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.

OBJECTIVES: To build and maintain a living database of the Pan American Health Organization/World Health Organization (PAHO/WHO) recommendations developed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). STUDY DESIGN AND SETTING: Guidelines are identified from WHO and PAHO databases. We periodically extract recommendations, according to the health and well-being targets of sustainable development goal 3 (SDG-3). RESULTS: As of March 2022, the International database of GRADE guidelines (https://bigg-rec.bvsalud.org/en) database hosted 2,682 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), noncommunicable diseases (677), maternal health (654), COVID-19 (224), use of psychoactive substances (99), tobacco (14) and road and traffic accidents (16). International database of GRADE guidelines 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.

Factores pronósticos de síndrome cardio-pulmonar y muerte por hantavirus Andes Sur: estudio de cohorte en San Carlos de Bariloche y su zona de influencia sanitaria / Prognostic factors for cardio-pulmonary syndrome and death by hantavirus Andes Sur: cohort study in San Carlos de Bariloche and health influence área

Resumen Las infecciones por hantavirus, ocurren a través de la inhalación de aerosoles provenientes de excretas de roedores infectados. Estos virus causan síndrome cardiopulmonar en el caso de la variante Andes Sur, con una mortalidad que puede alcanzar el 50%. Se presenta como casos esporádicos o en pequeños conglomerados, en los que predomina el contagio interhumano. En este estudio observacional de tipo cohorte histórica, en personas infectadas con hantavirus Andes Sur durante los años 2009 a 2019 que fueron asistidas en el subsector público de salud de San Carlos de Bariloche(Argentina), se buscó identificar factores que pudieran predecir mala evolución (síndrome cardiopulmonar y muerte). Para ello se caracterizó el riesgo para cada una de las variables y, para obtener información clave sobre las relaciones entre las mismas, se aplicó además un análisis de correspondencias múltiples. Durante el período de estudio, 38 personas fueron incluidas. La edad media fue de 35 años. Se sospechó contagio de persona a persona en 10/38 (26.8%) casos. El 21.1% (8/28) tuvo al momento del diagnóstico un síndrome pulmonar por hantavirus. Mientras que, 55.3% (21/38) lo desarrolló durante su evolución y 44.7% (17/38) de los infectados fallecieron durante la internación. La edad mayor a 15 años y la plaquetopenia, se asociaron con un mayor riesgo de progresión clínica, mientras que las formas de leves o las personas asintomáticas, el contagio persona a persona o durante un brote epidemiológico, se asociaron con un menor riesgo de muerte.

Abstract Hantavirus infections occur through the inhalation of aerosols from the excreta of infected rodents. These viruses cause a cardiopulmonary syn drome in the case of the Andes Sur variant, with a mortality that can reach 50%. It occurs in sporadic cases or in small clusters, in which interhuman contagion predominates. In this historical cohort-type observational study, in people infected with Andes Sur hantavirus during the years 2009 to 2019 who was assisted in the public health subsector of San Carlos de Bariloche (Argentina), it was sought to identify factors that could predict poor evolution (cardiopulmonary syndrome and death). For this, the risk for each of the variables was characterized and, to obtain key information about the relationships between them, a multiple correspondence analysis was also applied. During the study period, 38 people were included. The mean age was 35 years. Person-to-person contagion was suspected in 10/38 (26.8%) cases. 21.1% (8/28) presented a hantavirus pulmonary syndrome at the time of diagnosis, while 55.3% (21/38) developed it during their evolution, and 44.7% (17/38) of those infected died during hospitalization. Age over 15 years and thrombocytopenia were associated with a higher risk of clinical progression, while mild forms or asymptomatic people, person-to-person transmission, or during an epidemiological outbreak, were associated with a lower risk of death.

[Prognostic factors for cardio-pulmonary syndrome and death by hantavirus Andes Sur: cohort study in San Carlos de Bariloche and health influence area]. / Factores pronósticos de síndrome cardiopulmonar y muerte por hantavirus Andes Sur: Estudio de cohorte en San Carlos de Bariloche y su zona de influencia sanitaria.

