Dispersion patterns of SARS-CoV-2 variants Gamma, Lambda and Mu in Latin America and the Caribbean.

Latin America and Caribbean (LAC) regions were an important epicenter of the COVID-19 pandemic and SARS-CoV-2 evolution. Through the COVID-19 Genomic Surveillance Regional Network (COVIGEN), LAC countries produced an important number of genomic sequencing data that made possible an enhanced SARS-CoV-2 genomic surveillance capacity in the Americas, paving the way for characterization of emerging variants and helping to guide the public health response. In this study we analyzed approximately 300,000 SARS-CoV-2 sequences generated between February 2020 and March 2022 by multiple genomic surveillance efforts in LAC and reconstructed the diffusion patterns of the main variants of concern (VOCs) and of interest (VOIs) possibly originated in the Region. Our phylogenetic analysis revealed that the spread of variants Gamma, Lambda and Mu reflects human mobility patterns due to variations of international air passenger transportation and gradual lifting of social distance measures previously implemented in countries. Our results highlight the potential of genetic data to reconstruct viral spread and unveil preferential routes of viral migrations that are shaped by human mobility patterns.

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.

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.

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

[ABSTRACT]. 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 sig- nificant 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-presenta- tion 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.

[RESUMEN]. Objetivo. Caracterizar la frecuencia, las causas y los factores predictores del reingreso de pacientes con COVID–19 tras haber recibido el alta de un centro de salud o un servicio de urgencias, las intervenciones utilizadas para reducir los reingresos y los resultados de los pacientes con COVID-19 dados de alta de dichos entornos. Métodos. Se realizó una revisión sistemática de estudios de serie de casos y estudios observacionales publi- cados entre enero del 2020 y abril del 2021 en PubMed, Embase, LILACS y MedRxiv en los cuales se informó sobre la frecuencia, las causas o los factores de riesgo relativos al reingreso de pacientes y sobrevivientes de COVID-19. Se realizó una síntesis narrativa y se evaluó la calidad metodológica utilizando la lista de verifi- cación de evaluación crítica de JBI. Resultados. Se encontraron 44 estudios con datos de 10 países. La tasa media general de reingreso a los 30 días fue de 7,1%. Los reingresos variaron con la duración del seguimiento, y tuvieron lugar en <10,5%, <14,5%, <21,5% y <30%, respectivamente, a los 10, 30, 60 y 253 días después del alta. Entre los que reci- bieron seguimiento por 30 y 60 días, el tiempo medio entre el alta y la readmisión fue de 3 y de 8 a 11 días, respectivamente. El factor de riesgo significativo asociado al reingreso fue una estancia más corta, y entre las causas importantes se encontraron episodios respiratorios o tromboembólicos y enfermedades crónicas. El reingreso en el servicio de urgencias fue de >20% en cuatro estudios. Los factores de riesgo asociados con la mortalidad fueron sexo masculino, edad avanzada y comorbilidades. Conclusión. El reingreso de sobrevivientes de COVID-19 es frecuente, y la mortalidad después del alta es significativa en grupos poblacionales específicos. Existe una necesidad urgente de seguir examinando las razones subyacentes del reingreso temprano, así como de prevenir reingresos adicionales y resultados adversos en los sobrevivientes de COVID–19.

