term impact of COVID-19 pandemic on low back pain (LBP) outcomes in southern Brazil. METHODS: Data from the PAMPA Cohort were analyzed. Adults were recruited between June and July 2020 in the Rio Grande do Sul state using online-based strategies. Participants responded a self-reported, online questionnaire on LBP with two timepoints: before (retrospectively) and during COVID-19 pandemic. We assessed LBP experience, LBP-related activity limitation (no/yes), and LBP intensity (0 to 10 [strongest pain]). RESULTS: From a total sample of 2,321 respondents (mean age: 37.6 ± 13.5; 75.4% women), the prevalence of LBP did not change significantly from before (74.7% [95%CI 72.3; 76.9]) to the first months of pandemic (74.2% [95%CI 71.9; 76.3]). However, an increased pain levels (ß: 0.40; 95%CI 0.22; 0.58) and a higher likelihood for activity limitation due to LBP was observed (PR 1.14; 95%CI 1.01; 1.29). Longitudinal analyzes showed that age, gender, BMI, chronic diseases, physical activity, and anxiety and depression symptoms, were associated with LBP in the first pandemic months. CONCLUSION: Although the prevalence of LBP did not change at the first months of COVID-19 pandemic, LBP-induced impairment in daily activities and pain intensity was higher when compared to before the pandemic.


Subject(s)
COVID-19 , Low Back Pain , Adult , Humans , Female , Young Adult , Middle Aged , Male , Pandemics , Low Back Pain/epidemiology , Retrospective Studies , Brazil/epidemiology , COVID-19/epidemiology
10.
Stat Med ; 42(7): 993-1012, 2023 03 30.
Article in English | MEDLINE | ID: covidwho-2173448

ABSTRACT

In this paper, we apply statistical methods for functional data to explore the heterogeneity in the registered number of deaths of COVID-19, over time. The cumulative daily number of deaths in regions across Brazil is treated as continuous curves (functional data). The first stage of the analysis applies clustering methods for functional data to identify and describe potential heterogeneity in the curves and their functional derivatives. The estimated clusters are labeled with different "levels of alert" to identify cities in a possible critical situation. In the second stage of the analysis, we apply a functional quantile regression model for the death curves to explore the associations with functional rates of vaccination and stringency and also with several scalar geographical, socioeconomic and demographic covariates. The proposed model gave a better curve fit at different levels of the cumulative number of deaths when compared to a functional regression model based on ordinary least squares. Our results add to the understanding of the development of COVID-19 death counts.


Subject(s)
COVID-19 , Communicable Diseases , Humans , Brazil , Least-Squares Analysis , Cities
11.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.01.06.522349

ABSTRACT

Viruses mutate under a variety of selection pressures, allowing them to continuously adapt to their hosts. Mutations in SARS-CoV-2 have shown effective evasion of population immunity and increased affinity to host factors, in particular to the cellular receptor ACE2. In the dynamic environment of the respiratory tract, the question arises, if not only affinity, but also force-stability of the SARS-CoV-2:ACE2 bond, initiating infection of host cells, might be a selection factor for mutations. Here, we use magnetic tweezers (MT) to study the effect of amino acid substitutions in variants of concern (VOCs) on RBD:ACE2 bond kinetics with and without external load using a previously established assay. Matching bulk-affinity measurements determined in literature, we find higher affinity for all VOCs compared to wt. In contrast to that, Alpha is the only VOC markedly different from the wild type showing higher mechanical resilience under force. Investigating the RBD:ACE2 interactions with molecular dynamics simulations, we were able to rationalize the mechanistic molecular origins of this increase in force-stability. Our study emphasizes the diversity of contributions to the assertiveness of variants and establishes force-stability as one of several factors for fitness. Understanding fitness-advantages opens the possibility for prediction of likely mutations allowing rapid adjustment of therapeutics, vaccination, and intervention measures.


