Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
1.
Journal of Biological Chemistry ; : 102790, 2022.
Article in English | ScienceDirect | ID: covidwho-2149997

ABSTRACT

3CLpro is a promising drug target for COVID-19 and related coronavirus diseases due to the essential role of this protease in processing viral polyproteins after infection. Understanding the detailed catalytic mechanism of 3CLpro is essential for designing effective inhibitors of infection by SARS-CoV-2. Molecular dynamics studies have suggested pH-dependent conformational changes of 3CLpro, but experimental pH profiles of SARS-CoV-2 3CLpro and analyses of the conserved active site histidine residues have not been reported. In this work, pH dependence studies of the kinetic parameters of SARS-CoV-2 3CLpro revealed a bell-shaped pH profile with two pKa values (6.9 ± 0.1 and 9.4 ± 0.1) attributable to ionization of the catalytic dyad His41 and Cys145, respectively. Our investigation of the roles of conserved active site histidines showed that different amino acid substitutions of His163 produced inactive enzymes, indicating a key role of His163 in maintaining catalytically active SARS-CoV-2 3CLpro. By contrast, the H164A and H172A mutants retained 75% and 26% of the activity of wild type (WT), respectively. The alternative amino acid substitutions H172K and H172R did not recover the enzymatic activity, whereas H172Y restored activity to a level similar to that of the WT enzyme. The pH profiles of H164A, H172A, and H172Y were similar to those of the WT enzyme, with comparable pKa values for the catalytic dyad. Taken together, the experimental data support a general-base mechanism of SARS-CoV-2 3CLpro and indicate that the neutral states of the catalytic dyad and active site histidine residues are required for maximum enzyme activity.

2.
J Bras Pneumol ; 48(5): e20220018, 2022.
Article in English, Portuguese | MEDLINE | ID: covidwho-2156225

ABSTRACT

OBJECTIVE: To evaluate COVID-19 knowledge, attitudes, and practices among health care workers (HCWs) practicing in Latin American countries during the first surge of the COVID-19 pandemic. METHODS: This was a multinational cross-sectional survey study, using an online self-administered questionnaire. The final version of the questionnaire comprised 40 questions, organized in five sections: demographic and professional characteristics; COVID-19 knowledge; attitudes toward COVID-19; COVID-19 practices; and institutional resources. RESULTS: The study involved 251 HCWs from 19 Latin American countries who agreed to participate. In our sample, 77% of HCWs participated in some sort of institutional training on COVID-19, and 43% had a low COVID-19 knowledge score. COVID-19 knowledge was associated with the type of health center (public/private), availability of institutional training, and sources of information about COVID-19. Concerns about not providing adequate care were reported by 60% of the participants. The most commonly used ventilatory strategies were protective mechanical ventilation, alveolar recruitment maneuvers, and prone positioning, and the use of drugs to treat COVID-19 was mainly based on institutional protocols. CONCLUSIONS: In this multinational study in Latin America, almost half of HCWs had a low COVID-19 knowledge score, and the level of knowledge was associated with the type of institution, participation in institutional training, and information sources. HCWs considered that COVID-19 was very relevant, and more than half were concerned about not providing adequate care to patients.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/therapy , Pandemics , SARS-CoV-2 , Latin America/epidemiology , Health Knowledge, Attitudes, Practice , Cross-Sectional Studies , Health Personnel
3.
Cytokine ; 161:156084, 2023.
Article in English | ScienceDirect | ID: covidwho-2120084

