Quality of clinical evidence and political justifications of ivermectin mass distribution of COVID-19 kits in eight Latin American countries.

BACKGROUND: Several countries in Latin America conducted mass distribution of COVID-19 kits intended to treat mild COVID-19, thereby preventing excess hospitalisations. Many of the kits contained ivermectin, an antiparasitic medicine that was not approved at the time for the treatment of COVID-19. The study objective was to compare the timing of the publication of scientific evidence about the efficacy of ivermectin for COVID-19 with the timeline of distribution of COVID-19 kits in eight Latin American countries and to analyse whether evidence was used to justify ivermectin distribution. METHODS: We conducted a systematic review of randomised controlled trials (RCTs) published on the efficacy of ivermectin or ivermectin as adjuvant therapy on mortality from, or as prevention for, COVID-19. Each RCT was assessed using the Cochrane Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Information on the timing and justification of government decisions was collected through a systematic search of leading newspapers and government press releases. RESULTS: After removing the duplicates and abstracts without full text, 33 RCTs met our inclusion criteria. According to GRADE, the majority had a substantial risk of bias. Many government officials made claims that ivermectin was effective and safe in the prevention or treatment of COVID-19, despite the lack of published evidence. CONCLUSION: All eight governments distributed COVID-19 kits to their populations despite the absence of high-quality evidence on the efficacy of ivermectin for prevention, hospitalisation and mortality in COVID-19 patients. Lessons learnt from this situation could be used to strengthen government institutions' capacities to implement evidence-informed public health policies.

Streptococcus pyogenes infections in Spanish children before and after the COVID pandemic. Coming back to the previous incidence

Introduction Group A Streptococcus (GAS) causes mild diseases, and unfrequently invasive infections (iGAS). Following the December 2022 alert from the United Kingdom regarding the unusual increase in GAS and iGAS infections, we analyzed the incidence of GAS infections in 2018–2022 in our hospital. Methods We conducted a retrospective study of patients seen in a pediatric emergency department (ED) diagnosed with streptococcal pharyngitis and scarlet fever and patients admitted for iGAS during last 5 years. Results The incidence of GAS infections was 6.43 and 12.38/1000 ED visits in 2018 and 2019, respectively. During the COVID-19 pandemic the figures were 5.33 and 2.14/1000 ED visits in 2020 and 2021, respectively, and increased to 10.2/1000 ED visits in 2022. The differences observed were not statistically significant (p=0.352). Conclusions In our series, as in other countries, GAS infections decreased during the COVID-19 pandemic, and mild and severe cases increased considerably in 2022, but did not reach similar levels to those detected in other countries. Resumen Introducción Streptococcus del grupo A (GAS) causa infecciones leves y ocasionalmente invasivas (iGAS). Tras la alerta publicada en diciembre de 2022 en el Reino Unido respecto al aumento de infecciones por GAS leves e iGAS, analizamos la incidencia de estas infecciones en 2018-2022 en nuestro hospital. Métodos Realizamos un estudio retrospectivo de los niños atendidos en urgencias pediátricas (UP) diagnosticados de faringitis estreptocócica y escarlatina y los ingresados por iGAS durante 5 años. Resultados La incidencia de infecciones por GAS fue de 6,43 y de 12,38/1.000 visitas a UP en 2018 y 2019, respectivamente. Durante la pandemia fue de 5,33 y de 2,14/1.000 visitas en 2020 y 2021, respectivamente, y aumentó a 10,2/1.000 visitas en 2022. Estas diferencias no fueron estadísticamente significativas (p=0,352). Discusión En nuestra serie, al igual que en otros países, las infecciones por GAS disminuyeron durante la pandemia de COVID-19, pero en 2022 aumentaron considerablemente los casos leves y graves, sin alcanzar cifras similares a las detectadas en otros países.

Pooling sputum for Xpert MTB/RIF and Xpert Ultra testing during the Covid-19 pandemic in Lao People's Democratic Republic

