SARS-CoV-2 Pandemic Impacts on NASA Ground Operations to Protect ISS Astronauts

Abstract

NASA implements required medical tests and clinical monitoring to ensure the health and safety of its astronauts. These measures include a pre-launch quarantine to mitigate the risk of infectious diseases. During space missions, most astronauts experience perturbations to their immune system that manifest as a detectable secondary immunodeficiency. On return to Earth, after the stress of re-entry and landing, astronauts would be most vulnerable to infectious disease. In April 2020, a crew returned from International Space Station to NASA Johnson Space Center in Houston, Texas, during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Post-flight quarantine protocols (both crew and contacts) were enhanced to protect this crew from SARS-CoV-2. In addition, specific additional clinical monitoring was performed to determine post-flight immunocompetence. Given that coronavirus disease 2019 (COVID-19) prognosis is more severe for the immunocompromised, a countermeasures protocol for spaceflight suggested by an international team of scientists could benefit terrestrial patients with secondary immunodeficiency. NASA implements required medical tests and clinical monitoring to ensure the health and safety of its astronauts. These measures include a pre-launch quarantine to mitigate the risk of infectious diseases. During space missions, most astronauts experience perturbations to their immune system that manifest as a detectable secondary immunodeficiency. On return to Earth, after the stress of re-entry and landing, astronauts would be most vulnerable to infectious disease. In April 2020, a crew returned from International Space Station to NASA Johnson Space Center in Houston, Texas, during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Post-flight quarantine protocols (both crew and contacts) were enhanced to protect this crew from SARS-CoV-2. In addition, specific additional clinical monitoring was performed to determine post-flight immunocompetence. Given that coronavirus disease 2019 (COVID-19) prognosis is more severe for the immunocompromised, a countermeasures protocol for spaceflight suggested by an international team of scientists could benefit terrestrial patients with secondary immunodeficiency. On Wednesday, March 18, 2020, in response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the executive leadership at NASA Johnson Space Center (JSC) decreed a mandatory telework policy, effectively imposing a self-quarantine on its workforce. Until further notice, all work would continue remotely, except for mission-essential personnel, defined as those required for the protection of life or property, or critical to the completion of a flight-related objective. It was a bold decision, considering at the time there were no confirmed cases of coronavirus disease 2019 (COVID-19) at JSC, the caseload in Houston was far less dramatic than in other American cities, and Texas Governor Greg Abbott had not issued any social restrictions officially (his shelter-in-place decree occurred on March 31, nearly 2 weeks after JSC's decision). NASA medical personnel began mapping an Agency response in February 2020, culminating in a 4-stage strategy: level 1—status quo, with recommended precautionary measures; level 2—recommended telework policy; level 3—mandatory telework policy, except for mission essential work; level 4—a complete shutdown of operations. The Agency leadership team stated that their decision to escalate the response through the various stages of the strategy would be guided by the local conditions—the number of local cases reported by symptoms, the number of confirmed cases, and area hospital capacity. However, given the rapid spread of the virus across the United States (by March 17, all 50 states reported confirmed cases of infections and COVID-19 morbidity),1Schumaker E. Timeline: How coronavirus got started. ABC News. September 22, 2020.https://abcnews.go.com/Health/timeline-coronavirus-started/story?id=69435165Date accessed: May 5, 2020Google Scholar and the CDC's warning on March 15 against holding or attending gatherings larger than 50 people,1Schumaker E. Timeline: How coronavirus got started. ABC News. September 22, 2020.https://abcnews.go.com/Health/timeline-coronavirus-started/story?id=69435165Date accessed: May 5, 2020Google Scholar JSC management decided to transition to the strict stage 3 telework policy. Clearly, the JSC leadership team acted ahead of the local curve. Still, SARS-CoV-2 was rampant. With an astronaut crew returning from the International