Prognostic factors for mortality, ICU and hospital admission due to SARS-CoV-2: A systematic review and meta-analysis of cohort studies in Europe (preprint)

BackgroundAs mortality from COVID-19 is strongly age-dependent, we aimed to identify population subgroups at an elevated risk for adverse outcomes from COVID-19 using age/gender-adjusted data from European cohort studies with the aim to identify populations that could potentially benefit from booster vaccinations. MethodsWe performed a systematic literature review and meta-analysis to investigate the role of underlying medical conditions as prognostic factors for adverse outcomes due to SARS-CoV-2, including death, hospitalisation, Intensive Care Unit (ICU) admission, and mechanical ventilation within three separate settings (community, hospital and ICU). Cohort studies that reported at least age and gender-adjusted data from Europe were identified through a search of peer-reviewed articles published until 11th June 2021 in Ovid Medline and Embase. Results are presented as Odds Ratios (ORs) with 95% confidence intervals (95%C.I.) and absolute risk differences (RD) in deaths per 1,000 COVID-19 patients. FindingsWe included 88 cohort studies with age/gender adjusted data from 6,653,207 SARS-CoV-2 patients from Europe. Hospital-based mortality was associated with high and moderate certainty evidence for solid organ tumours, diabetes mellitus, renal disease, arrhythmia, ischemic heart disease, liver disease, and obesity, while a higher risk, albeit with low certainty, was noted for chronic obstructive pulmonary disease and heart failure. Community-based mortality was associated with a history of heart failure, stroke, diabetes, and end-stage renal disease. Evidence of high/moderate certainty revealed a strong association between hospitalisation for COVID-19 and solid organ transplant recipients, sleep apnoea, diabetes, stroke, and liver disease. InterpretationThe results confirmed the strong association between specific prognostic factors and mortality and hospital admission. Prioritisation of booster vaccinations and the implementation of non-pharmaceutical protective measures for these populations may contribute to a reduction in COVID-19 mortality, ICU and hospital admissions. FundingEuropean Centre for Disease Prevention and Control (ECDC) under specific contract No. 10 ECD.11843 within Framework contract ECDC/2019/001 Lot 1B.

Automated lung sound analysis using the LungPass platform: A sensitive and specific tool for identifying lower respiratory tract involvement in COVID-19. (preprint)

Background: Lower respiratory tract (LRT) involvement, observed in about 20% of patients suffering from coronavirus disease 2019 (COVID-19) is associated with a more severe clinical course, adverse outcomes and long-term sequelae. Early identification of LRT involvement could facilitated targeted and timely interventions that could alter the short- and long-term disease outcomes. The LungPass is an automated lung sound analysis platform developed using neural network technology and previously trained. We hypothesised that the LungPass could be used as a screening tool for LRT involvement in patients with COVID-19. Methods: In a prospective observational study involving 282 individuals with presenting in the emergency department with a strong clinical suspicion of COVID-19 and imaging findings consistent with COVID-19 LRT involvement (25.5% had concomitant hypoxia), and 32 healthy controls, we assessed the sensitivity and specificity of the LungPass in identifying LRT involvement in COVID-19. We also compared the auscultatory findings of the LungPass compared to a chest physician using a traditional, high-quality stethoscope. Results: Among individuals with COVID-19 LRT involvement, the LungPass identified crackles in at least one auscultation site in 93.6% and in two or more points in 84%. Moreover, the LungPass identified any abnormal lung sound (crackles or wheeze) in at least one auscultation site in 98.6% and in at least two points in 94% of the participants. The respective percentages for the respiratory physicians were lower. Considering the presence of any added abnormal sound (crackles or wheeze) in at least two auscultation points as evidence of LRT involvement, LungPass demonstrated a sensitivity of 98.6% (95% confidence intervals [CI]: 96.4%-99.6%) and a specificity of 96.9% (95% CI: 83.8%-99.9%) in identifying COVID-19 LRT involvement. Conclusion: This exploratory study suggests the LungPass is a sensitive and specific platform for identifying LRT involvement due to COVID-19, even before the development of hypoxia.

Self-reported real-world safety and reactogenicity of COVID-19 vaccines: An international vaccine-recipient survey. (preprint)

