Dermatitis during Spaceflight Associated with HSV-1 Reactivation

Abstract

Human alpha herpesviruses herpes simplex virus (HSV-1) and varicella zoster virus (VZV) establish latency in various cranial nerve ganglia and often reactivate in response to stress-associated immune system dysregulation. Reactivation of Epstein Barr virus (EBV), VZV, HSV-1, and cytomegalovirus (CMV) is typically asymptomatic during spaceflight, though live/infectious virus has been recovered and the shedding rate increases with mission duration. The risk of clinical disease, therefore, may increase for astronauts assigned to extended missions (>180 days). Here, we report, for the first time, a case of HSV-1 skin rash (dermatitis) occurring during long-duration spaceflight. The astronaut reported persistent dermatitis during flight, which was treated onboard with oral antihistamines and topical/oral steroids. No HSV-1 DNA was detected in 6-month pre-mission saliva samples, but on flight day 82, a saliva and rash swab both yielded 4.8 copies/ng DNA and 5.3 × 104 copies/ng DNA, respectively. Post-mission saliva samples continued to have a high infectious HSV-1 load (1.67 × 107 copies/ng DNA). HSV-1 from both rash and saliva samples had 99.9% genotype homology. Additional physiological monitoring, including stress biomarkers (cortisol, dehydroepiandrosterone (DHEA), and salivary amylase), immune markers (adaptive regulatory and inflammatory plasma cytokines), and biochemical profile markers, including vitamin/mineral status and bone metabolism, are also presented for this case. These data highlight an atypical presentation of HSV-1 during spaceflight and underscore the importance of viral screening during clinical evaluations of in-flight dermatitis to determine viral etiology and guide treatment.

Keywords: dermatitis; herpes; immune depression; spaceflight; stress; viral reactivation.

Figure 1

Schedule for collection of biological samples aboard ISS. Samples sent for sequencing are boxed in red. B—blood; S—liquid saliva; D—dry saliva; P—passive drool; U—urine; R—return after flight; FD—flight day. The subject was HSV-1 seropositive.

Figure 2

Mean distribution of salivary alpha amylase, cortisol, and DHEA before (green), during (red), and after (blue) the mission. Pre-mission samples are indicated by “L-“ referencing the number of days before launch. In-flight mission samples are indicated as FD, flight day. Post-mission samples are similarly indicated by “R+” for the days post-return. Statistical significance is indicated by * p < 0.05 and ** p < 0.01.

Figure 3

Adaptive regulatory (a) and inflammatory (b) plasma cytokines concentrations (pg/mL) measured via multiplex array before, during, and after the spaceflight. Pre-flight samples are indicated by “L-“ referencing the number of days before launch. In-flight (flight day) mission samples are indicated by “FD” followed by the number of days post launch. Post-flight samples are similarly indicated by “R+” for the days post-return.

Figure 4

Network graph demonstrating the relatedness of astronaut and other HSV-1 genomes. The two astronaut-derived HSV-1 genomes (orange) clustered nearest to HSV-1 genomes from China (CR-38) and Russia (L2). This graph-based SplitsTree network was generated from an alignment of the astronaut-derived HSV-1 genomes with 51 HSV-1 genomes that encompass the global genetic diversity of this virus. The Φ statistical test in SplitsTree4 found statistically significant evidence for recombination (p = 0.0), as expected based on prior analyses of HSV-1 phylogenies. The overall geographical origins of the prior HSV-1 genomes are European and North American (red); European, North American, Asian (blue), and African (green). The scale bar represents 0.1% nucleotide divergence. Supplementary Table S1 includes the names, accessions, and geographic origins of each strain.

Figure 5

The in-flight rash (FD82) HSV-1 sample contained far more minor variants in the viral genome population than the post-flight saliva (R + 0) HSV-1 sample. This included (a) 366 MVs in the in-flight rash vs. (b) 24 in the post-flight saliva HSV-1 samples. Minor variants (MVs) are plotted based on their location within the HSV-1 genome (x-axis) and the frequency of the detected MV allele (y-axis) at each position. Minor variants are color-coded according to their classification as missense (genic), synonymous (genic), or intergenic/other. A black line and arrowhead (right of each plot) indicate the MV detection threshold of 2% (0.02). A diagram of HSV-1 coding sequences is located below each x-axis to highlight the coding sequences that contain missense minor variants. Supplementary Table S3 includes the precise location, coverage depth (i.e., forward and reverse reads supporting the major vs. the minor allele), and a list of specific MV impacts within each gene.