ABSTRACT

The exacerbation of the inflammatory response caused by SARS-CoV-2 in adults promotes the production of soluble mediators that could act as diagnostic and prognostic biomarkers for COVID-19. Among the potential biomarkers, the soluble triggering receptor expressed on myeloid cell-1 (sTREM-1) has been described as a predictor of inflammation severity. The aim was to evaluate sTREM-1 and cytokine serum concentrations in pediatric patients during the acute and convalescent phases of COVID-19. This was a prospective study that included 53 children/adolescents with acute COVID-19 (Acute-CoV group);54 who recovered from COVID-19 (Post-CoV group) and 54 controls (Control group). Preexisting chronic conditions were present in the three groups, which were defined as follows: immunological diseases, neurological disorders, and renal and hepatic failures. The three groups were matched by age, sex, and similar preexisting chronic conditions. No differences in sTREM-1 levels were detected among the groups or when the groups were separately analyzed by preexisting chronic conditions. However, sTREM-1 analysis in the seven multisystemic inflammatory syndrome children (MIS-C) within the Acute-Cov group showed that sTREM-1 concentrations were higher in MIS-C vs non-MIS-C acute patients. Then, the receiver operating curve analysis (ROC) performed with MIS-C acute patients revealed a significant AUC of 0.870, and the sTREM-1 cutoff value of > 5781 pg/mL yielded a sensitivity of 71.4 % and a specificity of 91.3 % for disease severity, and patients with sTREM-1 levels above this cutoff presented an elevated risk for MIS-C development in 22.85-fold (OR = 22.85 [95 % CI 1.64–317.5], p = 0.02). The cytokine analyses in the acute phase revealed that IL-6, IL-8, and IL-10 concentrations were elevated regardless of whether the patient developed MIS-C, and those levels decreased in the convalescent phase, even when compared with controls. Spearman correlation analysis generated positive indexes between sTREM-1 and IL-12 and TNF-α concentrations, only within the Acute-CoV group. Our findings revealed that sTREM-1 in pediatric patients has good predictive accuracy as an early screening tool for surveillance of MIS-C cases, even in patients with chronic underlying conditions.

4.
Biochem J ; 479(20): 2175-2193, 2022 Oct 28.
Article in English | MEDLINE | ID: covidwho-2062282

ABSTRACT

Coronaviruses have been responsible for multiple challenging global pandemics, including coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Papain-like protease (PLpro), one of two cysteine proteases responsible for the maturation and infectivity of SARS-CoV-2, processes and liberates functional proteins from the viral polyproteins and cleaves ubiquitin and ISG15 modifications to inhibit innate immune sensing. Consequently, PLpro is an attractive target for developing COVID-19 therapies. PLpro contains a zinc-finger domain important for substrate binding and structural stability. However, the impact of metal ions on the activity and biophysical properties of SARS-CoV-2 PLpro has not been comprehensively studied. Here, we assessed the impacts of metal ions on the catalytic activity of PLpro. Zinc had the largest inhibitory effect on PLpro, followed by manganese. Calcium, magnesium, and iron had smaller or no effects on PLpro activity. EDTA at a concentration of 0.5 mM was essential for PLpro activity, likely by chelating trace metals that inhibit PLpro. IC50 values for ZnCl2, ZnSO4, and MnCl2 of 0.42 ± 0.02 mM, 0.35 ± 0.01 mM, and 2.6 ± 0.3 mM were obtained in the presence of 0.5 mM EDTA; in the absence of EDTA, the estimated IC50 of ZnCl2 was 14 µM. Tryptophan intrinsic fluorescence analysis confirmed the binding of zinc and manganese to PLpro, and differential scanning calorimetry revealed that zinc but not manganese reduced ΔHcal of PLpro. The results of this study provide a reference for further work targeting PLpro to prevent and treat COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Papain/chemistry , Papain/metabolism , COVID-19/drug therapy , Peptide Hydrolases/metabolism , Magnesium , Calcium , Tryptophan , Edetic Acid , Ubiquitin/metabolism , Polyproteins , Ions , Zinc , Iron
5.
Clinics (Sao Paulo) ; 77: 100110, 2022 Sep 12.
Article in English | MEDLINE | ID: covidwho-2031203

