Temporal and Spatial Heterogeneity of Host Response to SARS-CoV-2 Pulmonary Infection

  1. Niyati Desai
  2. Azfar Neyaz
  3. Annamaria Szabolcs
  4. Angela R. Shih
  5. Jonathan H. Chen
  6. Vishal Thapar
  7. Linda T. Nieman
  8. Alexander Solovyov
  9. Arnav Mehta
  10. David J. Lieb
  11. Anupriya S. Kulkarni
  12. Christopher Jaicks
  13. Christopher J. Pinto
  14. Dejan Juric
  15. Ivan Chebib
  16. Robert B. Colvin
  17. Arthur Y. Kim
  18. Robert Monroe
  19. Sarah E Warren
  20. Patrick Danaher
  21. Jason W Reeves
  22. Jingjing Gong
  23. Erroll H Rueckert
  24. Benjamin D. Greenbaum
  25. Nir Hacohen
  26. Stephen M. Lagana
  27. Miguel N. Rivera
  28. Lynette M. Sholl
  29. James R. Stone
  30. David T. Ting
  31. Vikram Deshpande
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Abstract

The relationship of SARS-CoV-2 lung infection and severity of pulmonary disease is not fully understood. We analyzed autopsy specimens from 24 patients who succumbed to SARS-CoV-2 infection using a combination of different RNA and protein analytical platforms to characterize inter- and intra-patient heterogeneity of pulmonary virus infection. There was a spectrum of high and low virus cases that was associated with duration of disease and activation of interferon pathway genes. Using a digital spatial profiling platform, the virus corresponded to distinct spatial expression of interferon response genes and immune checkpoint genes demonstrating the intra-pulmonary heterogeneity of SARS-CoV-2 infection.

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