Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America最新文献

Background: Most children recover quickly after coronavirus disease 2019 (COVID-19), but some may have ongoing symptoms. Follow-up studies have been limited by small sample sizes and lack of appropriate controls.

Methods: We used national testing data to identify children aged 2-16 years with a SARS-CoV-2 PCR test during 1-7 January 2021 and randomly selected 1500 PCR-positive cases and 1500 matched PCR-negative controls. Parents were asked to complete a questionnaire about the acute illness and prespecified neurological, dermatological, sensory, respiratory, cardiovascular, gastrointestinal, mental health (including emotional and behavioral well-being), and other symptoms experienced ≥5 times at 1 month after the PCR test.

Results: Overall, 35.0% (859/2456) completed the questionnaire, including 38.0% (472/1242) of cases and 32% (387/1214) of controls, of whom 68% (320/472) and 40% (154/387) were symptomatic, respectively. The most prevalent acute symptoms were cough (249/859, 29.0%), fever (236/859, 27.5%), headache (236/859, 27.4%), and fatigue (231/859, 26.9%). One month later, 21/320 (6.7%) of symptomatic cases and 6/154 (4.2%) of symptomatic controls (P = .24) experienced ongoing symptoms. Of the 65 ongoing symptoms solicited, 3 clusters were significantly (P < .05) more common, albeit at low prevalence, among symptomatic cases (3-7%) than symptomatic controls (0-3%): neurological, sensory, and emotional and behavioral well-being. Mental health symptoms were reported by all groups but more frequently among symptomatic cases than symptomatic controls or asymptomatic children.

Conclusions: Children with symptomatic COVID-19 had a slightly higher prevalence of ongoing symptoms than symptomatic controls, and not as high as previously reported. Healthcare resources should be prioritized to support the mental health of children.

Background: Based on interim analyses and modeling data, lower doses of bamlanivimab and etesevimab together (700/1400 mg) were investigated to determine optimal dose and expand availability of treatment.

Methods: This Phase 3 portion of the BLAZE-1 trial characterized the effect of bamlanivimab with etesevimab on overall patient clinical status and virologic outcomes in ambulatory patients ≥12 years old, with mild-to-moderate coronavirus disease 2019 (COVID-19), and ≥1 risk factor for progressing to severe COVID-19 and/or hospitalization. Bamlanivimab and etesevimab together (700/1400 mg) or placebo were infused intravenously within 3 days of patients' first positive COVID-19 test.

Results: In total, 769 patients were infused (median age [range]; 56.0 years [12, 93], 30.3% of patients ≥65 years of age and median duration of symptoms; 4 days). By day 29, 4/511 patients (0.8%) in the antibody treatment group had a COVID-19-related hospitalization or any-cause death, as compared with 15/258 patients (5.8%) in the placebo group (Δ[95% confidence interval {CI}] = -5.0 [-8.0, -2.1], P < .001). No deaths occurred in the bamlanivimab and etesevimab group compared with 4 deaths (all COVID-19-related) in the placebo group. Patients receiving antibody treatment had a greater mean reduction in viral load from baseline to Day 7 (Δ[95% CI] = -0.99 [-1.33, -.66], P < .0001) compared with those receiving placebo. Persistently high viral load at Day 7 correlated with COVID-19-related hospitalization or any-cause death by Day 29 in all BLAZE-1 cohorts investigated.

Conclusions: These data support the use of bamlanivimab and etesevimab (700/1400 mg) for ambulatory patients at high risk for severe COVID-19. Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants will require continued monitoring to determine the applicability of this treatment.

Clinical trials registration: NCT04427501.

Background: Evidence is lacking about any additional benefits of introducing remdesivir on top of dexamethasone, and the optimal timing of initiation.

Methods: In a territory-wide cohort of 10 445 coronavirus disease 2019 (COVID-19) patients from Hong Kong who were hospitalized between 21 January 2020 and 31 January 2021, 1544 had received dexamethasone during hospitalization. The exposure group consisted of patients who had initiated remdesivir prior to dexamethasone (n = 93) or co-initiated the 2 drugs simultaneously (n = 373), whereas the nonexposure group included patients who were given remdesivir after dexamethasone (n = 149) or those without remdesivir use (n = 929). Multiple imputation and inverse probability of treatment weighting for propensity score were applied and hazard ratios (HRs) of event outcomes were estimated using Cox regression models.

Results: Time to clinical improvement (HR = 1.23; 95% CI, 1.02-1.49; P = .032) and positive IgG antibody (HR = 1.22; 95% CI, 1.02-1.46; P = .029) were significantly shorter in the exposure group than that of nonexposure. The exposure group had a shorter hospital length of stay by 2.65 days among survivors, lower WHO clinical progression scale scores from 5 days of follow-up onwards, and lower risks of in-hospital death (HR = .59; 95% CI, .36-.98; P = .042) and composite outcomes; and without experiencing an increased risk of acute respiratory distress syndrome. Differences in the cumulative direct medical costs between groups were no longer significant from 17 days of follow-up onwards.

Conclusions: Initiation of remdesivir prior to or simultaneously with dexamethasone was associated with significantly shorter time to clinical improvement and positive IgG antibody, lower risk of in-hospital death, in addition to shorter length of hospital stay in patients with moderate COVID-19.

Background: Patients with immunodeficiency-associated antibody disorders are at a higher risk of prolonged/persistent COVID-19 infection, having no viable treatment options.