Hantavirus infections occur through the inhalation of aerosols from the excreta of infected rodents. These viruses cause a cardiopulmonary syndrome in the case of the Andes Sur variant, with a mortality that can reach 50%. It occurs in sporadic cases or in small clusters, in which interhuman contagion predominates. In this historical cohort-type observational study, in people infected with Andes Sur hantavirus during the years 2009 to 2019 who was assisted in the public health subsector of San Carlos de Bariloche (Argentina), it was sought to identify factors that could predict poor evolution (cardiopulmonary syndrome and death). For this, the risk for each of the variables was characterized and, to obtain key information about the relationships between them, a multiple correspondence analysis was also applied. During the study period, 38 people were included. The mean age was 35 years. Person-to-person contagion was suspected in 10/38 (26.8%) cases. 21.1% (8/28) presented a hantavirus pulmonary syndrome at the time of diagnosis, while 55.3% (21/38) developed it during their evolution, and 44.7% (17/38) of those infected died during hospitalization. Age over 15 years and thrombocytopenia were associated with a higher risk of clinical progression, while mild forms or asymptomatic people, person-to-person transmission, or during an epidemiological outbreak, were associated with a lower risk of death.

Las infecciones por hantavirus, ocurren a través de la inhalación de aerosoles provenientes de excretas de roedores infectados. Estos virus causan síndrome cardiopulmonar en el caso de la variante Andes Sur, con una mortalidad que puede alcanzar el 50%. Se presenta como casos esporádicos o en pequeños conglomerados, en los que predomina el contagio interhumano. En este estudio observacional de tipo cohorte histórica, en personas infectadas con hantavirus Andes Sur durante los años 2009 a 2019 que fueron asistidas en el subsector público de salud de San Carlos de Bariloche(Argentina), se buscó identificar factores que pudieran predecir mala evolución (síndrome cardiopulmonar y muerte). Para ello se caracterizó el riesgo para cada una de las variables y, para obtener información clave sobre las relaciones entre las mismas, se aplicó además un análisis de correspondencias múltiples. Durante el período de estudio, 38 personas fueron incluidas. La edad media fue de 35 años. Se sospechó contagio de persona a persona en 10/38 (26.8%) casos. El 21.1% (8/28) tuvo al momento del diagnóstico un síndrome pulmonar por hantavirus. Mientras que, 55.3% (21/38) lo desarrolló durante su evolución y 44.7% (17/38) de los infectados fallecieron durante la internación. La edad mayor a 15 años y la plaquetopenia, se asociaron con un mayor riesgo de progresión clínica, mientras que las formas de leves o las personas asintomáticas, el contagio persona a persona o durante un brote epidemiológico, se asociaron con un menor riesgo de muerte.

Correction: Prognostic factors for severity and mortality in patients infected with COVID-19: A systematic review.

[This corrects the article DOI: 10.1371/journal.pone.0241955.].

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.

[Clinical practice guideline: tocilizumab for patients with severe and critical COVID-19]. / Guía de práctica clínica: tocilizumab para pacientes con COVID-19 grave o crítica.

In COVID-19, there are states of hyperinflammation in severely or critically ill people, where immunosuppression and blocking of IL-6 receptors could be beneficial. Faced with this situation, with the support of a methods group using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, about the use of tocilizumab for patients with severe and critical illness coronavirus. This guide focuses on making recommendations for the use of tocilizumab in patients with severe and critical COVID-19. This clinical practice guideline was prepared following the WHO guideline development methods. A multidisciplinary development group was formed, with clinical and health policy experts, methodologists and users. Panel and methods group members signed a declaration of conflict of interest. We searched the Epistemonikos Foundation's LOVE database for randomized studies up to April 17, 2021. The synthesis and evidence profiles were prepared using the GRADE approach and an economic model was developed. Among hospitalized adults with progressive severe or critical COVID-19, the guideline panel su ggests tocilizumab. (Conditional recommendation, Moderate certainty of evidence) Implementation considerations. A. Dose: 8 mg/kg of actual weight, single-dose, intravenously), maximum dose 800 mg; B. Administer dexamethasone 8 mg (or equivalent) for 10 days together with tocilizumab; C. The recommendation applies to: 1. patients with severe disease defined as SpO2 = 92% with room air and/or patients receiving supplemental oxygen (including a high-flow nasal cannula and non-invasive ventilation); 2. critically ill patients: requiring invasive mechanical ventilation.