[RESUMO]. Objetivo. Caracterizar a frequência, as causas e os preditores de reinternação de pacientes com COVID-19 após a alta do estabelecimento de saúde ou do pronto-socorro, intervenções usadas para reduzir reinter- nações e desfechos de pacientes com COVID-19 que receberam alta de tais instalações. Métodos. Revisão sistemática de séries de casos e estudos observacionais publicados entre janeiro de 2020 e abril de 2021, indexados nos bancos de dados PubMed, Embase, LILACS e MedRxiv, que relatassem a fre- quência, as causas ou os fatores de risco para a reinternação de sobreviventes da COVID-19/pacientes com COVID-19. Realizamos uma síntese narrativa das evidências e avaliamos a qualidade metodológica utilizando a checklist de avaliação crítica do Joanna Briggs Institute (JBI). Resultados. Foram identificados 44 estudos, incluindo dados de 10 países. O índice médio geral de reinter- nação em 30 dias foi de 7,1%. A frequência das reinternações variou com o tempo de acompanhamento, com <10,5%, <14,5%, <21,5% e <30%, respectivamente, ocorrendo nos primeiros 10, 30, 60 e 253 dias após a alta. Dentre aqueles seguidos por 30 e 60 dias, o tempo médio da alta até a reinternação foi de 3 dias e 8 a 11 dias, respectivamente. O único fator de risco significativamente associado à reinternação foi ter um tempo de permanência hospitalar mais curto, e as causas importantes incluíram eventos respiratórios ou tromboembóli- cos e doenças crônicas. Em quatro estudos, >20% dos pacientes retornaram ao pronto-socorro. Os fatores de risco associados à mortalidade foram sexo masculino, idade avançada e comorbidades. Conclusões. A reinternação hospitalar é frequente em sobreviventes da COVID-19 e a mortalidade pós-alta é significativa em populações específicas. Há uma necessidade urgente de examinar melhor as razões que levam à reinternação precoce e de evitar reinternações adicionais e desfechos adversos em sobreviventes da 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.

Implementation of a COVID-19 Genomic Surveillance Regional Network for Latin America and Caribbean region.

The timely release of SARS-CoV-2 first genomic sequences allowed the identification of the etiologic agent and development of diagnostic protocols. Genomic sequencing was a crucial step in generating data for driving laboratory response and detections of SARS-CoV-2 since the start of the COVID-19 pandemic. Because of all the progression and achievements that timely release of genetic sequence data represents in the public health response, the Pan American Health Organization (PAHO) in collaboration with countries' public health laboratories, started implementation of a network for strengthening the Latin America and Caribbean (LAC) region on timely generation of SARS-CoV-2 genomic data. Here we describe the implementation of the COVID-19 Genomic Surveillance Regional Network in the Americas region during the beginning of the pandemic. The establishment of this network has strengthened laboratory response capacity at the country level, as well as facilitated timely release of SARS-CoV-2 genomic information to be used to complement the multiple response strategies for COVID-19 pandemic mitigation. As genomic epidemiology is useful for guiding public health decisions on outbreak and response, we also analysed the first SARS-CoV-2 genomic sequence data from countries of the Latin America and Caribbean 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.

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.

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.

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

ABSTRACT 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.

RESUMEN Objetivo. Caracterizar la frecuencia, las causas y los factores predictores del reingreso de pacientes con COVID-19 tras haber recibido el alta de un centro de salud o un servicio de urgencias, las intervenciones utilizadas para reducir los reingresos y los resultados de los pacientes con COVID-19 dados de alta de dichos entornos. Métodos. Se realizó una revisión sistemática de estudios de serie de casos y estudios observacionales publicados entre enero del 2020 y abril del 2021 en PubMed, Embase, LILACS y MedRxiv en los cuales se informó sobre la frecuencia, las causas o los factores de riesgo relativos al reingreso de pacientes y sobrevivientes de COVID-19. Se realizó una síntesis narrativa y se evaluó la calidad metodológica utilizando la lista de verificación de evaluación crítica de JBI. Resultados. Se encontraron 44 estudios con datos de 10 países. La tasa media general de reingreso a los 30 días fue de 7,1%. Los reingresos variaron con la duración del seguimiento, y tuvieron lugar en <10,5%, <14,5%, <21,5% y <30%, respectivamente, a los 10, 30, 60 y 253 días después del alta. Entre los que recibieron seguimiento por 30 y 60 días, el tiempo medio entre el alta y la readmisión fue de 3 y de 8 a 11 días, respectivamente. El factor de riesgo significativo asociado al reingreso fue una estancia más corta, y entre las causas importantes se encontraron episodios respiratorios o tromboembólicos y enfermedades crónicas. El reingreso en el servicio de urgencias fue de >20% en cuatro estudios. Los factores de riesgo asociados con la mortalidad fueron sexo masculino, edad avanzada y comorbilidades. Conclusión. El reingreso de sobrevivientes de COVID-19 es frecuente, y la mortalidad después del alta es significativa en grupos poblacionales específicos. Existe una necesidad urgente de seguir examinando las razones subyacentes del reingreso temprano, así como de prevenir reingresos adicionales y resultados adversos en los sobrevivientes de COVID-19.

