Project description:BackgroundAn unprecedented global monkeypox outbreak started in May, 2022. No data are yet available about the dynamics of the immune response against monkeypox virus. The aim of this study was to describe kinetics of T-cell response, inflammatory profile, and pox-specific T-cell induction in patients with laboratory-confirmed monkeypox.Methods17 patients with laboratory-confirmed monkeypox admitted at the Lazzaro Spallanzani National Institute for Infectious Diseases (Rome, Italy), from May 19, to July 7, 2022, were tested for differentiation and activation profile of CD4 and CD8 T (expression of CD38, PD-1, and CD57 assessed by flow cytometry), frequency of pox-specific T cells (by standard interferon-γ ELISpot), and release of interleukin (IL)-1β, IL-6, IL-8, and tumour necrosis factor (TNF) in plasma (by ELISA). All patients were tested 10-12 days after symptoms onset. In a subgroup of nine patients with a laboratory-confirmed monkeypox, the kinetics of the immune response were analysed longitudinally according to timing from symptoms onset and compared with ten healthy donors (ie, health-care workers recruited from the same institution).FindingsAmong the 17 patients, ten were HIV negative and seven HIV positive, all with good viro-immunological status. On days 0-3 from symptom onset, patients with laboratory-confirmed monkeypox were characterised by a statistically significant reduction in CD4+ T cells (p=0·0011) and a concurrent increase of CD8+ T cells (p=0·0057) compared with healthy donors. A lower proportion of naive (CD45RA+CD27+) CD4+ T cells was observed in six (67%) of nine patients and a concomitant higher proportion of effector memory (CD45RA-CD27-) CD4+ T cells in all patients; this skewed immune profile tended to normalise over time. A similar differentiated profile was also observed in CD8+ T cells with a consistent expansion of terminally differentiated CD8+ T cells. Patients with monkeypox had a higher proportion of CD4+CD38+ and CD38+CD8+ T-cells than healthy donors, which normalised after 12-20 days from symptom onset. The expression of PD-1 and CD57 on CD4+ and CD8+ T-cells showed kinetics similar to that observed for CD38. Furthermore, the inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF) were higher in patients with monkeypox than in healthy donors and, although they decreased over time, they remained elevated after recovery. Almost all patients (15 [94%] of 16) developed a pox-specific Th1 response. No differences in immune cells profile were observed between patients with and without HIV, whereas paucysimptomatic patients (without systemic symptoms, with less than five skin lesions, and no other mucosal localisation of monkeypox) showed a less perturbed immune profile early after symptom onset.InterpretationOur data showed the immunological signature of monkeypox virus infection, characterised by an early expansion of activated effector CD4+ and CD8+ T cells that persisted over time. Almost all patients, even regardless of HIV infection, developed a poxvirus-specific Th1 cell response. These results might have implications on the expected immunogenicity of monkeypox vaccination, suggesting that it might not be necessary to vaccinate people who have already been infected.FundingItalian Ministry of Health.TranslationFor the Italian translation of the abstract see Supplementary Materials section.
Project description:Phylogenetic analysis of monkeypox virus genomes showed statistically significant divergence and nascent subclades during the 2022 mpox outbreak. Frequency of G>A/C>T transitions has increased in recent years, probably resulting from apolipoprotein B mRNA editing enzyme catalytic polypeptide 3G (APOBEC3) deaminase editing. This microevolutionary pattern most likely reflects community spread of the virus and adaptation to humans.
Project description:BackgroundIn the 2022 mpox (monkeypox) outbreak, 79,000 global cases have been reported. Yet, limited dermatologic data have been published regarding lesion morphology and progression.ObjectiveThe objective of this study was to characterize skin lesion morphology, symptomatology, and outcomes of mpox infection over time.MethodsThe American Academy of Dermatology/International League of Dermatological Societies Dermatology COVID-19, Mpox, and Emerging Infections Registry captured deidentified patient cases of mpox entered by health care professionals.ResultsFrom August 4 to November 13, 2022, 101 cases from 13 countries were entered, primarily by dermatologists (92%). Thirty-nine percent had fewer than 5 lesions. In 54% of cases, skin lesions were the first sign of infection. In the first 1-5 days of infection, papules (36%), vesicles (17%), and pustules (20%) predominated. By days 6-10, pustules (36%) were most common, followed by erosions/ulcers (27%) and crusts/scabs (24%). Crusts/scabs were the predominant morphology after day 11. Ten cases of morbilliform rash were reported. Scarring occurred in 13% of the cases.LimitationsRegistry-reported data cannot address incidence. There is a potential reporting bias from the predilection to report cases with greater clinical severity.DiscussionThese findings highlight differences in skin findings compared to historical outbreaks, notably the presence of skin lesions prior to systemic symptoms and low overall lesion counts. Scarring emerged as a major possible sequela.
Project description:The outbreak-causing monkeypox virus of 2022 (2022 MPXV) is classified as a clade IIb strain and phylogenetically distinct from prior endemic MPXV strains (clades I or IIa), suggesting that its virological properties may also differ. Here, we used human keratinocytes and induced pluripotent stem cell-derived colon organoids to examine the efficiency of viral growth in these cells and the MPXV infection-mediated host responses. MPXV replication was much more productive in keratinocytes than in colon organoids. We observed that MPXV infections, regardless of strain, caused cellular dysfunction and mitochondrial damage in keratinocytes. Notably, a significant increase in the expression of hypoxia-related genes was observed specifically in 2022 MPXV-infected keratinocytes. Our comparison of virological features between 2022 MPXV and prior endemic MPXV strains revealed signaling pathways potentially involved with the cellular damages caused by MPXV infections and highlights host vulnerabilities that could be utilized as protective therapeutic strategies against human mpox in the future.
Project description:Monkeypox (Mpox) is a global health emergency. Yeh et al. analyze tandem repeats and linkage disequilibrium in monkeypox virus (MPXV) sequences from the 2022 pandemic to determine the virus evolution, showing that these are useful tools to monitor and track phylogenetic dynamics and recombination of MPXV.
Project description:Since early May 2022, numerous cases of Monkeypox (Mpox) have been reported globally in non-endemic areas. However, despite numerous reports worldwide, the epidemiological and genomic information related to the 2022 multi-country outbreak remains scarce in South America. By late June 2022, the first Mpox cases were detected in Colombia. Cartagena is a Colombian Caribbean city with high domestic and international connectivity, and, therefore, is vulnerable to the introduction of the Monkeypox virus (MPXV). This report provides an in-depth description of the epidemiological, clinical, and virological characteristics of the first four cases detected in Cartagena including three cases with no history of recent travel and one imported case. Using various laboratory tools based on PCR, next-generation sequencing, and viral isolation and quantification methods, the MPXV clade IIB was detected and isolated. Importantly, infectious viral particles were identified in lesion swabs collected from all cases and in oropharyngeal swabs collected from two cases. Blood samples tested negative using PCR and isolation. In summary, our work contributes complete genomic, clinical, and epidemiological information that will be useful for a number of studies going forward, and it also documents local information that contributes to our understanding of Mpox at the local level.
Project description:The genomes of two human monkeypox virus strains from recently reported cases in our local region that were associated with the 2022 global outbreak were sequenced. Genomes from clinical isolates provide valuable information for epidemiological tracking and analysis of strain evolution and can be especially important during the early phases of outbreaks.