Highlights Multisystem inflammatory syndrome in children affects young Chilean patients. Gastrointestinal symptoms and altered inflammation parameters predominate. Although intensive care was needed, favorable clinical outcomes were achieved. Cases appeared in clusters in the most vulnerable areas of Santiago. Clinical teams must be alert during the weeks after COVID-19 cases rise significantly.
Infection by RNA viruses is detected by the host through Toll-like receptors or RIG-I-like receptors. Toll-like receptors and RIG-I-like receptors signal through the adaptors MyD88 and MAVS, respectively, to induce type I IFNs (IFN-I) and other antiviral molecules, which are thought to be essential for activating the adaptive immune system. We investigated the role of these adaptors in innate and adaptive immune responses against respiratory syncytial virus (RSV), a common human pathogen. Deletion of Mavs abolished the induction of IFN-I and other proinflammatory cytokines by RSV. Genome-wide expression profiling in the lung showed that the vast majority of RSV-induced genes depended on MAVS. Although Myd88 deficiency did not affect most RSV-induced genes, mice lacking both adaptors harbored a higher and more prolonged viral load and exhibited more severe pulmonary disease than those lacking either adaptor alone. Surprisingly, Myd88 ؊/؊ Mavs ؊/؊ mice were able to activate a subset of pulmonary dendritic cells that traffic to the draining lymph node in response to RSV. These mice subsequently mounted a normal cytotoxic T-lymphocyte response and demonstrated delayed but effective viral clearance. These results provide an example of a normal and effective adaptive immune response in the absence of innate immunity mediated by MAVS and MyD88.adaptive immunity ͉ RSV ͉ IFN
Background By July 14, 2021, 81•3 % of adults (aged ≥18 years) in Chile had received a first SARS-CoV-2 vaccine and 72•3% had received a second SARS-CoV-2 vaccine, with the majority of people given Sinovac's inactivated CoronaVac vaccine (75•3% of vaccines dispensed) or Pfizer-BioNTech's mRNA BNT162b2 vaccine (20•9% of vaccines dispensed). Due to the absence of simultaneous real-world data for these vaccines, we aimed to compare SARS-CoV-2 IgG positivity between vaccines using a dynamic national monitoring strategy. Methods From March 12, 2021, 28 testing stations for SARS-CoV-2 IgG detection were installed in hotspots based on cellular-phone mobility tracking within the most populated cities in Chile. Individuals voluntarily approaching the testing stations were invited to do a lateral flow test by finger prick and respond to a questionnaire on sociodemographic characteristics, vaccination status (including type of vaccine if one was received), variables associated with SARS-CoV-2 exposure, and comorbidities. We compared the proportion of individuals testing positive for anti-SARS-CoV-2 IgG across sites by week since vaccination between recipients of CoronaVac and BNT162b2. Unvaccinated participants served as a control population and were matched to vaccinated individuals on the basis of date of presentation to the testing station, gender, and age group. Individuals were excluded from the analysis if they were younger than 18 years, had no declared gender, had an invalid IgG test result, had previously tested positive for SARS-CoV-2 infection on PCR, could not recall their vaccination status, or had been immunised against COVID-19 with vaccines other than CoronaVac or BNT162b2. Here, we report data collected up to July 2, 2021. Findings Of 64 813 individuals enrolled, 56 261 were included in the final analysis, of whom 33 533 (59•6%) had received at least one dose of the CoronaVac vaccine, 8947 (15•9%) had received at least one dose of the BNT162b2 vaccine, and 13 781 (24•5%) had not received a vaccine. SARS-CoV-2 IgG positivity during week 4 after the first dose of CoronaVac was 28•1% (95% CI 25•0-31•2; 220 of 783 individuals), reaching a peak of 77•4% (75•5-79•3; 1473 of 1902 individuals) during week 3 after the second dose. SARS-CoV-2 IgG positivity during week 4 after the first dose of the BNT162b2 vaccine was 79•4% (75•7-83•1; 367 of 462 individuals), increasing to 96•5% (94•9-98•1; 497 of 515 individuals) during week 3 after the second dose and remaining above 92% until the end of the study. For unvaccinated individuals, IgG seropositivity ranged from 6•0% (4•4-7•6; 49 of 810 individuals) to 18•7% (12•5-24•9; 28 of 150 individuals) during the 5 month period. Regression analyses showed that IgG seropositivity was significantly lower in men than women and in people with diabetes or chronic diseases for CoronaVac vaccine recipients (p<0•0001), and for individuals aged 60 years and older compared with people aged 18-39 years for both vaccines (p<0•0001), 3-16 weeks after the second dose.Interpretation IgG sero...
Background Systemic steroids have been advocated in addition to antimicrobial therapy for severe Mycoplasma pneumoniae pneumonia. We evaluated the efficacy of clarithromycin, dexamethasone, or combination therapy for M. pneumoniae respiratory infection. Methods Mice infected with M. pneumoniae were treated with clarithromycin, dexamethasone, combined clarithromycin/dexamethasone, or placebo daily; mice were evaluated at baseline and after 1, 3, and 6 days of therapy. Outcome variables included M. pneumoniae culture; lung histopathologic score (HPS); bronchoalveolar lavage cytokine, chemokine and growth factor concentrations. Results Clarithromycin monotherapy resulted in the greatest reductions in M. pneumoniae concentrations. After 3 days of treatment, combination therapy significantly reduced lung HPS compared with placebo, clarithromycin, and dexamethasone alone; while after 6 days of therapy, clarithromycin alone and combination therapy significantly reduced lung HPS compared with placebo. IL-12 p40, RANTES, MCP-1, and KC were significantly lower in mice treated with clarithromycin alone and/or combination therapy compared with dexamethasone alone and/or placebo; combination therapy resulted in a significantly greater reduction than clarithromycin alone for IL-12 p40 and RANTES. Conclusions While monotherapy with clarithromycin had the greatest effect on reducing concentrations of M. pneumoniae, combination therapy had the greatest effect on decreasing cytokines and chemokines, as well as pulmonary histologic inflammation.
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