Effect of tecovirimat on healing time and viral clearance by emulation of a target trial in patients hospitalized for mpox

Tecovirimat is a treatment option for severe mpox, although randomized clinical trials are ongoing. The aim of the study is to assess the effect of tecovirimat on healing time and the extent of viral clearance by target trial emulation using observational data. Clinical and virological data of patients hospitalized for mpox were collected. Samples from the upper respiratory tract (URT) were grouped in two time points: T1 (median 6 days from symptoms onset) and T2 (median 5 days from T1). Patients were followed-up until recovery. Average treatment effect (ATE) in patients untreated versus treated with tecovirimat was estimated on time to healing and variation in viral load in URT, using a weighted and cloning analysis. Among the 41 patients included, 19 completed a course of tecovirimat. The median time from symptoms onset to hospitalization and to drug-starting was 4 days and 10 days, respectively. No improvement in healing time in treated versus untreated was observed. No difference by treatment group in time to viral clearance was detected by ATE fitted in a subset of 13 patients after controlling for confounders. We found no evidence for a large effect of tecovirimat in shortening healing time and viral clearance. While awaiting the results of randomized studies, the use of tecovirimat should be restricted to the clinical trial setting

Spatial modes for transmission of chikungunya virus during a large chikungunya outbreak in Italy: a modeling analysis

14openInternationalBothBackground The spatial spread of many mosquito-borne diseases occurs by focal spread at the scale of a few hundred meters and over longer distances due to human mobility. The relative contributions of different spatial scales for transmission of chikungunya virus require definition to improve outbreak vector control recommendations. Methods We analyzed data from a large chikungunya outbreak mediated by the mosquito Aedes albopictus in the Lazio region, Italy, consisting of 414 reported human cases between June and November 2017. Using dates of symptom onset, geographic coordinates of residence, and information from epidemiological questionnaires, we reconstructed transmission chains related to that outbreak. Results Focal spread (within 1 km) accounted for 54.9% of all cases, 15.8% were transmitted at a local scale (1–15 km) and the remaining 29.3% were exported from the main areas of chikungunya circulation in Lazio to longer distances such as Rome and other geographical areas. Seventy percent of focal infections (corresponding to 38% of the total 414 cases) were transmitted within a distance of 200 m (the buffer distance adopted by the national guidelines for insecticide spraying). Two main epidemic clusters were identified, with a radius expanding at a rate of 300–600 m per month. The majority of exported cases resulted in either sporadic or no further transmission in the region. Conclusions Evidence suggest that human mobility contributes to seeding a relevant number of secondary cases and new foci of transmission over several kilometers. Reactive vector control based on current guidelines might allow a significant number of secondary clusters in untreated areas, especially if the outbreak is not detected early. Existing policies and guidelines for control during outbreaks should recommend the prioritization of preventive measures in neighboring territories with known mobility flows to the main areas of transmission.openGuzzetta, Giorgio; Vairo, Francesco; Mammone, Alessia; Lanini, Simone; Poletti, Piero; Manica, Mattia; Rosa, Roberto; Caputo, Beniamino; Solimini, Angelo; Torre, Alessandra Della; Scognamiglio, Paola; Zumla, Alimuddin; Ippolito, Giuseppe; Merler, StefanoGuzzetta, G.; Vairo, F.; Mammone, A.; Lanini, S.; Poletti, P.; Manica, M.; Rosa, R.; Caputo, B.; Solimini, A.; Torre, A.D.; Scognamiglio, P.; Zumla, A.; Ippolito, G.; Merler, S

Spatial modes for transmission of chikungunya virus during a large chikungunya outbreak in Italy. A modeling analysis

Background The spatial spread of many mosquito-borne diseases occurs by focal spread at the scale of a few hundred meters and over longer distances due to human mobility. The relative contributions of different spatial scales for transmission of chikungunya virus require definition to improve outbreak vector control recommendations. Methods We analyzed data from a large chikungunya outbreak mediated by the mosquito Aedes albopictus in the Lazio region, Italy, consisting of 414 reported human cases between June and November 2017. Using dates of symptom onset, geographic coordinates of residence, and information from epidemiological questionnaires, we reconstructed transmission chains related to that outbreak. Results Focal spread (within 1 km) accounted for 54.9% of all cases, 15.8% were transmitted at a local scale (1–15 km) and the remaining 29.3% were exported from the main areas of chikungunya circulation in Lazio to longer distances such as Rome and other geographical areas. Seventy percent of focal infections (corresponding to 38% of the total 414 cases) were transmitted within a distance of 200 m (the buffer distance adopted by the national guidelines for insecticide spraying). Two main epidemic clusters were identified, with a radius expanding at a rate of 300–600 m per month. The majority of exported cases resulted in either sporadic or no further transmission in the region. Conclusions Evidence suggest that human mobility contributes to seeding a relevant number of secondary cases and new foci of transmission over several kilometers. Reactive vector control based on current guidelines might allow a significant number of secondary clusters in untreated areas, especially if the outbreak is not detected early. Existing policies and guidelines for control during outbreaks should recommend the prioritization of preventive measures in neighboring territories with known mobility flows to the main areas of transmission

Bictegravir/emtricitabine/tenofovir alafenamide ensures high rates of virological suppression maintenance despite previous resistance in PLWH who optimize treatment in clinical practice

We evaluated virological response and resistance profile in virologically suppressed individuals switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in real-life

Detection of Viral RNA in Tissues following Plasma Clearance from an Ebola Virus Infected Patient

