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

Efeitos de extratos vegetais e antimicrobianos sobre a digestibilidade aparente, o desempenho, a morfometria dos órgãos e a histologia intestinal de leitões recém-desmamados

Objetivou-se com este trabalho avaliar o efeito de antimicrobianos e extratos vegetais sobre a digestibilidade, o desempenho, a morfometria e a histologia de leitões recém-desmamados. Foram realizados três experimentos de 35 dias (repetições no tempo), com um total de 120 leitões (40 leitões por experimento). O delineamento foi em blocos casualizados, com cinco tratamentos (controle - ração basal; antimicrobiano - ração basal com bacitracina de zinco, olaquindox e colistina (50 ppm de cada); extrato vegetal A, B e C - ração basal com 700, 1.400 e 2.100 ppm de extrato vegetal, respectivamente), 12 repetições por tratamento e dois animais por unidade experimental. O extrato vegetal continha óleo essencial de cravo, tomilho e orégano, acrescido de eugenol e carvacrol. A digestibilidade foi determinada em 40 leitões (quatro repetições por tratamento) utilizando-se o método de coleta parcial de fezes e o óxido de cromo como marcador. Ao final do primeiro experimento, foi abatido um animal de cada baia para coleta das amostras. A digestibilidade da MS no tratamento com extratos vegetais foi maior que nos tratamentos controle e com antimicrobianos. O tratamento antimicrobiano promoveu os melhores resultados de desempenho em todos períodos analisados. O maior nível de inclusão de extratos vegetais foi o que proporcionou os melhores resultados de desempenho e das demais variáveis. O tratamento com antimicrobianos resultou em menor peso relativo do trato gastrintestinal total e do intestino delgado vazio, além de maior altura de vilosidade e menor relação altura de vilosidade x profundidade de cripta do íleo que os tratamentos com extratos vegetais. Entretanto, são necessários mais estudos sobre os óleos essenciais a serem utilizados, a concentração de cada óleo, a melhor combinação e o melhor nível de inclusão na dieta

Efeitos de antimicrobianos e extratos vegetais sobre a microbiota intestinal e a freqüência de diarréia em leitões recém-desmamados Effects of antimicrobials and herbal extracts on intestinal microbiology and diarrhea incidence in weanling pigs

Foram realizados três experimentos envolvendo 120 leitões (21 aos 56 dias de idade) para avaliar os efeitos de antimicrobianos e extratos vegetais sobre a microbiota intestinal (experimento 1) e a freqüência de diarréia em leitões (experimentos 1, 2 e 3). Os animais foram distribuídos em pares (um macho castrado e uma fêmea) em 20 baias (unidade experimental), em um delineamento experimental de blocos casualizados, composto pelos tratamentos: controle - ração basal; antimicrobiano ração basal com bacitracina de zinco, olaquindox e colistina (50 ppm de cada); extrato vegetal A, B e C - ração basal com 700, 1.400 e 2.100 ppm de extrato vegetal, respectivamente. O extrato vegetal continha óleo essencial de cravo, tomilho, orégano, eugenol e carvacrol. Ao final do experimento 1, foi sacrificado um animal por unidade experimental e coletadas amostras do raspado do intestino delgado para a análise microbiológica. Não foram encontradas diferenças na análise microbiológica. A frequência de diarréia dos animais que receberam antimicrobianos foi inferior à observada nos tratamentos controle e com extratos vegetais no período de 1 a 35 dias de experimentação. Portanto, apesar de não terem sido detectadas diferenças na microbiota, os antimicrobianos foram efetivos no controle da diarréia.<br>Two experiments with a total of 120 weanling pigs (21 to 56 d of age) were conducted to evaluate the effects of antimicrobials and herbal extracts on intestinal microbiota (experiment 1) and on fecal score (experiments 1, 2 and 3). Pigs were allotted in pairs (pens with a barrow and a female) to a randomized complete block design 12 replications of five treatments. Treatments consisted of: control - basal diet; antimicrobial - basal diet plus Zn bacitracin, olaquindox, and colistin (50 ppm of each); herbal extract A, B and C - basal diet plus 700 ppm, 1,400 ppm and 2,100 ppm of herbal extract, respectively. The herbal extract consisted of a mixture of essential oils of thyme, clove, oregano, eugenol and carvacrol. At the end of experiment 1, one animal of each experimental unit was slaughtered to collect samples of small intestine for microbiological analysis, that showed no significant difference. During 1-35 days of experiment, diarrhea incidence of pigs fed antimicrobials was lower than those fed control or herbal extract diet. Therefore, even though no statistical difference was observed in intestinal microbiota, antimicrobials were effective in diarrhea control

A multi-country analysis of COVID-19 hospitalizations by vaccination status

Background: Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease&nbsp;that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes. Methods: Here, we use data from an international consortium to study this&nbsp;question and assess whether differences between these groups are&nbsp;context specific. Data from 83,163 hospitalized COVID-19 patients (34,843 vaccinated, 48,320 unvaccinated) from 38 countries were analyzed. Findings: While typical symptoms were more often reported in unvaccinated patients, comorbidities, including some associated with worse prognosis in previous studies, were more common in vaccinated patients. Considerable between-country variation in both in-hospital fatality risk and vaccinated-versus-unvaccinated difference in this outcome was observed. Conclusions: These findings will inform allocation of healthcare resources in future surges as well as design of longer-term international studies to characterize changes in clinical profile of hospitalized COVID-19 patients related to vaccination history. Funding: This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z, and 220757/Z/20/Z); the Bill&nbsp;&amp; Melinda Gates&nbsp;Foundation (OPP1209135); and the philanthropic support of the donors&nbsp;to the University of Oxford's COVID-19 Research Response Fund (0009109). Additional funders are listed in the "acknowledgments" section

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

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