Exercise as a countermeasure for latent viral reactivation during long duration space flight.

Latent viral reactivation is a commonly reported manifestation of immune system dysregulation during spaceflight. As physical fitness and exercise training have been shown to benefit multiple arms of the immune system, we hypothesized that higher levels of preflight physical fitness and/or maintaining fitness during a mission would protect astronauts from latent viral reactivation. Standardized tests of maximal strength, muscular endurance, flexibility, and cardiorespiratory fitness (CRF) were performed in 22 international space station (ISS) crewmembers before and after a ~6-month mission. Reactivation of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and varicella zoster virus (VZV) was determined in crewmembers and ground-based controls before, during, and after spaceflight. Crewmembers with higher CRF before spaceflight had a 29% reduced risk of latent viral reactivation compared to crew with lower CRF. Higher preflight upper body muscular endurance was associated with a 39% reduced risk of viral reactivation, a longer time to viral reactivation, and lower peak viral DNA concentrations, particularly for EBV and VZV. Latent viral reactivation rates were highest in crew with lower preflight CRF and higher levels of CRF deconditioning on return to Earth. We conclude that physical fitness may protect astronauts from latent viral reactivation during long duration spaceflight missions.

Inhibition of Human Cytomegalovirus Entry into Host Cells Through a Pleiotropic Small Molecule.

Human cytomegalovirus (HCMV) infections are wide-spread among the general population with manifestations ranging from asymptomatic to severe developmental disabilities in newborns and life-threatening illnesses in individuals with a compromised immune system. Nearly all current drugs suffer from one or more limitations, which emphasizes the critical need to develop new approaches and new molecules. We reasoned that a 'poly-pharmacy' approach relying on simultaneous binding to multiple receptors involved in HCMV entry into host cells could pave the way to a more effective therapeutic outcome. This work presents the study of a synthetic, small molecule displaying pleiotropicity of interactions as a competitive antagonist of viral or cell surface receptors including heparan sulfate proteoglycans and heparan sulfate-binding proteins, which play important roles in HCMV entry and spread. Sulfated pentagalloylglucoside (SPGG), a functional mimetic of heparan sulfate, inhibits HCMV entry into human foreskin fibroblasts and neuroepithelioma cells with high potency. At the same time, SPGG exhibits no toxicity at levels as high as 50-fold more than its inhibition potency. Interestingly, cell-ELISA assays showed downregulation in HCMV immediate-early gene 1 and 2 (IE 1&2) expression in presence of SPGG further supporting inhibition of viral entry. Finally, HCMV foci were observed to decrease significantly in the presence of SPGG suggesting impact on viral spread too. Overall, this work offers the first evidence that pleiotropicity, such as demonstrated by SPGG, may offer a new poly-therapeutic approach toward effective inhibition of HCMV.

Immune sensitization during 1 year in the Antarctic high-altitude Concordia Environment.

BACKGROUND: Antarctica is a challenging environment for humans. It serves as a spaceflight ground analog, reflecting some conditions of long-duration exploration class space missions. The French-Italian Concordia station in interior Antarctica is a high-fidelity analog, located 1000 km from the coast, at an altitude of 3232 m. The aim of this field study was to characterize the extent, dynamics, and key mechanisms of the immune adaptation in humans overwintering at Concordia for 1 year. METHODS: This study assessed immune functions in fourteen crewmembers. Quantitative and phenotypic analyses from human blood were performed using onsite flow cytometry together with specific tests on receptor-dependent and receptor-independent functional innate and adaptive immune responses. Transcriptome analyses and quantitative identification of key response genes were assessed. RESULTS: Dynamic immune activation and a two-step escalation/activation pattern were observed. The early phase was characterized by moderately sensitized global immune responses, while after 3-4 months, immune responses were highly upregulated. The cytokine responses to an ex vivo stimulation were markedly raised above baseline levels. These functional observations were reflected at the gene transcriptional level in particular through the modulation of hypoxia-driven pathways. CONCLUSIONS: This study revealed unique insights into the extent, dynamics, and genetics of immune dysfunctions in humans exposed for 1 year to the Antarctic environment at the Concordia station. The scale of immune function was imbalanced toward a sensitizing of inflammatory pathways.

Reactivation of Latent Epstein-Barr Virus: A Comparison after Exposure to Gamma, Proton, Carbon, and Iron Radiation.