RESUMO Objetivo. Caracterizar a frequência, as causas e os preditores de reinternação de pacientes com COVID-19 após a alta do estabelecimento de saúde ou do pronto-socorro, intervenções usadas para reduzir reinternações e desfechos de pacientes com COVID-19 que receberam alta de tais instalações. Métodos. Revisão sistemática de séries de casos e estudos observacionais publicados entre janeiro de 2020 e abril de 2021, indexados nos bancos de dados PubMed, Embase, LILACS e MedRxiv, que relatassem a frequência, as causas ou os fatores de risco para a reinternação de sobreviventes da COVID-19/pacientes com COVID-19. Realizamos uma síntese narrativa das evidências e avaliamos a qualidade metodológica utilizando a checklist de avaliação crítica do Joanna Briggs Institute (JBI). Resultados. Foram identificados 44 estudos, incluindo dados de 10 países. O índice médio geral de reinternação em 30 dias foi de 7,1%. A frequência das reinternações variou com o tempo de acompanhamento, com <10,5%, <14,5%, <21,5% e <30%, respectivamente, ocorrendo nos primeiros 10, 30, 60 e 253 dias após a alta. Dentre aqueles seguidos por 30 e 60 dias, o tempo médio da alta até a reinternação foi de 3 dias e 8 a 11 dias, respectivamente. O único fator de risco significativamente associado à reinternação foi ter um tempo de permanência hospitalar mais curto, e as causas importantes incluíram eventos respiratórios ou tromboembólicos e doenças crônicas. Em quatro estudos, >20% dos pacientes retornaram ao pronto-socorro. Os fatores de risco associados à mortalidade foram sexo masculino, idade avançada e comorbidades. Conclusões. A reinternação hospitalar é frequente em sobreviventes da COVID-19 e a mortalidade pós-alta é significativa em populações específicas. Há uma necessidade urgente de examinar melhor as razões que levam à reinternação precoce e de evitar reinternações adicionais e desfechos adversos em sobreviventes da COVID-19.

COVID-19 laboratory preparedness and response in the Americas Region: Lessons learned.

By the time the etiologic agent of the COVID-19 was identified as a novel coronavirus, no country in the Americas Region had laboratory capacity for detecting this new virus. A strategic multilevel approach with specific reagent purchase and delivery, regional trainings, in-country missions, and the provision of technical support was established for timely preparedness of national reference laboratories for SARS-CoV-2 detection. All countries should be prepared to timely detect any potential pandemic emerging agent. The rapid SARS-CoV-2 molecular detection implementation throughout the Americas showed the importance of an efficient and coordinated laboratory response for preparedness. Here we present how in 25 days the Americas Region went from no SARS-CoV-2 diagnostic capacity, to molecular detection fully implemented in 28 Member States, under the coordinated strategy of the Pan American Health Organization and collaborative work at regional and country level with national authorities and public health laboratories.

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.

Correction: Risk of bias and confounding of observational studies of Zika virus infection: A scoping review of research protocols.

[This corrects the article DOI: 10.1371/journal.pone.0180220.].

Geographic patterns and environmental factors associated with human yellow fever presence in the Americas.