Space Station (ISS) on April 17, 2020, the urgent task was now to augment standard operating procedures to ensure the health and safety of the astronauts from SARS-CoV-2 infection and morbidity. Physical and psychological stresses cause immune alterations, and these factors may be significant contributors to a compromised immune state associated with spaceflight. Data from studies of students during examination periods and military cadets during training, as well as studies of individuals participating in Antarctica winter-over missions, indicate significant immune effects from psychological stress.2Glaser R. Pearson G.R. Bonneau R.H. Esterling B.A. Atkinson C. Kiecolt-Glaser J.K. Stress and the memory T-cell response to the Epstein-Barr virus in healthy medical students.Health Psychol. 1993; 12: 435-442Crossref PubMed Scopus (120) Google Scholar, 3Feuerecker M. Crucian B.E. Quintens R. Buchheim J.I. Salam A.P. 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Mylabathula P.L. et al.NK cell function is impaired during long-duration spaceflight.J Appl Physiol (1985). 2019; 126: 842-853Crossref PubMed Scopus (56) Google Scholar Stress hormone levels are elevated after flight and correlate strongly with mission duration.12Stowe R.P. Sams C.F. Pierson D.L. Effects of mission duration on neuroimmune responses in astronauts.Aviat Space Environ Med. 2003; 74: 1281-1284PubMed Google Scholar,13Stowe R.P. Sams C.F. Pierson D.L. Adrenocortical and immune responses following short- and long-duration spaceflight.Aviat Space Environ Med. 2011; 82: 627-634Crossref PubMed Scopus (58) Google Scholar Altered cytokine production patterns and a potential Th2 shift have been observed during or after spaceflight.14Sonnenfeld G. Miller E.S. The role of cytokines in immune changes induced by spaceflight.J Leukoc Biol. 1993; 54: 253-258Crossref PubMed Scopus (26) Google Scholar, 15Sonnenfeld G. 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Sams C.F. et al.Latent virus reactivation in astronauts on the international space station.NPJ Microgravity. 2017; 3: 11Crossref PubMed Scopus (106) Google Scholar and correlates with dysregulated plasma cytokine levels, thus confirming a direct linkage between immune dysregulation and latent herpes virus reactivation.19Mehta S.K. Crucian B.E. Stowe R.P. Simpson R.J. Ott C.M. Sams C.F. et al.Reactivation of latent viruses is associated with increased plasma cytokines in astronauts.Cytokine. 2013; 61: 205-209Crossref PubMed Scopus (86) Google Scholar During long-duration flight, in vivo cell-mediated immunity is reduced in some subjects.20Taylor G.R. Janney R.P. In vivo testing confirms a blunting of the human cell-mediated immune mechanism during space flight.J Leukoc Biol. 1992; 51: 129-132Crossref PubMed Scopus (129) Google Scholar Although not a widespread clinical concern for astronauts, epidemiological studies of astronaut medical records have revealed incidence of some specific clinical events that could relate to altered immunity.21Crucian B. Babiak-Vazquez A. Johnston S. Pierson D.L. Ott C.M. Sams C. Incidence of clinical symptoms during long-duration orbital spaceflight.Int J Gen Med. 2016; 9: 383-391Crossref PubMed Scopus (113) Google Scholar A case study of an ISS astronaut further supports a linkage between immune dysregulation, latent virus reactivation (ie, Epstein-Barr virus [EBV], varicella-zoster virus [VZV], and herpes-simplex-1 [HSV-1]), and adverse clinical outcomes.22Crucian B. Johnston S. Mehta S. Stowe R. Uchakin P. Quiriarte H. et al.A case of persistent skin rash and rhinitis with immune system dysregulation onboard the International Space Station.J Allergy Clin Immunol Pract. 2016; 4: 759-762.e8Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Given that various physiological stressors associated with spaceflight are likely to increase during planned deep-space exploration missions, thereby increasing crew clinical risk, a discussion of immunological countermeasures for spaceflight has ensued.23Crucian B.E. Chouker A. Simpson R.J. Mehta S. Marshall G. Smith S.M. et al.Immune system dysregulation during spaceflight: potential countermeasures for deep space exploration missions.Front Immunol. 2018; 9: 1437Crossref PubMed Scopus (240) Google Scholar,24Makedonas G. Mehta S. Chouker A. Simpson R.J. Marshall G. Orange J.S. et al.Specific immunologic countermeasure protocol for deep-space exploration missions.Front Immunol. 