Natural History of Andes Virus Infection

Primary outcomes

• Time to first virologic detection (X0/E0→P0) [6 weeks]: Time from enrolment (X0/E0) to first detectable ANDV RNA (P0)
• Blood viral kinetics (trajectory endpoints) [6 weeks]: Viral load trajectories in blood, including peak, slope of increase/decrease, and time to clearance.
• Post-symptom RT-qPCR persistence [6 weeks]: Duration of RT-qPCR positivity after symptom resolution (where measured)
• Serologic conversion timing [6 weeks]: Time to IgM positivity, time to IgG positivity

Secondary outcomes

• Humoral immune kinetics [6 weeks]: IgM and IgG titres over time
• Longitudinal immune marker trajectories [6 weeks]: Longitudinal immune marker trajectories aligned to P0 and S0 (pre-specified panels)
• Symptom onset and symptom duration [6 weeks]: Symptom onset date (S0), symptom duration
• Clinical severity and healthcare utilisation outcomes [6 weeks]: Hospitalisation, ICU admission, organ support (as applicable), mortality (as applicable)
• Standardised in-hospital severity metrics (if hospitalised; clinical data only) [6 weeks]: WHO Ordinal Scale, SOFA score (if clinically available)
• Host genetic correlates of infection and disease outcomes [6 weeks]: Genetic associations with infection susceptibility (i.e., infected vs. uninfected among exposed participants). disease severity/progression (e.g., severe vs. mild disease outcomes), key clinical events (e.g., hospitalisation, ICU admission, organ support, mortality) and molecular and immune markers (e.g., differences in viral load kinetics or immune response levels)

Other outcomes

• Multi-compartment detection and shedding dynamics [6 weeks]: Time-to-first-detection in each compartment (blood/buffy coat, plasma if collected, nasopharyngeal swab, saliva, urine, feces) and lead/lag structure relative to P0, compartment-specific kinetic summaries (peak, time-to-peak, growth/decay rates, and AUC) per compartment, compartment-specific time to clearance and discordance patterns (persistence in non-blood compartments after blood clearance, or vice versa).
• Trigger-aligned serology endpoints (P0/S0 anchored) [6 weeks]: P0→IgM+, P0→IgG+, S0→IgM+, and S0→IgG+ intervals (trigger-aligned seroconversion timing), early titre kinetic features (e.g., early rise patterns) as predictors of downstream clinical outcomes (hypothesis-generating)
• Immune "inflection points" and trajectory phenotypes [6 weeks]: Earliest detectable immune activation relative to P0 and relative to S0 ("immune inflection point timing"), and peak/resolution kinetics of immune markers, data-driven immune trajectory phenotypes (e.g., clustered longitudinal patterns) and their association with clinical outcomes.
• Time-to-event progression endpoints [6 weeks]: Time-to-event endpoints such as P0→hospitalisation/ICU and S0→hospitalisation/ICU/organ support/death (as data allow), for early risk modelling and natural history characterization.
• Daily monitoring signal summaries [6 weeks]: Descriptive trajectories and derived summaries of daily monitoring measures (temperature, SpO₂, blood pressure, diuresis) and their association with subsequent clinical outcomes (hypothesis-generating)
• Convalescence and longer-term outcomes [6 months]: Convalescence pattern descriptors and longer-term outcomes through Month 6 (and beyond if extended), including persistence or resolution patterns as captured in follow-up

Sex: All

Inclusion Criteria:

1. No age restriction.
2. Persons diagnosed with or exposed to Andes Virus (ANDV). Exposure must comply with the national definition of ANDV exposure in each country, or satisfy at least one of the following criteria:

   1. Direct physical exposure to a person with ANDV infection
   2. Environmental and proximity exposure to a person with ANDV infection, i.e.:

      * Prolonged presence in an enclosed or poorly ventilated shared airspace. Note: Prolonged exposure is defined as cumulative exposure of 15 minutes or more within a 24-hour period in a confined space, or shared occupancy of an enclosed environment for more than 2 hours (ECDC).
      * Co-habitation in the same household, room, or cabin (e.g., maritime or shared residential settings).
      * Documented proximity during long-haul travel exceeding 4 hours. Note: Proximity is defined as sitting in an adjacent seat, defined as the same row or within two rows in front or behind. Long haul travel includes flight, bus, car or train. See Box 2 for justification of the 4 hour time threshold.
   3. Occupational or caregiving exposure

      * Provision of direct healthcare or personal care to a person with ANDV infection without the consistent use of recommended Personal Protective Equipment (PPE).
      * Direct handling of potentially contaminated fomites, such as soiled linens, clothing, or bedding used by a confirmed case.
      * Direct handling of laboratory samples form a confirmed case with noncompliance with standard biosafety protocols.
3. Ability to comply with confinement sampling and follow up procedures.
4. Informed consent by participant, parent/legal guardian, or surrogate where allowed and applicable; assent or consent for children aged <18 years or <16 years as per local regulations.

Exclusion Criteria:

* 1\. Current imprisonment (quarantine does not count).