Between January and August 2024, mpox cases have been reported in nearly all provinces of the Democratic Republic of the Congo (DRC). Monkeypox virus genome sequences were obtained from 11 mpox cases’ samples, collected in July–August 2024 in several health zones of Kinshasa. Characterisation of the sequences showed subclades Ia and Ib co-circulating in the Limete health zone, while phylogenetic analyses suggested multiple introductions of the two subclades in Kinshasa. This illustrates the growing complexity of Clade I mpox outbreaks in DRC.

Introductory paragraph: Since the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS- CoV-2 and develop bronchopneumonia and a strong inflammatory response in the lungs with neutrophil infiltration and edema. Moreover, we identify an exuberant innate immune response as a key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Finally, we assess SARS-CoV- 2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.

Background Recent reports raise concerns on the changing epidemiology of mpox in the Democratic Republic of the Congo (DRC), with increasing case counts, sexual contact-mediated clusters, and sustained human-to-human transmission driven by a novel monkeypox virus (MPXV) subclade, Clade Ib. Thus far, only a limited number of Clade I MPXV genomes have been characterized, and they are not representative across different regions and time periods. Methods We conducted whole genome sequencing of 603 mpox-positive samples that were collected from 581 patients between 2018-2024 in 17/26 provinces of the DRC. Results Genome coverage was at least 70% for 423/603 (70.1%) samples and near full-length MPXV genomes (>90% coverage) were obtained for 348/603 (57.7%) samples. All newly generated MPXV sequences belonged to Clade I, among which 17 were Clade Ib strains, all from patients infected in 2024 in the South-Kivu province. The large majority (95%) of the new strains fall within previously described Clade Ia groups and potential new groups have also been observed. Genetically diverse MPXV lineages co-circulate in small geographic areas during the same outbreak suggesting multiple zoonotic introductions over a short period from one or multiple reservoir species. The low number of APOBEC3 mutations found among Clade Ia suggests that most human mpox cases are probably linked to zoonotic transmissions. Recent identification of mpox cases in Kinshasa shows multiple virus lineages being present within a large urban center. Conclusion The mpox epidemic in the DRC exhibits two distinct patterns. In traditional endemic regions, the epidemic in DRC is predominated by zoonotic spillover events involving Clade Ia. Conversely, in the eastern part of the country, the Clade Ib outbreak is driven by human-to-human transmission highlighting the need for a coordinated response effort at the national, regional and international levels.