An unprecedented Ebola virus (EBOV) epidemic occurred in 2013–2016 in West Africa. Over this time the epidemic exponentially grew and moved to Europe and North America, with several imported cases and many Health Care Workers (HCW) infected. Better understanding of EBOV infection patterns in different body compartments is mandatory to develop new countermeasures, as well as to fully comprehend the pathways of human-to-human transmission. We have longitudinally explored the persistence of EBOV-specific negative sense genomic RNA (neg-RNA) and the presence of positive sense RNA (pos-RNA), including both replication intermediate (antigenomic-RNA) and messenger RNA (mRNA) molecules, in the upper and lower respiratory tract, as compared to plasma, in a HCW infected with EBOV in Sierra Leone, who was hospitalized in the high isolation facility of the National Institute for Infectious Diseases “Lazzaro Spallanzani” (INMI), Rome, Italy. We observed persistence of pos-RNA and neg-RNAs in longitudinally collected specimens of the lower respiratory tract, even after viral clearance from plasma, suggesting possible local replication. The purpose of the present study is to enhance the knowledge on the biological features of EBOV that can contribute to the human-to-human transmissibility and to develop effective intervention strategies. However, further investigation is needed in order to better understand the clinical meaning of viral replication and shedding in the respiratory tract

Measles outbreak on a cruise ship in the western Mediterranean, February 2014, preliminary report

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Emulation of a Target Trial From Observational Data to Compare Effectiveness of Casirivimab/Imdevimab and Bamlanivimab/Etesevimab for Early Treatment of Non-Hospitalized Patients With COVID-19

OBJECTIVES: Comparative analysis between different monoclonal antibodies (mAbs) against SARS-CoV-2 are lacking. We present an emulation trial from observational data to compare effectiveness of Bamlanivimab/Etesevimab (BAM/ETE) and Casirivimab/Imdevimab (CAS/IMD) in outpatients with early mild-to-moderate COVID-19 in a real-world scenario of variants of concern (VoCs) from Alpha to Delta. METHODS: Allocation to treatment was subject to mAbs availability, and the measured factors were not used to determine which combination to use. Patients were followed through day 30. Viral load was measured by cycle threshold (CT) on D1 (baseline) and D7. Primary outcome was time to COVID-19-related hospitalization or death from any cause over days 0-30. Weighted pooled logistic regression and marginal structural Cox model by inverse probability weights were used to compare BAM/ETE vs. CAS/IMD. ANCOVA was used to compare mean D7 CT values by intervention. Models were adjusted for calendar month, MASS score and VoCs. We evaluated effect measure modification by VoCs, vaccination, D1 CT levels and enrolment period. RESULTS: COVID19-related hospitalization or death from any cause occurred in 15 of 237 patients in the BAM/ETE group (6.3%) and in 4 of 196 patients in the CAS/IMD group (2.0%) (relative risk reduction [1 minus the relative risk] 72%; p=0.024). Subset analysis carried no evidence that the effect of the intervention was different across stratification factors. There was no evidence in viral load reduction from baseline through day 7 across the two groups (+0.17, 95% -1.41;+1.74, p=0.83). Among patients who experienced primary outcome, none showed a negative RT-PCR test in nasopharyngeal swab (p=0.009) and 82.4% showed still high viral load (p<0.001) on D7. CONCLUSIONS: In a pre-Omicron epidemiologic scenario, CAS/IMD reduced risk of clinical progression of COVID-19 compared to BAM/ETE. This effect was not associated with a concomitant difference in virological response

COVID-19 disease-Temporal analyses of complete blood count parameters over course of illness, and relationship to patient demographics and management outcomes in survivors and non-survivors: A longitudinal descriptive cohort study

BACKGROUND: Detailed temporal analyses of complete (full) blood count (CBC) parameters, their evolution and relationship to patient age, gender, co-morbidities and management outcomes in survivors and non-survivors with COVID-19 disease, could identify prognostic clinical biomarkers. METHODS: From 29 January 2020 until 28 March 2020, we performed a longitudinal cohort study of COVID-19 inpatients at the Italian National Institute for Infectious Diseases, Rome, Italy. 9 CBC parameters were studied as continuous variables [neutrophils, lymphocytes, monocytes, platelets, mean platelet volume, red blood cell count, haemoglobin concentration, mean red blood cell volume and red blood cell distribution width (RDW %)]. Model-based punctual estimates, as average of all patients' values, and differences between survivors and non-survivors, overall, and by co-morbidities, at specific times after symptoms, with relative 95% CI and P-values, were obtained by marginal prediction and ANOVA- style joint tests. All analyses were carried out by STATA 15 statistical package. MAIN FINDINGS: 379 COVID-19 patients [273 (72% were male; mean age was 61.67 (SD 15.60)] were enrolled and 1,805 measures per parameter were analysed. Neutrophils' counts were on average significantly higher in non-survivors than in survivors (P60 years (OR = 4.21; 95%CI 1.82-9.77; p = 0.001). Age (OR = 2.59; 95%CI 1.04-6.45; p = 0.042), obesity (OR = 5.13; 95%CI 1.81-14.50; p = 0.002), renal chronic failure (OR = 5.20; 95%CI 1.80-14.97; p = 0.002) and cardiovascular diseases (OR 2.79; 95%CI 1.29-6.03; p = 0.009) were independently associated with poor clinical outcome at 30 days after symptoms' onset. INTERPRETATION: Increased neutrophil counts, reduced lymphocyte counts, increased median platelet volume and anaemia with anisocytosis, are poor prognostic indicators for COVID19, after adjusting for the confounding effect of obesity, chronic renal failure, COPD, cardiovascular diseases and age >60 years