En COVID-19, existen estados de hiperinflamación, donde la inmunosupresión y bloqueo de receptores de IL-6 podría ser beneficiosa. Se desarrolló una guía de práctica clínica con apoyo del grupo metodológico, utilizando el método GRADE (Grading of Recommendations Assessment, Development and Evaluation) acerca del uso de tocilizumab para pacientes con COVID-19 grave y crítica. Siguiendo métodos de elaboración de guías de la OMS, se conformó un grupo multidisciplinario compuesto por expertos temáticos clínicos y en políticas públicas, metodólogos y usuarios. Todos lo s participantes del panel y del grupo desarrollador firmaron una declaración de conflicto de interés. Se realizaron búsquedas de estudios aleatorizados hasta el 17 de abril de 2021, en la base de datos LOVE de la fundación Epistemonikos. Se elaboró la síntesis y los perfiles de evidencia utilizando el enfoque GRADE y se desarrolló un modelo para valorar el impacto presupuestario de la incorporación de tociliuzmab. Posteriormente, la recomendación fue graduada en un panel de expertos temáticos. Se sugiere utilizar tocilizumab en hospitalizados con COVID-19 grave y crítica. Recomendación condicional, certeza en la evidencia moderada. Consideraciones para la implementación. A. Dosis: 8 mg/kg de peso real, única dosis, por vía endovenosa, dosis máxima 800 mg; B. Administrar dexametasona 8 mg (o equivalente) por 10 días conjuntamente con tocilizumab; C. La recomendación aplica a: 1. pacientes con enfermedad grave definida como SpO2 = 92% con aire ambiente y/o pacientes que reciben oxígeno suplementario (incluyendo cánula nasal de alto flujo y ventilación no invasiva); 2. pacientes con enfermedad crítica (ventilación mecánica invasiva).

Immunoglobulin G Immune Complexes May Contribute to Neutrophil Activation in the Course of Severe Coronavirus Disease 2019.

Severe coronavirus disease 2019 (COVID-19) is associated with an overactive inflammatory response mediated by macrophages. Here, we analyzed the phenotype and function of neutrophils in patients with COVID-19. We found that neutrophils from patients with severe COVID-19 express high levels of CD11b and CD66b, spontaneously produce CXCL8 and CCL2, and show a strong association with platelets. Production of CXCL8 correlated with plasma concentrations of lactate dehydrogenase and D-dimer. Whole blood assays revealed that neutrophils from patients with severe COVID-19 show a clear association with immunoglobulin G (IgG) immune complexes. Moreover, we found that sera from patients with severe disease contain high levels of immune complexes and activate neutrophils through a mechanism partially dependent on FcγRII (CD32). Interestingly, when integrated in immune complexes, anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies from patients with severe COVID-19 displayed a higher proinflammatory profile compared with antibodies from patients with mild disease. Our study suggests that IgG immune complexes might promote the acquisition of an inflammatory signature by neutrophils, worsening the course of COVID-19.

Guía de práctica clínica: tocilizumab para pacientes con COVID-19 grave o crítica / Clinical practice guideline: tocilizumab for patients with severe and critical COVID-19