The global Covid-19 pandemic has limited access to molecular TB diagnostics and National Programmes are struggling to maintain essential services. The pooling method (testing several samples together) could reduce the number of cartridges and staff time needed for TB diagnosis but has not been tested within the pandemic. We conducted two independent cross-sectional surveys. Pools composed of four sputum samples were tested using either Xpert-MTB/RIF or Xpert-Ultra. Pooled and individual results were compared to determine the level of agreement. Each survey included 840 participants and 210 pools. In the Xpert MTB/RIF survey, 77/81 (sensitivity 95.1%, 95%CI 87.8%-98.6%) pools containing ≥1 positive sample tested MTB-positive and 4/81 (4.9%, 95%CI 1.4%-12.2%) tested MTB-negative. All 129/129 pools containing MTB-negative samples tested MTB-negative (specificity 100%, 95%CI 97.2%-100%), with 98.1% agreement (Kappa: 0.959). In the Xpert-Ultra survey, 70/70 (sensitivity 100%, 95%CI 94.9%-100%) pools containing ≥ 1 MTB-positive sample tested MTB-positive and 140/140 (specificity 100%, 95%CI 97.4%-100%) pools containing only MTB-negative samples tested MTB-negative, with 100% agreement (Kappa: 1). Pooled testing with Xpert-MTB/RIF and Xpert-Ultra saved 38.3% and 41.7% (322/840 and 350/840, respectively) in cartridge costs alone. The pooling method with Xpert-MTB/RIF and Xpert-Ultra has similar performance to individual testing and can reduce the number of cartridges needed. These efficiencies can facilitate maintenance of stocks and sustain essential services as countries face difficulties for laboratory procurement during the pandemic and will provide cost and time savings post-pandemic.

SARS CoV-2 virus in cancer patients: a new unknown in an unsolved equation.

INTRODUCTION: Cancer patients are more susceptible to infections and infection can be more severe than in patients without cancer diagnosis. We conducted this retrospective study in patients admitted for SARS-CoV-2 infection in order to find differences in inflammatory markers and mortality in cancer patients compared to others. METHODS: We reviewed the electronic records of patients admitted for SARS-CoV-2 infection confirmed by PCR from March to September 2020. Data on socio-demographics, comorbidities, inflammatory makers and cancer-related features were analysed. RESULTS: 2,772 patients were admitted for SARS-CoV-2, to the Hospital Universitario Ramón y Cajal in Madrid during this period. Of these, 2597 (91%) had no history of neoplastic disease, 164 (5.9%) patients had a prior history of cancer but were not undergoing oncological treatment at the time of infection, and 81 (2.9%) were in active treatment. Mortality in patients without a history of cancer was 19.5%, 28.6% for patients with a prior history of cancer and 34% in patients with active cancer treatment. Patients in active oncology treatment with the highest mortality rate, were those diagnosed with lung cancer (OR 5.6 95% CI 2.2-14.1). In the multivariate study active oncological treatment (OR 2.259 95% IC 1.35-3.77) and chemotherapy treatment (OR 3.624 95% IC 1.17-11.17), were statistically significant factors for the risk of death for the whole group and for the group with active oncological treatment, respectively. CONCLUSION: Cancer patients on active systemic treatment have an increased risk of mortality after SARS-CoV-2 infection, especially with lung cancer or chemotherapy treatment.

Pooling samples to increase testing capacity with Xpert Xpress SARS-CoV-2 during the Covid-19 pandemic in Lao People's Democratic Republic.

The COVID-19 pandemic created the need for large-scale testing of populations. However, most laboratories do not have sufficient testing capacity for mass screening. We evaluated pooled testing of samples, as a strategy to increase testing capacity in Lao PDR. Samples of consecutive patients were tested in pools of four using the Xpert Xpress SARS CoV-2 assay. Positive pools were confirmed by individual testing, and we describe the performance of the test and savings achieved. We also diluted selected positive samples to describe its effect on the assays CT values. 1,568 patients were tested in 392 pools of four. 361 (92.1%) pools were negative and 31 (7.9%) positive. 29/31 (93.5% (95%CI 77-99%) positive pools were confirmed by individual testing of the samples but, in 2/31 (6.5%) the four individual samples were negative, suggesting contamination. Pools with only one positive sample had higher CT values (lower RNA concentrations) than the respective individual samples, indicating a dilution effect, which suggested an increased risk of false negative results with dilutions >1:10. However, this risk may be low if the prevalence of infection is high, when pools are more likely to contain more than one positive sample. Pooling saved 67% of cartridges and substantially increased testing capacity. Pooling samples increased SARS-CoV-2 testing capacity and resulted in considerable cartridge savings. Given the need for high-volume testing, countries may consider implementation of pooling for SARS-CoV-2 screening.

Advances in diagnostic tools for respiratory tract infections: from tuberculosis to COVID-19 - changing paradigms?