Among the many stressors astronauts are exposed to during spaceflight, cosmic radiation may lead to various serious health effects. Specifically, space radiation may contribute to decreased immunity, which has been documented in astronauts during short- and long-duration missions, as evidenced by several changes in cellular immunity and plasma cytokine levels. Reactivation of latent herpes viruses, either directly from radiation of latently infected cells and/or from perturbation of the immune system, may result in disease in astronauts. Epstein‒Barr virus (EBV) is one of the eight human herpes viruses known to infect more than 90% of human adults and persists for the life of the host without normally causing adverse effects. Reactivation of several latent viruses in astronauts is well documented, although the mechanism of reactivation is not well understood. We studied the effect of four different types of radiation, (1) 137Cs gamma rays, (2) 150-MeV protons, (3) 600 MeV/n carbon ions, and (4) 600 MeV/n iron ions on the activation of lytic gene transcription and of reactivation of EBV in a latently infected cell line (Akata) at doses of 0.1, 0.5, 1.0, and 2.0 Gy. The data showed that for all doses used in this study, lytic gene transcription was induced and median viral loads were significantly higher for all types of radiation than in corresponding control samples, with the increases detected as early as four days post-exposure and generally tapering off at later time points. The viability and size of EBV-infected Akata cells were highly variable and exhibited approximately the same trend in time for all radiation types at 0.1, 0.5, 1.0, and 2.0 Gy. This work shows that reactivation of viruses can occur due to the effect of different types of radiation on latently infected cells in the absence of changes or cytokines produced in the immune system. In general, gamma rays are more effective than protons, carbon ions, and iron ions in inducing latent virus reactivation, though these high-energy particles did induce more sustained and later reactivation of EBV lytic gene transcription. These findings also challenge the common relative biological effectiveness concept that is often used in radiobiology for other end points.

Localization of VZV in saliva of zoster patients.

Varicella zoster virus (VZV) in saliva from six herpes zoster patients and one chickenpox patient was found to be exclusively associated with epithelial cells by confocal microscopy. VZV localization with antibody specific to the VZV glycoprotein E was detected primarily on the membrane but was also inside the cell. Epithelial cells with VZV were still present in saliva in one out of two tested zoster patients after 10 months of recovery. Saliva from healthy controls (non-shingles patients, n = 5) did not show any sign of VZV by polymerase chain reaction or by confocal microscopy. No VZV was found in the liquid fraction of saliva. Further work is required to understand the movement of VZV in the saliva cells of infected patients.

Fitness level impacts salivary antimicrobial protein responses to a single bout of cycling exercise.

PURPOSE: Salivary antimicrobial proteins (sAMPs) protect the upper respiratory tract (URTI) from invading microorganisms and have been linked with URTI infection risk in athletes. While high training volume is associated with increased URTI risk, it is not known if fitness affects the sAMP response to acute exercise. This study compared the sAMP responses to various exercising workloads of highly fit experienced cyclists with those who were less fit. METHODS: Seventeen experienced cyclists (nine highly fit; eight less fit) completed three 30-min exercise trials at workloads corresponding to -5, +5 and +15 % of the individual blood lactate threshold. Saliva samples were collected pre- and post-exercise to determine the concentration and secretion of α-amylase, human neutrophil proteins 1-3 (HNP1-3) lactoferrin, LL-37, lysozyme, and salivary SIgA. RESULTS: The concentration and/or secretion of all sAMPs increased post-exercise, but only α-amylase was sensitive to exercise workload. Highly fit cyclists had lower baseline concentrations of α-amylase, HNP1-3, and lactoferrin, although secretion rates did not differ between the groups. Highly fit cyclists did, however, exhibit greater post-exercise increases in the concentration and/or secretion of a majority of measured sAMPs (percentage difference between highly fit and less fit in parentheses), including α-amylase concentration (+107 %) and secretion (+148 %), HNP1-3 concentration (+97 %) and secretion (+158 %), salivary SIgA concentration (+181 %), lactoferrin secretion (+209 %) and LL-37 secretion (+138 %). CONCLUSION: We show for the first time that fitness level is a major determinant of exercise-induced changes in sAMPs. This might be due to training-induced alterations in parasympathetic and sympathetic nervous system activation.

MALPOSITIONED LMA CONFUSED AS FOREIGN BODY IN NASAL CAVITY.

