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People with COVID-19 might have sustained postinfection sequelae. Known by a variety of names, including long COVID or long-haul COVID, and listed in the ICD-10 classification as post-COVID-19 condition since September, 2020, this occurrence is variable in its expression and its impact. The absence of a globally standardised and agreed-upon definition hampers progress in characterisation of its epidemiology and the development of candidate treatments. In a WHO-led Delphi process, we engaged with an international panel of 265 patients, clinicians, researchers, and WHO staff to develop a consensus definition for this condition. 14 domains and 45 items were evaluated in two rounds of the Delphi process to create a final consensus definition for adults: post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms might be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms might also fluctuate or relapse over time. A separate definition might be applicable for children. Although the consensus definition is likely to change as knowledge increases, this common framework provides a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy.

Access to critical care is a crucial component of healthcare systems. In low-income countries, the burden of critical illness is substantial, but the capacity to provide care for critically ill patients in intensive care units (ICUs) is unknown. Our aim was to systematically review the published literature to estimate the current ICU capacity in low-income countries. We searched 11 databases and included studies of any design, published 2004-August 2014, with data on ICU capacity for pediatric and adult patients in 36 low-income countries (as defined by World Bank criteria; population 850 million). Neonatal, temporary, and military ICUs were excluded. We extracted data on ICU bed numbers, capacity for mechanical ventilation, and information about the hospital, including referral population size, public accessibility, and the source of funding. Analyses were descriptive. Of 1,759 citations, 43 studies from 15 low-income countries met inclusion criteria. They described 36 individual ICUs in 31 cities, of which 16 had population greater than 500,000, and 14 were capital cities. The median annual ICU admission rate was 401 (IQR 234-711; 24 ICUs with data) and median ICU size was 8 beds (IQR 5-10; 32 ICUs with data). The mean ratio of adult and pediatric ICU beds to hospital beds was 1.5% (SD 0.9%; 15 hospitals with data). Nepal and Uganda, the only countries with national ICU bed data, had 16.7 and 1.0 ICU beds per million population, respectively. National data from other countries were not available. Low-income countries lack ICU beds, and more than 50% of these countries lack any published data on ICU capacity. Most ICUs in low-income countries are located in large referral hospitals in cities. A central database of ICU resources is required to evaluate health system performance, both within and between countries, and may help to develop related health policy.

Trial registration and timely reporting are critical safeguards against data manipulation, cherry-picking of results, and persisting biases in favor of publishing only positive findings. Withholding clinical trial findings is not only wasteful of research resources, but also leads to the risk of misinformed clinical decisions and dishonors the contributions of participants who agreed to take part in the trials--at times at serious risks to themselves--to help generate new knowledge about an intervention's safety, effectiveness, or both. Every set of trial results that fails to see the light of day compromises trial participants' investment and trust in the knowledge generation process.

PurposeWe conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products.SourceLiterature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv. Review 1: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure. Review 2: we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology.Principal findingsNo eligible studies included COVID-19 patients. Review 1: 12 RCTs (n = 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk [RR], 0.85; 95% confidence interval [CI], 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively). Review 2: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density.ConclusionsHigh-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.

During critical illness, there are a multitude of forces such as antibiotic use, mechanical ventilation, diet changes and inflammatory responses that could bring the microbiome out of balance. This so-called dysbiosis of the microbiome seems to be involved in immunological responses and may influence outcomes even in individuals who are not as vulnerable as a critically ill ICU population. It is therefore probable that dysbiosis of the microbiome is a consequence of critical illness and may, subsequently, shape an inadequate response to these circumstances. Bronchoscopic studies have revealed that the carina represents the densest site of bacterial DNA along healthy airways, with a tapering density with further bifurcations. This likely reflects the influence of micro-aspiration as the primary route of microbial immigration in healthy adults. Though bacterial DNA density grows extremely sparse at smaller airways, bacterial signal is still consistently detectable in bronchoalveolar lavage fluid, likely reflecting the fact that lavage via a wedged bronchoscope samples an enormous surface area of small airways and alveoli. The dogma of lung sterility also violated numerous observations that long predated culture-independent microbiology. The body’s resident microbial consortia (gut and/or respiratory microbiota) affect normal host inflammatory and immune response mechanisms. Disruptions in these host-pathogen interactions have been associated with infection and altered innate immunity. In this narrative review, we will focus on the rationale and current evidence for a pathogenic role of the lung microbiome in the exacerbation of complications of critical illness, such as acute respiratory distress syndrome and ventilator-associated pneumonia.

