PMID- 32997881
OWN - NLM
STAT- MEDLINE
DCOM- 20210430
LR  - 20220727
IS  - 1399-3062 (Electronic)
IS  - 1398-2273 (Print)
IS  - 1398-2273 (Linking)
VI  - 23
IP  - 2
DP  - 2021 Apr
TI  - COVID-19 in a lung transplant recipient: Exploring the diagnostic role of 
      circulating exosomes and the clinical impact of advanced immunosuppression.
PG  - e13480
LID - 10.1111/tid.13480 [doi]
LID - e13480
AB  - Exosomes isolated from plasma of lung transplant recipients with allograft injury 
      contain donor-derived lung self-antigens (collagen V and Kalpha1 tubulin) and human 
      leukocyte antigen (HLA) molecules. We present a case of a 76-year-old, female 
      lung transplant recipient treated for acute cellular rejection with 
      methylprednisolone and anti-thymocyte globulin, who subsequently contracted 
      SARS-CoV-2 and developed a sharp increase in the mean fluorescent intensity of 
      anti-HLA antibodies. Analysis of circulating exosomes during rejection, but 
      before SARS-CoV-2 infection, revealed the presence of lung self-antigens and HLA 
      class II molecules. After the patient contracted SARS-CoV-2, exosomes with the 
      SARS-CoV-2 spike protein were also found. After resolution of infectious 
      symptoms, exosomes with SARS-CoV-2 spike protein were no longer detected; 
      however, exosomes with lung self-antigens and HLA class II molecules persisted, 
      which coincided with a progressive decline in spirometric flows, suggesting 
      chronic lung allograft dysfunction. We propose that the analysis of circulating 
      exosomes may be used to detect allograft injury mediated by both rejection and 
      infection. Furthermore, the detection of exosomes containing viral proteins may 
      be helpful in identifying allograft injury driven by viral pathogens.
CI  - (c) 2020 Wiley Periodicals LLC.
FAU - Goodlet, Kellie J
AU  - Goodlet KJ
AUID- ORCID: 0000-0002-9736-0891
AD  - Department of Pharmacy Practice, College of Pharmacy, Midwestern University, 
      Glendale, AZ, USA.
FAU - Bansal, Sandhya
AU  - Bansal S
AD  - Norton Thoracic Institute, Dignity Health, St. Joseph's Hospital and Medical 
      Center, Phoenix, AZ, USA.
FAU - Arjuna, Ashwini
AU  - Arjuna A
AUID- ORCID: 0000-0002-4171-3184
AD  - Norton Thoracic Institute, Dignity Health, St. Joseph's Hospital and Medical 
      Center, Phoenix, AZ, USA.
FAU - Nailor, Michael D
AU  - Nailor MD
AD  - Department of Pharmacy Services, Dignity Health, St. Joseph's Hospital and 
      Medical Center, Phoenix, AZ, USA.
FAU - Buddhdev, Bhuvin
AU  - Buddhdev B
AD  - Norton Thoracic Institute, Dignity Health, St. Joseph's Hospital and Medical 
      Center, Phoenix, AZ, USA.
FAU - Abdelrazek, Hesham
AU  - Abdelrazek H
AD  - Norton Thoracic Institute, Dignity Health, St. Joseph's Hospital and Medical 
      Center, Phoenix, AZ, USA.
FAU - Mohamed, Hesham
AU  - Mohamed H
AD  - Norton Thoracic Institute, Dignity Health, St. Joseph's Hospital and Medical 
      Center, Phoenix, AZ, USA.
FAU - Omar, Ashraf
AU  - Omar A
AD  - Norton Thoracic Institute, Dignity Health, St. Joseph's Hospital and Medical 
      Center, Phoenix, AZ, USA.
FAU - Walia, Rajat
AU  - Walia R
AD  - Norton Thoracic Institute, Dignity Health, St. Joseph's Hospital and Medical 
      Center, Phoenix, AZ, USA.
FAU - Mohanakumar, Thalachallour
AU  - Mohanakumar T
AUID- ORCID: 0000-0001-9873-4018
AD  - Norton Thoracic Institute, Dignity Health, St. Joseph's Hospital and Medical 
      Center, Phoenix, AZ, USA.
FAU - Tokman, Sofya
AU  - Tokman S
AUID- ORCID: 0000-0003-2821-8776
AD  - Norton Thoracic Institute, Dignity Health, St. Joseph's Hospital and Medical 
      Center, Phoenix, AZ, USA.
LA  - eng
GR  - R01 HL056643/HL/NHLBI NIH HHS/United States
GR  - HL056643/NH/NIH HHS/United States
PT  - Case Reports
DEP - 20201013
PL  - Denmark
TA  - Transpl Infect Dis
JT  - Transplant infectious disease : an official journal of the Transplantation 
      Society
JID - 100883688
RN  - 0 (Antilymphocyte Serum)
RN  - 0 (Autoantigens)
RN  - 0 (Collagen Type V)
RN  - 0 (Glucocorticoids)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - 0 (Tubulin)
RN  - 0 (spike protein, SARS-CoV-2)
RN  - X4W7ZR7023 (Methylprednisolone)
SB  - IM
MH  - Aged
MH  - Antilymphocyte Serum/therapeutic use
MH  - Autoantigens/immunology/metabolism
MH  - Bronchiolitis Obliterans
MH  - COVID-19/immunology/*metabolism
MH  - Collagen Type V/immunology/metabolism
MH  - Disease Progression
MH  - Exosomes/*metabolism
MH  - Female
MH  - Glucocorticoids/adverse effects/therapeutic use
MH  - Graft Rejection/*drug therapy
MH  - HLA Antigens/immunology/metabolism
MH  - Histocompatibility Antigens Class II/immunology/*metabolism
MH  - Humans
MH  - Immunosuppressive Agents/*adverse effects/therapeutic use
MH  - *Lung Transplantation
MH  - Methylprednisolone/adverse effects/therapeutic use
MH  - SARS-CoV-2/immunology/metabolism
MH  - Spike Glycoprotein, Coronavirus/immunology/*metabolism
MH  - Tubulin/immunology/metabolism
PMC - PMC7536938
OTO - NOTNLM
OT  - COVID-19
OT  - allograft dysfunction
OT  - exosomes
OT  - lung self antigens
OT  - lung transplant
OT  - rejection
COIS- The authors of this manuscript have no disclosures to report.
EDAT- 2020/10/01 06:00
MHDA- 2021/05/01 06:00
PMCR- 2020/10/13
CRDT- 2020/09/30 17:13
PHST- 2020/09/10 00:00 [received]
PHST- 2020/09/20 00:00 [accepted]
PHST- 2020/10/01 06:00 [pubmed]
PHST- 2021/05/01 06:00 [medline]
PHST- 2020/09/30 17:13 [entrez]
PHST- 2020/10/13 00:00 [pmc-release]
AID - TID13480 [pii]
AID - 10.1111/tid.13480 [doi]
PST - ppublish
SO  - Transpl Infect Dis. 2021 Apr;23(2):e13480. doi: 10.1111/tid.13480. Epub 2020 Oct 
      13.