We present a case of confusing white foreign body in the nasal cavity detected during Endoscopic Sinus Surgery (ESS) in a 35-yr-old male which turned out to be a malposition of classic laryngeal mask airway (LMA). Although malposition of LMA is a known entity to the anesthesiologist, if ventilation is adequate, back folded LMA in nasal cavity might not be recognized by the surgeon and lead to catastrophic consequences during endoscopic sinus surgery. In principle, misfolding and malpositioning can be reduced by pre usage testing, using appropriate sizes, minimizing cuff volume, and early identification and correction of malposition.

Search for varicella zoster virus DNA in saliva of healthy individuals aged 20-59 years.

All neurological and ocular complications of varicella zoster virus (VZV) reactivation can occur without rash. Virological verification requires detection of VZV DNA or anti-VZV IgG antibody in cerebrospinal fluid (CSF), or anti-VZV IgM antibody in serum or CSF. If VZV were readily detected in other tissue in patients with neurological disease without rash and found to correlate with tests listed above, more invasive tests such as lumbar puncture might be obviated. Saliva is a potential source of VZV DNA. To study the potential diagnostic value of detecting VZV DNA in saliva from patients with neurological disease, saliva of healthy adults was searched for VZV DNA. A single saliva sample obtained by passive drool was centrifuged at 16,000g for 20 min. DNA was extracted from the supernatant and cell pellet and examined in triplicate for VZV DNA by real time PCR. A single random saliva sample from 80 healthy men and women aged 20-59 years revealed no VZV DNA (Table ), but was uniformly positive for cell (GAPdH) DNA. Because VZV DNA was not found in a random saliva sample from 80 individuals 20-59-year-old, a VZV-positive sample during neurologic disease may have potential significance. Further studies will determine whether VZV DNA in saliva correlates with VZV DNA or anti-VZV antibody in CSF in patients with neurological disease.

Terrestrial stress analogs for spaceflight associated immune system dysregulation.

Recent data indicates that dysregulation of the immune system occurs and persists during spaceflight. Impairment of immunity, especially in conjunction with elevated radiation exposure and limited clinical care, may increase certain health risks during exploration-class deep space missions (i.e. to an asteroid or Mars). Research must thoroughly characterize immune dysregulation in astronauts to enable development of a monitoring strategy and validate any necessary countermeasures. Although the International Space Station affords an excellent platform for on-orbit research, access may be constrained by technical, logistical vehicle or funding limitations. Therefore, terrestrial spaceflight analogs will continue to serve as lower cost, easier access platforms to enable basic human physiology studies. Analog work can triage potential in-flight experiments and thus result in more focused on-orbit studies, enhancing overall research efficiency. Terrestrial space analogs generally replicate some of the physiological or psychological stress responses associated with spaceflight. These include the use of human test subjects in a laboratory setting (i.e. exercise, bed rest, confinement, circadian misalignment) and human remote deployment analogs (Antarctica winterover, undersea, etc.) that incorporate confinement, isolation, extreme environment, physiological mission stress and disrupted circadian rhythms. While bed rest has been used to examine the effects of physical deconditioning, radiation and microgravity may only be simulated in animal or microgravity cell culture (clinorotation) analogs. This article will characterize the array of terrestrial analogs for spaceflight immune dysregulation, the current evidence base for each, and interpret the analog catalog in the context of acute and chronic stress.

Palmer Station, Antarctica: A ground-based spaceflight analog suitable for validation of biomedical countermeasures for deep space missions.