Consent forms have become too long and often do little to help people understand the risk elements of their participation in research, instead focusing on risk reduction for research institutions. Under the auspices of the Canadian Institutes of Health Research and the Canadian Critical Care Trials Group, we identified a core set of elements for participant consent documents to be used in clinical research and present these as a template consent form. Our guideline core team comprised experts in the legal and ethical aspects of research, and a clinical trialist–scientist. We conducted a directed review to compile a list of applicable regulatory, policy, and guidance requirements for the documentation of informed consent for research conducted with human participants in Canada. We used a gap analysis to identify the elements required in a research consent form, based on these documents and in comparison with 10 existing research ethics board (REB) informed-consent form templates. The guideline, as well as a fillable template for the form, was created with input from a pan-Canadian advisory group, interested parties, and broad public input. We tested the template with a small group of studies across several research domains. Our process for managing competing interests adhered to Guidelines International Network principles. From our gap analysis, we identified 75 core elements for participant consent forms in clinical research, which we have grouped under 6 main categories (i.e., information for potential participants about participating in research in general and in the particular study; harms and benefits of participation; protection of participant data; points of contact; and giving consent) in a fillable consent template. Because studies vary, specific elements should be included in a study consent form only if relevant to the type of research being conducted and the corresponding compliance requirements, as identified in our gap analysis. The template with the core set of required elements is intended to be used by any researcher applying for REB approval to document participant consent and, when applied with consideration of our associated guidance, is sufficient to meet regulatory requirements for research in Canada. Identifying the required elements for consent forms is intended to streamline consent documents across the country, facilitate multi-site projects, and simplify the approval process for all those involved.

Efforts to mitigate the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing Corona Virus Disease-19 (COVID-19) have largely relied on broad compliance with public health recommendations yet navigating the high volume of evolving information can be challenging. We assessed self-reported public perceptions related to COVID-19 including, beliefs (e.g., severity, concerns, health), knowledge (e.g., transmission, information sources), and behaviors (e.g., physical distancing) to understand perspectives in Canada and to inform future public health initiatives. We administered a national online survey aiming to obtain responses from 2000 adults in Canada. Respondent sampling was stratified by age, sex, and region. We used descriptive statistics to summarize responses and tested for regional differences using chi-squared tests, followed by weighted logistic regression. We collected 1,996 eligible questionnaires between April 26th and May 1st, 2020. One-fifth (20%) of respondents knew someone diagnosed with COVID-19, but few had tested positive themselves (0.6%). Negative impacts of pandemic conditions were evidenced in several areas, including concerns about healthcare (e.g. sufficient equipment, 52%), pandemic stress (45%), and worsening social (49%) and mental/emotional (39%) health. Most respondents (88%) felt they had good to excellent knowledge of virus transmission, and predominantly accessed (74%) and trusted (60%) Canadian news television, newspapers/magazines, or non-government news websites for COVID-19 information. We found high compliance with distancing measures (80% reported self-isolating or always physical distancing). We identified associations between region and self-reported beliefs, knowledge, and behaviors related to COVID-19. We found that information about COVID-19 is largely acquired through domestic news sources, which may explain high self-reported compliance with prevention measures. The results highlight the broader impact of a pandemic on the general public's overall health and wellbeing, outside of personal infection. The study findings should be used to inform public health communications during COVID-19 and future pandemics.