Evidence for Human-to-Human Transmission of Hantavirus: A Systematic Review.

BACKGROUND: Hantavirus is known to be transmitted from rodents to humans. However, some reports from Argentina and Chile have claimed that the hantavirus strain Andes virus (ANDV) can cause human-to-human transmission of the disease. The aim of this systematic review was to assess the evidence for human-to-human transmission of hantavirus. METHODS: We searched PubMed (inception to 28 February 2021), Cochrane Central, Embase, LILACS and SciELO (inception to 3 July 2020), and other sources. We included studies that assessed whether interpersonal contact with a person with laboratory-confirmed hantavirus infection led to human-to-human transmission. Two reviewers conducted screening, selection, data extraction, and risk of bias assessment. RESULTS: Twenty-two studies met the inclusion criteria. Meta-analysis was not possible due to heterogeneity. With the exception of 1 prospective cohort study of ANDV in Chile with serious risk of bias, evidence from comparative studies (strongest level of evidence available) does not support human-to-human transmission of hantavirus infection. Noncomparative studies with a critical risk of bias suggest that human-to-human transmission of ANDV may be possible. CONCLUSIONS: The balance of the evidence does not support the claim of human-to-human transmission of ANDV. Well-designed cohort and case-control studies that control for co-exposure to rodents are needed to inform public health recommendations.

Associated factors for mortality in a COVID-19 colombian cohort: is the third wave relevant when Mu variant was predominant epidemiologically?

OBJECTIVES: To evaluate the association between Colombia's third wave when the Mu variant was predominant epidemiologically (until 75%) in Colombia and COVID-19 all-cause in-hospital mortality. METHODS: In this retrospective cohort, we included hospitalized patients ≥18 years with SARS-CoV-2 infection between March 2020 to September 2021 in ten hospitals from three cities in Colombia. Description analysis, survival, and multivariate Cox regression analyses were performed to evaluate the association between the third epidemic wave and in-hospital mortality. RESULTS: A total of 25,371 patients were included. The age-stratified time-to-mortality curves showed differences according to epidemic waves in patients ≥75 years (log-rank test p = 0.012). In the multivariate Cox analysis, the third wave was not associated with increased mortality relative to the first wave (aHR 0.95; 95%CI 0.84-1.08), but there was an interaction between age ≥75 years and the third wave finding a lower HR for mortality (aHR 0.56, 95%CI 0.36-0.86). CONCLUSIONS: We did not find an increase in in-hospital mortality during the third epidemic wave in which the Mu variant was predominant in Colombia. The reduced hazard in mortality in patients ≥75 years hospitalized in the third wave could be explained by the high coverage of SARS-CoV-2 vaccination in this population and patients with underlying conditions.

[Mapping of research protocols, publications, and collaborations on COVID-19 in Latin America and the CaribbeanMapeamento de protocolos de pesquisa, publicações e colaborações sobre COVID-19 na América Latina e no Caribe]. / Mapeo de protocolos de investigación, publicaciones y colaboraciones sobre la COVID-19 en América Latina y el Caribe.

Objective: To map research protocols, publications, and collaborations on coronavirus disease 2019 (COVID-19) developed in Latin America and the Caribbean (LAC). Methods: Included were research protocols registered in international platforms and research publications containing populations, data, or authors from LAC. The source of information for protocols was primarily the International Clinical Trial Registry Platform (ICTRP) of the World Health Organization; for publications, specific electronic databases and repositories pertaining to COVID-19 were used. The search for publications was conducted up to 11 November; the search for protocols, up to 30 November 2020 (both dates inclusive). Data was extracted from protocols using standardized variables from the ICTRP, and from publications following pre-established criteria. Results: Among the protocols, 63.0% were therapeutic studies, 10% focused on prevention, and 45% were collaborative; 64% of the protocols received no funding from industry; 23% of the publications were not peer-reviewed and 23% were collaborative in nature. The most frequent study designs were systematic reviews and cross-sectional studies; 47.1% of studies were conducted in health facilities and 22% in community settings; 38.0% focused on diagnosis and 27.9% on prognosis. A qualitative synthesis was performed by line of care and approach strategies. Conclusions: There was an increase in the number of collaborative research studies relative to earlier studies and in protocols not funded by industry. The proposed research agenda was covered in large part as the pandemic unfolded.

