ABSTRACT
ImportanceEvidence suggests that early, robust type 1 interferon responses to SARS-CoV-2 are critical determinants for COVID-19 disease outcomes, accelerating viral clearance and limiting viral shedding. ObjectiveWe undertook a ring prophylaxis study to determine whether pegylated IFN{beta}-1 could reduce SARS-CoV-2 household transmission. DesignA cluster randomized clinical trial of pegylated IFN{beta}-1 conducted in Santiago, Chile. Recruitment was conducted between December 4th 2020, and 31st May 2021, with the last follow-up completed June 29th 2021. SettingThe study was conducted across 341 households in the metropolitan area of Santiago, Chile. ParticipantsIndex cases were identified from databases of those with confirmed SARS-CoV-2 from COVID-19 clinics and emergency room visits in Santiago, Chile. 5,154 index cases were assessed for eligibility, 1,372 index cases were invited to participate, and 341 index cases and their household contacts (n = 831) were enrolled in the study. InterventionHouseholds were cluster randomized to receive 125{micro}g subcutaneous pegylated IFN{beta}-1 (n = 172 households, 607 participants), or standard care (n = 169 households, 565 participants). Main Outcome(s) and Measure(s)Frequentist and Bayesian analyses were undertaken to determine the effects of treatment on (i) reducing viral shedding in index cases and (ii) reducing viral transmission to treatment-eligible household contacts. Four secondary outcomes were assessed including duration of viral shedding, effects on viral transmission and seroconversion, incidence of hospitalization, and incidence and severity of reported adverse events. A post-hoc at risk population was defined as households where the index case was positive at the start of the study and there was at least one treatment eligible contact in a household who tested negative for SARS-CoV-2. ResultsIn total, 1172 participants in 341 households underwent randomization, with 607 assigned to receive IFN{beta}-1 and 565 to standard care. Based on intention to treat and per protocol analyses, IFN{beta}-1 treatment was ineffective. However, in the at risk population, the relative risk of infection was reduced by 23% in treated individuals and that there was a 95% probability that IFN{beta}-1 reduced household transmission Conclusions and RelevanceRing prophylaxis with IFN{beta}-1 reduces the probability of SARS-CoV-2 transmission within a household. Trial RegistrationClinicaltrials.gov identifier: NCT04552379
ABSTRACT
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.
ABSTRACT
RationaleWhether asthma constitutes a risk factor for COVID-19 is unclear. MethodsWe performed a systematic literature search in three stages: First, we reviewed PubMed, EMBASE and CINAHL for systematic reviews of SARS-CoC-2 and COVID-19 in pediatric populations, and reviewed their primary articles; next, we searched PubMed for studies on COVID-19 or SARS-CoV-2 and asthma/wheeze, and evaluated whether the resulting studies included pediatric populations; lastly, we repeated the second search in BioRxiv.org and MedRxiv.org to find pre-prints that may have information on pediatric asthma. ResultsIn the first search, eight systematic reviews were found, of which five were done in pediatric population; after reviewing 67 primary studies we found no data on pediatric asthma as a comorbidity for COVID-19. In the second search, we found 25 results in PubMed, of which five reported asthma in adults, but none included data on children. In the third search, 14 pre-prints in MedRxiv were identified with data on asthma, but again none with pediatric data. We found only one report by the U.S. CDC stating that 40/345 (~11.5%) children with data on chronic conditions had "chronic lung diseases including asthma". ConclusionThere is scarcely any data on whether childhood asthma (or other pediatric respiratory diseases) constitute risk factors for SARS-CoV-2 infection or COVID-19 severity. Studies are needed that go beyond counting the number of cases in the pediatric age range.