Astronauts are known to exhibit a variety of immunological alterations during spaceflight including changes in leukocyte distribution and plasma cytokine concentrations, a reduction in T-cell function, and subclinical reactivation of latent herpesviruses. These alterations are most likely due to mission-associated stressors including circadian misalignment, microgravity, isolation, altered nutrition, and increased exposure to cosmic radiation. Some of these stressors may also occur in terrestrial situations. This study sought to determine if crewmembers performing winterover deployment at Palmer Station, Antarctica, displayed similar immune alterations. The larger goal was to validate a ground analog suitable for the evaluation of countermeasures designed to protect astronauts during future deep space missions. For this pilot study, plasma, saliva, hair, and health surveys were collected from Palmer Station, Antarctica, winterover participants at baseline, and at five winterover timepoints. Twenty-six subjects consented to participate over the course of two seasons. Initial sample processing was performed at Palmer, and eventually stabilized samples were returned to the Johnson Space Center for analysis. A white blood cell differential was performed (real time) using a fingerstick blood sample to determine alterations in basic leukocyte subsets throughout the winterover. Plasma and saliva samples were analyzed for 30 and 13 cytokines, respectively. Saliva was analyzed for cortisol concentration and three latent herpesviruses (DNA by qPCR), EBV, HSV1, and VZV. Voluntary surveys related to general health and adverse clinical events were distributed to participants. It is noteworthy that due to logistical constraints caused by COVID-19, the baseline samples for each season were collected in Punta Arenas, Chile, after long international travel and during isolation. Therefore, the Palmer pre-mission samples may not reflect a true normal 'baseline'. Minimal alterations were observed in leukocyte distribution during winterover. The mean percentage of monocyte concentration elevated at one timepoint. Plasma G-CSF, IL1RA, MCP-1, MIP-1ß, TNFα, and VEGF were decreased during at least one winterover timepoint, whereas RANTES was significantly increased. No statistically significant changes were observed in mean saliva cytokine concentrations. Salivary cortisol was substantially elevated throughout the entire winterover compared to baseline. Compared to shedding levels observed in healthy controls (23%), the percentage of participants who shed EBV was higher throughout all winterover timepoints (52-60%). Five subjects shed HSV1 during at least one timepoint throughout the season compared to no subjects shedding during pre-deployment. Finally, VZV reactivation, common in astronauts but exceptionally rare in ground-based stress analogs, was observed in one subject during pre-deployment and a different subject at WO2 and WO3. These pilot data, somewhat influenced by the COVID-19 pandemic, do suggest that participants at Palmer Station undergo immunological alterations similar to, but likely in reduced magnitude, as those observed in astronauts. We suggest that winterover at Palmer Station may be a suitable test analog for spaceflight biomedical countermeasures designed to mitigate clinical risks for deep space missions.

Immune system dysregulation preceding a case of laboratory-confirmed zoster/dermatitis on board the International Space Station.

A case report detailing, for the first time, a case of laboratory-confirmed zoster in an astronaut on board the International Space Station is presented. The findings of reduced T-cell function, cytokine imbalance, and increased stress hormones which preceded the event are detailed. Relevance for deep space countermeasures is discussed.

Immune system dysregulation occurs during short duration spaceflight on board the space shuttle.

BACKGROUND: Post-flight data suggests immunity is dysregulated immediately following spaceflight, however this data may be influenced by the stress effects of high-G entry and readaptation to terrestrial gravity. It is unknown if immunity is altered during spaceflight. METHODS: Blood samples were collected from 19 US Astronauts onboard the Space Shuttle ~24 h prior to landing and returned for terrestrial analysis. Assays consisted of leukocyte distribution, T cell blastogenesis and cytokine production profiles. RESULTS: Most bulk leukocyte subsets (WBC, differential, lymphocyte subsets) were unaltered during spaceflight, but were altered following landing. CD8+ T cell subsets, including cytotoxic, central memory and senescent were altered during spaceflight. T cell early blastogenesis varied by culture mitogen. Functional responses to staphylococcal enterotoxin were reduced during and following spaceflight, whereas response to anti-CD3/28 antibodies was elevated post-flight. The level of virus specific T cells were generally unaltered, however virus specific T cell function was depressed both during and following flight. Plasma levels of IFNα, IFNγ, IL-1ß, IL-4, IL-10, IL-12, and TNFα were significantly elevated in-flight, while IL-6 was significantly elevated at R + 0. Cytokine production profiles following mitogenic stimulation were significantly altered both during, and following spaceflight. Specifically, production of IFNγ, IL-17 and IL-10 were reduced, but production of TNFα and IL-8 were elevated during spaceflight. CONCLUSIONS: This study indicates that specific parameters among leukocyte distribution, T cell function and cytokine production profiles are altered during flight. These findings distinguish in-flight dysregulation from stress-related alterations observed immediately following landing.

Time-resolved molecular measurements reveal changes in astronauts during spaceflight.