Background: Monkeypox virus (MPXV) is endemic to the Democratic Republic of the Congo (DRC), and historically has been reported in rural, forested regions with limited household and primarily zoonotic transmission. With the emergence of subclade Ib and increasing reported human-to-human transmission of MPXV we sought to characterize both the epidemiologic and genomic characteristics of confirmed mpox cases in Kinshasa, DRC, following confirmed MPXV introduction in August 2023. Methods: This retrospective observational study leveraged demographic and case-investigation data, as well as biological samples, collected from suspected mpox cases in Kinshasa from January 2023 to September 2024 as part of routine national surveillance. Samples were tested at the Institut National de Recherche Biomédicale first by qPCR to confirm MPXV, and subsequently sequenced for genomic analysis for those samples with a cycle threshold value <31. Findings: Epidemiological characterization of all confirmed mpox cases in Kinshasa indicated two distinct periods of MPXV introduction and circulation: first, following the initial case in August 2023, self-limiting transmission chains of subclade Ia primarily among men. Case investigations from this period suggest human-human transmission. The second period is marked by the introduction of subclade Ib to the city and expanded co-circulation of both subclades – with Limete health zone reporting the most cases of both subclades. Of those samples sequenced, genomic analysis indicated that greater than 60% of mutations in both subclades were consistent with APOBEC3-driven mutations. Interpretation: These data suggest that as of July 2024, MPXV in Kinshasa has undergone an epidemiological shift with sustained human-to-human transmission and co-circulation of two distinct subclades. Additionally, high rates of APOBEC3-driven changes further support this shift towards human-to-human transmission. While sexual-contact transmission cannot be confirmed without further case investigation, these data highlight important changes in mpox dynamics which may better guide mpox mitigation and containment strategies in Kinshasa. RESEARCH IN CONTEXT: Evidence before this study: Historically, human infections with Clade I monkeypox virus (MPXV) have been driven through zoonotic transmission with limited secondary transmission. However, sexual contact-mediated transmission of Clade I MPXV among a small cluster of cases was identified for the first time in Kwango Province, DRC, in mid-2023. We searched PubMed, bioRxiv, and medRxiv for articles published from database inception to 11 November 2024, with no language restrictions, using the terms “mpox, monkeypox, Congo Basin, Clade I, AND outbreak”. All articles were published from 2010, with the majority published from 2022-2024, and included reviews, case reports, and laboratory investigations. Early reports on mpox outbreaks demonstrated that most infections resulted from zoonotic transmission events and the risks of sustained human-to-human transmission were considered to be very low. Assessment of human-to-human transmission of MPXV in the DRC between 1970-1980 and 1981-1986 suggested that there was no evidence for changes in secondary attack rates. This included a study of 93 MPXV-infected individuals who became symptomatic following close contact with mpox patients from 1981-1986 in DRC. Here, 69 cases resulted from transmission during the first virus generation, 19 in the second generation, and five cases in both the third and fourth generation. During the 1996-1997 mpox outbreak in DRC, it was reported that 73% of cases had contact with an mpox patient. A study of Clade I mpox in the Republic of the Congo from April-July 2003 suggested that up to seven sequential virus generations had occurred during the outbreak and was supported by the clustering of cases, uniform intervals of cases, and prior exposure histories of the patients. High secondary attack rates were also reported during an outbreak of Clade I mpox from July-December 2013 in the DRC where transmissions within the community were estimated to be ≥7 virus generations. While these observations suggested potential increased patterns of human-to-human MPXV transmission, these continued to be linked to close, sustained contacts primarily within households and among caregivers. However, the first report of a cluster of mpox cases in DRC linked to sexual contacts in 2023 suggested that intimate contact, including through heterosexual and same-sex contacts, could result in Clade I MPXV transmission. Viral genome sequences isolated from this case cluster demonstrated the highest sequence similarity with a 2022 Clade I MPXV sequence from DRC. Subsequent investigation of surveillance data in South Kivu province, DRC, from September 2023 to January 2024 identified 241 suspected mpox cases that included sustained human-to-human transmission. Among PCR-confirmed mpox cases, the median age was 22 years with 29% of individuals identifying as sex workers. Genomic analysis identified a distinct clade I lineage, named as subclade Ib, with a predominance of APOBEC3 mutations. Rapid geographic expansion of subclade Ib has resulted in introduction of MPXV to multiple neighboring countries for the first time and including sustained chains of virus transmission, most notably in Burundi. Subclade Ia MPXV has undergone rapid and extensive geographic expansion in DRC since 2023. A recent longitudinal analysis of MPXV genomes from 2018-2024 demonstrated that all non-South Kivu Province sequences exhibited high genetic diversity, low incidences of APOBEC3 mutations as compared to subclade Ib, and likely resulted from multiple zoonotic introductions. Collectively, historic mpox case data and recent observations since 2023 have suggested that human mpox cases in DRC have been driven by zoonotic transmissions of subclade Ia and an increasing burden of sustained...

SARS-CoV-2, the causative agent of COVID-19 was first detected in Belgium on 3rd February 2020, albeit the first epidemiological wave started in March and ended in June 2020. One year after the first epidemiological wave hit the country data analyses reveled the temporal and variant distribution of SARS-CoV-2 and its implication with Belgian epidemiological measures. In this study, 766 complete SARS-CoV-2 genomes of samples originating from the first epidemiological were sequenced to characterize the temporal and geographic distribution of the COVID-19 pandemic in Belgium through phylogenetic and variant analysis. Our analysis reveals the presence of the major circulating SARS-CoV-2 clades (G, GH and GR) and lineages circulating in Belgium at that time. Moreover, it contextualizes the density of SARS-CoV-2 cases over time with non-intervention measures taken to prevent the spread of SARS-CoV-2 in Belgium, specific international case imports and the functional implications of the most representative non-synonymous mutations present in Belgium between February to June 2020.

It has been demonstrated that infection with human parvovirus B19 (B19V) is associated with rash-fever illnesses. The present study aimed to investigate B19V as an aetiological agent of rash-fever syndromes in Congolese children confirmed as measles and rubella IgM-negative. An ELISA IgM test and PCR were performed to screen for B19V. A total of 177 archived serum samples were randomly selected from the measles biobank of the National Institute for Biomedical Research (INRB). Samples were investigated for anti-B19V IgM and B19V DNA. These samples originated from children <5years of age with measles-like rashes, previously confirmed as negative for both measles and rubella IgM. Out of 177 serum samples tested by ELISA and 168 tested by PCR, 109 were positive for B19V IgM antibodies (61.6%) and 87 (51.8%) were positive for B19V DNA. Positive samples in both assays were from all provinces of DRC. B19V plays a role in rash-fever illnesses in children under 5 years of age suspected of having measles or rubella infections in DRC. As an aetiological cause of rash and fever syndromes, the present study demonstrates that B19V should also be considered during the laboratory investigation of rash-fever illnesses in DRC, particularly in the paediatric population. There is a need to conduct further studies in order to gain a better understanding of the spatiotemporal pattern of B19V and to define the genotype(s) of B19V circulating in DRC.