Clinical Characterization and Outcomes of Human Clade IIb Mpox Virus Disease: A European Multicenter Mpox Observational Cohort Study (MOSAIC)

Abstract

Background: The global mpox outbreak that started in May 2022 was caused by a novel clade IIb variant of the mpox virus (Orthopoxvirus monkeypox, MPXV). It differed from the traditional Western and Central Africa disease in transmission patterns and clinical presentation.

Methods: To address the need for detailed clinical and virologic data, we conducted an observational cohort study (MOSAIC) during May 2022-July 2023 in individuals with confirmed MPXV infection enrolled in 6 European countries. Case management decisions were left to the attending physician. Participants were monitored for up to 6 months for clinical signs/symptoms and clinical and virologic outcomes through hospital visits, phone interviews, and self-administered questionnaires. Outcomes included time to lesion resolution, clinical status, and virus clearance.

Results: The 518 participants not receiving any specific treatment ("untreated") were diagnosed a median 5 days from symptom onset; 90% were managed as outpatients. Lesions were mostly cutaneous (88%) and perigenital (74%). By day 14 from the first polymerase chain reaction (PCR)-positive sample, 39% had resolved lesions. Time to 95% unculturable virus was longest in cutaneous lesions (52 days). A putative systemic antiviral was available for 57 participants, 44% as inpatients; 34% and 58% had resolved lesions by day 14 from the first PCR-positive sample and from treatment start, respectively. Time to 95% unculturable virus was 60 days in skin and oropharynx. No death or recrudescence occurred by day 180.

Conclusions: MOSAIC provides comprehensive insights into the clinical and virologic characteristics of mpox caused by the clade IIb variant. The study forms the basis of clinical characterization for ongoing mpox outbreaks.

Keywords: clade IIb; lesion resolution; mpox; observational cohort; viral load.

Graphical Abstract

This graphical abstract is also available at Tidbit: https://tidbitapp.io/institutional-portal/clinical-infectious-diseases/tidbits/clinical-characterisation-and-outcomes-of-human-clade-iib-mpox-virus-disease-a-european-multicentre-observational-cohort-study-mosaic/update

Figure 1.

Flowchart summarizing study enrollment, eligibility, and inclusion in the analysis population. Abbreviations: BE, Belgium; CH, Switzerland; FR, France; IT, Italy; PCR, polymerase chain reaction; SP, Spain; UK, United Kingdom.

Figure 2.

Estimated cumulative probability of lesion resolution based on Kaplan-Meier estimates for untreated participants from the date of polymerase chain reaction (PCR) diagnosis to day 28 (A) and treated participants from either date of PCR diagnosis to day 28 or treatment initiation to day 28 (B).

Figure 3.

Clinical scales at day 14 and day 28 by treatment status for participants attending the day 14 and day 28 follow-up visits. Abbreviation: PCR, polymerase chain reaction.

Figure 4.

Sankey diagrams from day (D) 14 to D28 for participants attending the D14 and D28 follow-up visits. Abbreviation: PCR, polymerase chain reaction, TD, Treatment Day.

Figure 5.

Spaghetti plots of cycle threshold (Ct) values over time for treated and untreated participants with at least 1 virological sample in 1 of the 4 compartments of interest (days [D] since symptom onset).

Figure 6.

Simulated cumulative incidence of undetectability (mean and 95% confidence intervals [CIs]) for untreated (A) and treated (B) participants. Means and associated 95% CIs are depicted with solid lines and shaded areas, respectively. The dashed line represents the cumulative incidence calculated on the fitted individuals.