ABSTRACT

OBJECTIVES: To evaluate seroconverted asymptomatic COVID-19 in pediatric Autoimmune Rheumatic Diseases (ARDs) patients and to identify the risk factors related to contagion. METHODS: A cross-sectional study was conducted in March 2021, before vaccination of children and adolescents in Brazil, including 77 pediatric ARDs patients, followed at a tertiary hospital and 45 healthy controls, all of them without a previous diagnosis of COVID-19. Data was obtained by a questionnaire with demographic data, symptoms compatible with COVID-19 over the previous year, and contact with people with confirmed COVID-19. Patient's medical records were reviewed to access data regarding disease and current medications. A qualitative immunochromatographic SARS-CoV-2 test was performed on all participants. RESULTS: Patients and controls were similar in terms of female gender (70.1% vs. 57.8%, p = 0.173), age (14 vs. 13 years, p = 0.269) and SARS-CoV-2 positive serology (22% vs. 15.5%, p = 0.481). 80.5% of rheumatic patients were in use of immunosuppressive drugs: 27.3% of them used corticosteroids (33.3% in high doses), and 7.8% on immunobiologicals. No statistical differences were found between positive (n = 17) and negative serology (n = 60) patients regarding demographic/socioeconomic data, contact with people with confirmed COVID-19, use and number of immunosuppressive drugs, use and dose of corticosteroids, use of hydroxychloroquine and immunobiological drugs (p > 0.05). CONCLUSIONS: Pediatric rheumatic disease patients were infected at the same rate as healthy ones. Neither the underlying pathology nor its immunosuppressive treatment seemed to interfere with contagion risk.

6.
J Biol Chem ; 298(6): 102023, 2022 06.
Article in English | MEDLINE | ID: covidwho-1930937

ABSTRACT

3C-like protease (3CLpro) processes and liberates functional viral proteins essential for the maturation and infectivity of severe acute respiratory syndrome coronavirus 2, the virus responsible for COVID-19. It has been suggested that 3CLpro is catalytically active as a dimer, making the dimerization interface a target for antiviral development. Guided by structural analysis, here we introduced single amino acid substitutions at nine residues at three key sites of the dimer interface to assess their impact on dimerization and activity. We show that at site 1, alanine substitution of S1 or E166 increased by twofold or reduced relative activity, respectively. At site 2, alanine substitution of S10 or E14 eliminated activity, whereas K12A exhibited ∼60% relative activity. At site 3, alanine substitution of R4, E290, or Q299 eliminated activity, whereas S139A exhibited 46% relative activity. We further found that the oligomerization states of the dimer interface mutants varied; the inactive mutants R4A, R4Q, S10A/C, E14A/D/Q/S, E290A, and Q299A/E were present as dimers, demonstrating that dimerization is not an indication of catalytically active 3CLpro. In addition, present mostly as monomers, K12A displayed residual activity, which could be attributed to the conspicuous amount of dimer present. Finally, differential scanning calorimetry did not reveal a direct relationship between the thermodynamic stability of mutants with oligomerization or catalytic activity. These results provide insights on two allosteric sites, R4/E290 and S10/E14, that may promote the design of antiviral compounds that target the dimer interface rather than the active site of severe acute respiratory syndrome coronavirus 2 3CLpro.


Subject(s)
Coronavirus 3C Proteases , SARS-CoV-2 , Alanine/chemistry , Amino Acid Substitution , Antiviral Agents/chemistry , Coronavirus 3C Proteases/metabolism , Protein Multimerization , SARS-CoV-2/enzymology
8.
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
9.
Clinics (Sao Paulo) ; 76: e3501, 2021.
Article in English | MEDLINE | ID: covidwho-1534496

ABSTRACT

OBJECTIVE: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI). RESULTS: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p<0.001). CONCLUSION: Self-reported increases in screen time and intrafamilial violence report impacted sleep quality in both healthy adolescents and those with chronic conditions. Decreased health-related quality of life was observed in adolescents with poor sleep quality.


Subject(s)
COVID-19 , Quality of Life , Adolescent , Child , Chronic Disease , Cross-Sectional Studies , Female , Humans , Quarantine , SARS-CoV-2 , Sleep , Surveys and Questionnaires
10.
Sci Rep ; 10(1): 22200, 2020 12 17.
Article in English | MEDLINE | ID: covidwho-1493197

ABSTRACT

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is responsible for the novel coronavirus disease 2019 (COVID-19). An appealing antiviral drug target is the coronavirus 3C-like protease (3CLpro) that is responsible for the processing of the viral polyproteins and liberation of functional proteins essential for the maturation and infectivity of the virus. In this study, multiple thermal analytical techniques have been implemented to acquire the thermodynamic parameters of 3CLpro at different buffer conditions. 3CLpro exhibited relatively high thermodynamic stabilities over a wide pH range; however, the protease was found to be less stable in the presence of salts. Divalent metal cations reduced the thermodynamic stability of 3CLpro more than monovalent cations; however, altering the ionic strength of the buffer solution did not alter the stability of 3CLpro. Furthermore, the most stable thermal kinetic stability of 3CLpro was recorded at pH 7.5, with the highest enthalpy of activation calculated from the slope of Eyring plot. The biochemical and biophysical properties of 3CLpro explored here may improve the solubility and stability of 3CLpro for optimum conditions for the setup of an enzymatic assay for the screening of inhibitors to be used as lead candidates in the discovery of drugs and design of antiviral therapeutics against COVID-19.


