Viral load decrease in SARS-CoV-2 BA.1 and BA.2 Omicron sublineages infection after treatment with monoclonal antibodies and direct antiviral agents

BACKGROUND: The efficacy on the Omicron variant of the approved early- coronavirus disease 2019 (COVID-19) therapies, especially monoclonal antibodies, has been challenged by in vitro neutralization data, while data on in vivo antiviral activity are lacking. MATERIALS AND METHODS: We assessed potential decrease from day1 to day7 viral load (VL) in nasopharyngeal swabs of outpatients receiving Sotrovimab, Molnupiravir, Remdesivir, or Nirmatrelvir/ritonavir for mild-to-moderate COVID-19 due to sublineages BA.1 or BA.2, and average treatment effect (ATE) by weighted marginal linear regression models. RESULTS: A total of 521 patients [378 BA.1 (73%),143 (27%) BA.2] received treatments (Sotrovimab 202, Molnupiravir 117, Nirmatrelvir/ritonavir 84, and Remdesivir 118): median age 66 years, 90% vaccinated, median time from symptoms onset 3 days. Day1 mean viral load was 4.12 log2 (4.16 for BA.1 and 4.01 for BA.2). The adjusted analysis showed that Nirmatrelvir/ritonavir significantly reduced VL compared to all the other drugs, except vs. Molnupiravir in BA.2. Molnupiravir was superior to Remdesivir in both BA.1 and BA.2, and to Sotrovimab in BA.2. Sotrovimab had better activity than Remdesivir only against BA.1. CONCLUSIONS: Nirmatrelvir/ritonavir showed the greatest antiviral activity against Omicron variant, comparable to Molnupiravir only in the BA.2 subgroup. VL decrease could be a valuable surrogate of drug activity in the context of the high prevalence of vaccinated people and low probability of hospital admission. This article is protected by copyright. All rights reserved

A large ongoing outbreak of hepatitis A predominantly affecting young males in Lazio, Italy; August 2016 - March 2017

<div><p>The hepatitis A virus (HAV) is mainly transmitted through the faecal-oral route. In industrialized countries HAV infection generally occurs as either sporadic cases in travelers from endemic areas, local outbreak within closed/semi-closed population and as foodborne community outbreak. Recently, an increasing number of HAV infection clusters have been reported among young men-who-have-sex-with-men (MSM).</p><p>The Lazio Regional Service for the epidemiology and control for infectious diseases (SeRESMI) has noticed an increase of acute hepatitis A (AHA) since September 2016. Temporal analysis carried out with a discrete Poisson model using surveillance data between January 2016 and March 2017 evidenced an ongoing outbreak of AHA that started at the end of August. Molecular investigation carried out on 130 out of 513 cases AHA reported until March 2017 suggests that this outbreak is mainly supported by an HAV variant which is currently spreading within MSM communities across Europe (VRD_521_2016).</p><p>The report confirms that AHA is an emerging issue among MSM. In addition through the integration of standard (case based) surveillance with molecular investigation we could discriminate, temporally concomitant but epidemiologically unrelated, clusters due to different HAV variants. As suggested by the WHO, in countries with low HAV circulation, vaccination programmes should be tailored on the local epidemiological patterns to prevent outbreaks among high risk groups and eventual spillover of the infection in the general population.</p></div

Immunogenicity to COVID-19 mRNA vaccine third dose in people living with HIV

HIV infection may affect the immune response to vaccination. Here the authors show that humoral response in persons living with HIV after the third dose of a SARS-CoV-2 vaccine is strong and higher than that achieved with the second dose, while cell-mediated immunity remains stable.In order to investigate safety and immunogenicity of SARS-CoV-2 vaccine third dose in people living with HIV (PLWH), we analyze anti-RBD, microneutralization assay and IFN-gamma production in 216 PLWH on ART with advanced disease (CD4 count &lt;200 cell/mm(3) and/or previous AIDS) receiving the third dose of a mRNA vaccine (BNT162b2 or mRNA-1273) after a median of 142 days from the second dose. Median age is 54 years, median CD4 nadir 45 cell/mm(3) (20-122), 93% HIV-RNA &lt; 50 c/mL. In 68% of PLWH at least one side-effect, generally mild, is recorded. Humoral response after the third dose was strong and higher than that achieved with the second dose (&gt;2 log(2) difference), especially when a heterologous combination with mRNA-1273 as third shot is used. In contrast, cell-mediated immunity remain stable. Our data support usefulness of third dose in PLWH currently receiving suppressive ART who presented with severe immune dysregulation

Incidence of AHA cases.

<p>A) Incidence of the AHA cases occurred among people resident in Lazio, according to area of residence (i.e. Frosione (FR) 17 cases; Latina (LT) 13 cases; Rieti (RI) 6 cases; Metropolitan area of Rome (RM) 61 cases; City of Rome (ROMA) 377 cases; Viterbo (VT) 12 cases; total cases: 486). Cases occurred in non-resident people (N = 27) were not included. B B) Temporal distribution of the 513 cases of AHA occurred in Lazio between 1 January 2016 and 31 March 2017, according to risk class, i.e. men (N = 449); women (N = 32); children (N = 32).</p

Geographical distribution of HAV isolates.

<p>The figure describes the distribution in Lazio of the 125 HAV isolates according to the 5 clusters (i.e.: Cluster A N = 112 -red, cluster B N = 6 -green, cluster C N = 3 -blue, cluster D N = 3 -orange, cluster E N = 1 -yellow). The figure did not include the 5 sporadic HAV isolates.</p

Temporal cluster analysis.

<p>Temporal cluster analysis.</p

Phylogenetic analysis.

<p>Phylogenetic tree, built with a total of 174 460nt-long sequences encompassing the VP1/2A junction region of HAV genome, based on the maximum-likelihood method with the Hasegawa-Kishino-Yano model + G. All the sequences obtained in 2016–2017 from Lazio region (N = 130, patient number, in red) are included. In addition, HAV sequences from Lazio cases referred to the Laboratory from 2013–2015 (N = 24, patient number, in black) are included. The tree also includes 16 reference sequences from GenBank (genotype IA: X75215; EU131373; AB020565; X83302; genotype IB: M14707; DQ646426; NC001489; AF314208; genotype IIA: AJ644676; genotype IIB: AY644670; genotype IIIA: AJ299464; DQ991030; AB279733; genotype IIIB: AB279735; AB425339; AB258387, in blue), and the 4 sequences (VRD_521_2016 and RIVM-HAV16-90, RIVM-HAV16-69 and V16_25801, in green) recently reported to be associated with epidemic clusters among MSM in other European countries (in blue). One genotype IIA sequence (AY644676) was used as the outgroup. The bar represents the genetic distance (substitution per nucleotide position). Bootstrap analysis with 1000 replicates was performed to assess the significance of the nodes; values greater than 80.</p