PULMONARY CMV REACTIVATION FOLLOWING SARS-CoV-2: IMPLICATIONS for IMMUNOPATHOLOGY
Topics in Antiviral Medicine
; 30(1 SUPPL):75, 2022.
Article
in English
| EMBASE | ID: covidwho-1880788
ABSTRACT
Background:
SARS-CoV-2 infection results in a spectrum of disease severity attributable to the magnitude of the underlying inflammatory response. Aged individuals with co-morbidities are most vulnerable and severely affected, but the mechanisms driving aberrant immune responses fueling SARS-CoV-2 immunopathology in this high-risk population are not fully elucidated. We hypothesized that asymptomatic CMV infection might exacerbate SARS-CoV-2 pathogenesis since its replication is both a cause and consequence of inflammation and appears to worsen oxygenation in critically ill patients (Limaye, JAMA, 2017). CMV-seropositivity was associated with increased hospitalization among people with SARS-CoV-2 infection (Shrock, Science, 2020). To begin to address this hypothesis, we utilized the rhesus macaque model of natural rhesus (Rh)CMV infection to investigate the extent to which SARS-CoV-2 induces CMV reactivation in the anatomic sites of SARS-CoV-2 pathology.Methods:
To assess CMV reactivation, eight aged, type 2 diabetic RhCMV-seropositive rhesus macaques (sera anti-CMV IgG 300-1400 ng/ml) were infected with high-dose SARS-CoV-2 (2.5x10 6 PFU) and monitored for 7 days prior to euthanasia. Samples from the respiratory tract, intestinal tract, and blood were collected to assess viral and inflammatory dynamics in distinct tissue compartments.Results:
Following infection, SARS-CoV-2 replication was observed throughout the respiratory tract, which was associated with local and systemic inflammation and immune activation. Lung histopathological assessments revealed development of interstitial pneumonia with colocalization of SARS nucleocapsid protein within pneumocytes. qPCR assays targeting RhCMV gB showed CMV DNA within the caudal lung lobe (up to 103 CMV DNA copies/mg of tissue) in all animals at day 7, and the animal with the highest CMV DNA presented with the most profound clinical symptoms. Strikingly, CMV DNA copies strongly correlated with CD4 and CD8 T cell activation indices in blood and spleen (r = 0.96, p< 0.001). Additionally, we found RhCMV reactivation in the ileum, where high levels of ACE2 are reported.Conclusion:
SARS-CoV-2 infection of RhCMV-seropositive macaques results in CMV reactivation in the anatomic sites where SARS-CoV-2 causes pathology. Future experimental studies should address whether CMV reactivation exacerbates SARS-CoV-2 pathogenesis.
CD4 antigen; Cytomegalovirus antibody; endogenous compound; nucleocapsid protein; adult; animal cell; animal experiment; animal model; animal tissue; CD8+ T lymphocyte; conference abstract; controlled study; coronavirus disease 2019; critically ill patient; cytomegalovirus infection; drug megadose; euthanasia; experimental study; female; histopathology; hospitalization; human; ileum; immunopathology; immunostimulation; inflammation; interstitial pneumonia; lung alveolus cell; lung lobe; male; non insulin dependent diabetes mellitus; nonhuman; oxygenation; rhesus monkey; severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; spleen; T lymphocyte activation
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Topics in Antiviral Medicine
Year:
2022
Document Type:
Article
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