2019; 10: 2407Crossref PubMed Scopus (28) Google Scholar Crewmembers returning from space reside in crew quarters at JSC for medical observation, with limited contacts. However, they do interact with family members, medical personnel, researchers conducting biomedical experiments, and media members on occasion. From the study of ISS and Shuttle crews post-flight, there is no evidence of an increased incidence of respiratory or other viral infections over pre-flight rates. However, the SARS-CoV-2 pandemic is without precedent with regard to risk for hospitalization and severe illness. Therefore, an abundance of caution is necessary in managing post-flight crews, to limit their exposure to those with the potential to transmit SARS-CoV-2. On recommendation from specialists in infectious disease, specialists providing care in pandemic-affected areas, and specialists in spaceflight immunology, NASA implemented enhanced precautionary measures to shield the recently returned ISS astronauts (Soyuz 61S) from SARS-CoV-2. Astronauts returning from the ISS via the Russian Soyuz land in Kazakhstan. NASA works closely with the Russian medical and search and rescue (SAR) teams, weeks ahead of landing to organize logistical support of retrieving returning astronauts and cosmonauts. NASA deploys a team on a NASA-operated Gulfstream aircraft to a staging area in the country the week before the proposed landing date to finalize and rehearse the landing operation with their Russian counterparts. The NASA landing team, also known as the Direct Return team, comprises flight surgeons, ISS Program representatives, an Astronaut Office representative, aircrew, and their backups. In preparation for the Soyuz 61S landing, special precautions were taken by the landing team to minimize risk of exposure to SARS-CoV-2. These precautions included strict home quarantine beginning 14 days before departure from Houston to Kazakhstan by all team members and backups, temperature checks and symptom screening twice daily, and optimizing sleep, diet, and daily exercise. On arrival at the Houston airport, and throughout the duration of the 5-day astronaut retrieval mission, all Direct Return team members donned personal protective equipment (PPE), per CDC-recommended protocols. The interior surfaces of, and the equipment aboard, the Gulfstream aircraft were sanitized according to a CDC-recommended method. The US crew surgeons did not know whether the Russian SAR and medical teams practiced the same precautionary measures as the US team. However, in Kazakhstan, all personnel that the US landing party encountered donned Tyvek white suits, facemasks, face shields, gloves, and practiced physical distance. The gear and luggage were sanitized with a dilute bleach solution. The vehicle drivers that accompanied the US team to the landing site wore PPE. Fifteen kilometers from the Baikonur Cosmodrome (the spaceport facility), armed Russian military personnel, donning PPE, performed body temperature checks of the US team via infrared forehead scans, and requested proof of a recent negative SARS-CoV-2 polymerase chain reaction (PCR) test, as well as diplomatic papers attesting they had been in quarantine for 14 days before arrival. Before the space crews' deorbit and return to Earth, the briefings between the Russian and US SAR teams proceeded by video conference. On the day of landing, before deploying the Russian Mi-8 helicopters, the Russian ambulances that would be used to transport the US astronauts to the NASA jet in Kyzlorda, 4 hours away, were certified to comply with measures preventive for infectious diseases. At the spacecraft-landing site, all personnel donned facemasks and gloves (Figure 1). The American flight surgeons were assured that all Russian aircrew and support personnel had performed a 14-day quarantine and tested negative for SARS CoV-2 immediately before landing. To this day, none of the US or Russian landing teams, surgeons, or returning astronauts have ever exhibited symptoms of COVID-19 or tested positive for SARS-CoV-2 infection, following the landing operation. After return to Houston, the astronaut crew, flight surgeons, and immediate family support—who performed a home quarantine, and documented temperature and symptom checks twice daily for the 14 days leading up to landing—proceeded to a strict quarantine facility onsite at JSC, with limited outside contact for a 7-day period after landing. The limited medical and research laboratory personnel that interacted with the crew had performed a strict 14-day home quarantine and donned full PPE in the presence of the crewmembers. Typical immunologic research investigations at NASA surveil crewmembers at single or multiple time points before flight, in flight, at landing, and after flight, anywhere from 30 to 90 days in order