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1.
PLoS One ; 15(12): e0243887, 2020.
Article in English | MEDLINE | ID: covidwho-2266241

ABSTRACT

The clinical condition COVID-19, caused by SARS-CoV-2, was declared a pandemic by the WHO in March 2020. Currently, there are more than 5 million cases worldwide, and the pandemic has increased exponentially in many countries, with different incidences and death rates among regions/ethnicities and, intriguingly, between sexes. In addition to the many factors that can influence these discrepancies, we suggest a biological aspect, the genetic variation at the viral S protein receptor in human cells, ACE2 (angiotensin I-converting enzyme 2), which may contribute to the worse clinical outcome in males and in some regions worldwide. We performed exomics analysis in native and admixed South American populations, and we also conducted in silico genomics databank investigations in populations from other continents. Interestingly, at least ten polymorphisms in coding, noncoding and regulatory sites were found that can shed light on this issue and offer a plausible biological explanation for these epidemiological differences. In conclusion, there are ACE2 polymorphisms that could influence epidemiological discrepancies observed among ancestry and, moreover, between sexes.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/genetics , Polymorphism, Single Nucleotide/genetics , COVID-19/virology , Exome/genetics , Female , Humans , Male , Open Reading Frames/genetics , RNA, Untranslated/genetics , Regulatory Sequences, Ribonucleic Acid/genetics , South America
2.
Medwave ; 23(2)2023 Mar 10.
Article in English | MEDLINE | ID: covidwho-2279676

ABSTRACT

Lipschütz ulcer is a non-sexually transmitted genital lesion of unknown etiology, which presents as a painful vulvar ulcer. Lipschütz ulcers have been described in most continents. This is the first case reported in Peru and South America. We present the case of a 33-year-old female patient with a Lipschütz ulcer after being vaccinated with the second dose of the AstraZeneca COVID-19 vaccine. She reported having had only one sexual partner in her lifetime. Laboratory results were negative for herpes simplex 2, Cytomegalovirus, Toxoplasma gondii, Epstein-Barr virus, and syphilis. The patient received symptomatic treatment. Ten days after the onset, the patient was significantly better during follow-up. This case report displays a potential adverse effect of the AstraZeneca COVID-19 vaccine as a Lipschütz ulcer triggered by the host humoral immune response. However, further research is needed to establish the causal relationship between these two.


La úlcera de Lipschütz es una lesión genital no transmitidas por vía sexual de etiología desconocida, se presenta como una úlcera vulvar muy dolorosa. Las úlceras de Lipschütz se han descrito en la mayoría de los continentes. Este es el primer caso que se reporta en Perú y Sudamérica. En este reporte de caso se presentauna paciente de 33 años con una úlcera de Lipschütz luego de haber sido vacunada con la segunda dosis de la vacuna AstraZeneca COVID-19. Refirió haber tenido una sola pareja sexual a lo largo de su vida. Los resultados de laboratorio fueron negativos para herpes simplex 2, Citomegalovirus, Toxoplasma gondii, virus de Epstein-Barr y sífilis. La paciente recibió tratamiento sintomático. Diez días después, durante el seguimiento, la paciente estaba significativamente mejor. Este reporte de caso expone un potencial efecto adverso de la vacuna AstraZeneca COVID-19, en forma de úlcera de Lipschütz, desencadenado por la respuesta inmune humoral del huésped. Sin embargo, es necesario realizar más investigación para establecer la relación causal entre ambos.