Resumen En COVID-19, existen estados de hiperinflamación, donde la inmunosupresión y bloqueo de receptores de IL-6 podría ser beneficiosa. Se desarrolló una guía de práctica clínica con apoyo del gru po metodológico, utilizando el método GRADE (Grading of Recommendations Assessment, Development and Evaluation) acerca del uso de tocilizumab para pacientes con COVID-19 grave y crítica. Siguiendo métodos de elaboración de guías de la OMS, se conformó un grupo multidisciplinario compuesto por expertos temáticos clí nicos y en políticas públicas, metodólogos y usuarios. Todos lo s participantes del panel y del grupo desarrollador firmaron una declaración de conflicto de interés. Se realizaron búsquedas de estudios aleatorizados hasta el 17 de abril de 2021, en la base de datos L.OVE de la fundación Epistemonikos. Se elaboró la síntesis y los perfiles de evidencia utilizando el enfoque GRADE y se desarrolló un modelo para valorar el impacto presupuestario de la incorporación de tociliuzmab. Posteriormente, la recomendación fue graduada en un panel de expertos temáti cos. Se sugiere utilizar tocilizumab en hospitalizados con COVID-19 grave y crítica. Recomendación condicional, certeza en la evidencia moderada. Consideraciones para la implementación. A. Dosis: 8 mg/kg de peso real, única dosis, por vía endovenosa, dosis máxima 800 mg; B. Administrar dexametasona 8 mg (o equivalente) por 10 días conjuntamente con tocilizumab; C. La recomendación aplica a: 1. pacientes con enfermedad grave definida como SpO2 ≤ 92% con aire ambiente y/o pacientes que reciben oxígeno suplementario (incluyendo cánula nasal de alto flujo y ventilación no invasiva); 2. pacientes con enfermedad crítica (ventilación mecánica invasiva).

Abstract In COVID-19, there are states of hyperinflammation in severely or critically ill people, where immu nosuppression and blocking of IL-6 receptors could be beneficial. Faced with this situation, with the support of a methods group using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, about the use of tocilizumab for patients with severe and critical illness coronavirus. This guide fo cuses on making recommendations for the use of tocilizumab in patients with severe and critical COVID-19. This clinical practice guideline was prepared following the WHO guideline development methods. A multidisciplinary development group was formed, with clinical and health policy experts, methodologists and users. Panel and methods group members signed a declaration of conflict of interest. We searched the Epistemonikos Founda tion's L.OVE database for randomized studies up to April 17, 2021. The synthesis and evidence profiles were prepared using the GRADE approach and an economic model was developed. Among hospitalized adults with progressive severe or critical COVID-19, the guideline panel su ggests tocilizumab. (Conditional recommendation, Moderate certainty of evidence) Implementation considerations. A. Dose: 8 mg/kg of actual weight, single-dose, intravenously), maximum dose 800 mg; B. Administer dexamethasone 8 mg (or equivalent) for 10 days together with tocilizumab; C. The recommendation applies to: 1. patients with severe disease defined as SpO2 ≤ 92% with room air and/or patients receiving supplemental oxygen (including a high-flow nasal cannula and non-invasive ventilation); 2. critically ill patients: requiring invasive mechanical ventilation.

Clinical practice guideline for transcatheter versus surgical valve replacement in patients with severe aortic stenosis in Latin America.

In elderly (75 years or older) patients living in Latin America with severe symptomatic aortic stenosis candidates for transfemoral approach, the panel suggests the use of transcatheter aortic valve implant (TAVI) over surgical aortic valve replacement (SAVR). This is a conditional recommendation, based on moderate certainty in the evidence (⨁⨁⨁Ο).This recommendation does not apply to patients in which there is a standard of care, like TAVI for patients at very high risk for cardiac surgery or inoperable patients, or SAVR for non-elderly patients (eg, under 65 years old) at low risk for cardiac surgery. The suggested age threshold of 75 years old is based on judgement of limited available literature and should be used as a guide rather than a determinant threshold.The conditional nature of this recommendation means that the majority of patients in this situation would want a transfemoral TAVI over SAVR, but some may prefer SAVR. For clinicians, this means that they must be familiar with the evidence supporting this recommendation and help each patient to arrive at a management decision integrating a multidisciplinary team discussion (Heart Team), patient's values and preferences through shared decision-making, and available resources. Policymakers will require substantial debate and the involvement of various stakeholders to implement this recommendation.

