# Fluid shifts are main drivers for microgravity simulation-induced immune-physiological changes: findings from the VIVALDI studies

## TL;DR

This study shows that fluid shifts during microgravity simulations cause immune changes in both men and women, with effects stronger than other methods.

## Contribution

The study introduces a new perspective on how fluid shifts, not biological sex, primarily drive immune changes during microgravity simulations.

## Key findings

- Both sexes showed increased granulocytes and NK cells and decreased T-cells during dry immersion.
- Females had higher Torque-Teno-virus shedding after the simulation.
- Dry immersion caused stronger immune and fluid changes compared to head-down tilt bed rest.

## Abstract

Microgravity strongly affects human physiology during spaceflight. Biological sex has not yet been sufficiently considered as a variable for spaceflight deconditioning. The VivalDI studies investigated physiological systems affected by 5-days dry immersion (DI) in females and males, with a focus on immune changes in this report. In both sexes proportions of peripheral granulocytes and NK cells were elevated during DI and T-cell numbers were reduced. Leukocyte activation and cytokine levels were moderately affected. Females showed a higher Torque-Teno-virus shedding at the end of DI. Noradrenaline concentrations increased during the study with sex-specific patterns. Hemodynamics suggest that immunological changes were caused by DI-induced fluid shifts. Moreover, male study participants’ patterns were compared to a historical data set from a 5-days head-down-tilt bed rest (HDT-BR) study. Changes in leukocyte proportions and body fluid indicators were stronger in DI versus HDT-BR. These analyses indicate that fluid shifts primarily drive intervention-related immune-physiological differences, independent of biological sex. ClinicalTrials.gov, TRN: NCT05043974 and NCT05493176.