Subject(s)
COVID-19 Vaccines , COVID-19 , Vulvar Diseases , Adult , Female , Humans , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , South America , Ulcer/etiology , Ulcer/drug therapy , Vaccination , Vulvar Diseases/etiology , Vulvar Diseases/drug therapy , Vulvar Diseases/pathology
3.
Glob Health Res Policy ; 8(1): 2, 2023 02 01.
Article in English | MEDLINE | ID: covidwho-2232760

ABSTRACT

South America, once an epicenter of COVID-19, has stayed on the road of continued management of the pandemic. The region initially struggled to cope with the pandemic as it experienced spiraling numbers of infections and overwhelmed public health systems. South America has risen in its pandemic response to be the region with the highest global vaccination rate. The region posed a strong vaccination drive, with over 76% of its population fully vaccinated with the initial protocol. South America leveraged its deeply rooted vaccination culture and public health confidence among its population. Herd immunity is an integral concept in population infectious disease management. Attaining herd immunity is presently not feasible with available vaccines, but the high vaccination rate in the region depicts the acceptance of vaccination as a strategy for population protection. The availability of effective transmission-blocking vaccines, the continuous implementation of strategies that will enable the undisrupted supply of the vaccines, equity in access to the vaccines, improved vaccine acceptance, and trust in the vaccination and public health systems will help shepherd the region towards herd immunity. Local vaccine production backed with investment in infrastructure and international collaboration for research and knowledge development will also drive population safety.


Subject(s)
COVID-19 , Vaccines , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Immunity, Herd , Vaccination , South America
4.
Curr Opin Pediatr ; 35(2): 147-154, 2023 04 01.
Article in English | MEDLINE | ID: covidwho-2230051

ABSTRACT

PURPOSE OF REVIEW: Dengue is the most important arthropod-borne viral disease of public health significance. Its geographic distribution includes 128 countries worldwide, affecting 390 million people every year causing significant morbidity and mortality in children and adults everywhere. RECENT FINDINGS: In the past, severe dengue affected mostly adults in the Americas; this scenario has changed and now cases of dengue, severe dengue, and dengue deaths have increased in children under 15 years in Brazil and in Colombia. Dengue and COVID-19 co-infections have been reported in South America, with increased hospitalization. A dengue vaccine for 9-year-old children and older children and adults who have serological evidence of previous dengue has been licensed in many countries; a different dengue vaccine trial for 4-16-year-old children has demonstrated decrease in clinical dengue and decrease in dengue hospitalizations. SUMMARY: There is no specific treatment of dengue, and a changing climate, insecticide resistance and urban expansion have permitted the vector's spread, making the vector control almost impossible. The hope for dengue control relies on vaccine development; there is important research on this area with one vaccine already licensed and another one showing promising results.


Subject(s)
COVID-19 , Dengue Vaccines , Dengue , Adult , Humans , Child , Adolescent , Child, Preschool , Dengue/epidemiology , Dengue/prevention & control , Dengue Vaccines/therapeutic use , Public Health , South America/epidemiology
5.
Sci Rep ; 13(1): 1525, 2023 01 27.
Article in English | MEDLINE | ID: covidwho-2221857

ABSTRACT

A dramatic increase in the number of outbreaks of dengue has recently been reported, and climate change is likely to extend the geographical spread of the disease. In this context, this paper shows how a neural network approach can incorporate dengue and COVID-19 data as well as external factors (such as social behaviour or climate variables), to develop predictive models that could improve our knowledge and provide useful tools for health policy makers. Through the use of neural networks with different social and natural parameters, in this paper we define a Correlation Model through which we show that the number of cases of COVID-19 and dengue have very similar trends. We then illustrate the relevance of our model by extending it to a Long short-term memory model (LSTM) that incorporates both diseases, and using this to estimate dengue infections via COVID-19 data in countries that lack sufficient dengue data.


