Latent virus reactivation in astronauts on the international space station, 2017, Mehta et al.

[SNT Gatchaman]

Latent virus reactivation in astronauts on the international space station
Mehta, Satish K.; Laudenslager, Mark L.; Stowe, Raymond P.; Crucian, Brian E.; Feiveson, Alan H.; Sams, Clarence F.; Pierson, Duane L.

Reactivation of latent herpes viruses was measured in 23 astronauts (18 male and 5 female) before, during, and after long-duration (up to 180 days) spaceflight onboard the international space station.

Twenty age-matched and sex-matched healthy ground-based subjects were included as a control group. Blood, urine, and saliva samples were collected before, during, and after spaceflight. Saliva was analyzed for Epstein–Barr virus, varicella-zoster virus, and herpes simplex virus type 1.

Urine was analyzed for cytomegalovirus. One astronaut did not shed any targeted virus in samples collected during the three mission phases. Shedding of Epstein–Barr virus, varicella-zoster virus, and cytomegalovirus was detected in 8 of the 23 astronauts. These viruses reactivated independently of each other. Reactivation of Epstein–Barr virus, varicella-zoster virus, and cytomegalovirus increased in frequency, duration, and amplitude (viral copy numbers) when compared to short duration (10 to 16 days) space shuttle missions. No evidence of reactivation of herpes simplex virus type 1, herpes simplex virus type 2, or human herpes virus 6 was found.

The mean diurnal trajectory of salivary cortisol changed significantly during flight as compared to before flight (P = 0.010). There was no statistically significant difference in levels of plasma cortisol or dehydoepiandosterone concentrations among time points before, during, and after flight for these international space station crew members, although observed cortisol levels were lower at the mid and late- flight time points.

The data confirm that astronauts undertaking long-duration spaceflight experience both increased latent viral reactivation and changes in diurnal trajectory of salivary cortisol concentrations.

Link | PDF (Nature npj Microgravity)

 

[Hutan]

It's an interesting paper.

Here's the change in plasma cortisol over the course of the mission.



The levels don't get very low. I think the pattern of trends to lowered cortisol levels during the time in space is consistent with what I think happens with us - our reduced activity results in less need for cortisol. Then when the astronauts come back to earth and their bodies are having to work so much harder in gravity, their cortisol levels trend up. It's also worth reiterating that there was no statistically valid difference between cortisol levels in the different phases.

Median plasma cortisol levels ranged from 15.2 μg/dL (late flight) to 24.8 μg/dL (late recovery). The overall test for differences in medians between the seven time points was not significant (bootstrapped median regression: P = 0.086).

It's hardly surprising that there was a minor change in diurnal cortisol patterns, with days not being clearly marked by workloads. Probably some astronauts would have had tasks to do at various times over the 24 hours.

 

[Hutan]

In an environment of immune dysfunction, our hypothesis is that viral reactivation and shedding of these herpes viruses will also increase in astronauts during long- duration space flight as observed in ground-based space analogs.8

Ref 8 is
Mehta, S. K., Pierson, D. L., Cooley, H., Dubow, R. & Lugg, D. Epstein-Barr virus reactivation associated with diminished cell-mediated immunity in antarctic expeditioners. J. Med. Virol. 61, 235–240 (2000).
That paper could be interesting to look at.

 

[SNT Gatchaman]

I am interested in the viral reactivation findings, less so with the cortisol findings. The authors do seem to like to emphasise the psychosocial explanations, with the remarkable biophysical changes almost an afterthought —

Virus reactivation was shown to be associated with the unique combination of stressors associated with spaceflight which include psychosocial stressors of isolation, confinement, anxiety, sleep deprivation, as well as physical exertion, noise, increased radiation, and microgravity.

Also, really?

The apparent higher salivary cortisol profile predicted in diurnal cortisol is similar to dysregulation associated with psychosocial challenges such as chronic caregiving stress, early trauma, and breast cancer.

When attempting to reproduce the mission environments, except not in space, viral reactivation didn't occur —

Furthermore, in the MARS500 investigation, no relevant shedding was observed during or after isolation, again suggesting the impact of spaceflight (in particular, long-duration spaceflight) as a key contributor to the current findings.

We'll have to look at the Antarctic study @Hutan noted above and I also wonder if there are useful equivalent studies in submariners. To my mind the physical environment is the key attribute in this. In space, they've identified increased radiation and microgravity among other factors, but neither of those are features of the Antarctic or the MARS500 environments. Well, it may be that the previous Ozone hole over the Antarctic could increase radiation but not to the level of deep space.

One question I would be particularly interested in is: while cosmic, gamma etc radiation exposure is increased, is there a reduction in near-infrared radiation uptake during spaceflight? That could negatively affect mitochondria. Alternatively if near-IR exposure is also increased, is a specific wavelength interfering with the mitochondrial ETC via cytochrome C oxidase?