Subject(s)
Seizures
13.
Ment Health Phys Act ; 23: 100468, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2036366

ABSTRACT

We examined the longitudinal association between physical activity (PA) and the incidence of self-reported diagnosed depression in adults in southern Brazil during the COVID-19 pandemic. Data from the PAMPA (Prospective Study About Mental and Physical Health) cohort was used. Data collection for baseline was carried out on June-July 2020, with two follow-up assessments taking place six months apart. An online, self-reported questionnaire assessed depression and PA. Depression was assessed by asking participants whether they were ever diagnosed with depression. We included 441 participants (women: 75.9%; mean age [SD]: 38.0 [13.5]) in southern Brazil. Over the follow-up, 21.8% (95% confidence interval [CI]: 18.1%-25.9%) were diagnosed with depression. Insufficiently active (<150 min per week of physical activity) (Incidence rate [IR]: 61.9; 95%CI: 39.5-102.4; p = 0.047) and active (≥150 min per week of physical activity) (IR: 50.4; 95%CI: 31.9-84.0; p = 0.015) participants had reduced IR of depression per 1000 persons-year at risk compared to inactive ones (0 min per week of physical activity) (IR: 99.9; 95%CI: 79.7-126.8). In the adjusted analyses, participants in the insufficient active (hazard ratio [HR]: 0.58; 95%CI: 0.34-0.98) and active (HR: 0.53; 95%CI: 0.31-0.93) group had a lower risk of developing depression than the inactive group. PA both at and out of home reduced the risk of incident depression (HR: 0.49; 95%CI: 0.25-0.98) compared to no physical activity. Endurance (HR: 0.52; 95%CI: 0.28-0.97) and endurance plus strengthening (HR: 0.40; 95%CI: 0.17-0.95) PA reduced the risk of incident depression compared to none. Being physically active during pandemic, regardless of the amount of PA practiced, reduced the incidence of depression in adults in southern Brazil.

14.
Zdm ; : 1-14, 2022.
Article in English | EuropePMC | ID: covidwho-2033921

ABSTRACT

The global COVID-19 pandemic has provided an opportunity to re-examine the possibility of organising virtual conferences in mathematics education, in which the social needs of participants can also be addressed. In this study we investigated the future impact that this change may have on the format and nature of mathematics education conferences. The study was conducted in two phases. We used an online questionnaire in which we asked participants to give us some input on the issues above. In the second phase of the project, focus group interviews were conducted with international mathematics education researchers. This study is an exploratory study, in which the sample was not developed in a way that could generate comparisons. The aim of the study was to raise possibilities about what may be the future of mathematics education conferences. Findings indicate that although academics are pro-actively thinking about alternative conference formats, the proven value of face-to-face conferences is still very real, showing that it is too early for us to have a clear vision of the future format of academic conferences.

15.
Vaccine ; 40(32): 4307-4311, 2022 07 30.
Article in English | MEDLINE | ID: covidwho-1882612

ABSTRACT

We described clinical characteristics and outcome of 160 patients over 65 years (01 September to 31 August 2021) who had a first positive SARS-CoV-2 PCR- test more than 14 days after full vaccination and were hospitalized with COVID-19. Median age of included patients was 84 years, 61.2% were over 80 years; 50.6% were male and most (82.5%) has at least one comorbidity. Up to 84% received specific treatment against COVID-19, including 76.9% low-flow oxygen therapy. We found that overall mortality was 25.6% and 30.6% in those older than 80 years. A higher mortality was significantly associated with older age and treatment with tocilizumab. Our data showed that although COVID-19 vaccines continue protecting elderly patients against hospitalization and death and might improve the prognosis after hospitalization in patients with breakthrough infections, mortality in this population -especially in those older than 80 years- remains very high.