Subject(s)
COVID-19 , Dengue , Humans , Dengue/epidemiology , COVID-19/epidemiology , Asia, Southeastern , South America/epidemiology , Disease Outbreaks
6.
Salud Publica Mex ; 64(4, jul-ago): 342-343, 2022 Jul 08.
Article in Spanish | MEDLINE | ID: covidwho-2204870
7.
Int J Environ Res Public Health ; 19(22)2022 Nov 19.
Article in English | MEDLINE | ID: covidwho-2115978

ABSTRACT

The aim of this research was to analyze the lifestyles of adults from Spanish-speaking countries in South America during the COVID-19 pandemic using a cross-sectional, analytical, and multicenter study. The target population was composed of people aged 18 and older who resided in South America during the pandemic; the final sample comprised 16,811 participants who were predominantly female, with ages ranging from 18 to 79 years. The results showed that approximately six out of ten respondents did not engage in any physical activity; only one in four respondents indicated that their diet was sufficient and balanced; and most washed their hands frequently and showered every day. Regarding the type of isolation, half reported that it was voluntary and the rest mandatory or restricted. Regarding mobility, six out of ten surveyed leave their residence on a weekly basis. Regarding the use of personal protective equipment, the majority used masks and a smaller proportion used gloves. In conclusion, the majority of respondents did not perform any physical activity; moreover, one in four reported having a sufficient balanced diet. We therefore recommend an improvement of public policies to promote better lifestyles in South America, in particular the reorientation of the health system to prevent similar situations.


Subject(s)
COVID-19 , Adult , Humans , Female , Male , Cross-Sectional Studies , COVID-19/epidemiology , Pandemics , South America/epidemiology , Life Style
8.
PLoS One ; 17(9): e0275255, 2022.
Article in English | MEDLINE | ID: covidwho-2054368

ABSTRACT

BACKGROUND: To understand provider perceptions of the COVID-19 pandemic on priorities of severe pediatric traumatic brain injury (TBI) care across hospitals in South America. METHODS: Site principal investigators (PIs) from 17 hospitals in South America enrolled in the PEGASUS-Argentina randomized controlled trial completed questionnaires regarding order of tasks performed in the care of a typical pediatric patient with severe TBI before (2019) and during (2021) the COVID-19 pandemic. Acute care processes were examined by quintiles to identify early, mid, and late actions and were categorized and compared. Associations of hospital volume and subspecialty resource availability with prioritization of key process actions were examined. FINDING: Site PIs from 15 and 16 hospitals completed the surveys in 2019 and 2021, respectively, including 14 who completed both. Action category order was stable between 2019 and 2021 and were ranked in priorities as: initial encounter, primary survey, interventions and invasive monitors, diagnostics, medications, staff communication, then disposition (in 2019) or nutrition (in 2021). There was variation in specific action order between hospitals at both timepoints, with only a few initial encounter and disposition actions limited to a single quintile. There was no reported association between hospital volume or subspecialty resource availability with prioritization of key process actions. INTERPRETATION: Despite novel healthcare challenges presented by the COVID-19 pandemic, providers in South America perceived maintaining standard severe pediatric TBI care consistent with BTF guidelines. There was large variability in specific action order between individual hospitals reported.


Subject(s)
Brain Injuries, Traumatic , COVID-19 , Brain Injuries, Traumatic/epidemiology , Brain Injuries, Traumatic/therapy , COVID-19/epidemiology , Child , Hospitals , Humans , Pandemics , South America/epidemiology
9.
Sensors (Basel) ; 22(15)2022 Aug 07.
Article in English | MEDLINE | ID: covidwho-1994138

ABSTRACT

The maritime transport of containers between ports accounts for the bulk of global trade by weight and value. Transport impedance among ports through transit times and port infrastructures can, however, impact accessibility, trade performance, and the attractiveness of ports. Assessments of the transit routes between ports based on performance and attractiveness criteria can provide a topological liner shipping network that quantifies the performance profile of ports. Here, we constructed a directed global liner shipping network (GLSN) of the top six liner shipping companies between the ports of Africa, Asia, North/South America, Europe, and Oceania. Network linkages and community groupings were quantified through a container port accessibility evaluation model, which quantified the performance of the port using betweenness centrality, the transport impedance among ports with the transit time, and the performance of ports using the Port Liner Shipping Connectivity Index. The in-degree and out-degree of the GLSN conformed to the power-law distribution, respectively, and their R-square fitting accuracy was greater than 0.96. The community partition illustrated an obvious consistence with the actual trading flow. The accessibility evaluation result showed that the ports in Asia and Europe had a higher accessibility than those of other regions. Most of the top 30 ports with the highest accessibility are Asian (17) and European (10) ports. Singapore, Port Klang, and Rotterdam have the highest accessibility. Our research may be helpful for further studies such as species invasion and the planning of ports.


