Frederico was a student of the Master in Biostatistics from the Faculty of Sciences at the University of Lisbon, Portugal. He joined the group on February 1st, 2021 to conduct his project entitled "Longitudinal analysis of viral shedding in astronauts before, during, and after a mission to the International Space Station". His project was supervised by Nuno Sepúlveda and Marília Antunes and concluded on September 29th, 2022.
Title of Project:
Longitudinal analysis of viral shedding in astronauts before, during, and after a mission to the International Space Station
Herpesviruses were measured in 23 astronauts with the objective of understanding their reactivation pattern during a long-duration space mission. The measurements consisted of the number of viral copies of cytomegalovirus (CMV), Epstein-Barr (EBV), and varicella-zoster (VZV) viruses collected at different moments: two before (L−180, L−45), three during (Early, Mid, Late) and two after (R+0, R+30) a spaceflight. These data present three difficulties: small sample size, zero inflation, and missing responses. The methods used were confidence intervals for pro- portions, McNemar’s exact test, linear models for categorical data, multiple imputation using chained equations (MICE), and logistic regression mixed models (LRMM).
CMV was only measured once during the flight (During). There was a significant increase in the reactivation proportion during the flight compared to before and after flight measures L−180 and R+30. The LRMM fitted for binary CMV that had moments with reactivation as fixed effects and random effect subject was significant at coefficient R+30 (p=0.043), although During (p=0.078) had a p-value close to the statistical significance of 5%.
EBV and VZV were measured in saliva samples and have missing responses for the inflight moments. An increase of the amplitude of reactivation was detected at Late for both viruses. The data seemed to follow a missing-completely-at-random mechanism for both viruses (p=0.490 and 0.070 for EBV and VZV, respectively). Fifty imputed data sets were generated for each virus. For EBV the pooled estimates for the reactivation probability were 0.126, 0.239, 0.454 for Early, Mid, Late, respectively, and for VZV 0.488, 0.330, 0.617, respectively. The pooled LRMM of EBV with L−180 as baseline was significant at L−45 (p=0.029) and Late (p=0.022), and R+0 (p=0.053) was close to significance. For VZV, R+30 was the only significantly different from baseline Early(p=0.002).
In conclusion, the stress conditions of the space flight affected the reactivation dynamics of all three viruses.
Missing data; multiple imputation based on chained equations; categorical data analysis with missing responses; longitudinal models.