Subject(s)
COVID-19 , Aged , Aged, 80 and over , COVID-19/prevention & control , COVID-19 Vaccines , Comorbidity , Female , Hospitalization , Humans , Male , SARS-CoV-2
16.
Topics in Antiviral Medicine ; 30(1 SUPPL):177, 2022.
Article in English | EMBASE | ID: covidwho-1880029

ABSTRACT

Background: Recent studies suggest that baricitinib added to dexamethasone may reduce mortality in hospitalized COVID-19 patients requiring supplemental oxygen Methods: In a multicenter open-label, pragmatic, randomized clinical trial in 25 hospitals in Spain we included symptomatic participants with SARS-CoV-2 detected by PCR or antigenic test, with a creatinine clearance >60 mL/min, > 60 years or younger if they had at least two comorbidities (hypertension, obesity, diabetes, cirrhosis, chronic neurologic disease, active cancer, heart failure, coronary heart disease or COPD). Participants were initially randomized to receive or not tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). At any moment during the trial participants with room air 02 saturation < 95% and at least one increased inflammatory biomarker could be randomized to dexamethasone (D) or dexamethasone plus baricitinib (DB). Primary outcome was 28 days mortality. Secondary outcomes were disease progression (increase of O2 requirements, mechanical ventilation or increase in medical therapy: steroid dose, need for starting tocilizumab) Results: Out of the 355 participants included in the trial 287 (80.8%) were randomized to D (n=142) or DB (n=145), 264 (91.9%) simultaneously with the TDF/FTC randomization and 23 (8.1%) later on. Median age 67 years (IQR 62, 73), male (65.5%), with median 8 days of symptoms (IQR 5-10), 28.6% with ≤ 5 days of symptoms, 100% hospitalized, 31.6% with one and 38.7% with ≥ 2 comorbidities (most common: 35.9% hypertension, 9.4% diabetes, 1.7 % obesity), 14.3% receiving remdesivir and 49.1% TDF/FTC. Endpoints in participants treated with D vs. those treated with DB favored DB without achieving statistical significance: mortality 4.9%/2.1%, disease progression 27.5%/24.8%, mechanical ventilation (invasive or noninvasive) 25.4%/23.4%, days since randomization until discharge (median [IQR]) 7 [5, 12]/7 [5, 13.5], discharge before 28 days 89%/94.2%. By Cox regression Hazard Ratio (95% CI) of 28-day mortality was 0.51 (0.13-2.06) for participants treated with DB. Serious adverse events occurred in 9.9%/9.7% of participants treated with D or DB respectively. Adverse events leading to B discontinuation occurred in 3.45% of participants. Conclusion: In this clinical trial of high-risk patients with COVID-19 all disease outcomes favored baricitinb added to dexamethasone but differences did not reach statistical significance. Overall mortality was unexpectedly low.

17.
J Allergy Clin Immunol Glob ; 1(3): 106-111, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1814604

ABSTRACT

Background: In 2020, a unique social experience was provided by the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2. Interventions to tackle the pandemic may affect the burden of other respiratory diseases. Objective: This study aims to assess the impact of the COVID-19 mitigation strategies on hospitalizations for asthma in children aged between 1 and 14 years, adults aged between 20 and 59 years, and elderly older than 60 years. Methods: Data from hospital admissions for asthma were obtained from the Department of Informatics of Brazilian Public Health System database in the period between January 2016 and December 2020 and analyzed by age groups. To evaluate the effect of containment measures on the incidence of asthma and respiratory system diseases (total), the absolute reduction and relative reduction were calculated by analyzing the subsets from 2016 to 2019 versus 2020. Results: There was a significant reduction in the average incidence of hospitalizations in 2020, with numbers ranging from -59% (incidence rate ratio, 0.41 [0.37-0.45]) for age 1 to 14 years (prepandemic 1,393.2/100,000 vs pandemic 574.9/100.000), -37% (incidence rate ratio, 0.63 [0.49-0.80]) for age 20 to 59 years (prepandemic 160.2/100,000 vs pandemic 101.1/100,000), and -60% (incidence rate ratio, 0.40 [0.33-0.47]) for older than 60 years (prepandemic 460.6/100,000 vs pandemic 185.3/100,000). Conclusions: Ashtma hospitalizations decreased in 2020, especially in the pediatric group and the older group during the COVID-19 pandemic, which may be associated with the reduction in the incidence of many respiratory viral infections.