Subject(s)
Ships , Asia , Europe , Singapore , South America
10.
Glob Health Epidemiol Genom ; 2022: 8551576, 2022.
Article in English | MEDLINE | ID: covidwho-1950442

ABSTRACT

Since the zoonotic event from which SARS-CoV-2 started infecting humans late in 2019, the virus has caused more than 5 million deaths and has infected over 500 million people around the world. The pandemic has had a severe impact on social and economic activities, with greater repercussions in low-income countries. South America, with almost 5% of the world's population, has reckoned with almost a fifth of the total people infected and more than 26% (>1/4) of the deceased. Fortunately, the full genome structure and sequence of SARS-CoV-2 have been rapidly obtained and studied thanks to all the scientific efforts and data sharing around the world. Such molecular analysis of SARS-CoV-2 dynamics showed that rates of mutation, similar to other members of the Coronaviridae family, along with natural selection forces, could result in the emergence of new variants; few of them might be of high consequence. However, this is a serious threat to controlling the pandemic and, of course, enduring the process of returning to normalization with the implicit monetary cost of such a contingency. The lack of updated knowledge in South America justifies the need to develop a structured genomic surveillance program of current and emerging SARS-CoV-2 variants. The modeling of the molecular events and microevolution of the virus will contribute to making better decisions on public health management of the pandemic and developing accurate treatments and more efficient vaccines.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Genomics , Humans , SARS-CoV-2/genetics , South America/epidemiology
11.
Viruses ; 14(6)2022 06 07.
Article in English | MEDLINE | ID: covidwho-1884385

ABSTRACT

Genomic surveillance of SARS-CoV-2 is one of the tools that provide genomic information on circulating variants. Given the recent emergence of the Omicron (B.1.1.529) variant, this tool has provided data about this lineage's genomic and epidemiological characteristics. However, in South America, this variant's arrival and genomic diversity are scarcely known. Therefore, this study determined the genomic diversity and phylogenetic relationships of 21,615 Omicron genomes available in public databases. We found that in South America, BA.1 (n = 15,449, 71%) and BA.1.1 (n = 6257, 29%) are the dominant sublineages, with several mutations that favor transmission and antibody evasion. In addition, these lineages showed cryptic transmission arriving on the continent in late September 2021. This event may have contributed to the dispersal of Omicron sublineages and the acquisition of new mutations. Considering the genomic and epidemiological characteristics of these lineages, especially those with a high number of mutations in their genome, it is important to conduct studies and surveillance on the dynamics of these lineages to identify the mechanisms of mutation acquisition and their impact on public health.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Genomics , Humans , Phylogeny , SARS-CoV-2/genetics , South America/epidemiology
12.
Age Ageing ; 51(5)2022 05 01.
Article in English | MEDLINE | ID: covidwho-1860798

ABSTRACT

Latin American countries (LAC), with their culturally and ethnically diverse populations, form a region that is difficult to define and to understand. The region's health systems are deeply fragmented, which poses great challenges to overall equity levels in health. This is also one of the fastest ageing regions in the world, with increasing demands as well for acute and long-term care (LTC). Demographic and epidemiological transitions across the region are heterogeneous. In this context, health systems are in general, largely unprepared to face the challenge of promoting healthy ageing. This unpreparedness has been magnified by the Coronavirus disease-2019 pandemic. Here, we analyse the burden of disease in the older population and identify priorities to improve the care and quality of life for people living in LAC. Besides an adequately prepared workforce, we must remediate disparities and inequities; develop and implement integrated care; achieve patient-centred care and further develop palliative and end-of-life care; simultaneously, we must develop the structure and financing of LTC services and strengthen the role of public health making healthy ageing an essential component.