BackgroundThe safety of COVID-19 vaccines has been demonstrated in selected populations in recent studies, but more data in specific groups is needed to inform vaccine choice and health policy. ObjectivesAn international, online survey was conducted to compare the safety, tolerability and reactogenicity of available COVID-19 vaccines in different recipient groups. MethodsThis survey was launched in February 2021, for 11 days. Recipients of a first COVID-19 vaccine dose [≥]7 days prior to survey completion were eligible. The incidence and severity of vaccination side effects were assessed. ResultsSurvey was completed by 2,002 respondents, of whom 26.6% had prior COVID-19 infection (68.8% laboratory confirmed). Prior COVID-19 infection was associated with increased risk of any side effect (risk ratio 1.08, 95% confidence intervals [1.05-1.11]), fever (2.24 [1.86-2.70]), breathlessness (2.05 [1.28-3.29]), flu-like illness (1.78 [1.51-2.10]), fatigue (1.34 [1.20-1.49]) and local reactions (1.10 [1.06-1.15]). It was also associated with increased risk of severe side effects, leading to hospital care (1.56 [1.14-2.12]). While mRNA vaccines were associated with a higher incidence of any side effect (1.06 [1.01-1.11]) compared to viral vector-based vaccines, these were generally milder (p<0.001), mostly local reactions. Importantly, mRNA vaccine-recipients reported considerably lower incidence of systemic reactions (RR<0.6) including anaphylaxis, swelling, flu-like illness, breathlessness and fatigue, and of side effects requiring hospital care (0.42 [0.31-0.58]). ConclusionFor the first time, our study links prior COVID-19 illness with increased incidence of vaccination side effects and demonstrates that mRNA vaccines cause milder, less frequent systemic side effects, but more local reactions. Key messages- People with prior COVID-19 illness appear to experience significantly increased incidence and severity of side effects after receiving the COVID-19 vaccine. - In this first head-to-head comparison of the safety and reactogenicity of different types of vaccines, it was demonstrated that mRNA vaccines cause milder, less frequent systemic side effects, compared to viral vector vaccines, but more local reactions. Tweetable SummaryA survey of >2000 COVID-19 vaccine-recipients links prior COVID-19 illness with increased incidence of vaccination side effects; mRNA vaccines cause milder, less frequent systemic side effects, but more local reactions.

Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multi-national cohort. (preprint)

ImportanceImportance: The interplay between COVID-19 pandemic and asthma in children is still unclear. ObjectiveWe evaluated the impact of COVID-19 pandemic on childhood asthma outcomes. DesignThe PeARL multinational cohort included children with asthma and non-asthmatic controls recruited during the COVID-19 pandemic and compared current disease activity with data available from the previous year. SettingPediatric outpatient clinics. ParticipantsThe study included 1,054 children with asthma and 505 non-asthmatic controls, aged between 4-18 years, from 25 pediatric departments, from 15 countries globally. ExposuresCOVID-19 pandemic first wave, starting from the date of the first fatality in the respective country. Main outcomes and measuresWe assessed the pandemics impact on the frequency of respiratory infections, emergency presentations and hospital admissions in asthmatic versus non-asthmatic participants, controlling for confounding factors including the pandemics duration and the frequency of such acute events during 2019. Using paired analyses, we evaluated the impact of the pandemic on the annualized frequency of asthma attacks and the previously mentioned acute events, asthma control, and pulmonary function in children with asthma, compared to their baseline disease activity, during the preceding year. ResultsDuring the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks and hospitalizations due to asthma, in comparison to the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimally clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were also improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not found to be at increased risk of LRTIs, episodes of pyrexia, emergency visits or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. Conclusions and relevanceChildhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent. Key PointsO_ST_ABSQuestionC_ST_ABSWhat was the impact of COVID-19 pandemic on childhood asthma outcomes? FindingsDuring the first wave of the pandemic, children with asthma have experienced improved outcomes, as evidenced by fewer asthma attachks, hospitalizations, improved scores in validated asthma control measures and improved pulmonary function. MeaningThis is the first study to show a positive impact of COVID-19 pandemic on childhood asthma activity. This is probably the result of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the hypothesis that childhood asthma may be a risk factor for COVID-19.

Outcomes evaluated in controlled clinical trials on the management of COVID-19: A methodological systematic review (preprint)

It is crucial that randomized controlled trials (RCTs) on the management of coronavirus disease 2019 (COVID-19) evaluate the outcomes that are critical to patients and clinicians, to facilitate relevance, interpretability, and comparability. This methodological systematic review describes the outcomes evaluated in 415 RCTs on the management of COVID-19, that were registered with ClinicalTrials.gov, by 5/5/2020. Significant heterogeneity was observed in the selection of outcomes and the instruments used to measure them. Mortality, adverse events and treatment success or failure are only evaluated in 64.4%, 48.4% and 43% of the included studies, respectively, while other outcomes are selected less often. Studies focusing on more severe presentations (hospitalized patients or requiring intensive care) most frequently evaluate mortality and adverse events, while hospital admission and viral detection/load are most frequently assessed in the community setting. Outcome measurement instruments are poorly reported and heterogeneous. In general, simple instruments that can control for important sources of bias are favoured. Follow-up does not exceed one month in 64.3% of these earlier trials, and long-term COVID-19 burden is rarely assessed. The methodological issues identified could delay the introduction of potentially life-saving treatments in clinical practice. Our findings demonstrate the need for consensus in the design of RCTs.