Chemical and biological characterization of halophyte plants with ethnopharmacological use in the Algarve coast

This work aimed to investigate the potential of medicinal halophytes as sources of bioactive compounds with health-promoting properties, while validating their traditional uses and searching for new bioactivities/applications. Halophytes are salt-tolerant plants that survive in extreme biotopes and, to cope with environmental stress, are equipped with powerful defence mechanisms, including highly bioactive compounds. Several medicinal halophytes are used in folk therapeutics but, despite their ethnopharmacological importance, are still underexplored. This study focused on five medicinal halophytes from southern Portugal, namely Artemisia campestris L. subsp. maritima Arcangeli (dune wormwood), Crithmum maritimum L. (sea fennel), Eryngium maritimum L. (sea holly), Helichrysum italicum (Roth) G.Don subsp. picardii (Boiss&Reuter) Franco (everlasting), and Plantago coronopus L. (buckshorn plantain). Water and organic extracts were prepared from different plant organs, assessed for in vitro antioxidant, anti-diabetic, anti-hyperpigmentation and anti-protozoan activities, and chemically characterized. The large majority of the extracts have high polyphenolic content and are a potentially good source of these bioactive phytochemicals. They presented a wide diversity of phenolics, especially coumaric, ferulic, syringic, chlorogenic, and p-hydroxybenzoic acids. Minerals were also analysed, and some species may have a nutritional role as mineral supplementary source, particularly sea fennel for macronutrients and dune wormwood for microelements. A preliminary toxicological assessment showed that extracts had overall low toxicity. As for bioactivities, results confirm the strong in vitro antioxidant capacity of the extracts. Everlasting, dune wormwood and sea holly also showed anti-diabetic activity, while dune wormwood had additional anti-hyperpigmentation capacity, and sea fennel had activity against Trypanosoma cruzi. In conclusion, all halophytes can be useful sources of antioxidants to potentially help prevent oxidative-stress related diseases, while everlasting, dune wormwood and sea holly may additionally help control glucose levels. Dune wormwood is also a prospective source of compounds to prevent skin darkening and sea fennel may provide effective anti-T. cruzi molecule(s).Este trabalho teve como objetivo principal explorar o potencial de plantas halófilas medicinais enquanto fontes de compostos bioativos com aplicação terapêutica, e ao mesmo tempo validar os seus usos na “medicina” popular e procurar novas bioatividades e / ou aplicações. As plantas halófilas possuem uma elevada tolerância ao sal e completam o seu ciclo de vida em biótopos extremos, tais como zonas costeiras de influência salina. Para resistirem ao stress ambiental, estão equipadas com poderosos mecanismos de defesa que incluem a produção de compostos altamente bioativos, cujas atividades biológicas poderão ajudar a explicar a utilização de algumas destas plantas como remédios populares e para alimentação humana (e animal). De facto, inúmeras plantas halófilas são utilizadas no tratamento de várias doenças e infeções, principalmente em áreas rurais onde as plantas medicinais ainda são uma importante fonte terapêutica. No entanto, estas plantas são pouco exploradas e são também poucas as descrições das suas bioatividades, apesar da sua importância etnofarmacológica. Na região do Algarve (sul de Portugal), poucas espécies têm sido estudadas apesar do seu potencial conteúdo em moléculas bioativas. Assim, com o intuito de expandir o nosso conhecimento acerca das possíveis propriedades terapêuticas e promotoras de saúde e bem-estar deste tipo de plantas, este trabalho estudou cinco plantas halófilas medicinais comuns no Algarve, escolhidas pelos seus usos medicinais e potenciais atividades biológicas, nomeadamente Artemisia campestris L. subsp. maritima Arcangeli (madorneira), Crithmum maritimum L. (funcho marítimo), Eryngium maritimum L. (cardo marítimo), Helichrysum italicum (Roth) G.Don subsp. picardii (Boiss&Reuter) Franco (perpétua das areias) e Plantago coronopus L. (diabelha). O objetivo foi desvendar o seu potencial enquanto fontes de compostos e / ou extratos bioativos com aplicações terapêuticas, cosméticas e / ou nutricionais. Para tal, à semelhança de preparações tradicionais, foram preparados extratos aquosos e / ou orgânicos de diferentes órgãos (raízes, caules, folhas e / ou flores), e avaliados quanto às suas atividades antioxidante, antidiabética, anti-hiperpigmentação e anti-protozoária in vitro. Adicionalmente, para o funcho marítimo, cardo marítimo e perpétua das areias, os extratos foram estudados na sua dose de ingestão tradicional, i.e., usando a medida “chávena-de-chá” (e também a medida “gotas”, no caso das tinturas do cardo), para analisar as plantas duma perspetiva de utilização medicinal típica. Os extratos foram ainda caracterizados quimicamente. Os extratos foram caracterizados em relação aos compostos fitoquímicos presentes por métodos espectrofotométricos para determinar o seu conteúdo em fenólicos