Respiratory tract infections (RTIs) are one of the most common reasons for seeking healthcare, but are amongst the most challenging diseases in terms of clinical decision-making. Proper and timely diagnosis is critical in order to optimise management and prevent further emergence of antimicrobial resistance by misuse or overuse of antibiotics. Diagnostic tools for RTIs include those involving syndromic and aetiological diagnosis: from clinical and radiological features to laboratory methods targeting both pathogen detection and host biomarkers, as well as their combinations in terms of clinical algorithms. They also include tools for predicting severity and monitoring treatment response. Unprecedented milestones have been achieved in the context of the COVID-19 pandemic, involving the most recent applications of diagnostic technologies both at genotypic and phenotypic level, which have changed paradigms in infectious respiratory diseases in terms of why, how and where diagnostics are performed. The aim of this review is to discuss advances in diagnostic tools that impact clinical decision-making, surveillance and follow-up of RTIs and tuberculosis. If properly harnessed, recent advances in diagnostic technologies, including omics and digital transformation, emerge as an unprecedented opportunity to tackle ongoing and future epidemics while handling antimicrobial resistance from a One Health perspective.

Measuring T-Cell Responses against SARS-CoV-2 Is of Utility for Disease and Vaccination Management.

The measurement of specific T-cell responses can be a useful tool for COVID-19 diagnostics and clinical management. In this study, we evaluated the IFN-γ T-cell response against the main SARS-CoV-2 antigens (spike, nucleocapsid and membrane) in acute and convalescent individuals classified according to severity, and in vaccinated and unvaccinated controls. IgG against spike and nucleocapsid were also measured. Spike antigen triggered the highest number of T-cell responses. Acute patients showed a low percentage of positive responses when compared to convalescent (71.6% vs. 91.7%, respectively), but increased during hospitalization and with severity. Some convalescent patients showed an IFN-γ T-cell response more than 200 days after diagnosis. Only half of the vaccinated individuals displayed an IFN-γ T-cell response after the second dose. IgG response was found in a higher percentage of individuals compared to IFN-γ T-cell responses, and moderate correlations between both responses were seen. However, in some acute COVID-19 patients specific T-cell response was detected, but not IgG production. We found that the chances of an IFN-γ T-cell response against SARS-CoV-2 is low during acute phase, but may increase over time, and that only half of the vaccinated individuals had an IFN-γ T-cell response after the second dose.

Advances in diagnostic tools for respiratory tract infections. From tuberculosis to COVID19: changing paradigms?

Respiratory tract infections (RTI) are one of the commonest reasons for seeking healthcare, but are amongst the most challenging diseases in terms of clinical decision making. Proper and timely diagnosis is critical in order to optimize management and prevent further emergence of antimicrobial resistance by misuse, or overuse of antibiotics. Diagnostic tools for RTI include those involving syndromic and etiological diagnosis: from clinical and radiological features to laboratory methods targeting both pathogen detection and host biomarkers, as well as their combinations in terms of clinical algorithms. They also include tools for predicting severity and monitoring treatment response. Unprecedented milestones have been achieved in the context of the COVID-19 pandemic, involving the most recent applications of diagnostic technologies both at genotypic and phenotypic level, which have changed paradigms in infectious respiratory diseases in terms of why, how and where diagnostics are performed. The aim of this review is to discuss advances in diagnostic tools that impact clinical decision making, surveillance and follow-up of RTI and tuberculosis. If properly harnessed, recent advances in diagnostic technologies, including omics and digital transformation emerge as an unprecedented opportunity to tackle ongoing and future epidemics while handling antimicrobial resistance from a One Health perspective.

Pooling sputum for Xpert MTB/RIF and Xpert Ultra testing during the Covid-19 pandemic in Lao People's Democratic Republic.

The global Covid-19 pandemic has limited access to molecular TB diagnostics and National Programmes are struggling to maintain essential services. The pooling method (testing several samples together) could reduce the number of cartridges and staff time needed for TB diagnosis but has not been tested within the pandemic. We conducted two independent cross-sectional surveys. Pools composed of four sputum samples were tested using either Xpert-MTB/RIF or Xpert-Ultra. Pooled and individual results were compared to determine the level of agreement. Each survey included 840 participants and 210 pools. In the Xpert MTB/RIF survey, 77/81 (sensitivity 95.1%, 95%CI 87.8%-98.6%) pools containing ≥1 positive sample tested MTB-positive and 4/81 (4.9%, 95%CI 1.4%-12.2%) tested MTB-negative. All 129/129 pools containing MTB-negative samples tested MTB-negative (specificity 100%, 95%CI 97.2%-100%), with 98.1% agreement (Kappa: 0.959). In the Xpert-Ultra survey, 70/70 (sensitivity 100%, 95%CI 94.9%-100%) pools containing ≥ 1 MTB-positive sample tested MTB-positive and 140/140 (specificity 100%, 95%CI 97.4%-100%) pools containing only MTB-negative samples tested MTB-negative, with 100% agreement (Kappa: 1). Pooled testing with Xpert-MTB/RIF and Xpert-Ultra saved 38.3% and 41.7% (322/840 and 350/840, respectively) in cartridge costs alone. The pooling method with Xpert-MTB/RIF and Xpert-Ultra has similar performance to individual testing and can reduce the number of cartridges needed. These efficiencies can facilitate maintenance of stocks and sustain essential services as countries face difficulties for laboratory procurement during the pandemic and will provide cost and time savings post-pandemic.