From the early days of spaceflight to current missions, astronauts continue to be exposed to multiple hazards that affect human health, including low gravity, high radiation, isolation during long-duration missions, a closed environment and distance from Earth. Their effects can lead to adverse physiological changes and necessitate countermeasure development and/or longitudinal monitoring. A time-resolved analysis of biological signals can detect and better characterize potential adverse events during spaceflight, ideally preventing them and maintaining astronauts' wellness. Here we provide a time-resolved assessment of the impact of spaceflight on multiple astronauts (n=27) by studying multiple biochemical and immune measurements before, during, and after long-duration orbital spaceflight. We reveal space-associated changes of astronauts' physiology on both the individual level and across astronauts, including associations with bone resorption and kidney function, as well as immune-system dysregulation.

Time-resolved molecular measurements reveal changes in astronauts during spaceflight.

From the early days of spaceflight to current missions, astronauts continue to be exposed to multiple hazards that affect human health, including low gravity, high radiation, isolation during long-duration missions, a closed environment and distance from Earth. Their effects can lead to adverse physiological changes and necessitate countermeasure development and/or longitudinal monitoring. A time-resolved analysis of biological signals can detect and better characterize potential adverse events during spaceflight, ideally preventing them and maintaining astronauts' wellness. Here we provide a time-resolved assessment of the impact of spaceflight on multiple astronauts (n = 27) by studying multiple biochemical and immune measurements before, during, and after long-duration orbital spaceflight. We reveal space-associated changes of astronauts' physiology on both the individual level and across astronauts, including associations with bone resorption and kidney function, as well as immune-system dysregulation.

Changes in Immune Function during Initial Military Training.

PURPOSE: Initial military training (IMT) is a transitionary period wherein immune function may be suppressed and infection risk heightened due to physical and psychological stress, communal living, and sleep deprivation. This study characterized changes in biomarkers of innate and adaptive immune function, and potential modulators of those changes, in military recruits during IMT. METHODS: Peripheral leukocyte distribution and mitogen-stimulated cytokine profiles were measured in fasted blood samples, Epstein-Barr (EBV), varicella zoster (VZV), and herpes simplex 1 (HSV1) DNA was measured in saliva by quantitative polymerase chain reaction as an indicator of latent herpesvirus reactivation, and diet quality was determined using the healthy eating index measured by food frequency questionnaire in 61 US Army recruits (97% male) at the beginning (PRE) and end (POST) of 22-wk IMT. RESULTS: Lymphocytes and terminally differentiated cluster of differentiation (CD)4+ and CD8+ T cells increased PRE to POST, whereas granulocytes, monocytes, effector memory CD4+ and CD8+ T cells, and central memory CD8+ T cells decreased ( P ≤ 0.02). Cytokine responses to anti-CD3/CD28 stimulation were higher POST compared with PRE, whereas cytokine responses to lipopolysaccharide stimulation were generally blunted ( P < 0.05). Prevalence of EBV reactivation was higher at POST ( P = 0.04), but neither VZV nor HSV1 reactivation was observed. Diet quality improvements were correlated with CD8+ cell maturation and blunted proinflammatory cytokine responses to anti-CD3/CD28 stimulation. CONCLUSIONS: Lymphocytosis, maturation of T-cell subsets, and increased T-cell reactivity were evident POST compared with PRE IMT. Although EBV reactivation was more prevalent at POST, no evidence of VZV or HSV1 reactivation, which are more common during severe stress, was observed. Findings suggest increases in the incidence of EBV reactivation were likely appropriately controlled by recruits and immune-competence was not compromised at the end of IMT.

Varicella zoster virus DNA at inoculation sites and in saliva after Zostavax immunization.

Analysis of 36 individuals over age 60 years who were immunized with Zostavax revealed varicella zoster virus (VZV) DNA in swabs of skin inoculation sites obtained immediately after immunization in 18 (50%) of 36 subjects (copy number per nanogram of total DNA, 28 to 2.1 × 10(6)) and in saliva collected over 28 days in 21 (58%) of 36 subjects (copy number, 20 to 248). Genotypic analysis of DNA extracted from 9 random saliva samples identified vaccine virus in all instances. In some immunized individuals over age 60, vaccine virus DNA is shed in saliva up to 4 weeks.

Persistence of varicella zoster virus DNA in saliva after herpes zoster.