totais (TPC), para além do conteúdo em outros grupos fenólicos (flavonóides totais, taninos condensados, etc.). Em geral, todos os extratos analisados têm um elevado conteúdo polifenólico e são, potencialmente, boas fontes destes compostos fitoquímicos bioativos. De um modo geral, os extratos da perpétua das areias tiveram o maior conteúdo em fenólicos totais, seguidos pelos extratos da madorneira, enquanto que o cardo marítimo teve o mais baixo TPC. De notar que, globalmente, os órgãos aéreos (folhas e flores) de todas as plantas mostraram ter conteúdos fenólicos mais elevados do que os restantes órgãos. Os extratos foram ainda caracterizados por Cromatografia Líquida de Alta Eficiência (HPLC) ou por Ultra-HPLC para determinar o seu perfil polifenólico e outros compostos tentativamente identificáveis. Foi encontrada uma grande diversidade de fenólicos nestas plantas halófilas, sendo os mais abundantes: verbascósido e luteolina-7-O-glucosídeo na diabelha, ácidos clorogénico, neo- e cripto-clorogénico no funcho marítimo, ácidos quínico e clorogénico na perpétua das areias e na madorneira, e carvacrol e naringenina no cardo marítimo. Os compostos fenólicos mais comuns foram os ácidos fenólicos, com uma ligeira prevalência dos ácidos hidroxicinâmicos. Os ácidos cumárico e ferúlico foram identificados nas cinco plantas, e os ácidos p-hidroxibenzoico, siríngico e clorogénico estavam presentes em pelo menos quatro das espécies. O conteúdo em minerais foi também analisado nos extratos das folhas da diabelha e dos órgãos do funcho marítimo, cardo marítimo e madorneira. O sódio foi o elemento mais abundante encontrado, e os outros minerais estavam presentes em valores representativos de uma pequena porção da ingestão diária recomendada para adultos. De um modo geral, os resultados salientaram um possível papel nutricional destas plantas enquanto fonte mineral suplementar, particularmente o funcho marítimo para os macronutrientes e a madorneira para os micronutrientes. Foi efetuada também uma avaliação toxicológica preliminar aos extratos do funcho marítimo, madorneira e perpétua das areias, através da sua capacidade para diminuir a viabilidade de diferentes linhas celulares. Os extratos apresentaram, de um modo geral, baixa toxicidade. Os extratos foram também analisados quanto a propriedades antioxidante, antidiabética e anti-hiperpigmentação, através de uma bateria de ensaios para testar in vitro atividades de captação de radicais e de quelação de metais, capacidade de inibição de enzimas digestivas e de inibição da tirosinase, respetivamente. As decocções, tinturas e óleos essenciais da perpétua das areias e do funcho marítimo, foram também testados in vitro para a atividade antiprotozoária contra Trypanosoma cruzi, o agente causativo da doença de Chagas. Os extratos da perpétua das areias e da madorneira detiveram a maior capacidade antioxidante, seguidas pelos do funcho marítimo; contudo, os extratos do cardo marítimo demonstraram a mais potente atividade quelante do ferro. Os extratos da perpétua, madorneira e cardo revelaram ainda atividade antidiabética, apesar de apenas os do cardo serem capazes de inibir todas as enzimas hidrolisantes de hidratos de carbono; contudo, os extratos da madorneira foram os mais eficientes a inibir a α-glucosidase, mais ainda que o controlo positivo (acarbose). Apenas os extratos da madorneira apresentaram capacidade de inibir a tirosinase. O extrato aquoso do funcho marítimo foi o mais ativo e seletivo contra T. cruzi. De um modo geral, os resultados confirmaram a forte capacidade antioxidante in vitro dos extratos, evidenciando que todas as cinco plantas halófilas podem ser úteis como fontes de moléculas ou produtos antioxidantes e, como tal, poderão ajudar a prevenir doenças relacionadas com stress oxidativo. O potencial antidiabético dos extratos da perpétua das areias, da madorneira e do cardo marítimo podem ainda auxiliar no controlo dos níveis de glucose, ajudando pacientes com diabetes mellitus tipo 2. Por outro lado, os extratos da madorneira são também possíveis fontes de compostos para prevenção / tratamento de hiperpigmentação da pele, enquanto que os do funcho marítimo poderão ser fontes de moléculas anti-T. cruzi. No geral e em conclusão, o resultado deste trabalho demonstra que as cinco espécies de plantas halófilas estudadas são prospectivamente boas candidatas a serem utilizadas como alimento (as folhas da diabelha, por exemplo), em bebidas à base de plantas (como por exemplo tisanas de funcho e cardo marítimos e de perpétua das areias), como fontes de moléculas de relevo (ex.: compostos anti-T. cruzi do funcho marítimo), ou como matéria prima para as indústrias cosmética (como a madorneira para problemas de hiperpigmentação) e farmacêutica (ex.: a perpétua das areias, a madorneira e o cardo marítimo para o controlo da diabetes), e ainda para o segmento comercial de alimentos funcionais e / ou nutracêuticos (todas as cinco plantas halófilas enquanto antioxidantes potentes para prevenção de condições relacionadas com stress oxidativo). Adicionalmente, o perfil químico e atividades biológicas podem ajudar a explicar os usos tradicionais destas plantas