Objetivo: Mapear protocolos de pesquisa, publicações e colaborações sobre a doença causada pelo coronavírus 2019 (COVID-19, na sigla em inglês) desenvolvidos na América Latina e no Caribe (ALC). Métodos: Foram incluídos protocolos registrados em plataformas internacionais e publicações de pesquisas que consideraram população, dados e autores da ALC. A fonte de informação para os protocolos foi principalmente a Plataforma Internacional de Registros de Ensaios Clínicos (ICTRP, na sigla em inglês) da Organização Mundial da Saúde. Para as publicações, foram utilizadas bases de dados eletrônicas e repositórios específicos sobre COVID-19. As publicações foram pesquisadas até 11 de novembro, e os protocolos, até 30 de novembro de 2020 (inclusive). As informações dos protocolos foram extraídas de acordo com variáveis padronizadas da plataforma ICTRP e das publicações, segundo critérios pré-estabelecidos. Resultados: Dos protocolos, 63% eram estudos sobre terapias, 10% sobre prevenção e 45% eram colaborativos. Em relação ao financiamento, 64% dos protocolos não vieram da indústria. Em relação às publicações, 23% eram sem revisão por pares e 23% eram colaborativas. Os delineamentos mais frequentes foram revisões sistemáticas e estudos transversais; 47,1% foram realizados em serviços de saúde e 22% no âmbito comunitário; 38,0% focaram no diagnóstico e 27,9% no prognóstico. Realizou-se uma síntese qualitativa segundo a linha de cuidado e as estratégias de abordagem. Conclusões: Observou-se um aumento no número de pesquisas colaborativas (em comparação com estudos anteriores) e de protocolos não financiados pela indústria. A agenda de pesquisa proposta foi coberta, em grande parte, à medida que a pandemia progredia.

Viral reactivations and co-infections in COVID-19 patients: a systematic review.

BACKGROUND: Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses. METHODS: Our population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle-Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables. RESULTS: In total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals. CONCLUSION: Overall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients.

The BIGG-REC database makes available all WHO/PAHO evidence informed recommendations.

OBJECTIVE: To build and maintain a living database of the Pan American Health Organization/World Health Organization (PAHO/WHO) recommendations developed using GRADE. STUDY DESIGN AND SETTING: Guidelines are identified from WHO and PAHO databases. We periodically extract recommendations, according to the health and wellbeing targets of Sustainable Development Goal 3. RESULTS: As of March 2022, the BIGG-REC (https://bigg-rec.bvsalud.org/en) database hosted 2682 recommendations contained in 285 WHO/PAHO guidelines. Recommendations were classified as follows: communicable diseases (1,581), children's health (1,182), universal health (1,171), sexual and reproductive health (910), non-communicable diseases (677), maternal health (654), COVID-19 (224), use of psychoactive substances (99), tobacco (14) and road and traffic accidents (16). BIGG-REC allows searching by SDG-3, condition or disease, type of intervention, institution, year of publication and age. CONCLUSION: Recommendation maps provide an important resource for health professionals, organizations and Member States that use evidence-informed guidance to make better decisions, providing a source for the adoption or adaptation of recommendations to meet their needs. This one-stop shop database of evidence-informed recommendations built with intuitive functionalities undoubtedly represents a long-needed tool for decision-makers, guideline developers and the public at large.

Hospital readmissions and emergency department re-presentation of COVID-19 patients: a systematic review.

Objective: To characterize the frequency, causes, and predictors of readmissions of COVID-19 patients after discharge from heath facilities or emergency departments, interventions used to reduce readmissions, and outcomes of COVID-19 patients discharged from such settings. Methods: We performed a systematic review for case series and observational studies published between January 2020 and April 2021 in PubMed, Embase, LILACS, and MedRxiv, reporting the frequency, causes, or risk factors for readmission of COVID-19 survivors/patients. We conducted a narrative synthesis and assessed the methodological quality using the JBI critical appraisal checklist. Results: We identified 44 studies including data from 10 countries. The overall 30-day median readmission rate was 7.1%. Readmissions varied with the length of follow-up, occurring <10.5%, <14.5%, <21.5%, and <30%, respectively, for 10, 30, 60, and 253 days following discharge. Among those followed up for 30 and 60 days, the median time from discharge to readmission was 3 days and 8-11 days, respectively. The significant risk factor associated with readmission was having shorter length of stay, and the important causes included respiratory or thromboembolic events and chronic illnesses. Emergency department re-presentation was >20% in four studies. Risk factors associated with mortality were male gender, advanced age, and comorbidities. Conclusions: Readmission of COVID-19 survivors is frequent, and post-discharge mortality is significant in specific populations. There is an urgent need to further examine underlying reasons for early readmission and to prevent additional readmissions and adverse outcomes in COVID-19 survivors.