Subject(s)
COVID-19 , Quality of Life , Aged , COVID-19/epidemiology , Delivery of Health Care , Humans , Long-Term Care , South America/epidemiology
13.
Front Cell Infect Microbiol ; 12: 787987, 2022.
Article in English | MEDLINE | ID: covidwho-1731761

ABSTRACT

BACKGROUND: Although RT-qPCR remains the gold-standard for COVID-19 diagnosis, anti-SARS-CoV-2 serology-based assays have been widely used during 2020 as an alternative for individual and mass testing, and are currently used for seroprevalence studies. OBJECTIVE: To study the clinical performance of seven commercial serological tests for COVID-19 diagnosis available in South America. METHODS: We conducted a blind evaluation of five lateral-flow immunoassays (LFIA) and two enzyme-linked immunosorbent assays (ELISAs) for detecting anti-SARS-CoV-2 antibodies. RESULTS: We found no statistically significant differences among ELISA kits and LFIAs for anti-SARS-CoV-2 IgG sensitivity (values ranging from 76.4% to 83.5%) and specificity (100% for the seven serological assays). For anti-SARS-CoV-2 IgM, the five LFIAs have a significantly higher sensitivity for samples collected 15 days after the first time RT-qPCR positive test, with values ranging from 47.1% to 88.2%; moreover, the specificity varied from 85% to 100%, but the only LFIA brand with a 100% specificity had the lowest sensitivity. CONCLUSION: The diagnostic performance of the seven serological tests was acceptable for the seven brands tested for anti-SARS-CoV-2 IgG detection for seroprevalence screening purposes. On the other hand, our results show the lack of accuracy of anti-SARS-CoV-2 IgM detection in LFIAs as a tool for SARS-CoV-2 acute-phase infection diagnosis.


Subject(s)
COVID-19 , Antibodies, Viral , COVID-19/diagnosis , COVID-19 Testing , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin M , SARS-CoV-2 , Sensitivity and Specificity , Seroepidemiologic Studies , Serologic Tests/methods , South America
14.
Sci Rep ; 12(1): 1748, 2022 02 02.
Article in English | MEDLINE | ID: covidwho-1671626

ABSTRACT

African horse sickness is a vector-borne, non-contagious and highly infectious disease of equines caused by African horse sickness viruses (AHSv) that mainly affect horses. The occurrence of the disease causes huge economic impacts because of its high fatality rate, trade ban and disease control costs. In the planning of vectors and vector-borne diseases like AHS, the application of Ecological niche models (ENM) used an enormous contribution in precisely delineating the suitable habitats of the vector. We developed an ENM to delineate the global suitability of AHSv based on retrospective outbreak data records from 2005 to 2019. The model was developed in an R software program using the Biomod2 package with an Ensemble modeling technique. Predictive environmental variables like mean diurnal range, mean precipitation of driest month(mm), precipitation seasonality (cv), mean annual maximum temperature (oc), mean annual minimum temperature (oc), mean precipitation of warmest quarter(mm), mean precipitation of coldest quarter (mm), mean annual precipitation (mm), solar radiation (kj /day), elevation/altitude (m), wind speed (m/s) were used to develop the model. From these variables, solar radiation, mean maximum temperature, average annual precipitation, altitude and precipitation seasonality contributed 36.83%, 17.1%, 14.34%, 7.61%, and 6.4%, respectively. The model depicted the sub-Sahara African continent as the most suitable area for the virus. Mainly Senegal, Burkina Faso, Niger, Nigeria, Ethiopia, Sudan, Somalia, South Africa, Zimbabwe, Madagascar and Malawi are African countries identified as highly suitable countries for the virus. Besides, OIE-listed disease-free countries like India, Australia, Brazil, Paraguay and Bolivia have been found suitable for the virus. This model can be used as an epidemiological tool in planning control and surveillance of diseases nationally or internationally.