Analysis of saliva samples from individuals aged ≥ 60 years who had a history of zoster (group 1), zoster and postherpetic neuralgia (PHN; group 2), or no history of zoster (group 3) revealed varicella zoster virus (VZV) DNA in saliva samples from 11 of 17 individuals in group 1, 10 of 15 individuals in group 2, and 2 of 17 individuals in group 3. The frequency of VZV DNA detection was significantly higher (P = .001) in saliva of subjects with a history of zoster, with or without PHN (21 [67%] of 32 subjects in groups 1 and 2), than in saliva of age-matched subjects with no zoster history (2 [12%] of 17 subjects in group 3). Thus, persistence of VZV DNA in saliva is the outcome of zoster, independent of PHN. Because VZV infection can produce neurological and ocular disease without zoster rash, future studies are needed to establish whether VZV DNA can be detected in the saliva of such patients.

Silent Reactivation of Varicella Zoster Virus in Pregnancy: Implications for Maintenance of Immunity to Varicella.

We encountered two cases of varicella occurring in newborn infants. Because the time between birth and the onset of the illness was much shorter than the varicella incubation period, the cases suggested that the infection was maternally acquired, despite the fact that neither mother experienced clinical zoster. Thus, we tested the hypothesis that VZV frequently reactivates asymptomatically in late pregnancy. The appearance of DNA-encoding VZV genes in saliva was used as an indicator of reactivation. Saliva was collected from 5 women in the first and 14 women in the third trimesters of pregnancy and analyzed at two different sites, at one using nested PCR and at the other using quantitative PCR (qPCR). No VZV DNA was detected at either site in the saliva of women during the first trimester; however, VZV DNA was detected in the majority of samples of saliva (11/12 examined by nested PCR; 7/10 examined by qPCR) during the third trimester. These observations suggest that VZV reactivation occurs commonly during the third trimester of pregnancy. It is possible that this phenomenon, which remains in most patients below the clinical threshold, provides an endogenous boost to immunity and, thus, is beneficial.

Microbial Tracking-2, a metagenomics analysis of bacteria and fungi onboard the International Space Station.

BACKGROUND: The International Space Station (ISS) is a unique and complex built environment with the ISS surface microbiome originating from crew and cargo or from life support recirculation in an almost entirely closed system. The Microbial Tracking 1 (MT-1) project was the first ISS environmental surface study to report on the metagenome profiles without using whole-genome amplification. The study surveyed the microbial communities from eight surfaces over a 14-month period. The Microbial Tracking 2 (MT-2) project aimed to continue the work of MT-1, sampling an additional four flights from the same locations, over another 14 months. METHODS: Eight surfaces across the ISS were sampled with sterile wipes and processed upon return to Earth. DNA extracted from the processed samples (and controls) were treated with propidium monoazide (PMA) to detect intact/viable cells or left untreated and to detect the total DNA population (free DNA/compromised cells/intact cells/viable cells). DNA extracted from PMA-treated and untreated samples were analyzed using shotgun metagenomics. Samples were cultured for bacteria and fungi to supplement the above results. RESULTS: Staphylococcus sp. and Malassezia sp. were the most represented bacterial and fungal species, respectively, on the ISS. Overall, the ISS surface microbiome was dominated by organisms associated with the human skin. Multi-dimensional scaling and differential abundance analysis showed significant temporal changes in the microbial population but no spatial differences. The ISS antimicrobial resistance gene profiles were however more stable over time, with no differences over the 5-year span of the MT-1 and MT-2 studies. Twenty-nine antimicrobial resistance genes were detected across all samples, with macrolide/lincosamide/streptogramin resistance being the most widespread. Metagenomic assembled genomes were reconstructed from the dataset, resulting in 82 MAGs. Functional assessment of the collective MAGs showed a propensity for amino acid utilization over carbohydrate metabolism. Co-occurrence analyses showed strong associations between bacterial and fungal genera. Culture analysis showed the microbial load to be on average 3.0 × 105 cfu/m2 CONCLUSIONS: Utilizing various metagenomics analyses and culture methods, we provided a comprehensive analysis of the ISS surface microbiome, showing microbial burden, bacterial and fungal species prevalence, changes in the microbiome, and resistome over time and space, as well as the functional capabilities and microbial interactions of this unique built microbiome. Data from this study may help to inform policies for future space missions to ensure an ISS surface microbiome that promotes astronaut health and spacecraft integrity. Video Abstract.

Dermatitis during Spaceflight Associated with HSV-1 Reactivation.

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.