to determine immune recovery. Because of the COVID-19 threat, the flight surgeons requested specific immunological assessments at landing, as well as 3 and 7 days after landing. This strategy enabled the surgeons to define the immune competence of the astronauts more quickly, before releasing them to home quarantine. T cell frequency and function was the focus of the post-flight testing augment because the early literature describing the immunology of patients with COVID-19 suggests T cells play a vital role in the defense against SARS-CoV-2. Severe COVID-19 prognosis correlates highly with reductions (at initial presentation) of absolute T cell (CD4 and CD8) counts,25Chen G. Wu D. Guo W. Cao Y. Huang D. Wang H. et al.Clinical and immunological features of severe and moderate coronavirus disease 2019.J Clin Invest. 2020; 130: 2620-2629Crossref PubMed Scopus (3388) Google Scholar and a frequency of T cells is a of on the study of patients with R.H. Wang W. Cao M. et of for patients with COVID-19 by a 2020; PubMed Scopus Google Scholar the the absolute of T the the virus Y. D. et and of viral in 2019 coronavirus disease J 2020; PubMed Scopus Google Scholar memory and T cell of patients with COVID-19 a of M. Y. Wang G. G. S. D. et of in COVID-19 Immunol. 2020; PubMed Scopus Google Scholar of T cells to correlate with to COVID-19 disease T cells are an for and a for immune Immune of NASA astronauts has been defined by the of absolute the frequency of and T cell function in response to of cellular and B. Stowe R.P. Mehta S. Quiriarte H. Pierson D. Sams C. Alterations in adaptive immunity persist during long-duration spaceflight.NPJ Microgravity. 2015; 1: 15013Crossref PubMed Scopus (168) Google Scholar,18Mehta S.K. Laudenslager M.L. Stowe R.P. Crucian B.E. Feiveson A.H. Sams C.F. et al.Latent virus reactivation in astronauts on the international space station.NPJ Microgravity. 2017; 3: 11Crossref PubMed Scopus (106) Google Scholar Given the in the immune correlates of spaceflight-induced immune and COVID-19 used to these from the of the returning 61S astronauts. In addition, reactivation and shedding of and in an for immune was by The was performed on returning US crewmembers. all reported to were with The returning crewmembers demonstrated a of immune dysregulation associated with B. Stowe R.P. Mehta S. Quiriarte H. Pierson D. Sams C. Alterations in adaptive immunity persist during long-duration spaceflight.NPJ Microgravity. 2015; 1: 15013Crossref PubMed Scopus (168) Google Scholar to by 3 to 7 days after landing. studies have revealed that for ISS persist for up to 30 days after B. Stowe R.P. Mehta S. Quiriarte H. Pierson D. Sams C. Alterations in adaptive immunity persist during long-duration spaceflight.NPJ Microgravity. 2015; 1: 15013Crossref PubMed Scopus (168) Google Scholar A recent study that some and biomedical countermeasures a positive effect on immunity in B.E. G. Sams C.F. Pierson D.L. Simpson R. Stowe R.P. et in immune system dysregulation and latent reactivation onboard the International Space for deep space and terrestrial 2020; PubMed Scopus Google Scholar the pandemic this immunological protocol could be for before and after Because deep-space exploration for an of with increased of is to a incidence of To this NASA a of potential countermeasures to the immune associated with B.E. Chouker A. Simpson R.J. Mehta S. Marshall G. Smith S.M. et al.Immune system dysregulation during spaceflight: potential countermeasures for deep space exploration missions.Front Immunol. 2018; 9: 1437Crossref PubMed Scopus (240) Google Scholar NASA a specific and immune countermeasure for astronauts on deep-space G. Mehta S. Chouker A. Simpson R.J. Marshall G. Orange J.S. et al.Specific immunologic countermeasure protocol for deep-space exploration missions.Front Immunol. 2019; 10: 2407Crossref PubMed Scopus (28) Google Scholar This protocol of various a a specific protocol that as was ISS and the of daily via a guided and to augment the medical for deep-space include and to immunity include and SARS-CoV-2 infection frequency and COVID-19 and prognosis are more severe for patients with an of immune that the protocol for astronauts has a terrestrial augment standard of patients with secondary those with A to the risk of infectious disease for astronauts has been the and the of the NASA Program The SARS-CoV-2 pandemic an medical The precautionary procedures implemented for this Soyuz landing to protect astronaut health be and and protocols may be enhanced for space and It is essential that the ISS be from SARS-CoV-2. 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