Cohort study protocol of the Brazilian collaborative research network on COVID-19: strengthening WHO global data.

INTRODUCTION: With the COVID-19 pandemic, hospitals in low-income countries were faced with a triple challenge. First, a large number of patients required hospitalisation because of the infection's more severe symptoms. Second, there was a lack of systematic and broad testing policies for early identification of cases. Third, there were weaknesses in the integration of information systems, which led to the need to search for available information from the hospital information systems. Accordingly, it is also important to state that relevant aspects of COVID-19's natural history had not yet been fully clarified. The aim of this research protocol is to present the strategies of a Brazilian network of hospitals to perform systematised data collection on COVID-19 through the WHO platform. METHODS AND ANALYSIS: This is a multicentre project among Brazilian hospitals to provide data on COVID-19 through the WHO global platform, which integrates patient care information from different countries. From October 2020 to March 2021, a committee worked on defining a flowchart for this platform, specifying the variables of interest, data extraction standardisation and analysis. ETHICS AND DISSEMINATION: This protocol was approved by the Research Ethics Committee (CEP) of the Research Coordinating Center of Brazil (CEP of the Hospital Nossa Senhora da Conceicao), on 29 January 2021, under approval No. 4.515.519 and by the National Research Ethics Commission (CONEP), on 5 February 2021, under approval No. 4.526.456. The project results will be explained in WHO reports and published in international peer-reviewed journals, and summaries will be provided to the funders of the study.

Hospital readmissions and emergency department re-presentation of COVID-19 patients: a systematic review Reingreso de pacientes con COVID-19 a salas de hospitalización y servicios de urgencias: una revisión sistemática Reinternação hospitalar e retorno ao pronto-socorro de pacientes com COVID-19: revisão sistemática

Objective. To characterize the frequency, causes, and predictors of readmissions of COVID-19 patients after discharge from heath facilities or emergency departments, interventions used to reduce readmissions, and outcomes of COVID-19 patients discharged from such settings. Methods. We performed a systematic review for case series and observational studies published between January 2020 and April 2021 in PubMed, Embase, LILACS, and MedRxiv, reporting the frequency, causes, or risk factors for readmission of COVID-19 survivors/patients. We conducted a narrative synthesis and assessed the methodological quality using the JBI critical appraisal checklist. Results. We identified 44 studies including data from 10 countries. The overall 30-day median readmission rate was 7.1%. Readmissions varied with the length of follow-up, occurring <10.5%, <14.5%, <21.5%, and <30%, respectively, for 10, 30, 60, and 253 days following discharge. Among those followed up for 30 and 60 days, the median time from discharge to readmission was 3 days and 8–11 days, respectively. The significant risk factor associated with readmission was having shorter length of stay, and the important causes included respiratory or thromboembolic events and chronic illnesses. Emergency department re-presentation was >20% in four studies. Risk factors associated with mortality were male gender, advanced age, and comorbidities. Conclusions. Readmission of COVID-19 survivors is frequent, and post-discharge mortality is significant in specific populations. There is an urgent need to further examine underlying reasons for early readmission and to prevent additional readmissions and adverse outcomes in COVID-19 survivors.

BIGG, the international database of GRADE Guidelines

To date, the database offers more than 1300 guidelines in several languages that cover a wide range of health topics related to the SDG3 and other health priorities, including COVID-19.

Evidence in decision-making in the context of COVID-19 in Latin America.