Methods: A retrospective analysis of patients with primary and/or secondary immunodeficiency-associated antibody disorders who received casirivimab and imdevimab (REGEN-COV®) under emergency compassionate use. Objective were to describe safety and response to REGEN-COV, focusing on the subset of patients who had COVID-19 duration ≥21 days before treatment.

Results: Quantitative (change in oxygenation status and/or viral load) and/or qualitative (physician-reported clinical status) outcomes data are reported from 64 patients. Improvement in ≥1 outcome was observed in 90.6% of the overall patient group. Thirty-seven of these had COVID-19 duration ≥21 days before treatment; median time from diagnosis to REGEN-COV treatment was 60.5 days. Of the 29 patients with COVID-19 duration ≥21 days before treatment and available outcome data, 96.6% showed improvement in ≥1 outcome. In the 14 patients with post-treatment reverse transcription-polymerase chain reaction (RT-PCR) results available, 11 (78.6%) reported a negative RT-PCR following treatment, with 5 (45.5%) and 8 (72.7%) patients reporting a negative RT-PCR within 5 days and 21 days of treatment, respectively. Ten of 85 patients (11.8%) experienced serious adverse events; only one was an infusion-related reaction, possibly related to REGEN-COV. Two deaths were reported; neither were attributed to REGEN-COV.

Conclusions: In this retrospective analysis of immunodeficient patients granted REGEN-COV under emergency compassionate use, REGEN-COV treatment was associated with rapid viral clearance and clinical improvement in patients with longstanding COVID-19. Adverse events were consistent with COVID-19 and its associated complications, and due to patients' concurrent medical conditions.

This multicenter, cross-sectional study provides evidence on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated emergency department visits and hospitalizations in pediatric wards and intensive care units after school reopening during the SARS-CoV-2 Alpha (B.1.1.7) variant spread in Israel. Study findings suggest that school reopening was not followed by an increase in SARS-CoV-2-related pediatric morbidity.

Background: Cerebral malaria in adults is associated with brain hypoxic changes on magnetic resonance (MR) images and has a high fatality rate. Findings of neuroimaging studies suggest that brain involvement also occurs in patients with uncomplicated malaria (UM) or severe noncerebral malaria (SNCM) without coma, but such features were never rigorously characterized.

Methods: Twenty patients with UM and 21 with SNCM underwent MR imaging on admission and 44-72 hours later, as well as plasma analysis. Apparent diffusion coefficient (ADC) maps were generated, with values from 5 healthy individuals serving as controls.

Results: Patients with SNCM had a wide spectrum of cerebral ADC values, including both decreased and increased values compared with controls. Patients with low ADC values, indicating cytotoxic edema, showed hypoxic patterns similar to cerebral malaria despite the absence of deep coma. Conversely, high ADC values, indicative of mild vasogenic edema, were observed in both patients with SNCM and patients with UM. Brain involvement was confirmed by elevated circulating levels of S100B. Creatinine was negatively correlated with ADC in SNCM, suggesting an association between acute kidney injury and cytotoxic brain changes.

Conclusions: Brain involvement is common in adults with SNCM and a subgroup of hospitalized patients with UM, which warrants closer neurological follow-up. Increased creatinine in SNCM may render the brain more susceptible to cytotoxic edema.

Background: Estimating the transmissibility of infectious diseases is key to inform situational awareness and for response planning. Several methods tend to overestimate the basic (R0) and effective (Rt) reproduction numbers during the initial phases of an epidemic. In this work we explore the impact of incomplete observations and underreporting of the first generations of infections during the initial epidemic phase.

Methods: We propose a debiasing procedure that utilizes a linear exponential growth model to infer unobserved initial generations of infections and apply it to EpiEstim. We assess the performance of our adjustment using simulated data, considering different levels of transmissibility and reporting rates. We also apply the proposed correction to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence data reported in Italy, Sweden, the United Kingdom, and the United States.

Results: In all simulation scenarios, our adjustment outperforms the original EpiEstim method. The proposed correction reduces the systematic bias, and the quantification of uncertainty is more precise, as better coverage of the true R0 values is achieved with tighter credible intervals. When applied to real-world data, the proposed adjustment produces basic reproduction number estimates that closely match the estimates obtained in other studies while making use of a minimal amount of data.

Conclusions: The proposed adjustment refines the reproduction number estimates obtained with the current EpiEstim implementation by producing improved, more precise estimates earlier than with the original method. This has relevant public health implications.

Background: Coronavirus disease 2019 was first diagnosed in Israel at the end of February 2020. By the end of June 2021, there were 842 536 confirmed cases and 6428 deaths. Our aim in this multicenter, retrospective, cohort study is to describe the demographic and clinical characteristics of hospitalized patients and compare the pandemic waves before immunization.

Methods: Of 22 302 patients hospitalized in general medical centers, we randomly selected 6329 for the study. Of these, 3582 and 1106 were eligible for the study in the first period (first and second waves) and in the second period (third wave), respectively.

Results: Thirty-day mortality was higher in the second period than in the first period, 25.20% vs 13.68% (P < .001). Invasive mechanical ventilation supported 9.19% and 14.21% of patients in the first period and second period, respectively. Extracorporeal membrane oxygenation (ECMO) was used more than twice as often in the second period.

Conclusions: Invasive ventilation, use of ECMO, and mortality rate were 1.5 to 2 times higher in the second period than in the first period. In the second period, patients had a more severe presentation and higher mortality than those in the first period.