Subject(s)
African Horse Sickness Virus , African Horse Sickness , Ecosystem , Models, Statistical , Africa/epidemiology , African Horse Sickness/epidemiology , African Horse Sickness/transmission , Animals , Ceratopogonidae/virology , Disease Outbreaks/veterinary , Horses , India/epidemiology , Insect Vectors/virology , Software , South Africa/epidemiology , South America/epidemiology , Temperature , Vector Borne Diseases/epidemiology , Vector Borne Diseases/transmission , Vector Borne Diseases/veterinary
15.
Virus Res ; 311: 198688, 2022 04 02.
Article in English | MEDLINE | ID: covidwho-1636439

ABSTRACT

The pandemic of coronavirus disease 2019 (COVID-19) is caused by a novel member of the family Coronaviridae, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent studies revealed the emergence of virus variants with substitutions in the spike and/or nucleocapsid and RNA-dependent RNA polymerase proteins that are partly responsible for enhanced transmission and reduced or escaped anti-SARS-CoV-2 antibodies that may reduce the efficacy of antibodies and vaccines against the first identified SARS-CoV-2 strains. In order to gain insight into the emergence and evolution of SARS-CoV-2 variants circulating in the South American region, a comprehensive phylogenetic study of SARS-CoV-2 variants circulating in this region was performed. The results of these studies revealed sharp increase in virus effective population size from March to April of 2020. At least 62 different genotypes were found to circulate in this region. Variants of concern (VOCs) Alpha, Beta, Gamma and Delta co-circulate in the region, together with variants of interest (VOIs) Lambda, Mu and Zeta. Most of SARS-CoV-2 variants circulating in the South American region belongs to B.1 genotypes and have substitutions in the spike and/or nucleocapsid and polymerase proteins that confer high transmissibility and/or immune resistance. 148 amino acid positions of the spike protein and 70 positions of the nucleocapsid were found to have substitutions in different variants isolated in the region by comparison with reference strain Wuhan-Hu-1. Significant differences in codon usage among spike genes of SARS-CoV-2 strains circulating in South America was found, which can be linked to SARS-CoV-2 genotypes.


Subject(s)
COVID-19 , Phylogeny , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/virology , COVID-19 Vaccines , Humans , SARS-CoV-2/classification , SARS-CoV-2/genetics , South America , Spike Glycoprotein, Coronavirus/genetics
17.
Pathog Glob Health ; 116(4): 236-243, 2022 06.
Article in English | MEDLINE | ID: covidwho-1585287

ABSTRACT

Vaccine hesitancy is considered one of the greatest threats to the ongoing coronavirus disease 2019 (COVID-19) vaccination programs. Lack of trust in vaccine benefits, along with concerns about side effects of the newly developed COVID-19 vaccine, might significantly contribute to COVID-19 vaccine hesitancy. The objective of this study was to determine the level of vaccine hesitancy among communities in particular their belief in vaccination benefits and perceived risks of new vaccines. An online cross-sectional study was conducted in 10 countries in Asia, Africa, and South America from February to May 2021. Seven items from the WHO SAGE Vaccine Hesitancy Scale were used to measure a construct of belief in vaccination benefit, and one item measured perceived riskiness of new vaccines. A logistic regression was used to determine which sociodemographic factors were associated with both vaccine hesitancy constructs. A total of 1,832 respondents were included in the final analysis of which 36.2% (range 5.6-52.2%) and 77.6% (range 38.3-91.2%) of them were classified as vaccine hesitant in terms of beliefs in vaccination benefits and concerns about new vaccines, respectively. Respondents from Pakistan had the highest vaccine hesitancy while those from Chile had the lowest. Being females, Muslim, having a non-healthcare-related job and not receiving a flu vaccination during the past 12 months were associated with poor beliefs of vaccination benefits. Those who were living in rural areas, Muslim, and those who did not received a flu vaccination during the past 12 months had relatively higher beliefs that new vaccines are riskier. High prevalence of vaccine hesitancy in some countries during the COVID-19 pandemic might hamper COVID-19 vaccination programs worldwide. Programs should be developed to promote vaccination in those sociodemographic groups with relatively high vaccine hesitancy.