Background: The pace of the COVID-19 pandemic poses an unprecedented challenge to the evidence-to-decision process. Latin American countries have responded to COVID-19 by introducing interventions to both mitigate the risk of infection and to treat cases. Understanding how evidence is used to inform government-level decision-making at a national scale is crucial for informing country and regional actors in ongoing response efforts. Objectives: This study was undertaken between February-May 2021 and aims to characterise the best available evidence (BAE) and assess the extent to which it was used to inform decision-making in 21 Latin American countries, in relation to pharmaceutical (PI) and non-pharmaceutical interventions (NPI) related to COVID-19, including the use of therapeutics (corticosteroids, hydroxychloroquine/chloroquine and ivermectin), facemask use in the community setting and the use of diagnostic tests as a requirement for international travel. Method: A three-phase methodology was used to; (i) characterise the BAE for each intervention using an umbrella review, (ii) identify government-level decisions for each intervention through a document review and (iii) assess the use of evidence to inform decisions using a novel adapted framework analysis. Findings: The BAE is characterized by 17 living and non-living systematic reviews as evolving, and particularly uncertain for NPIs. 107 country-level documents show variation in both content and timing of decision outcomes across intervention types, with the majority of decisions taken at a time of evidence uncertainty, with only 5 documents including BAE. Seven out of eight key indicators of an evidence-to-decision process were identified more frequently among PIs than either NPI of facemask use or testing prior to travel. Overall evidence use was reported more frequently among PIs than either NPI of facemask use or travel testing (92%, 28% and 29%, respectively). Interpretation: There are limitations in the extent to which evidence use in decision-making is reported across the Latin America region. Institutionalising this process and grounding it in existing and emerging methodologies can facilitate the rapid response in an emergency setting. Funding: No funding was sourced for this work.

Methodological guidance for incorporating equity when informing rapid-policy and guideline development.

OBJECTIVES: We provide guidance for considering equity in rapid reviews through examples of published COVID-19 rapid reviews. STUDY DESIGN AND SETTING: This guidance was developed based on a series of methodological meetings, review of internationally renowned guidance such as the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for equity-focused systematic reviews (PRISMA-Equity) guideline. We identified Exemplar rapid reviews by searching COVID-19 databases and requesting examples from our team. RESULTS: We proposed the following key steps: 1. involve relevant stakeholders with lived experience in the conduct and design of the review; 2. reflect on equity, inclusion and privilege in team values and composition; 3. develop research question to assess health inequities; 4. conduct searches in relevant disciplinary databases; 5. collect data and critically appraise recruitment, retention and attrition for populations experiencing inequities; 6. analyse evidence on equity; 7. evaluate the applicability of findings to populations experiencing inequities; and 8. adhere to reporting guidelines for communicating review findings. We illustrated these methods through rapid review examples. CONCLUSION: Implementing this guidance could contribute to improving equity considerations in rapid reviews produced in public health emergencies, and help policymakers better understand the distributional impact of diseases on the population.

Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: analysis of data from the WHO Global Clinical Platform of COVID-19.

BACKGROUND: WHO has established a Global Clinical Platform for the clinical characterisation of COVID-19 among hospitalised individuals. We assessed whether people living with HIV hospitalised with COVID-19 had increased odds of severe presentation and of in-hospital mortality compared with individuals who were HIV-negative and associated risk factors. METHODS: Between Jan 1, 2020, and July 1, 2021, anonymised individual-level data from 338 566 patients in 38 countries were reported to WHO. Using the Platform pooled dataset, we performed descriptive statistics and regression analyses to compare outcomes in the two populations and identify risk factors. FINDINGS: Of 197 479 patients reporting HIV status, 16 955 (8·6%) were people living with HIV. 16 283 (96.0%) of the 16 955 people living with HIV were from Africa; 10 603 (62·9%) were female and 6271 (37·1%) were male; the mean age was 45·5 years (SD 13·7); 6339 (38·3%) were admitted to hospital with severe illness; and 3913 (24·3%) died in hospital. Of the 10 166 people living with HIV with known antiretroviral therapy (ART) status, 9302 (91·5%) were on ART. Compared with individuals without HIV, people living with HIV had 15% increased odds of severe presentation with COVID-19 (aOR 1·15, 95% CI 1·10-1·20) and were 38% more likely to die in hospital (aHR 1·38, 1·34-1·41). Among people living with HIV, male sex, age 45-75 years, and having chronic cardiac disease or hypertension increased the odds of severe COVID-19; male sex, age older than 18 years, having diabetes, hypertension, malignancy, tuberculosis, or chronic kidney disease increased the risk of in-hospital mortality. The use of ART or viral load suppression were associated with a reduced risk of poor outcomes; however, HIV infection remained a risk factor for severity and mortality regardless of ART and viral load suppression status. INTERPRETATION: In this sample of hospitalised people contributing data to the WHO Global Clinical Platform for COVID-19, HIV was an independent risk factor for both severe COVID-19 at admission and in-hospital mortality. These findings have informed WHO immunisation policy that prioritises vaccination for people living with HIV. As the results mostly reflect the data contribution from Africa, this analysis will be updated as more data from other regions become available. FUNDING: None. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

A multistakeholder development process to prioritize and translate COVID-19 health recommendations for patients, caregivers and the public. A case study of the COVID-19 recommendation map.