BACKGROUND: In the Americas, yellow fever virus transmission is a latent threat due to the proximity between urban and wild environments. Although yellow fever has nearly vanished from North and Central America, there are still 13 countries in the Americas considered endemic by the World Health Organization. Human cases usually occur as a result of the exposure to sylvatic yellow fever in tropical forested environments; but urban outbreaks reported during the last decade demonstrate that the risk in this environment still exists. The objective of this study was to identify spatial patterns and the relationship between key geographic and environmental factors with the distribution of yellow fever human cases in the Americas. METHODOLOGY/PRINCIPAL FINDINGS: An ecological study was carried out to analyze yellow fever human cases reported to the Pan American Health Organization from 2000 to 2014, aggregated by second administrative level subdivisions (counties). Presence of yellow fever by county was used as the outcome variable and eight geo-environmental factors were used as independent variables. Spatial analysis was performed to identify and examine natural settings per county. Subsequently, a multivariable logistic regression model was built. During the study period, 1,164 cases were reported in eight out of the 13 endemic countries. Nearly 83.8% of these cases were concentrated in three countries: Peru (37.4%), Brazil (28.1%) and Colombia (18.4%); and distributed in 57 states/provinces, specifically in 286 counties (3.4% of total counties). Yellow fever presence was significantly associated with altitude, rain, diversity of non-human primate hosts and temperature. A positive spatial autocorrelation revealed a clustered geographic pattern in 138/286 yellow fever positive counties (48.3%). CONCLUSIONS/SIGNIFICANCE: A clustered geographic pattern of yellow fever was identified mostly along the Andes eastern foothills. This risk map could support health policies in endemic countries. Geo-environmental factors associated with presence of yellow fever could help predict and adjust the limits of other risk areas of epidemiological concern.

Risk of bias and confounding of observational studies of Zika virus infection: A scoping review of research protocols.

INTRODUCTION: Given the severity and impact of the current Zika virus (ZIKV) outbreak in the Americas, numerous countries have rushed to develop research studies to assess ZIKV and its potential health consequences. In an effort to ensure that studies are comprehensive, both internally and externally valid, and with reliable results, the World Health Organization, the Pan American Health Organization, Institut Pasteur, the networks of Fiocruz, the Consortia for the Standardization of Influenza Seroepidemiology (CONSISE) and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) have generated six standardized clinical and epidemiological research protocols and questionnaires to address key public health questions on ZIKV. METHODS: We conducted a systematic search of ongoing study protocols related to ZIKV research. We analyzed the content of protocols of 32 cohort studies and 13 case control studies for systematic bias that could produce erroneous results. Additionally we aimed to characterize the risks of bias and confounding in observational studies related to ZIKV and to propose ways to minimize them, including the use of six newly standardized research protocols. RESULTS: Observational studies of ZIKV face an array of challenges, including measurement of exposure and outcomes (microcephaly and Guillain-Barré Syndrome). Potential confounders need to be measured where known and controlled for in the analysis. Selection bias due to non-random selection is a significant issue, particularly in the case-control design, and losses to follow-up is equally important for the cohort design. CONCLUSION: Observational research seeking to answer key questions on the ZIKV should consider these restrictions and take precautions to minimize bias in an effort to provide reliable and valid results. Utilization of the standardized research protocols developed by the WHO, PAHO, Institut Pasteur, and CONSISE will harmonize the key methodological aspects of each study design to minimize bias at different stages of the study. Biases need to be considered by researchers implementing the standardized protocols as well as by users of observational epidemiological studies of ZIKV.

Interventions for treating patients with chikungunya virus infection-related rheumatic and musculoskeletal disorders: A systematic review.