Development of simple and sensitive score to assess the risk of pneumonia in Covid-19 patients

ABSTRACT Background: Severe pneumonia is the most common cause of intensive care unit (ICU) admission and death due to novel coronavirus (SARS-CoV-2) respiratory disease (COVID-19). Due to its rapid outbreak, units for the evaluation of febrile patients in the pre-hospital setting were created. Objective: The objective of the study was to develop a sensitive and simple tool to assess the risk of pneumonia in COVID-19 patients and thus select which patients would require a chest imaging study. Materials and Methods: We conducted a cross-sectional study in a cohort of individuals with suspected COVID-19 evaluated in a public academic healthcare center in Buenos Aires city. All adult patients with positive RT-PCR assay for SARS-COV2 between April 24 and May 19 of 2020 were included in the study. Pneumonia was defined as the presence of compatible signs and symptoms with imaging confirmation. Univariate and multivariate logistic regression was performed. A risk indicator score was developed. Results: One hundred and forty-eight patients were included, 71 (48%) received the diagnosis of pneumonia. The final clinical model included four variables: age ≥ 40 years, cough, absence of sore throat, and respiratory rate ≥ 22. To create the score, we assigned values to the variables according to their ORs: 2 points for respiratory rate ≥ 22 and 1 point to the other variables. The AUC of the ROC curve was 0.80 (CI 95% 0.73-0.86). A cutoff value of 2 showed a sensitivity of 95.7% and a specificity of 43.24%. Conclusion: This sensible score may improve the risk stratification of COVID-19 patients in the pre-hospital setting. (REV INVEST CLIN. 2021;73(1):52-8)

Efectos del tratamiento con plasma de convaleciente con COVID-19 Revisión sistemática y metaanálisis / Effects of convalescent plasma treatment in patients with COVID-19: systematic review and meta-analysis

INTRODUCCIÓN: Se ha sugerido que el tratamiento con plasma de convaleciente en la enfermedad por coronavirus (COVID-19) mejora la evolución clínica en los casos moderados a graves. Este estudio fue diseñado para evaluar los efectos de este tratamiento en comparación con el tratamiento estándar o placebo en la mortalidad, el ingreso a asistencia ventilatoria mecánica y otros desenlaces críticos en personas hospitalizados con COVID-19 moderada a grave. MÉTODOS: Se siguieron los lineamientos PRISMA para la realización de una revisión sistemática. Se realizó una búsqueda sistemática en la plataforma L·OVE (Living OVerview of Evidence) de COVID-19 hasta el 15 de enero de 2021. Se incluyeron ensayos clínicos en los cuales se estudiaron personas con COVID-19 moderada, grave o crítica. La certeza de la evidencia se analizó mediante el enfoque de evaluación, desarrollo y evaluación de recomendaciones (GRADE, por su sigla en inglés). RESULTADOS: Se identificaron 10 ensayos controlados aleatorizados que incluyeron 11 854 pacientes, en los que se comparó el tratamiento con plasma de convaleciente y las medidas estándares de cuidado o placebo en pacientes con COVID-19. Estos no mostraron diferencias significativas sobre la mortalidad (riesgo relativo: 1,02; intervalo de confianza del 95%: 0,94-1,12). Podría producir un aumento marginal en el ingreso a ventilación mecánica y de los eventos adversos graves. DISCUSION: La evidencia actual muestra que el uso de plasma de convaleciente no tiene efecto en desenlaces críticos en pacientes con COVID-19 moderada o grave.

INTRODUCTION: It has been suggested that treatment with convalescent plasma in coronavirus disease (COVID-19) improves the clinical course in moderate to severe cases. This study was designed to evaluate the effects of this treatment compared to standard treatment or placebo on mortality, admission to mechanical ventilation, and other critical outcomes in people hospitalized with moderate to severe COVID-19. METHODS: The PRISMA guidelines were followed to carry out a systematic review. A systematic search was carried out on the L·OVE (Living OVerview of Evidence) platform for COVID-19 until January 15, 2021. Clinical trials were included in which people with moderate, severe or critical COVID-19 were studied. The certainty of the evidence was analyzed using the recommendation evaluation, development and evaluation (GRADE) approach. RESULTS: We identified 10 randomized controlled trials involving 11 854 patients in which convalescent plasma treatment and standard measures of care or placebo were compared in patients with COVID-19. These did not show significant differences on mortality (relative risk: 1.02; 95% confidence interval: 0.94-1.12). It could produce a marginal increase in admission to mechanical ventilation and serious adverse events. DISCUSSION: Current evidence shows that the use of convalescent plasma has no effect on critical outcomes in patients with moderate or severe COVID-19

Prognostic factors for severity and mortality in patients infected with COVID-19: A systematic review.