BACKGROUND AND OBJECTIVES: To develop a digital communication tool to improve the implementation of up-to-date COVID-19 recommendations. Specifically, to improve patient, caregiver and public understanding of healthcare recommendations on prevention, diagnoses and treatment. METHODS: Multi-stakeholder engagement design. In conjunction with the COVID-19 Recommendations and Gateway to Contextualization RecMap, we co-developed a stakeholder prioritization, drafting and editing process to enhance guideline communication and understanding. RESULTS: This paper presents the multi-stakeholder development process with three distinct plain language recommendation formats: formal recommendation, good practice statement, and additional guidance. Our case study of COVID-19 plain language recommendations PLRs addresses both public health interventions (e.g., vaccination, face masks) and clinical interventions (e.g., home pulse oximetry). CONCLUSION: This paper presents a novel approach to engaging stakeholders in improving the communication and understanding of published guidelines during the COVID-19 pandemic.

Characterising COVID-19 empirical research production in Latin America and the Caribbean: A scoping review.

INTRODUCTION: The Coronavirus Disease 2019 (COVID19) pandemic has struck Latin America and the Caribbean (LAC) particularly hard. One of the crucial areas in the international community's response relates to accelerating research and knowledge sharing. The aim of this article is to map and characterise the existing empirical research related to COVID-19 in LAC countries and contribute to identify opportunities for strengthening future research. METHODS: In this scoping review, articles published between December 2019 and 11 November 2020 were selected if they included an empirical component (explicit scientific methods to collect and analyse primary data), LAC population was researched, and the research was about the COVID-19 pandemic, regardless of publication status or language. MEDLINE, EMBASE, LILACS, Scielo, CENTRAL and Epistemonikos were searched. All titles and abstracts, and full texts were screened by two independent reviewers. Data from included studies was extracted by one reviewer and checked by a second independent reviewer. RESULTS: 14,406 records were found. After removing duplicates, 5,458 titles and abstracts were screened, of which 2,323 full texts were revised to finally include 1,626 empirical studies. The largest portion of research came from people/population of Brazil (54.6%), Mexico (19.1%), Colombia (11.2%), Argentina (10.4%), Peru (10.3%) and Chile (10%), while Caribbean countries concentrated 15.3%. The methodologies most used were cross-sectional studies (34.7%), simulation models (17.5%) and randomized controlled trials (RCTs) (13.6%). Using a modified version of WHO's COVID-19 Coordinated Global Research Roadmap classification, 54.2% were epidemiological studies, followed by clinical management (22.3%) and candidate therapeutics (12.2%). Government and public funds support were reported in 19.2% of studies, followed by universities or research centres (9%), but 47.5% did not include any funding statement. CONCLUSION: During the first part of the COVID-19 pandemic, LAC countries have contributed to the global research effort primarily with epidemiological studies, with little participation on vaccines research, meaning that this type of knowledge would be imported from elsewhere. Research agendas could be further coordinated aiming to enhance shared self-sufficiency regarding knowledge needs in the region.

Cardiac Manifestations in Patients with COVID-19: A Scoping Review.

Background: Coronavirus disease 2019 (COVID-19), commonly affects the lungs, but the involvement of other organs, particularly the heart, is highly prevalent as has been reported in several studies. The overall aim of this review was to provide an in-depth description of the available literature related to the cardiac system and COVID-19 infection. It focuses on type and the frequency of cardiac manifestations, clinical parameters and cardiac biomarkers that support the prognosis of COVID-19 patients, and the cardiac adverse events and outcomes related to pharmacotherapy. Methods: A scoping review was conducted searching Embase, PubMed, Epistomonikos, Medrxiv, BioRxiv databases, up to November 2020, for systematic reviews relevant to cardiac manifestations in adult COVID-19 patients. Relevant articles were screened and extracted to summarize key outcomes and findings. Results: A total of 63 systematic reviews met the inclusion criteria. The overall frequency of acute cardiac injury ranged from 15% to 33% in the reporting studies. The main cardiac complications were arrhythmias (3.1% to 6.9% in non-severe patients, 33.0% to 48.0% in severe disease), acute coronary syndromes (6% to 33% in severe disease), and myocarditis. Most studies found no association with the use of Renin-angiotensin-aldosterone system inhibitors (RAASI) with COVID-19 outcomes such as susceptibility to infection, hospitalization, severity, and mortality. Conclusion: This study provided an overview of the several cardiac complications associated with Covid-19. Cardiac injury, arrhythmias, myocarditis, cardiac failure, and acute coronary syndrome, are prevalent and clinically significant and associated with COVID-19 disease severity and mortality. Other studies are needed to clearly identify what is the part of viral heart infection and what is the part of cardiac injury secondary to acute respiratory failure and inflammation. In the therapeutic field, these systematic reviews gave heterogenous results. This underlines the importance of randomized trials to determine the right therapeutic approach.

