Reply to “Risk of severe COVID-19 infection in International Space Station astronauts despite routine pre-mission measures”

To the Editor:

We thank Mortazavi et al¹ for their interest in our article.² In their commentary, the salient point raised is that risk for SARS-CoV-2 reactivation during spaceflight is a concern that was unaddressed in our original article.

The point of the article was to share how the National Aeronautics and Space Administration (NASA) adjusted protocols to reduce risk for returning astronauts during the initial stages of the pandemic. Returning astronauts manifest a defined pattern of immune dysregulation, and the early-pandemic crews returned through a unique set of vehicle transfers (International Space Station [ISS] to Houston, via Kazakhstan) making clinical care a unique challenge. The article details all of the protocols put in place to protect crewmembers who are perceived to be more vulnerable to a serious prognosis if infected immediately after landing. The protocols span various operational impacts, including limiting contacts, adjusting postflight schedules, and for the first returning crew, monitoring of immune status before release from quarantine.

The commentary authors speculate that SARS-CoV-2 infection is challenging to detect (“hidden, inactive, or dormant”), and therefore an astronaut may launch to space with an asymptomatic but active infection that would worsen owing to immune compromise during flight. In fact, our article did not address protections for launching crewmembers; it was specific to returning crewmembers. The launch and landing clinical care scenarios are very different, and even more so because most American astronauts will now launch from US soil on a SpaceX Dragon capsule. Nevertheless, the commentary supposition is interesting and certainly worth considering. NASA protocols, including some specific for SARS-CoV-2, are designed to protect crews before launch. They should mitigate to the maximum extent possible the risk for an astronaut launching with an asymptomatic case. These protocols include (1) a health stabilization program, essentially a preflight quarantine in place since Apollo and extremely effective at reducing crew infectious disease; (2) enhanced isolation protocols specific for SARS-CoV-2; (3) vaccination for SARS-CoV-2 and documented induction of protective antibody, and (4) frequent polymerase chain reaction tests for the crew and all crew contacts. During the pandemic, crews launching on Soyuz before vaccine was available were given a polymerase chain reaction test before launch, and no related clinical incidence was observed during the mission. This package of protections makes it extremely unlikely that future crews will launch with active infection, asymptomatic or otherwise.

The commentary authors are correct that crews manifest immune compromise during flight, and the pattern of dysregulation was found to be similar to that observed in zoster patients.³ Recent evidence suggests that multisystem biomedical countermeasures already deployed to ISS benefit immunity.⁴ However, because some of these ISS countermeasures do not readily translate to deep space missions, NASA and its international partners have embarked on the development of a countermeasure protocol that will benefit immunity and be compatible with deep space missions.⁵ This international team of translational scientists created a protocol consisting of specific nutritional supplements, monitoring, stress-relieving techniques, specific duration and loads of aerobic and resistive exercise, and medications.⁶ Immunity during deep space missions must be maintained regardless of SARS-CoV-2. Solar particle events, latent herpesvirus reactivation, mutagenic transformation, and increased microbial virulence within the vehicle microbiome will all require full crew immunocompetence. Planned research will validate countermeasures package to be effective at protecting deep space crewmembers during their transit phases of flight.