BACKGROUND AND PURPOSE: The objective of our systematic review is to identify prognostic factors that may be used in decision-making related to the care of patients infected with COVID-19. DATA SOURCES: We conducted highly sensitive searches in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase. The searches covered the period from the inception date of each database until April 28, 2020. No study design, publication status or language restriction were applied. STUDY SELECTION AND DATA EXTRACTION: We included studies that assessed patients with confirmed or suspected SARS-CoV-2 infectious disease and examined one or more prognostic factors for mortality or disease severity. Reviewers working in pairs independently screened studies for eligibility, extracted data and assessed the risk of bias. We performed meta-analyses and used GRADE to assess the certainty of the evidence for each prognostic factor and outcome. RESULTS: We included 207 studies and found high or moderate certainty that the following 49 variables provide valuable prognostic information on mortality and/or severe disease in patients with COVID-19 infectious disease: Demographic factors (age, male sex, smoking), patient history factors (comorbidities, cerebrovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, cardiovascular disease, cardiac arrhythmia, arterial hypertension, diabetes, dementia, cancer and dyslipidemia), physical examination factors (respiratory failure, low blood pressure, hypoxemia, tachycardia, dyspnea, anorexia, tachypnea, haemoptysis, abdominal pain, fatigue, fever and myalgia or arthralgia), laboratory factors (high blood procalcitonin, myocardial injury markers, high blood White Blood Cell count (WBC), high blood lactate, low blood platelet count, plasma creatinine increase, high blood D-dimer, high blood lactate dehydrogenase (LDH), high blood C-reactive protein (CRP), decrease in lymphocyte count, high blood aspartate aminotransferase (AST), decrease in blood albumin, high blood interleukin-6 (IL-6), high blood neutrophil count, high blood B-type natriuretic peptide (BNP), high blood urea nitrogen (BUN), high blood creatine kinase (CK), high blood bilirubin and high erythrocyte sedimentation rate (ESR)), radiological factors (consolidative infiltrate and pleural effusion) and high SOFA score (sequential organ failure assessment score). CONCLUSION: Identified prognostic factors can help clinicians and policy makers in tailoring management strategies for patients with COVID-19 infectious disease while researchers can utilise our findings to develop multivariable prognostic models that could eventually facilitate decision-making and improve patient important outcomes. SYSTEMATIC REVIEW REGISTRATION: Prospero registration number: CRD42020178802. Protocol available at: https://www.medrxiv.org/content/10.1101/2020.04.08.20056598v1.

Development of Simple and Sensitive Score to Assess the Risk of Pneumonia in COVID-19 Patients.

BACKGROUND: Severe pneumonia is the most common cause of intensive care unit (ICU) admission and death due to novel coronavirus (SARS-CoV-2) respiratory disease (COVID-19). Due to its rapid outbreak, units for the evaluation of febrile patients in the pre-hospital setting were created. OBJECTIVE: The objective of the study was to develop a sensitive and simple tool to assess the risk of pneumonia in COVID-19 patients and thus select which patients would require a chest imaging study. MATERIALS AND METHODS: We conducted a cross-sectional study in a cohort of individuals with suspected COVID-19 evaluated in a public academic healthcare center in Buenos Aires city. All adult patients with positive RT-PCR assay for SARS-COV2 between April 24 and May 19 of 2020 were included in the study. Pneumonia was defined as the presence of compatible signs and symptoms with imaging confirmation. Univariate and multivariate logistic regression was performed. A risk indicator score was developed. RESULTS: One hundred and forty-eight patients were included, 71 (48%) received the diagnosis of pneumonia. The final clinical model included four variables: age >- 40 years, cough, absence of sore throat, and respiratory rate >- 22. To create the score, we assigned values to the variables according to their ORs: 2 points for respiratory rate >- 22 and 1 point to the other variables. The AUC of the ROC curve was 0.80 (CI 95% 0.73-0.86). A cutoff value of 2 showed a sensitivity of 95.7% and a specificity of 43.24%. CONCLUSION: This sensible score may improve the risk stratification of COVID-19 patients in the pre-hospital setting.