Bias as a source of inconsistency in ivermectin trials for COVID-19: A systematic review. Ivermectin's suggested benefits are mainly based on potentially biased results.

OBJECTIVE: The objective of this systematic review is to summarize the effects of ivermectin for the prevention and treatment of patients with COVID-19 and to assess inconsistencies in results from individual studies with focus on risk of bias due to methodological limitations. METHODS: We searched the L.OVE platform through July 6, 2021 and included randomized trials (RCTs) comparing ivermectin to standard or other active treatments. We conducted random-effects pairwise meta-analysis, assessed the certainty of evidence using the GRADE approach and performed sensitivity analysis excluding trials with risk of bias. RESULTS: We included 29 RCTs which enrolled 5592 cases. Overall, the certainty of the evidence was very low to low suggesting that ivermectin may result in important benefits. However, after excluding trials classified as "high risk" or "some concerns" in the risk of bias assessment, most estimates of effect changed substantially: Compared to standard of care, low certainty evidence suggests that ivermectin may not reduce mortality (RD 7 fewer per 1000) nor mechanical ventilation (RD 6 more per 1000), and moderate certainty evidence shows that it probably does not increase symptom resolution or improvement (RD 14 more per 1000) nor viral clearance (RD 12 fewer per 1000). CONCLUSION: Ivermectin may not improve clinically important outcomes in patients with COVID-19 and its effects as a prophylactic intervention in exposed individuals are uncertain. Previous reports concluding important benefits associated with ivermectin are based on potentially biased results reported by studies with substantial methodological limitations. Further research is needed.

Pathological findings in organs and tissues of patients with COVID-19: A systematic review.

BACKGROUND: Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs. METHODS AND FINDINGS: A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings. CONCLUSIONS: The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

The landscape of COVID-19 clinical trials in Latin America and the Caribbean: assessment and challenges.

A considerable number of clinical trials is being conducted globally in response to the COVID-19 pandemic, including in low- and middle-income countries such as those in the Latin America and Caribbean region (LAC). Yet, an abundance of studies does not necessarily shorten the path to find safe and efficacious interventions for COVID-19. We analyze the trials for COVID-19 treatment and prevention that are registered from LAC countries in the International Clinical Trials Registry Platform, and identify a trend towards small repetitive non-rigorous studies that duplicate efforts and drain limited resources without producing meaningful conclusions on the safety and efficacy of the interventions being tested. We further assess the challenges to conducting scientifically sound and socially valuable research in the LAC region in order to inform recommendations to encourage clinical trials that are most likely to produce robust evidence during the pandemic.

Se está llevando a cabo un número considerable de ensayos clínicos en todo el mundo en respuesta a la pandemia de COVID-19, incluso en países de ingresos bajos y medios como los de la región de América Latina y el Caribe. Sin embargo, la abundancia de estudios no necesariamente acorta el camino para encontrar intervenciones seguras y eficaces frente a la COVID-19. Se analizaron los ensayos para el tratamiento y la prevención de la COVID-19 de los países de América Latina y el Caribe que están registrados en la Plataforma de Registros Internacionales de Ensayos Clínicos de la Organización Mundial de la Salud, y se identificó una tendencia hacia la realización de estudios pequeños, repetitivos y no rigurosos que duplican los esfuerzos y merman recursos limitados sin producir conclusiones significativas sobre la seguridad y la eficacia de las intervenciones evaluadas. Se evaluaron asimismo los desafíos que plantea la realización de investigaciones científicamente sólidas y socialmente valiosas en la región de América Latina y el Caribe a fin de brindar recomendaciones que alienten la realización de ensayos clínicos que tengan más probabilidades de producir evidencia sólida durante la pandemia.