i n h u m a n l u n g . I  F  N  b  e  t  a  -d  e  p  e  n  d  e  n  t  u  p  r  e  g  u  l  a  t  i  o  n  o  f  C  D  7  3  i  n  h  u  m  a  n   l  u  n  g  t  i  s  s  u  e  .  A  d  d  i  t  i  o  n  a  l  l  y  ,  w  e  f  o  u  n  d  t  h  a  t  u  s  e  o  f  g  l  u  c  o  c  o  r  t  i  c  o  i  d  s  w  i  t  h  I  F  N  b  e  t  a  -1  a  w  a  s  i  n  d  e  p  e  n  d  e  n  t  l  y   a  s  s  o  c  i  a  t  e  d  w  i  t  h  i  n  c  r  e  a  s  e  d  m  o  r  t  a  l  i  t  y  (  O  R  5  .  4  ,  9  5  %  C  I  2  .  1  -1  3  .  9  ,  P  <  0  .  0  0  1  )  i  n  t  h  e  I  N  T  E  R  E  S  T  -t  r  i  a  l  .   C  o  n  c  l  u  s  i  o  n  s  :   G  l  u  c  o  c  o  r  t  i  c  o  i  d  s  i  n  h  i  b  i  t  t  y  p  e  I  I  F  N  b  e  t  a  s  i  g  n  a  l  i  n  g  a  n  d  t  h  e  u  p  r  e  g  u  l  a  t  i  o  n  o  f  C  D  7  3  i  n   h  u  m  a  n  l  u  n  g  .  T  h  i  s  p  r  o  v  i  d  e  s  t  h  e  m  e  c  h  a  n  i  s  t  i  c  b  a  s  i  s  f  o  r  t  h  e  h  a  r  m  f  u  l  a  s  s  o  c  i  a  t  i  o  n  o  f  g  l  u  c  o  c  o  r  t  i  c  o  i  d  s  i  n   I  F  N  b  e  t  a  t  r  e  a  t  e  d  p  a  t  i  e  n  t  s  i  n  t  h  e  I  N  T  E  R  E  S  T  -t  r  i  a  l  .  M  o  s  t  i  m  p  o  r  t  a  n  t  l  y  ,  i  t  s  t  r  o  n  g  l  y  s  p  e  a  k  s  a  g  a  i  n  s  t  t  h  e   u  s  e  o  f  g  l  u  c  o  c  o  r  t  i  c  o  i  d  s  i  n  v  i  r  a  l  -i  n  d  u  c  e  d  A  R  D  S  s  u  c  h  a  s  i  n  t  h  e  c  u  r  r  e  n  t  l  y  e  x  p  a  n  d  i  n  g  c  o  r  o  n  a  v  i  r  u  s   o  u  t  b  r  e  a  k  .  (  2  4  6  w  o  r  d  s  )   K  e  y  w  o  r  d  s  :   C  D  7  3  ,  e  n  d  o  t  h  e  l  i  u  m  ,  A  R  D  S  ,  i  n  t  e  r  f  e  r  o  n  ,  g  l  u  c  o  c  o  r  t  i  c  o  i  d  s All rights reserved. No reuse allowed without permission.
