A total of 33 participants who received both doses of the Moderna mRNA-1273 vaccine against SARS-CoV-2 had blood drawn over a period of 6 months after vaccination. SARS-CoV-2 neutralizing activity ...was maintained in all the patients through the entire period of follow-up. A half-life of 202 days was determined for the live-virus neutralization activity.
Background. Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease. ...Methods. We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929 eligible cases. We included in the database only those cases for which the underlying condition, the pattern of infection, the surgical and antifungal treatments, and survival were described. Results. The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were 36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and 66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of patients with disseminated disease died, 85% with gastrointestinal infection died, and 76% with pulmonary infection died. The majority of patients with malignancy (92 60% of 154) had pulmonary disease, whereas the majority of patients with diabetes (222 66% of 337) had sinus disease. Rhinocerebral disease was seen more frequently in patients with diabetes (145 33% of 337), compared with patients with malignancy (6 4% of 154). Hematogenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324 of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone, and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection due to Cunninghamella species and disseminated disease were independently associated with increased rates of death (odds ratios, 2.78 and 11.2, respectively). Conclusions. Outcome from zygomycosis varies as a function of the underlying condition, site of infection, and use of antifungal therapy.
BACKGROUND:Zygomycosis has emerged as an increasingly important infection with a high mortality especially in immunocompromised patients. No comprehensive analysis of pediatric zygomycosis cases has ...been published to date.
METHODS:We used a PUBMED search for English publications of pediatric (0–18 years) zygomycosis cases and references from major books as well as single case reports or case series. Individual references were reviewed for additional cases. Data were entered into Filemaker-pro database and analyzed by logistic regression analysis.
RESULTS:One hundred fifty-seven cases (64% male) were found with median age 5 years (range, 0.16–13). Underlying conditions included neutropenia (18%), prematurity (17%), diabetes mellitus (15%), ketoacidosis (10%), and no apparent underlying condition (14%). The most common patterns of zygomycosis were cutaneous (27%), gastrointestinal (21%), rhinocerebral (18%), and pulmonary (16%). Among 77 culture-confirmed cases, Rhizopus spp. (44%) and Mucor spp. (15%) were most commonly identified. Of 81 patients who were given antifungal therapy, 73% received an amphotericin B formulation only. The remaining patients received mostly amphotericin B in combination with other antifungal agents. Mortality in patients without antifungal therapy was higher than in those with therapy (88% versus 36%, P < 0.0001). Ninety-two (59%) patients underwent surgery. Cerebral, gastrointestinal, disseminated and cutaneous zygomycosis were associated with mortality rates of 100, 100, 88, and 0%, respectively. Independent risk factors for death were disseminated infection (OR7.18; 95% CI3.02–36.59) and age <1 year (OR3.85; 95% CI1.05–7.43). Antifungal therapy and particularly surgery reduced risk of death by 92% (OR0.07; 95% CI0.04–0.25) and 84% (OR0.16; 95% CI0.09–0.61), respectively.
CONCLUSIONS:Zygomycosis is a life-threatening infection in children with neutropenia, diabetes mellitus, and prematurity as common predisposing factors, and there is high mortality in untreated disease, disseminated infection, and age <1 year. Amphotericin B and surgery significantly improve outcome.
Lipid formulations of amphotericin B are increasingly used in lieu of deoxycholate amphotericin B for primary treatment of zygomycosis, but little is known about the efficacy of the former antifungal ...in treating this fungal disease. We therefore undertook an analysis of a case series of all patients with zygomycosis who received L-AMB for primary antifungal therapy in five major mid-Atlantic medical centers. Among the categories of variables studied were demographics, methods of diagnosis, microbiology, sites of infection, global responses, and survival. The median patient age was 44 years and 71% were male. Immunosuppressive hematological disorders (54%) were the most common underlying condition. Pulmonary disease constituted 50% of infections, sinus infection 29%, and cutaneous disease 18%. Members of the genus Rhizopus were the most common recovered agents. Success as defined by complete or partial positive response was noted in 32% of the cases. Concomitant surgery was performed in 46% of the cases, with similar response rates (31%). Overall survival was 39%. L-AMB was effective as primary therapy in only some patients in this cohort of highly immunocom-promised individuals with invasive zygomycosis underscoring the importance of host response and the need for further advances for treatment of this lethal infection.
Two inoculations with a new SARS-CoV-2 mRNA-based vaccine that encodes a protein in the coronavirus spike elicited high titers of virus-neutralizing antibody in healthy adult volunteers. ...Virus-specific T-cell responses were also elicited. Interim findings indicated that a dose of 100 μg per injection maximized immune response and minimized the reactogenicity of the vaccine.
The Moderna mRNA-1273 vaccine, which elicited antibodies and T cells specific for the Covid-19 virus in adults 55 years of age or younger, elicited similarly high levels of neutralizing-antibody and ...CD4 T-cell responses in a small group of older adults, including those 71 years of age or older.
Thirty-four adults received two 100-μg injections of Moderna’s mRNA SARS-CoV-2 vaccine, and serum anti–spike protein and neutralizing antibody titers were measured at day 119 — 90 days after the ...second injection. By three different assays, binding and neutralizing antibody titers declined slightly but remained elevated and higher than titers in convalescent plasma.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations may diminish vaccine-induced protective immune responses, particularly as antibody titers wane over time. Here, we assess the ...effect of SARS-CoV-2 variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.429 (Epsilon), B.1.526 (Iota), and B.1.617.2 (Delta) on binding, neutralizing, and angiotensin-converting enzyme 2 (ACE2)–competing antibodies elicited by the messenger RNA (mRNA) vaccine mRNA-1273 over 7 months. Cross-reactive neutralizing responses were rare after a single dose. At the peak of response to the second vaccine dose, all individuals had responses to all variants. Binding and functional antibodies against variants persisted in most subjects, albeit at low levels, for 6 months after the primary series of the mRNA-1273 vaccine. Across all assays, B.1.351 had the lowest antibody recognition. These data complement ongoing studies to inform the potential need for additional boost vaccinations.
A surge of human influenza A(H7N9) cases began in 2016 in China due to an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated ...influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs.
Healthy adults (n=180), ages 19-50 years, were enrolled into this partially-blinded, randomized, multi-center Phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with two different boost intervals (21 versus 120 days) and two dosages (3.75 or 15 μg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition (HAI) and neutralizing antibody titers were assessed.
Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest HAI GMT (95%CI) observed against the 2017 A(H7N9) strain was 133.4 (83.6, 212.6) among participants who received homologous, adjuvanted 3.75 ug+AS03/2017 doses with delayed boost interval.
Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. (NCT03589807).
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