18.
BMC Sports Sci Med Rehabil ; 14(1): 58, 2022 Apr 04.
Article in English | MEDLINE | ID: covidwho-1775334

ABSTRACT

BACKGROUND: A continuous tracking of the PA level during the COVID-19 pandemic is important to understand how people's behaviour has varied along time. The aim of this study was to evaluate the physical activity (PA) trajectory over the first 10 months of the COVID-19 pandemic in the south of Brazil. METHODS: Data from three timepoints of the PAMPA Cohort were used, as follows: (1) pre-COVID-19 (retrospective); (2) Jun/Jul 2020; (3) Dec 2020/Jan 2021. Self-reported PA practice, frequency, duration, as well as place where activities were performed (at or out of home) were assessed. RESULTS: A reduction in any (from 68.7 to 47.7%), sufficient (from 41.5 to 22.1%) and out of home PA (from 59.4 to 30.1%) was observed from the first (pre-COVID-19) to the second (Jun/Jul 2020) timepoint, followed by an increase in the third timepoint (Dec 2020/Jan 2021) (60.1%, 37.9%, and 54.3% for any, sufficient, and out of home PA, respectively). The PA trajectory was similar, regardless of sex, educational level or income. Only any (p = 0.0007) and sufficient (p = 0.0012) PA showed significant interaction with time by sex. Female participants were less likely to engage in any (OR 0.45 95% CI 0.26; 0.77) and sufficient PA (OR 0.40 95% CI 0.24; 0.66). CONCLUSION: During the first 10 months of COVID-19 pandemic there was a marked fluctuation on PA pattern in adults from southern Brazil. An ongoing tracking of PA behaviour during COVID-19 pandemic is important to understand how this behaviour varies. Public policies should focus on increasing PA in a higher standard than pre-COVID levels.

19.
Proc Natl Acad Sci U S A ; 119(14): e2114397119, 2022 04 05.
Article in English | MEDLINE | ID: covidwho-1751828

ABSTRACT

SignificanceIn the dynamic environment of the airways, where SARS-CoV-2 infections are initiated by binding to human host receptor ACE2, mechanical stability of the viral attachment is a crucial fitness advantage. Using single-molecule force spectroscopy techniques, we mimic the effect of coughing and sneezing, thereby testing the force stability of SARS-CoV-2 RBD:ACE2 interaction under physiological conditions. Our results reveal a higher force stability of SARS-CoV-2 binding to ACE2 compared to SARS-CoV-1, causing a possible fitness advantage. Our assay is sensitive to blocking agents preventing RBD:ACE2 bond formation. It will thus provide a powerful approach to investigate the modes of action of neutralizing antibodies and other agents designed to block RBD binding to ACE2 that are currently developed as potential COVID-19 therapeutics.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , COVID-19/virology , Host-Pathogen Interactions , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/chemistry , COVID-19/diagnosis , Disease Susceptibility , Humans , Protein Binding
20.
Clinics (Sao Paulo) ; 76: e3547, 2021.
Article in English | MEDLINE | ID: covidwho-1574414

ABSTRACT

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19. METHODS: Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations. RESULTS: Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor. CONCLUSION: D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.


Subject(s)
Biomarkers , COVID-19 , Biomarkers/analysis , C-Reactive Protein , COVID-19/diagnosis , COVID-19/therapy , Fibrin Fibrinogen Degradation Products , Humans , Prospective Studies , Receptors, Immunologic/analysis , SARS-CoV-2
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