author/funder, who has granted medRxiv a license to display the preprint in perpetuity. I  n  t  r  o  d  u  c  t  i  o  n   A  c  u  t  e  r  e  s  p  i  r  a  t  o  r  y  d  i  s  t  r  e  s  s  s  y  n  d  r  o  m  e  (  A  R  D  S  )  i  s  a  c  o  n  d  i  t  i  o  n  c  h  a  r  a  c  t  e  r  i  z  e  d  b  y  p  u  l  m  o  n  a  r  y   i  n  f  l  a  m  m  a  t  i  o  n  ,  d  i  f  f  u  s  e  p  u  l  m  o  n  a  r  y  e  d  e  m  a  a  n  d  r  e  f  r  a  c  t  o  r  y  h  y  p  o  x  e  m  i  a  t  h  a  t  m  a  y  c  o  m  p  l  i  c  a  t e  e  n  d  o  t  h  e  l  i  a  l  -a  l  v  e  o  l  a  r  b  a  r  r  i  e  r  w  i  t  h  i  n  c  r  e  a  s  e  d  p  u  l  m  o  n  a  r  y  v  a  s  c  u  l  a  r  l  e  a  k  a  g  e  [  1  ,  3 ] . E  n  d  o  g  e  n  o  u  s  p  r  o  d  u  c  t  i  o  n  o  f  t  y  p  e  I  I  F  N  s  (  I  F  N  b  e  t  a  a  n  d  a  l  p  h  a  )  i  s  o  f  o  u  t  m  o  s  t  i  m  p  o  r  t  a  n  c  e  t  o   f  i  g  h  t  a  g  a  i  n  s  t  v  i  r  a  l  a  n  d  b  a  c  t  e  r  i  a  l  i  n  f  e  c  t  i  o  n  s  [  4  ]  ,  s  i  n  c  e  i  t  u  p  r  e  g  u  l  a  t  e  s  c  l  u  s  t  e  r  o  f  d  i  f  f  e  r  e  n  t  i  a  t  i  o  n  7  3   (  C  D  7  3  )  e  x  p  r  e  s  s  e  d  o  n  e  n  d  o  t  h  e  l  i  u  m  c  e  l  l  s  .  C  D  7  3  i  s  a  n  e  n  z  y  m  e  c  o  n  t  r  o  l  l  i  n  g  e  n  d  o  t  h  e  l  i  a  l  b  a  r  r  i  e  r  f  u  n  c  t  i  o  n   a  n  d  l  e  u  c  o  c  y  t  e  r  e  c  r  u  i  t  m  e  n  t  t  o  s  i  t  e  s  o  f  i  n  f  l  a  m  m  a  t  i  o  n  v  i  a  t  h  e  p  r  o  d  u  c  t  i  o  n  o  f  a  d  e  n  o  s  i  n  e  [  5  -7  ]  ,  a  h  i  g  h  l  y   a  n  t  i  -i  n  f  l  a  m  m  a  t  o  r  y  s  u  b  s  t  a  n  c  e  h  a  v  i  n  g  c  a  r  d  i  o  p  r  o  t  e  c  t  i  v  e  ,  n  e  u  r  o  p  r  o  t  e  c  t  i  v  e  ,  v  a  s  o  d  i  l  a  t  o  r  y  a  n  d   a  n  g  i  o  g  e  n  i  c  p  r  o  p  e  r  t  i  e  s  [  8  ]  .  A  p  h  a  s  e  I  I  t  r  i  a  l  s  h  o  w  e  d  t  h  a  t  u  p  r  e  g  u  l  a  t  i  o  n  o  f  C  D  7  3  v  i  a  i  n  t  r  a  v  e  n  o  u  s   a  d  m  i  n  i  s  t  r  a  t  i  o  n  o  f  r  e  c  o  m  b  i  n  a  n  t  h  u  m  a  n  i  n  t  e  r  f  e  r  o  n  i  s  a  s  s  o  c  i  a  t  e  d  w  i  t  h  a  r  e  d  u  c  t  i  o  n  i  n  2 c  o  n  t  r  o  l  l  e  d  p  h  a  s  e  I  I  I  t  r  i  a  l  (  I  N  T  E  R  E  S  T  )  s  h  o  w  e  d  t  h  a  t  i  n  t  r  a  v  e  n  o  u  s   r  e  c  o  m  b  i  n  a  n  t  h  u  m  a  n  i  n  t  e  r  f  e  r  o  n  b  e  t  a  -1  a   d  i  d  n  o  t  i   m  p  r  o  v  e  o  u  t  c  o  m  e  i  n  p  a  t  i  e  n  t  s  w  i  t  h  A  R  D  S  [  1  0  ]  .   H  o  w  e  v  e  r  ,  t  h  e  s  t  u  d  y  s  h  o  w  e  d  t  h  a  t  u  s  e  o  f  c  o  r  t  i  c  o  s  t  e  r  o  i  d  s  a  t  b  a  s  e  l  i  n  e  w  a  s  h  i  g  h  e  r  t  h  a  n  5  0  %  a  n  d  p  o  s t -All rights reserved. No reuse allowed without permission.