Tratamiento con hidroxicloroquina en pacientes con COVID-19: informe rápido de evaluación de tecnología sanitaria / Hydroxychloroquine treatment in patients with COVID-19: Rapid Health Technology Assessment Report

RESUMEN INTRODUCCIÓN la pandemia por la enfermedad por el nuevo coronavirus (COVID-19) ya ha provocado cientos de miles de muertes y aún no hay un tratamiento específico. OBJETIVO se intenta responder si el tratamiento con cloroquina e hidroxicloroquina, en comparación con el tratamiento de soporte habitual, disminuye el riesgo de mortalidad, el tiempo para la mejoría clínica, y evaluar su seguridad en pacientes con neumonía grave por COVID-19. MÉTODOS se conformó un equipo multidisciplinario independiente para realizar una evaluación de tecnología sanitaria con base en una revisión sistemática y un metaanálisis. Se incluyeron estudios publicados en español, portugués e inglés hasta junio de 2020. RESULTADOS se identificaron 169 estudios. Se incluyeron 6 en la revisión cualitativa, 4 en el metaanálisis y 14 como otros documentos. En el análisis cuantitativo encontramos un riesgo relativo (RR) de 1,52 con un intervalo de confianza del 95% (IC95%) de 1,14-2,04 para la mejoría clínica o tomográfica antes de los 14 días, con baja certeza en la evidencia. Los eventos adversos a los 7 y a los 28 días presentaron un RR de 2,22 (IC95%: 0,45-10,91) con baja certeza de evidencia. Las recomendaciones de sociedades científicas y autoridades sanitarias fueron heterogéneas. CONCLUSIONES la evidencia encontrada es de baja a muy baja confianza, por lo cual cualquier resultado estimado es muy incierto. Por otro lado, no se encontraron datos sobre mortalidad ni sobre disminución del tiempo en asistencia respiratoria mecánica, por lo que se requieren más estudios que incluyan estos desenlaces. El proceso de consentimiento informado resulta imprescindible, ya sea que se utilice en el contexto de una investigación o como una utilización off-label en la práctica habitual.

ABSTRACT INTRODUCTION the COVID-19 pandemic has already caused hundreds of thousands of deaths and there is no specific treatment. OBJECTIVE we intend to answer whether, in patients with severe pneumonia caused by COVID-19, treatment with chloroquine/hydroxychloroquine compared to the usual support treatment reduces the risk of mortality, the time for clinical improvement, and to evaluate its safety. METHODS An independent multidisciplinary team was formed to conduct a health technology assessment including a systematic review and meta-analysis. Studies published in Spanish, Portuguese and English until June 2020 were included. RESULTS 169 studies were identified. 6 were included in the qualitative review, 4 in the meta-analysis and 14 as other documents. In the quantitative analysis we found a relative risk (RR) of 1.52, 95% confidence interval (95%CI) of 1.14-2.04 for clinical or tomographic improvement before 14 days, with low certainty in the evidence. Adverse events at 7 and 28 days had a RR of 2.22 (95%CI: 0.45-10.91) with low certainty of evidence. The recommendations of scientific societies and health authorities were heterogeneous. CONCLUSIONS the evidence found is from low to very low confidence, therefore any estimated result is highly uncertain. On the other hand, no data were found on mortality or on the reduction of time in mechanical respiratory support, so more studies are required that include these outcomes. The informed consent process is essential, whether it is used in the context of an investigation or as an off-label use in routine practice.

COVID-19 associated with AIDS-related disseminated histoplasmosis: a case report.

Limited information is available concerning the coexistence of COVID-19 and opportunistic infections in people living with HIV. The possible association of COVID-19 with AIDS-related respiratory diseases should be considered, particularly in patients with advance immunosuppression. We report the case of a male patient with AIDS-related disseminated histoplasmosis associated with COVID-19.