Subject(s)
COVID-19/virology , Chymases/metabolism , Coronavirus 3C Proteases/metabolism , Peptide Hydrolases/metabolism , SARS-CoV-2/metabolism , Antiviral Agents/therapeutic use , Humans , Hydrogen-Ion Concentration , Protease Inhibitors/therapeutic use , Thermodynamics
11.
FASEB J ; 35(8): e21774, 2021 08.
Article in English | MEDLINE | ID: covidwho-1331587

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), one of the most challenging global pandemics of the modern era. Potential treatment strategies against COVID-19 are yet to be devised. It is crucial that antivirals that interfere with the SARS-CoV-2 life cycle be identified and developed. 3-Chymotrypsin-like protease (3CLpro) is an attractive antiviral drug target against SARS-CoV-2, and coronaviruses in general, because of its role in the processing of viral polyproteins. Inhibitors of 3CLpro activity are screened in enzyme assays before further development of the most promising leads. Dimethyl sulfoxide (DMSO) is a common additive used in such assays and enhances the solubility of assay components. However, it may also potentially affect the stability and efficiency of 3CLpro but, to date, this effect had not been analyzed in detail. Here, we investigated the effect of DMSO on 3CLpro-catalyzed reaction. While DMSO (5%-20%) decreased the optimum temperature of catalysis and thermodynamic stability of 3CLpro, it only marginally affected the kinetic stability of the enzyme. Increasing the DMSO concentration up to 20% improved the catalytic efficiency and peptide-binding affinity of 3CLpro. At such high DMSO concentration, the solubility and stability of peptide substrate were improved because of reduced aggregation. In conclusion, we recommend 20% DMSO as the minimum concentration to be used in screens of 3CLpro inhibitors as lead compounds for the development of antiviral drugs against COVID-19.


Subject(s)
COVID-19/virology , Coronavirus 3C Proteases/metabolism , Dimethyl Sulfoxide/pharmacology , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Viral/drug effects , SARS-CoV-2/enzymology , Computer Simulation , Coronavirus 3C Proteases/genetics , Humans , Microfluidic Analytical Techniques , Peptides/metabolism , Protein Stability
12.
Front Chem ; 9: 692168, 2021.
Article in English | MEDLINE | ID: covidwho-1305633

ABSTRACT

Coronaviruses are responsible for multiple pandemics and millions of deaths globally, including the current pandemic of coronavirus disease 2019 (COVID-19). Development of antivirals against coronaviruses, including the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) responsible for COVID-19, is essential for containing the current and future coronavirus outbreaks. SARS-CoV-2 proteases represent important targets for the development of antivirals because of their role in the processing of viral polyproteins. 3-Chymotrypsin-like protease (3CLpro) is one such protease. The cleavage of SARS-CoV-2 polyproteins by 3CLpro is facilitated by a Cys145-His41 catalytic dyad. We here characterized the catalytic roles of the cysteine-histidine pair for improved understanding of the 3CLpro reaction mechanism, to inform the development of more effective antivirals against Sars-CoV-2. The catalytic dyad residues were substituted by site-directed mutagenesis. All substitutions tested (H41A, H41D, H41E, C145A, and C145S) resulted in a complete inactivation of 3CLpro, even when amino acids with a similar catalytic function to that of the original residues were used. The integrity of the structural fold of enzyme variants was investigated by circular dichroism spectroscopy to test if the catalytic inactivation of 3CLpro was caused by gross changes in the enzyme secondary structure. C145A, but not the other substitutions, shifted the oligomeric state of the enzyme from dimeric to a higher oligomeric state. Finally, the thermodynamic stability of 3CLpro H41A, H41D, and C145S variants was reduced relative the wild-type enzyme, with a similar stability of the H41E and C145A variants. Collectively, the above observations confirm the roles of His41 and Cys145 in the catalytic activity and the overall conformational fold of 3CLpro SARS-CoV-2. We conclude that the cysteine-histidine pair should be targeted for inhibition of 3CLpro and development of antiviral against COVID-19 and coronaviruses.

