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Anat Rec (Hoboken) ; 305(8): 2065-2074, 2022 08.
Article in English | MEDLINE | ID: covidwho-1787646


The nasopharynx is an integral component of the upper aerodigestive tract, whose morphologic features share an intimate relationship with a vast array of clinical, functional, and quality of life conditions related to contemporary humans. Its composite architecture and central location amidst the nasal cavity, pharyngotympanic tube, palate, and skull base bears implications for basic physiologic functions including breathing, vocalization, and alimentation. Over the course of evolution, morphological modifications of nasopharyngeal anatomy have occurred in genus Homo which serve to distinguish the human upper aerodigestive tract from that of other mammals. Understanding of these adaptive changes from both a comparative anatomy and clinical perspective offers insight into the unique blueprint which underpins many clinical pathologies currently encountered by anthropologists, scientists, and otorhinolaryngologists alike. This discussion intends to familiarize readers with the fundamental role that nasopharyngeal morphology plays in upper aerodigestive tract conditions, with consideration of its newfound clinical relevance in the era of the COVID-19 pandemic.

COVID-19 , Hominidae , Animals , Humans , Mammals , Nasopharynx/anatomy & histology , Nasopharynx/physiology , Pandemics , Quality of Life
EBioMedicine ; 66: 103316, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1163668


BACKGROUND: Angiotensin converting enzyme 2 (ACE2) protein serves as the host receptor for SARS-CoV-2, with a critical role in viral infection. We aim to understand population level variation of nasopharyngeal ACE2 transcription in people tested for COVID-19 and the relationship between ACE2 transcription and SARS-CoV-2 viral load, while adjusting for expression of: (i) the complementary protease, Transmembrane serine protease 2 (TMPRSS2), (ii) soluble ACE2, (iii) age, and (iv) biological sex. The ACE2 gene was targeted to measure expression of transmembrane and soluble transcripts. METHODS: A cross-sectional study of n = 424 "participants" aged 1-104 years referred for COVID-19 testing was performed in British Columbia, Canada. Patients who tested positive for COVID-19 were matched by age and biological sex to patients who tested negative. Viral load and host gene expression were assessed by quantitative reverse-transcriptase polymerase chain reaction. Bivariate analysis and multiple linear regression were performed to understand the role of nasopharyngeal ACE2 expression in SARS-CoV-2 infection. FINDINGS: Analysis showed no association between age and nasopharyngeal ACE2 transcription in those who tested negative for COVID-19 (P = 0•092). Mean relative transcription of transmembrane (P = 0•00012) and soluble (P<0•0001) ACE2 isoforms, as well as TMPRSS2 (P<0•0001) was higher in COVID-19-negative participants than COVID--19 positive ones, yielding a negative correlation between targeted host gene expression and positive COVID-19 diagnosis. In bivariate analysis of COVID-19-positive participants, transcription of transmembrane ACE2 positively correlated with SARS-CoV-2 viral RNA load (B = 0•49, R2=0•14, P<0•0001), transcription of soluble ACE2 negatively correlated (B= -0•85, R2= 0•26, P<0•0001), and no correlation was found with TMPRSS2 transcription (B= -0•042, R2=<0•10, P = 0•69). Multivariable analysis showed that the greatest viral RNA loads were observed in participants with high transmembrane ACE2 transcription (Β= 0•89, 95%CI: [0•59 to 1•18]), while transcription of the soluble isoform appears to protect against high viral RNA load in the upper respiratory tract (Β= -0•099, 95%CI: [-0•18 to -0•022]). INTERPRETATION: Nasopharyngeal ACE2 transcription plays a dual, contrasting role in SARS-CoV-2 infection of the upper respiratory tract. Transcription of the transmembrane ACE2 isoform positively correlates, while transcription of the soluble isoform negatively correlates with viral RNA load after adjusting for age, biological sex, and transcription of TMPRSS2. FUNDING: This project (COV-55) was funded by Genome British Columbia as part of their COVID-19 rapid response initiative.

Angiotensin-Converting Enzyme 2/genetics , COVID-19 Testing , COVID-19/genetics , Nasopharynx/virology , Adult , Age Factors , Aged , Aged, 80 and over , British Columbia , COVID-19/virology , Cross-Sectional Studies , Female , Host-Pathogen Interactions/genetics , Humans , Male , Middle Aged , Nasopharynx/physiology , RNA, Viral/analysis , Serine Endopeptidases/genetics , Transcription, Genetic , Viral Load