Towards Accurate Point-of-Care Tests for Tuberculosis in Children.

In childhood tuberculosis (TB), with an estimated 69% of missed cases in children under 5 years of age, the case detection gap is larger than in other age groups, mainly due to its paucibacillary nature and children's difficulties in delivering sputum specimens. Accurate and accessible point-of-care tests (POCTs) are needed to detect TB disease in children and, in turn, reduce TB-related morbidity and mortality in this vulnerable population. In recent years, several POCTs for TB have been developed. These include new tools to improve the detection of TB in respiratory and gastric samples, such as molecular detection of Mycobacterium tuberculosis using loop-mediated isothermal amplification (LAMP) and portable polymerase chain reaction (PCR)-based GeneXpert. In addition, the urine-based detection of lipoarabinomannan (LAM), as well as imaging modalities through point-of-care ultrasonography (POCUS), are currently the POCTs in use. Further to this, artificial intelligence-based interpretation of ultrasound imaging and radiography is now integrated into computer-aided detection products. In the future, portable radiography may become more widely available, and robotics-supported ultrasound imaging is currently being trialed. Finally, novel blood-based tests evaluating the immune response using "omic-"techniques are underway. This approach, including transcriptomics, metabolomic, proteomics, lipidomics and genomics, is still distant from being translated into POCT formats, but the digital development may rapidly enhance innovation in this field. Despite these significant advances, TB-POCT development and implementation remains challenged by the lack of standard ways to access non-sputum-based samples, the need to differentiate TB infection from disease and to gain acceptance for novel testing strategies specific to the conditions and settings of use.

Molecular and Cellular Mechanisms of M. tuberculosis and SARS-CoV-2 Infections-Unexpected Similarities of Pathogenesis and What to Expect from Co-Infection.

Tuberculosis is still an important medical and social problem. In recent years, great strides have been made in the fight against M. tuberculosis, especially in the Russian Federation. However, the emergence of a new coronavirus infection (COVID-19) has led to the long-term isolation of the population on the one hand and to the relevance of using personal protective equipment on the other. Our knowledge regarding SARS-CoV-2-induced inflammation and tissue destruction is rapidly expanding, while our understanding of the pathology of human pulmonary tuberculosis gained through more the 100 years of research is still limited. This paper reviews the main molecular and cellular differences and similarities caused by M. tuberculosis and SARS-CoV-2 infections, as well as their critical immunological and pathomorphological features. Immune suppression caused by the SARS-CoV-2 virus may result in certain difficulties in the diagnosis and treatment of tuberculosis. Furthermore, long-term lymphopenia, hyperinflammation, lung tissue injury and imbalance in CD4+ T cell subsets associated with COVID-19 could propagate M. tuberculosis infection and disease progression.

Pooled testing of sputum with Xpert MTB/RIF and Xpert Ultra during tuberculosis active case finding campaigns in Lao People's Democratic Republic.

INTRODUCTION: Active case finding (ACF) of individuals with tuberculosis (TB) is a key intervention to find the 30% of people missed every year. However, ACF requires screening large numbers of individuals who have a low probability of positive results, typically <5%, which makes using the recommended molecular tests expensive. METHODS: We conducted two ACF surveys (in 2020 and 2021) in high TB burden areas of Lao PDR. Participants were screened for TB symptoms and received a chest X-ray. Sputum samples of four consecutive individuals were pooled and tested with Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF) (Xpert-MTB/RIF) (2020) or Xpert-Ultra (2021). The agreement of the individual and pooled samples was compared and the reasons for discrepant results and potential cartridge savings were assessed. RESULTS: Each survey included 436 participants, which were tested in 109 pools. In the Xpert-MTB/RIF survey, 25 (sensitivity 89%, 95% CI 72.8% to 96.3%) of 28 pools containing MTB-positive samples tested positive and 81 pools containing only MTB-negative samples tested negative (specificity 100%, 95% CI 95.5% to 100%). In the Xpert-Ultra survey, all 32 (sensitivity 100%, 95% CI 89.3% to 100%) pools containing MTB-positive samples tested positive and all 77 (specificity 100%, 95% CI 95.3% to 100%) containing only MTB-negative samples tested negative. Pooling with Xpert-MTB/RIF and Xpert-Ultra saved 52% and 46% (227/436 and 199/436, respectively) of cartridge costs alone. CONCLUSION: Testing single and pooled specimens had a high level of agreement, with complete concordance when using Xpert-Ultra. Pooling samples could generate significant cartridge savings during ACF campaigns.