13.
Ann Intensive Care ; 11(1): 92, 2021 Jun 07.
Article in English | MEDLINE | ID: covidwho-1259216

ABSTRACT

BACKGROUND: Approximately 5% of COVID-19 patients develop respiratory failure and need ventilatory support, yet little is known about the impact of mechanical ventilation strategy in COVID-19. Our objective was to describe baseline characteristics, ventilatory parameters, and outcomes of critically ill patients in the largest referral center for COVID-19 in Sao Paulo, Brazil, during the first surge of the pandemic. METHODS: This cohort included COVID-19 patients admitted to the intensive care units (ICUs) of an academic hospital with 94 ICU beds, a number expanded to 300 during the pandemic as part of a state preparedness plan. Data included demographics, advanced life support therapies, and ventilator parameters. The main outcome was 28-day survival. We used a multivariate Cox model to test the association between protective ventilation and survival, adjusting for PF ratio, pH, compliance, and PEEP. RESULTS: We included 1503 patients from March 30 to June 30, 2020. The mean age was 60 ± 15 years, and 59% were male. During 28-day follow-up, 1180 (79%) patients needed invasive ventilation and 666 (44%) died. For the 984 patients who were receiving mechanical ventilation in the first 24 h of ICU stay, mean tidal volume was 6.5 ± 1.3 mL/kg of ideal body weight, plateau pressure was 24 ± 5 cmH2O, respiratory system compliance was 31.9 (24.4-40.9) mL/cmH2O, and 82% of patients were ventilated with protective ventilation. Noninvasive ventilation was used in 21% of patients, and prone, in 36%. Compliance was associated with survival and did not show a bimodal pattern that would support the presence of two phenotypes. In the multivariable model, protective ventilation (aHR 0.73 [95%CI 0.57-0.94]), adjusted for PF ratio, compliance, PEEP, and arterial pH, was independently associated with survival. CONCLUSIONS: During the peak of the epidemic in Sao Paulo, critically ill patients with COVID-19 often required mechanical ventilation and mortality was high. Our findings revealed an association between mechanical ventilation strategy and mortality, highlighting the importance of protective ventilation for patients with COVID-19.

14.
Am J Trop Med Hyg ; 104(3_Suppl): 25-33, 2021 Jan 06.
Article in English | MEDLINE | ID: covidwho-1013476

ABSTRACT

Infection prevention and control (IPC) strategies are key in preventing nosocomial transmission of COVID-19. Several commonly used IPC practices are resource-intensive and may be challenging to implement in resource-constrained settings. An international group of healthcare professionals from or with experience in low- and middle-income countries (LMICs) searched the literature for relevant evidence. We report on a set of pragmatic recommendations for hospital-based IPC practices in resource-constrained settings of LMICs. For cases of confirmed or suspected COVID-19, we suggest that patients be placed in a single isolation room, whenever possible. When single isolation rooms are unavailable or limited, we recommend cohorting patients with COVID-19 on dedicated wards or in dedicated hospitals. We also recommend that cases of suspected COVID-19 be cohorted separately from those with confirmed disease, whenever possible, to minimize the risk of patient-to-patient transmission in settings where confirmatory testing may be limited. We suggest that healthcare workers be designated to care exclusively for patients with COVID-19, whenever possible, as another approach to minimize nosocomial spread. This approach may also be beneficial in conserving limited supplies of reusable personal protective equipment (PPE). We recommend that visitors be restricted for patients with COVID-19. In settings where family members or visitors are necessary for caregiving, we recommend that the appropriate PPE be used by visitors. We also recommend that education regarding hand hygiene and donning/doffing procedures for PPE be provided. Last, we suggest that all visitors be screened for symptoms before visitation and that visitor logs be maintained.