BACKGROUND: Chikungunya virus infection (CHIKV) is caused by a mosquito-borne alphavirus. CHIKV causes high fever and painful rheumatic disorders that may persist for years. Because little is known about interventions for treating CHIKV-related illness, we conducted a systematic review. METHODS: We used Cochrane methods. We searched PubMed, EMBASE, Cochrane Library, LILACS and other sources from the earliest records to March 2016. We had no language restrictions. We included randomized controlled trials assessing any intervention for treating acute or chronic CHIKV-related illness. Our primary outcomes were pain relief, global health status (GHS) or health related quality of life (HRQL), and serious adverse events (SAEs). We assessed bias risk with the Cochrane tool and used GRADE to assess evidence quality. RESULTS: We screened 2,229 records and found five small trials with a total of 402 participants. Patients receiving chloroquine (CHQ) had better chronic pain relief than those receiving placebo (relative risk [RR] 2.67, 95% confidence interval [CI] 1.23 to 5.77, N = 54), but acute pain relief was marginally not different between groups (mean difference [MD] 1.46, 95% CI 0.00 to 2.92, N = 54). SAEs were similar (RR = 15.00, 95% CI 0.90 to 250.24, N = 54). Comparing CHQ with paracetamol (PCM), CHQ patients had better pain relief (RR = 1.52, 95% CI 1.20 to 1.93, N = 86). Compared with hydroxychloroquine (HCHQ), disease-modifying anti-rheumatic drugs (DMARDs) reduced pain (MD = -14.80, 95% CI -19.12 to -10.48, N = 72). DMARDs patients had less disability (MD = -0.74, 95% CI -0.92 to -0.56, N = 72) and less disease activity (MD = -1.35; 95% CI -1.70 to -1.00; N = 72). SAEs were similar between DMARDs and HCHQ groups (RR = 2.84, 95% CI 0.12 to 67.53, N = 72). Comparing meloxicam (MXM) with CHQ, there was no difference in pain relief (MD = 0.24, 95% CI = -0.81 to 1.29; p = 0.65, N = 70), GHS or HRQL (MD = -0.31, 95% CI -2.06 to 1.44, N = 70) or SAEs (RR = 0.85, 95% CI 0.30 to 2.42, N = 70). Finally, a four-arm trial (N = 120) compared aceclofenac (ACF) monotherapy to ACF+HCHQ, ACF+ prednisolone (PRD), or ACF+HCHQ+PRD. Investigators found reduced pain (p<0.001) and better HRQL (p<0.001) in the two patient groups receiving PRD, compared to those receiving ACF monotherapy or ACF+HCHQ. Trials were at high risk of bias. GRADE evidence quality for all outcomes was very low. CONCLUSION: Results from these small trials provide insufficient evidence to draw conclusions about the efficacy or safety of CHIKV interventions. Physicians should be cautious in prescribing and policy-makers should be cautious in recommending any intervention reviewed here. Rigorous trials with sufficient statistical power are urgently needed, with results stratified by disease stage and symptomology.

Leptospirosis in Latin America: exploring the first set of regional data

Objectives. To demonstrate the importance of country surveillance systems for leptospirosis and their use for preliminary epidemiological analysis, as well as to generate research questions for future, more comprehensive studies on the disease. Methods. In 2015, for the first time, the Pan American Health Organization (PAHO) included human cases of leptospirosis in its Regional Core Health Data Initiative, an open-access database that collects annual health indicators from the countries and territories of the Americas. This new information was used to analyze leptospirosis cases by country and sex and to calculate cumulative incidence rates. Maps were used to help present the results. To supplement that general review of leptospirosis in the Americas, more detailed descriptions of the epidemiological situation and the surveillance programs of four selected countries (Brazil, Colombia, Cuba, and Honduras) were provided. Results. In this first year of PAHO requesting leptospirosis data, of the 49 countries and territories in the Americas, 38 of them (77.6%) reported information. Among those 38, 28 of them (73.7%) reported the presence of human cases; the majority of instances of zero cases were in Caribbean territories. From those 28, a total of 10 702 human cases were recorded. The largest numbers of cases in Latin America were in Brazil (40.2%), Peru (23.6%), Colombia (8.8%), and Ecuador (7.2%). The cumulative incidence rate for Latin America was estimated to be 2.0 per 100 000 population. On average, 65.1% of cases were males. Conclusions. This study demonstrates that many countries in Latin America are making efforts to establish strong surveillance systems and programs for leptospirosis. The study also shows the importance of having leptospirosis surveillance systems as well as how the information generated can be used for evidence-based decision-making on leptospirosis.