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved

Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

International audienceBackground: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs).Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support.Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]).Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

Association of Country Income Level With the Characteristics and Outcomes of Critically Ill Patients Hospitalized With Acute Kidney Injury and COVID-19

Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods: This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results: Among patients with COVID-19 admitted to the intensive care unit, AKI incidence was highest in patients in LLMIC, followed by patients in upper-middle income countries (UMIC) and high-income countries (HIC) (53%, 38%, and 30%, respectively), whereas dialysis rates were lowest among patients with AKI from LLMIC and highest among those from HIC (27% vs. 45%). Patients with AKI in LLMIC had the largest proportion of community-acquired AKI (CA-AKI) and highest rate of in-hospital death (79% vs. 54% in HIC and 66% in UMIC). The association between AKI, being from LLMIC and in-hospital death persisted even after adjusting for disease severity. Conclusions: AKI is a particularly devastating complication of COVID-19 among patients from poorer nations where the gaps in accessibility and quality of healthcare delivery have a major impact on patient outcomes

Thrombotic and hemorrhagic complications of COVID-19 in adults hospitalized in high-income countries compared with those in adults hospitalized in low- and middle-income countries in an international registry

Background: COVID-19 has been associated with a broad range of thromboembolic, ischemic, and hemorrhagic complications (coagulopathy complications). Most studies have focused on patients with severe disease from high-income countries (HICs). Objectives: The main aims were to compare the frequency of coagulopathy complications in developing countries (low- and middle-income countries [LMICs]) with those in HICs, delineate the frequency across a range of treatment levels, and determine associations with in-hospital mortality. Methods: Adult patients enrolled in an observational, multinational registry, the International Severe Acute Respiratory and Emerging Infections COVID-19 study, between January 1, 2020, and September 15, 2021, met inclusion criteria, including admission to a hospital for laboratory-confirmed, acute COVID-19 and data on complications and survival. The advanced-treatment cohort received care, such as admission to the intensive care unit, mechanical ventilation, or inotropes or vasopressors; the basic-treatment cohort did not receive any of these interventions. Results: The study population included 495,682 patients from 52 countries, with 63% from LMICs and 85% in the basic treatment cohort. The frequency of coagulopathy complications was higher in HICs (0.76%-3.4%) than in LMICs (0.09%-1.22%). Complications were more frequent in the advanced-treatment cohort than in the basic-treatment cohort. Coagulopathy complications were associated with increased in-hospital mortality (odds ratio, 1.58; 95% CI, 1.52-1.64). The increased mortality associated with these complications was higher in LMICs (58.5%) than in HICs (35.4%). After controlling for coagulopathy complications, treatment intensity, and multiple other factors, the mortality was higher among patients in LMICs than among patients in HICs (odds ratio, 1.45; 95% CI, 1.39-1.51). Conclusion: In a large, international registry of patients hospitalized for COVID-19, coagulopathy complications were more frequent in HICs than in LMICs (developing countries). Increased mortality associated with coagulopathy complications was of a greater magnitude among patients in LMICs. Additional research is needed regarding timely diagnosis of and intervention for coagulation derangements associated with COVID-19, particularly for limited-resource settings