Subject(s)
COVID-19/prevention & control , Delivery of Health Care/methods , Developing Countries , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Practice Guidelines as Topic , COVID-19/epidemiology , Health Personnel , Humans , Infection Control , Personal Protective Equipment
15.
Am J Trop Med Hyg ; 104(3_Suppl): 12-24, 2020 Dec 22.
Article in English | MEDLINE | ID: covidwho-1000463

ABSTRACT

Infection prevention and control measures to control the spread of COVID-19 are challenging to implement in many low- and middle-income countries (LMICs). This is compounded by the fact that most recommendations are based on evidence that mainly originates in high-income countries. There are often availability, affordability, and feasibility barriers to applying such recommendations in LMICs, and therefore, there is a need for developing recommendations that are achievable in LMICs. We used a modified version of the GRADE method to select important questions, searched the literature for relevant evidence, and formulated pragmatic recommendations for safety while caring for patients with COVID-19 in LMICs. We selected five questions related to safety, covering minimal requirements for personal protective equipment (PPE), recommendations for extended use and reuse of PPE, restriction on the number of times healthcare workers enter patients' rooms, hand hygiene, and environmental ventilation. We formulated 21 recommendations that are feasible and affordable in LMICs.


Subject(s)
COVID-19/prevention & control , Delivery of Health Care/standards , Developing Countries , Infection Control/standards , Medical Staff, Hospital , Practice Guidelines as Topic , Safety , Hand Hygiene , Humans , Personal Protective Equipment , SARS-CoV-2 , Ventilation
16.
Ferreira, Juliana C.; Ho, Yeh-Li, Besen, Bruno A. M. P.; Malbuisson, Luiz M. S.; Taniguchi, Leandro U.; Mendes, Pedro V.; Costa, Eduardo L. V.; Park, Marcelo, Daltro-Oliveira, Renato, Roepke, Roberta M. L.; Silva Jr, João M.; Carmona, Maria José C.; Carvalho, Carlos Roberto Ribeiro, Hirota, Adriana, Kanasiro, Alberto Kendy, Crescenzi, Alessandra, Fernandes, Amanda Coelho, Miethke-Morais, Anna, Bellintani, Arthur Petrillo, Canasiro, Artur Ribeiro, Carneiro, Bárbara Vieira, Zanbon, Beatriz Keiko, Batista, Bernardo Pinheiro De Senna Nogueira, Nicolao, Bianca Ruiz, Besen, Bruno Adler Maccagnan Pinheiro, Biselli, Bruno, Macedo, Bruno Rocha De, Toledo, Caio Machado Gomes De, Pompilio, Carlos Eduardo, Carvalho, Carlos Roberto Ribeiro De, Mol, Caroline Gomes, Stipanich, Cassio, Bueno, Caue Gasparotto, Garzillo, Cibele, Tanaka, Clarice, Forte, Daniel Neves, Joelsons, Daniel, Robira, Daniele, Costa, Eduardo Leite Vieira, Silva Júnior, Elson Mendes Da, Regalio, Fabiane Aliotti, Segura, Gabriela Cardoso, Marcelino, Gustavo Brasil, Louro, Giulia Sefrin, Ho, Yeh-Li, Ferreira, Isabela Argollo, Gois, Jeison de Oliveira, Silva Junior, Joao Manoel Da, Reusing Junior, Jose Otto, Ribeiro, Julia Fray, Ferreira, Juliana Carvalho, Galleti, Karine Vusberg, Silva, Katia Regina, Isensee, Larissa Padrao, Oliveira, Larissa dos Santos, Taniguchi, Leandro Utino, Letaif, Leila Suemi, Lima, Lígia Trombetta, Park, Lucas Yongsoo, Chaves Netto, Lucas, Nobrega, Luciana Cassimiro, Haddad, Luciana, Hajjar, Ludhmila, Malbouisson, Luiz Marcelo, Pandolfi, Manuela Cristina Adsuara, Park, Marcelo, Carmona, Maria José Carvalho, Andrade, Maria Castilho Prandini H. De, Santos, Mariana Moreira, Bateloche, Matheus Pereira, Suiama, Mayra Akimi, Oliveira, Mayron Faria de, Sousa, Mayson Laercio, Louvaes, Michelle, Huemer, Natassja, Mendes, Pedro, Lins, Paulo Ricardo Gessolo, Santos, Pedro Gaspar Dos, Moreira, Pedro Ferreira Paiva, Guazzelli, Renata Mello, Reis, Renato Batista Dos, Oliveira, Renato Daltro De, Roepke, Roberta Muriel Longo, Pedro, Rodolpho Augusto De Moura, Kondo, Rodrigo, Rached, Samia Zahi, Fonseca, Sergio Roberto Silveira Da, Borges, Thais Sousa, Ferreira, Thalissa, Cobello Junior, Vilson, Sales, Vivian Vieira Tenório, Ferreira, Willaby Serafim Cassa, Group, E. PICCoV Study.
Clinics ; 75:e2294-e2294, 2020.
Article in English | LILACS (Americas) | ID: grc-742344