---
Photobiomodulation of Cytochrome c Oxidase by Chronic Transcranial Laser in Young and Aged Brains (2022, Frontiers in Neuroscience)
Red light photobiomodulation rescues murine brain mitochondrial respiration after acute hypobaric hypoxia (2022, Journal of Photochemistry and Photobiology B: Biology)
Inhibitory modulation of cytochrome c oxidase activity with specific near-infrared light wavelengths attenuates brain ischemia/reperfusion injury (2018, Nature Scientific Reports)

 

[SNT Gatchaman]

Mehta, S. K., Pierson, D. L., Cooley, H., Dubow, R. & Lugg, D. Epstein-Barr virus reactivation associated with diminished cell-mediated immunity in antarctic expeditioners. J. Med. Virol. 61, 235–240 (2000).
That paper could be interesting to look at.

Summary quotes —

These stations are among the most isolated on Earth and expose expeditioners to various types and levels of stress. Living on one of these stations is similar in many ways to living in space, and recently the Antarctic has been identified as a valuable ground-based analog to simulate some aspects of space flight

The CMI [Cell Mediated Immunity] response has been studied extensively at the Antarctic stations and been found to decrease during the winter-over isolation period. This study was undertaken to assess concurrently the CMI and the reactivation and shedding of EBV during the 8-month total physical isolation of an Antarctic winter-over expedition.

Sixteen subjects (14 males and 2 females) aged 26–56 years participated in this study at 2 Antarctic stations. [...] Both stations are inside the Antarctic Circle. All expeditioners selected for the winter isolation undergo a rigorous medical examination to ensure a healthy population for the 9 to 10 months of total physical isolation during the Antarctic winter.

Saliva samples were collected upon arising between 1 and 3 times a week before, during, and after the isolation. A total of 642 saliva samples were collected [...]. Samples were stored at −70°C until the completion of the winter-over period, when they were [...] flown to the Johnson Space Center in Houston for analysis.

Delayed-type hypersensitivity (DTH) skin testing was used as an indication of cell-mediated immunity (CMI) [...] The antigens in this test were tetanus, diphtheria, Streptococcus, tuberculin, Candida albicans, Trichophyton, and Proteus. Reactions were recorded after 48 hr as the area of induration measured in millimeters with calipers; reactions were considered positive if the diameter of induration was ≥2 mm.

 

[SNT Gatchaman]

Cont'd —

All 16 subjects shed EBV DNA during the expedition. EBV DNA was detected in 17% (111/642) of the samples collected from subjects before, during, and after the winter isolation period. As expected, the shedding frequency varied considerably among individuals. The shedding frequencies observed at the 2 stations, however, were not significantly different (P 4 0.168). Salivary shedding frequencies varied from 2 to 39% among the expeditioners. Shedding patterns of 2 subjects with the highest shedding frequencies (39% and 38%) are shown in Figure 1.

Fig 1. (The DTH responses are on the right axis and represented by the curved lines interpolating normal, hypoergic and anergic)

This is the first report of increased salivary EBV shedding with diminished CMI response in Antarctic expeditioners. [...] Our observation of diminished CMI responses in over 50% of the subjects during winter isolation agrees with previous findings.

[...] DTH responses observed during a 56-day expedition in Antarctica returned to normal values after the subjects returned to Australia. [...]
similar DTH reductions in astronauts during short space flights

EBV DNA was found in saliva of astronauts participating in four 9- to 14-day flights aboard the space shuttle. DTH was not measured on these missions. EBV DNA shedding, however, was monitored during 60- and 90-day closed-chamber studies and was found to occur more frequently during the in-chamber phase than before or after isolation. CMI status was measured (using DTH reaction) during the 90-day chamber study and was found to be diminished similar to those reported in the Antarctic studies and during space flight.

In the current study, the observed diminished DTH response and increased EBV DNA shedding in saliva may be the result of stress during the winter isolation. It is interesting that no clinical symptoms were attributable to the observed decreased cellular immunity and increased EBV DNA shedding during the winter-over isolation. Perhaps increased EBV shedding may serve as an early, asymptomatic indicator of decreased cellular immunity.

Meehan et al. [1992] described the effects of psychoneuroendocrine factors during space flight. Many of these effects are mediated through the hypothalamus-pituitary-adrenal axis. Future studies integrating stress evaluations and measurements of stress hormones, immune functions, and latent virus reactivation are scheduled for an upcoming Antarctic expedition.

 

[Hutan]

I guess it could be emotional stress, but also perhaps lack of sunlight on the skin, and/or exposure to temperature extremes and disruption of usual sleep/wake routines? For the Antarctic over-winterers, I think physical stress and lack of sun are more likely causes of increased shedding than emotional stress.