Evidence map›Paper›PMID 36408607›Full record

ArticleThe Journal of infectious diseases2023

Human Cytomegalovirus Infection of Epithelial Cells Increases SARS-CoV-2 Superinfection by Upregulating the ACE2 Receptor.

Marianne R Perera, Edward J D Greenwood, Thomas W M Crozier, Elizabeth G Elder, Janika Schmitt, Colin M Crump, Paul J Lehner, Mark R Wills, John H Sinclair, Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research COVID BioResource Collaboration

Open access · hybridAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. Challenges and opportunities in the management of severe pneumonia. Key concepts from the Seventh Annual Meeting of Spanish Experts 2025.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2026
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  4. The immune response to human cytomegalovirus: impact of age, co-morbidities and the significance of anti-viral activity assessment.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Marianne R PereraDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.ORCID 0000-0001-9175-0568
Edward J D GreenwoodDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Thomas W M CrozierDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Elizabeth G ElderDepartment of Microbiology, National Veterinary Institute Uppsala, Sweden.
Janika SchmittDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Colin M CrumpDepartment of Pathology, University of Cambridge, Cambridge, United Kingdom.
Paul J LehnerDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Mark R WillsDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
John H SinclairDepartment of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research COVID BioResource Collaboration
University of Cambridge · GBSwedish Veterinary Agency · SE

Funding

Medical Research Council MR/S00081X/1Medical Research Council MR/V011561/1Medical Research Council RG86932Wellcome Trust 210688/Z/18/Z
6 · The paper itself

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused widespread morbidity and mortality since its onset in late 2019. Here, we demonstrate that prior infection with human cytomegalovirus (HCMV) substantially increases infection with SARS-CoV-2 in vitro. HCMV is a common herpesvirus carried by 40%-100% of the population, which can reactivate in the lung under inflammatory conditions, such as those resulting from SARS-CoV-2 infection. We show in both endothelial and epithelial cell types that HCMV infection upregulates ACE2, the SARS-CoV-2 cell entry receptor. These observations suggest that HCMV reactivation events in the lung of healthy HCMV carriers could exacerbate SARS-CoV-2 infection and subsequent COVID-19 symptoms. This effect could contribute to the disparity of disease severity seen in ethnic minorities and those with lower socioeconomic status, due to their higher CMV seroprevalence. Our results warrant further clinical investigation as to whether HCMV infection influences the pathogenesis of SARS-CoV-2.

Indexed as

COVID-19Cytomegalovirus InfectionsSuperinfectionAngiotensin-Converting Enzyme 2Epithelial CellsHumansPeptidyl-Dipeptidase ASARS-CoV-2Seroepidemiologic StudiesAngiotensin-Converting Enzyme 2Peptidyl-Dipeptidase AACE2coinfectionCOVID-19HCMVhuman cytomegalovirusSARS-CoV-2

Identifiers

PMID36408607
PMCPMC9927080
OpenAlexW4309510532

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.