ABSTRACT

OBJECTIVES: We designed a cohort study to describe characteristics and outcomes of patients with coronavirus disease (COVID-19) admitted to the intensive care unit (ICU) in the largest public hospital in Sao Paulo, Brazil, as Latin America becomes the epicenter of the pandemic. METHODS: This is the protocol for a study being conducted at an academic hospital in Brazil with 300 adult ICU beds dedicated to COVID-19 patients. We will include adult patients admitted to the ICU with suspected or confirmed COVID-19 during the study period. The main outcome is ICU survival at 28 days. Data will be collected prospectively and retrospectively by trained investigators from the hospital's electronic medical records, using an electronic data capture tool. We will collect data on demographics, comorbidities, severity of disease, and laboratorial test results at admission. Information on the need for advanced life support and ventilator parameters will be collected during ICU stay. Patients will be followed up for 28 days in the ICU and 60 days in the hospital. We will plot Kaplan-Meier curves to estimate ICU and hospital survival and perform survival analysis using the Cox proportional hazards model to identify the main risk factors for mortality. ClinicalTrials.gov: NCT04378582. RESULTS: We expect to include a large sample of patients with COVID-19 admitted to the ICU and to be able to provide data on admission characteristics, use of advanced life support, ICU survival at 28 days, and hospital survival at 60 days. CONCLUSIONS: This study will provide epidemiological data about critically ill patients with COVID-19 in Brazil, which could inform health policy and resource allocation in low- and middle-income countries.

17.
Clinics (Sao Paulo) ; 75: e2294, 2020.
Article in English | MEDLINE | ID: covidwho-769762

ABSTRACT

OBJECTIVES: We designed a cohort study to describe characteristics and outcomes of patients with coronavirus disease (COVID-19) admitted to the intensive care unit (ICU) in the largest public hospital in Sao Paulo, Brazil, as Latin America becomes the epicenter of the pandemic. METHODS: This is the protocol for a study being conducted at an academic hospital in Brazil with 300 adult ICU beds dedicated to COVID-19 patients. We will include adult patients admitted to the ICU with suspected or confirmed COVID-19 during the study period. The main outcome is ICU survival at 28 days. Data will be collected prospectively and retrospectively by trained investigators from the hospital's electronic medical records, using an electronic data capture tool. We will collect data on demographics, comorbidities, severity of disease, and laboratorial test results at admission. Information on the need for advanced life support and ventilator parameters will be collected during ICU stay. Patients will be followed up for 28 days in the ICU and 60 days in the hospital. We will plot Kaplan-Meier curves to estimate ICU and hospital survival and perform survival analysis using the Cox proportional hazards model to identify the main risk factors for mortality. ClinicalTrials.gov: NCT04378582. RESULTS: We expect to include a large sample of patients with COVID-19 admitted to the ICU and to be able to provide data on admission characteristics, use of advanced life support, ICU survival at 28 days, and hospital survival at 60 days. CONCLUSIONS: This study will provide epidemiological data about critically ill patients with COVID-19 in Brazil, which could inform health policy and resource allocation in low- and middle-income countries.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Betacoronavirus , Brazil , COVID-19 , Cohort Studies , Hospital Mortality , Hospitals, University , Humans , Intensive Care Units , Observational Studies as Topic , Pandemics , Research Design , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL