The Goblet and Ciliated cells in the human nasal passage have high levels of entry proteins that the COVID-19 virus uses to get into our body, according to researchers.
In two studies, published in Nature Medicine and in the journal Cell, the researchers indicated that goblet cells highly express a receptor enzyme called ACE2 that binds to the spikes covering the outer surface of SARS-CoV-2, the virus that causes the COVID-19 disease.
"These studies largely agree with each other and provide new insights into the specific type of cells targeted by the SARS-CoV-2 infection," said Dr. Nicholas Banovich, a TGen Assistant Professor and member of the Lung Biological Network of the Human Cell Atlas, an international effort to create comprehensive reference maps of all human cells as a basis for diagnosing, monitoring and treating disease.
In both studies, Goblet cells - which produce mucus in the nasal passages - were found to overly express angiotensin-converting enzyme 2 (ACE2), which serves as the entry point into cells for some coronaviruses. This could help explain the high rate of transmission of the virus.
"A lot of information was known about the path of infection from previous studies of SARS-CoV, including the fact that the first step in viral entry into the human body is the binding of the coronavirus spike protein to the ACE2 human receptor and an associated gene called TMPRSS2, which helps activate the coronavirus spike protein, enabling it to enter the cell," Dr. Banovich said.
Using data sets from the Human Cell Atlas, the Nature Medicine study used single-cell profiling of healthy samples to examine cells exclusively in the human airways, including nasal passages, lower airways and the lungs. The study revealed that two types of cells in the nasal passage -goblet and ciliated cells-most highly expressed ACE2 and TMPRSS2.
In addition, it found that ACE2 also is expressed in AT2 cells in the lungs.
"The results of these studies suggest that these cells in the nasal passage may serve as a viral reservoir, helping to disseminate the virus within an individual and spread the disease between individuals," Dr. Banovich said.
Using existing and new data, the Cell study looked at multiple human, primate and mouse tissues. This study also found that nasal goblet cells highly express ACE2. In addition, researchers found expression of ACE2 in absorptive enterocytes within the gut, which could help explain why many COVID-19 patients have GI symptoms.
The most significant finding in this study, however, is that ACE2 is stimulated by interferon, which is released by the body's immune system in response to viral infections.
"The body's own immune system may be causing neighboring cells to become targets of the virus," Dr. Banovich explained. "A patient's own immune response may be creating new shots on goal for the virus' target."
"These two studies really demonstrate the power of the Human Cell Atlas community and of single cell RNA sequencing. Pulling together this large group of researchers and data sets allowed the science to move at incredible speed," Dr. Banovich said.
The study with Human Cell Atlas Lung Biological Network found that cells in the eye and some other organs also contain the viral-entry proteins.
The identification of these cells by researchers from the Wellcome Sanger Institute, University Medical Centre Groningen, University Cote d'Azur and CNRS, Nice and their collaborators in their study further shows that cells in the eye and some other organs also contain the viral-entry proteins.
The study also predicts how a key entry protein is regulated with other immune system genes and reveals potential targets for the development of treatments to reduce transmission.
The two key entry proteins ACE2 and TMPRSS2 were also found in cells in the cornea of the eye and in the lining of the intestine.
This suggests another possible route of infection via the eye and tear-ducts, and also revealed a potential for faecal-oral transmission, as per the study.