Subject(s)
COVID-19 , Influenza Vaccines , Africa , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Cross-Sectional Studies , Female , Humans , Male , Pakistan , Pandemics , SARS-CoV-2 , South America/epidemiology , Vaccination , Vaccination Hesitancy
18.
Pediatr Neurol ; 128: 33-44, 2022 03.
Article in English | MEDLINE | ID: covidwho-1586880

ABSTRACT

BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.


Subject(s)
COVID-19/complications , Nervous System Diseases/epidemiology , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/epidemiology , Acute Disease , Adolescent , Brain Diseases/epidemiology , Brain Diseases/etiology , COVID-19/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Headache/epidemiology , Headache/etiology , Humans , Infant , Intensive Care Units, Pediatric/statistics & numerical data , Logistic Models , Male , Nervous System Diseases/etiology , Prevalence , Risk Factors , South America/epidemiology , United States/epidemiology
19.
Lancet Respir Med ; 9(12): 1407-1418, 2021 12.
Article in English | MEDLINE | ID: covidwho-1545515

ABSTRACT

BACKGROUND: Baricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties. This study evaluates the efficacy and safety of baricitinib in combination with standard of care for the treatment of hospitalised adults with COVID-19. METHODS: In this phase 3, double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28, assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. This study is registered with ClinicalTrials.gov, NCT04421027. FINDINGS: Between June 11, 2020, and Jan 15, 2021, 1525 participants were randomly assigned to the baricitinib group (n=764) or the placebo group (n=761). 1204 (79·3%) of 1518 participants with available data were receiving systemic corticosteroids at baseline, of whom 1099 (91·3%) were on dexamethasone; 287 (18·9%) participants were receiving remdesivir. Overall, 27·8% of participants receiving baricitinib and 30·5% receiving placebo progressed to meet the primary endpoint (odds ratio 0·85 [95% CI 0·67 to 1·08], p=0·18), with an absolute risk difference of -2·7 percentage points (95% CI -7·3 to 1·9). The 28-day all-cause mortality was 8% (n=62) for baricitinib and 13% (n=100) for placebo (hazard ratio [HR] 0·57 [95% CI 0·41-0·78]; nominal p=0·0018), a 38·2% relative reduction in mortality; one additional death was prevented per 20 baricitinib-treated participants. The 60-day all-cause mortality was 10% (n=79) for baricitinib and 15% (n=116) for placebo (HR 0·62 [95% CI 0·47-0·83]; p=0·0050). The frequencies of serious adverse events (110 [15%] of 750 in the baricitinib group vs 135 [18%] of 752 in the placebo group), serious infections (64 [9%] vs 74 [10%]), and venous thromboembolic events (20 [3%] vs 19 [3%]) were similar between the two groups. INTERPRETATION: Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard of care alone, and was associated with reduced mortality in hospitalised adults with COVID-19. FUNDING: Eli Lilly and Company. TRANSLATIONS: For the French, Japanese, Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.


Subject(s)
Azetidines/therapeutic use , COVID-19 Drug Treatment , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Adenosine Monophosphate/analogs & derivatives , Adrenal Cortex Hormones , Adult , Alanine/analogs & derivatives , Antiviral Agents , Asia , Dexamethasone , Double-Blind Method , Europe , Humans , North America , SARS-CoV-2 , South America , Treatment Outcome
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