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Molecular signature of postmortem lung tissue from COVID-19 patients suggests distinct trajectories driving mortality.
Budhraja, Anshul; Basu, Anubhav; Gheware, Atish; Abhilash, Dasari; Rajagopala, Seesandra; Pakala, Suman; Sumit, Madhuresh; Ray, Animesh; Subramaniam, Arulselvi; Mathur, Purva; Nambirajan, Aruna; Kumar, Sachin; Gupta, Ritu; Wig, Naveet; Trikha, Anjan; Guleria, Randeep; Sarkar, Chitra; Gupta, Ishaan; Jain, Deepali.
  • Budhraja A; Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, New Delhi 110016, India.
  • Basu A; Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, New Delhi 110016, India.
  • Gheware A; Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India.
  • Abhilash D; Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, New Delhi 110016, India.
  • Rajagopala S; Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Pakala S; Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Sumit M; Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, New Delhi 110016, India.
  • Ray A; Department of Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India.
  • Subramaniam A; Department of Laboratory Medicine, JPNATC, All India Institute of Medical Sciences, New Delhi 110029, India.
  • Mathur P; Department of Laboratory Medicine, JPNATC, All India Institute of Medical Sciences, New Delhi 110029, India.
  • Nambirajan A; Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India.
  • Kumar S; Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi 110029, India.
  • Gupta R; Laboratory Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital (IRCH), All India Institute of Medical Sciences, New Delhi 110029, India.
  • Wig N; Department of Medicine, All India Institute of Medical Sciences, New Delhi, 110029, India.
  • Trikha A; Department of Anaesthesiology, Critical Care and Pain Medicine, All India Institute of Medical Sciences, New Delhi 110029, India.
  • Guleria R; Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi 110029, India.
  • Sarkar C; Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India.
  • Gupta I; Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, New Delhi 110016, India.
  • Jain D; Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India.
Dis Model Mech ; 15(5)2022 05 01.
Article in English | MEDLINE | ID: covidwho-1793721
ABSTRACT
To elucidate the molecular mechanisms that manifest lung abnormalities during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, we performed whole-transcriptome sequencing of lung autopsies from 31 patients with severe COVID-19 and ten uninfected controls. Using metatranscriptomics, we identified the existence of two distinct molecular signatures of lethal COVID-19. The dominant 'classical' signature (n=23) showed upregulation of the unfolded protein response, steroid biosynthesis and complement activation, supported by massive metabolic reprogramming leading to characteristic lung damage. The rarer signature (n=8) that potentially represents 'cytokine release syndrome' (CRS) showed upregulation of cytokines such as IL1 and CCL19, but absence of complement activation. We found that a majority of patients cleared SARS-CoV-2 infection, but they suffered from acute dysbiosis with characteristic enrichment of opportunistic pathogens such as Staphylococcus cohnii in 'classical' patients and Pasteurella multocida in CRS patients. Our results suggest two distinct models of lung pathology in severe COVID-19 patients, which can be identified through complement activation, presence of specific cytokines and characteristic microbiome. These findings can be used to design personalized therapy using in silico identified drug molecules or in mitigating specific secondary infections.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Limits: Humans Language: English Journal subject: Medicine Year: 2022 Document Type: Article Affiliation country: Dmm.049572

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Limits: Humans Language: English Journal subject: Medicine Year: 2022 Document Type: Article Affiliation country: Dmm.049572