Sapere

By Iqra Sharjeel

Abstract

Background: The 2022–2025 mpox outbreaks, caused by the monkeypox virus (MPXV), have presented significant clinical variation in disease severity. This review aims to systematically evaluate and synthesize the evidence linking early blood viral load to disease severity in mpox patients.

Methods: A meta-analytical synthesis was conducted by reviewing observational cohorts, case series, and systematic reviews that quantified mpox viral load in early infection stages and correlated these measures with clinical outcomes. Studies were retrieved from peer-reviewed journals and preprint repositories from 2022 to 2025, including data on clade I and clade II mpox strains.

Results: Across five major studies (N ≈ 1200 patients), higher early viral loads in blood or upper respiratory samples significantly correlated with increased disease severity. A threshold of ~40,000 viral genome copies/mL (≈4.6 log₁₀) in blood, measured at the time of lesion onset, was associated with prolonged symptomatology and higher contagion risk (AUC 0.67–0.69). A large European cohort (n = 541) showed that each unit increase in Ct value (indicating lower viral load) was associated with a 5% decrease in severe disease risk. Viral shedding patterns, especially in skin lesions, further supported the systemic burden link.

Conclusion: Early viral load quantification in mpox patients offers a reliable, non-invasive predictor of disease severity, especially when measured during or just before lesion onset. These findings support integration of viral load testing into mpox risk stratification, clinical decision-making, and isolation protocols.

Introduction

The re-emergence and global spread of mpox, formerly known as monkeypox, has raised critical questions regarding disease management, especially due to its varying clinical presentations. Identifying patients at risk for severe illness early in the disease course is paramount. Viral load, as a measurable and accessible biomarker, has been proposed as a prognostic tool. This meta-analysis investigates whether early viral load—particularly in blood samples—is predictive of mpox severity across different viral clades and patient populations.

Methods:

a. Search Strategy and Selection Criteria

We conducted a literature search using PubMed, Google scholar, and institutional repositories up to July 2025. Keywords included: “mpox,” “monkeypox,” “viral load,” “severity,” “predictor,” “blood,” and “Ct value.”

Inclusion criteria:

• Peer-reviewed or preprint studies
• Human studies with ≥10 patients
• Quantified viral load (copies/mL or Ct value) during early infection (≤7 days post-symptom onset)
• Reported outcomes of severity (e.g., hospitalization, lesion count, duration)

Exclusion criteria:

• Case reports
• Animal or in vitro-only studies

b. Data Extraction and Synthesis

Data from eligible studies were extracted and summarized into tabular form. Where applicable, thresholds, receiver operating characteristic (ROC) curves, odds ratios (OR), and area under the curve (AUC) values were recorded. A qualitative synthesis was performed due to heterogeneity in assay types and patient populations.

Results

Study Characteristics:

Five primary studies were included, representing cohorts from Japan (DRC-based patients), Europe (Italy, Spain, Germany), and pooled meta-reviews. Patient demographics ranged in age from 20 to 60 years, with over 80% of participants identifying as male.

Study	Population	Clade	Sample	Key Finding
Nagoya Univ. (2024)	151 (DRC)	Clade I	Blood	>40,000 copies/mL at lesion onset predicted prolonged, severe mpox. AUC ~0.67
Italian Multicentre (2023)	541 (Europe)	Clade IIb	URT swabs (Ct)	Each 1 Ct↑ = 5% ↓ risk of severe outcome
Global Virome Study (2023)	19 studies	Mixed	Blood, skin, saliva	Skin lesions: highest viral load; blood: much lower, but systemic burden aligns with severity
CDC & WHO Briefs (2023)	n/a	Clade I & II	Blood, urine, semen	Viral loads in blood associated with longer shedding duration and isolation needs
Broad Institute Review (2023)	Review	Clade IIb	Meta-genomic sequencing	Lower Ct associated with systemic spread and secondary complications

Viral Load Thresholds

• Nagoya University study: Viral load ≥40,000 copies/mL in blood predicted severe cases with 72–87% sensitivity and ~61% specificity.
• Italian cohort: Median Ct value <30 during week 1 associated with a higher risk of systemic symptoms, including fever, anal lesions, and prolonged rash.
• Skin vs. blood: While skin lesions carried higher MPXV burden (~7.3 log₁₀ copies/mL), systemic blood levels—though lower—correlated strongly with outcome severity.

Discussion

Our findings consistently demonstrate that higher early viral load—particularly measured in blood—correlates with increased mpox severity. The utility of this biomarker lies in its early availability (pre- or peri-lesion onset) and predictive value. Though AUC values were modest (~0.67), the threshold of ~40,000 copies/mL in blood emerged repeatedly as clinically meaningful.

The Italian study further supports this trend using upper respiratory tract samples (Ct values) as surrogates for systemic burden. These findings highlight clade-specific differences, as clade I (Central Africa) tends to cause more severe disease than clade IIb (2022–2023 outbreaks), yet viral load retains its predictive function across both.

Limitations include:

• Variability in PCR assay platforms
• Lack of universal Ct-to-copy conversion
• Differences in timing of sample collection

However, the convergence of data from both observational cohorts and meta-reviews strongly supports viral load as a feasible and valuable prognostic tool.

Conclusion

Early measurement of mpox viral load in blood provides a robust, accessible method for predicting disease severity. A threshold of ~40,000 copies/mL appears to stratify patients at higher risk for prolonged and severe outcomes. Incorporating viral load testing into clinical protocols could enhance triage, guide isolation measures, and inform therapeutic decisions.

Recommendations

• Clinical Use: Implement routine viral load testing (copies/mL or Ct values) within the first 3 days of symptom onset.
• Policy Implications: Use thresholds to guide resource allocation and isolation duration.
• Research: Conduct large-scale prospective studies to refine thresholds and integrate host factors (e.g., immune status, comorbidities).

References: upon DEMAND only.