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The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.01.20049700 doi: medRxiv preprint I  g  a  s  a  n  e  g  a  t  i  v  e  c  o  n  t  r  o  l  .  T  h  e  s  e  c  o  n  d  s  t  a  g  e  a  n  t  i  b  o  d  y  w  a  s  F  I  T  C a n t i - 
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The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.01.20049700 doi: medRxiv preprint  s  h  o  c  k  3  3  %  ,  a  n  t  i  -i  n  f  l  a  m  m  a  t  o  r  y  1  7  %  ,  A  R  D  S  1  4  %  a  n  d  o  t  h  e  r  3  6  %  (  f  i  b  r  o  s  i  s  ,  i  m  m  u  n  o  s  u  p  p  r  e  s  s  i  o  n  p  o  s All rights reserved. No reuse allowed without permission.
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The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.01.20049700 doi: medRxiv preprint  T  o  f  u  r  t  h  e  r  c  o  n  f  i  r  m  t  h  e  s  e  f  i  n  d  i  n  g  s  ,  w  e  i  s  o  l  a  t  e  d  t  h  e  n  u  c  l  e  a  r  a  n  d  c  y  t  o  p  l  a  s  m  i  c  c  o  m  p  a  r  t  m  e  n  t  s  o  f author/funder, who has granted medRxiv a license to display the preprint in perpetuity. author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.01.20049700 doi: medRxiv preprint  A  s  S  T  A  T  1  -S  T  A  T  2  -I  R  F  9  c  o  m  p  l  e  x  a  l  s  o  d  r  i  v  e  s  t  h  e  e  x  p  r  e  s  s  i  o  n  o  f  H  I  F  -1  a  [  3  2  ]  ,  i  t  c  a  n  b  e   e  n  v  i  s  i  o  n  e  d  t  h  a  t  a  l  s  o  t  h  e  e  x  p  r  e  s  s  i  o  n  o  f  H  I  F  -1  a  i  s  d  e  c  r  e  a  s  e  d  d  u  e  t  o  g  l  u  c  o  c  o  r  t  i  c  o  i  d  u  s  e  .  I  n  a  d  d  i  t  i  o  n  ,   H  I  F  -1  a  m  e  d  i  a  t  e  d  t  r  a  n  s  a  c  t  i  v  a  t  i  o  n  o  f  g  e  n  e  s  m  a  y  a  l  s  o  b  e  i  m  p  a  c  t  e  d  a  s  g  l  u  c  o  c  o  r  t author/funder, who has granted medRxiv a license to display the preprint in perpetuity. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.01.20049700 doi: medRxiv preprint  T  a  b  l  e  1  .   B  a  s  e  l  i  n  e  d  e  m  o  g  r  a  p  h  i  c  s  a  n  d  2  8  -d  a  y  m  o  r  t  a  l  i  t  y  i  n  t  h  e  I  F  N  b  e  t  a  -1  a  a  r  m  o  f  t  h  e  I  N  T  E author/funder, who has granted medRxiv a license to display the preprint in perpetuity. T  a  b  l  e  2  .   B  a  s  e  l  i  n  e  d  e  m  o  g  r  a  p  h  i  c  s  a  n  d  2  8  -d  a  y  m  o  r  t  a  l  i  t  y  f  o  r  p  r  o  p  e  n  s  i  t  y  -m  a  t  c  h  e  d  I  F  N  b  e  t  a  -1  a  t  r  e  a  t  e All rights reserved. No reuse allowed without permission.
author/funder, who has granted medRxiv a license to display the preprint in perpetuity. T  a  b  l  e  3   .   (  A  )   I  n  d  e  p  e  n  d  e  n  t  f  a  c  t  o  r  s  a  s  s  o  c  i  a  t  e  d  w  i  t  h  2  8  -d  a  y  m  o  r  t  a  l  i  t  y  i  n  a  l  l  I  F  N  b  e  t  a  -1  a  t  r  e  a  t  e All rights reserved. No reuse allowed without permission.
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author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.01.20049700 doi: medRxiv preprint  r  e  p  r  e  s  e  n  t  t  h  e  p  l  a  c  e  b  o  i  n  d  u  c  e  d  l  e  v  e  l  o  f  C  D  7  3  e  x  p  r  e  s  s  i  o  n  .  S  t  a  t  i  s  t  i  c  a  l  s  i  g  n  i  f  i  c  a  n  c  e  w  a  s  a  n  a  l  y  z  e  d  u  s  i  n All rights reserved. No reuse allowed without permission.
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.01.20049700 doi: medRxiv preprint