Objetivos. Demostrar la importancia de los sistemas nacionales de vigilancia de la leptospirosis y su uso para realizar el análisis epidemiológico preliminar, así como para generar preguntas de investigación que se utilicen en futuros estudios más integrales sobre la enfermedad. Métodos. En el año 2015, la Organización Panamericana de la Salud (OPS) incluyó por primera vez casos humanos de leptospirosis en su Iniciativa Regional de Datos Básicos de Salud, base de datos de acceso abierto que recoge indicadores de salud anuales de los países y territorios de la Región de las Américas. Esta nueva información fue utilizada para analizar los casos de leptospirosis por país y sexo, así como para calcular las tasas de incidencia acumulada, y los resultados se presentaron en mapas. Para complementar ese examen general de la leptospirosis en esta Región, se aportó una descripción más detallada de la situación epidemiológica y los programas de vigilancia de cuatro países (Brasil, Colombia, Cuba y Honduras). Resultados. En este primer año en que la OPS solicitó datos sobre la leptospirosis, de los 49 países y territorios en la Región de las Américas, aportaron información 38 (77,6 %). De esos 38, 28 (73,7 %) notificaron casos humanos; la mayor parte de las instancias sin ningún caso humano se registraron en territorios del Caribe. En esos 28 países y territorios, se registraron 10 702 casos humanos. En América Latina, los países que registraron los números más altos de casos fueron Brasil (40,2 %), Perú (23,6 %), Colombia (8,8 %) y Ecuador (7,2 %). Se calculó que la tasa de incidencia acumulada de América Latina es de 2,0 por 100 000 habitantes. En promedio, 65,1 % de los casos correspondieron a hombres. Conclusiones. Este estudio demuestra que muchos países de América Latina están tomando medidas para instaurar sistemas y programas sólidos de vigilancia de la leptospirosis. Asimismo, revela la importancia de los sistemas de vigilancia de la leptospirosis, así como el modo en que la información generada puede servir para tomar decisiones basadas en la evidencia acerca de esta enfermedad.

Objetivos. Demonstrar a importância dos sistemas nacionais de vigilância para a leptospirose e seu uso na análise epidemiológica preliminar, além de gerar perguntas de pesquisa para futuros estudos mais aprofundados sobre a doença. Métodos. Em 2015, a Organização Pan-Americana da Saúde (OPAS) incluiu, pela primeira vez, casos humanos de leptospirose em sua Iniciativa Regional de Dados Básicos de Saúde, uma base de dados de acesso aberto que coleta indicadores de saúde anuais nos países e territórios das Américas. Utilizamos estas novas informações para analisar os casos de leptospirose por país e por sexo e calcular as taxas de incidência acumuladas. A apresentação dos dados é facilitada pelo uso de mapas. Para complementar esta revisão geral da leptospirose nas Américas, apresentamos descrições mais detalhadas da situação epidemiológica e dos programas de vigilância de quatro países selecionados (Brasil, Colômbia, Cuba e Honduras). Resultados. Neste primeiro ano em que a OPAS solicitou dados sobre a leptospirose, 38 dos 49 países e territórios das Américas (77,6%) apresentaram informações. Destes 38, 28 (73,7%) notificaram a presença de casos humanos; em sua maioria, os que não apresentaram nenhum caso foram territórios do Caribe. Dentre os 28, foi registrado um total de 10.702 casos humanos. O maior número de casos na América Latina foi observado no Brasil (40,2%), Peru (23,6%), Colômbia (8,8%) e Equador (7,2%). A taxa de incidência acumulada para a América Latina foi estimada em 2,0 por 100.000 habitantes. Em média, 65,1% dos casos foram em homens. Conclusões. Este estudo demonstra que muitos países da América Latina estão fazendo esforços para estabelecer fortes sistemas de vigilância e programas contra a leptospirose. O estudo também revela a importância da existência de sistemas de vigilância para a leptospirose e demonstra que as informações geradas podem ser usadas para a tomada de decisões baseadas em evidências científicas para a leptospirose.