Why does COVID-19 affect people so differently? 

In a study from McMaster University, new clues have emerged that may solve the mystery of why COVID-19 infection affects patients in such different ways. The research challenges the widely accepted notion that the ACE2 receptor serves as the cellular gateway for SARS-COV-2. 

In collaboration with experts at the University of Waterloo, the researchers have been investigating how the virus infects the lungs. Scientists had previously determined that the coronavirus gains entry into lung cells through ACE2 receptors located on their surface. 

However, in the new study, the researchers discovered that the ACE2 receptor is at very low levels in human lung tissue.

“Our finding is somewhat controversial, as it suggests that there must be other ways, other receptors for the virus, that regulate its infection of the lungs,” said study co-author Professor Jeremy Hirota.

“We were surprised that the fundamental characterization of the candidate receptors in human lung tissue had not yet been done in a systematic way with modern technologies.”

Professor Andrew Doxey said that finding such low levels of ACE2 in lung tissue has important implications for how we think about this virus. “ACE2 is not the full story and may be more relevant in other tissues such as the vascular system.”

The team’s findings have been independently confirmed by other researchers in Molecular Systems Biology.

To explore additional infection pathways and different patient responses to infection, the team is using nasal swabs that were collected for clinical diagnoses of COVID-19. The samples can be analyzed to link the genes expressed in a patient’s cells to the progression of the disease in that individual.

The study will ultimately lead to a system for better identifying and treating patients who are the most likely to develop serious complications.

“It is clear that some individuals respond better than others to the same SARS-CoV-2 virus. The differential response to the same virus suggests that each individual patient, with their unique characteristics, heavily influences COVID-19 disease severity,” said Hirota.

“We think it is the lung immune system that differs between COVID-19 patients, and by understanding which patients’ lung immune systems are helpful and which are harmful, we may be able to help physicians proactively manage the most at-risk patients.”

The study is published in the European Respiratory Journal.

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By Chrissy Sexton, Earth.com Staff Writer