Neurological complications of COVID-19 in hospitalized patients: The registry of a neurology department in the first wave of the pandemic.

OBJECTIVE: To describe the spectrum of neurological complications observed in a hospital-based cohort of COVID-19 patients who required a neurological assessment. METHODS: We conducted an observational, monocentric, prospective study of patients with a COVID-19 diagnosis hospitalized during the 3-month period of the first wave of the COVID-19 pandemic in a tertiary hospital in Madrid (Spain). We describe the neurological diagnoses that arose after the onset of COVID-19 symptoms. These diagnoses could be divided into different groups. RESULTS: Only 71 (2.6%) of 2750 hospitalized patients suffered at least one neurological complication (77 different neurological diagnoses in total) during the timeframe of the study. The most common diagnoses were neuromuscular disorders (33.7%), cerebrovascular diseases (CVDs) (27.3%), acute encephalopathy (19.4%), seizures (7.8%), and miscellanea (11.6%) comprising hiccups, myoclonic tremor, Horner syndrome and transverse myelitis. CVDs and encephalopathy were common in the early phase of the COVID-19 pandemic compared to neuromuscular disorders, which usually appeared later on (p = 0.005). Cerebrospinal fluid severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction was negative in 15/15 samples. The mortality was higher in the CVD group (38.1% vs. 8.9%; p = 0.05). CONCLUSIONS: The prevalence of neurological complications is low in patients hospitalized for COVID-19. Different mechanisms appear to be involved in these complications, and there was no evidence of direct invasion of the nervous system in our cohort. Some of the neurological complications can be classified into early and late neurological complications of COVID-19, as they occurred at different times following the onset of COVID-19 symptoms.

SARS-CoV-2 Infection in Multiple Sclerosis: Results of the Spanish Neurology Society Registry.

OBJECTIVE: To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. METHODS: Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. RESULTS: Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. CONCLUSIONS: This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal disease.

Risk and outcomes of COVID-19 in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Limited information is available on incidence and outcomes of COVID-19 in patients with multiple sclerosis (MS). This study investigated the risks of SARS-CoV-2 infection and COVID-19-related outcomes in patients with MS, and compared these with the general population. METHODS: A regional registry was created to collect data on incidence, hospitalization rates, intensive care unit admission, and death in patients with MS and COVID-19. National government outcomes and seroprevalence data were used for comparison. The study was conducted at 14 specialist MS treatment centers in Madrid, Spain, between February and May 2020. RESULTS: Two-hundred nineteen patients were included in the registry, 51 of whom were hospitalized with COVID-19. The mean age ± standard deviation was 45.3 ± 12.4 years, and the mean duration of MS was 11.9 ± 8.9 years. The infection incidence rate was lower in patients with MS than the general population (adjusted incidence rate ratio = 0.78, 95% confidence interval [CI] = 0.70-0.80), but hospitalization rates were higher (relative risk = 5.03, 95% CI = 3.76-6.62). Disease severity was generally low, with only one admission to an intensive care unit and five deaths. Males with MS had higher incidence rates and risk of hospitalization than females. No association was found between the use of any disease-modifying treatment and hospitalization risk. CONCLUSIONS: Patients with MS do not appear to have greater risks of SARS-CoV-2 infection or severe COVID-19 outcomes compared with the general population. The decision to start or continue disease-modifying treatment should be based on a careful risk-benefit assessment.

IoT garment for remote elderly care network.

The elderly is a continuous growth sector thanks to the life expectancy increase in Western society. This sector is especially at risk from the appearance of respiratory diseases and, therefore, is the most affected sector in the COVID-19 epidemic. Many of these elderly require continuous care in residences or by specialized caregivers, but these personal contacts put this sector at risk. In this work, an IoT system for elderly remote monitoring is studied, designed, developed and tested. This system is composed by a smart garment that records information from various physiological sensors in order to detect falls, sudden changes in body temperature, heart problems and heat stroke; This information is sent to a cloud server through a gateway located in the patient's residence, allowing to real-time monitor remotely patient's activity using a customized App, as well as receiving alerts in dangerous situations. This system has been tested with professional caregivers, obtaining usability and functionality surveys; and, in addition, a detailed power-consumption study has been carried out. The results, compared with other similar systems, demonstrate that the proposed one is useful, usable, works in real time and has a decent power consumption that allows the patient to carry it during all day without charging the battery.