COVID-19: Does Omicron cause less damage to the lungs?

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Does Omicron cause less lung damage than Delta? David Paul Morris / Bloomberg via Getty Images
  • Animal studies and experiments involving cells grown in the laboratory suggest that the Omicron variant may have a reduced ability to infect the lungs compared to the Delta variant.
  • This could explain why the Omicron variant appears to cause less severe disease than the Delta variant.
  • These studies suggest that the Omicron variant could be more effective in infecting the upper respiratory tract than the Delta variant, potentially explaining its increased infectivity.
  • The ability of the Omicron variant to avoid neutralizing antibodies may also be responsible for its increased tolerability.

Early reports following the emergence of the Omicron variant suggest that this variant is more likely to cause less severe disease than previous variants of SARS-CoV-2.

Omicron genome sequencing suggests that this variant carries a large number of mutations, including on the spike protein. The large number of mutations carried by Omicron could be a potential reason for this reduction in disease severity.

However, a milder illness caused by Omicron infection could also be due to a person’s boosted immunity, acquired through vaccination, or past SARS-CoV-2 infections.

Although increased immunity may affect disease severity, studies on animals and cells grown in the laboratory suggest that mutations carried by the Omicron variant have made it less effective in infecting the lungs than the Delta variant. This could explain the less severe disease that the Omicron variant causes.

Laboratory and animal studies

SARS-CoV-2 virus can affect both the upper and lower respiratory tract. The upper respiratory tract consists of the nose, sinuses and throat, while the lower respiratory tract includes the trachea and lungs.

Mild illness or early SARS-CoV-2 infections are likely to include upper respiratory symptoms such as runny nose and sore throat.

Severe disease due to wild type SARS-CoV-2 and previous variants often includes infection and pneumonia.

Inflammation can cause fluid to build up in air sacs or alveoli in the lungs, reducing the lungs’ capacity to carry oxygen to the blood.

The scientists conducted experiments using animal models and laboratory lung cell cultures to characterize Omicron’s ability to infect the airways and cause severe disease.

This includes a study conducted at the University of Hong Kong that used laboratory-grown human lung cells to analyze the ability of the Omicron variant to infect the lungs. These cells were grown from lung tissue removed during lung treatment. Usually this tissue is discarded.

In the study, Omicron replicated 70 times faster than Delta in the human bronchi, which are the tubes that connect the trachea to the lungs. However, it was less effective in replication in lung tissue than Delta and wild-type SARS-CoV-2.

Other research groups compared the ability of Omicron, Delta, and other variants of SARS-CoV-2 to cause disease in animal models, such as hamsters and mice.

There is a link between infection with Delta and other variants and weight loss in hamsters and mice after 1 week, and some data suggest a correlation between increased levels of the virus in the respiratory tract and weight loss.

However, different research groups have independently demonstrated absence such weight loss in hamsters and mice after Omicron infection.

Moreover, these studies showed that hamsters with Omicron infection showed higher or similar virus levels compared to wild-type SARS-CoV-2 and the Delta variant in the upper respiratory tract. In contrast, the researchers observed lower levels of the virus in the lower respiratory tract after infection with the Omicron variant, compared to the Delta variant.

In short, these studies show that Omicron may be less effective in infecting the lungs. Significantly, these animal studies show that Omicron is an infection Results in lower levels of inflammation and lung injury.

Accordingly, there is growing evidence to suggest that people with Omicron infection are less likely to be hospitalized or need admission to an intensive care unit or mechanical ventilation than people with the Delta variant.

Micro B life spoke with Dr. Scott Roberts, professor of infectious diseases at the Yale School of Medicine in New Haven, CT. He said,

“A number of laboratory studies have now shown that the Omicron variant is less able to infect the lungs than other variants and, as a result, leads to fewer patients admitted with pneumonia who need oxygen and ventilators.”

“We see [that] most patients infected with Omicron have a mild disease that is more localized in the upper respiratory tract and that hospitalizations do not grow as fast as with previous variants, ”added Dr. Roberts.

“However, hospitalizations and deaths lag behind the total number of cases, and as our cases continue to grow and set daily records, we ultimately have to wait a few more weeks to get a full picture of the severity of the disease here in the United States.”

Change the preference for the route to enter the station

A potential reason for less severe lower respiratory tract infection with Omicron in these studies may be changes in the ability of this variant to enter cells in the lower respiratory tract.

The Omicron variant carries a large number mutations in a gene encoding a spike protein, which is expressed on the surface of the SARS-CoV-2 virus.

The spice protein SARS-CoV-2 binds to the ACE2 receptor expressed on lung cells and helps the virus to enter the cell. Cleavage of the spiky protein by the so-called enzyme TMPRSS2 the presence on the surface of human cells is necessary before the membrane of the virus merges with the membrane of the human cell.

The SARS-CoV-2 virus can also enter human cells in an alternative way. This pathway involves ingestion of the virus by endosomes, which are membrane-bound sacs present within the cell.

Studies using laboratory-grown cells suggest that mutations in the Omikron spike protein altered its ability to enter human cells with the help of TMPRSS2.

These studies found that the Omicron variant was less effective in infecting laboratory-grown lung cells expressing TMPRSS2 than the Delta variant.

In contrast, Omicron is more effective than Delta in infecting cells that allow cells to enter through the endosomal pathway.

The ACE2 receptor and TMPRSS2 are expressed at higher levels in cells derived from the human lower respiratory tract than in cells from the upper respiratory tract. This could potentially explain why the Omicron variant may be less effective in infecting the lower respiratory tract and causing severe disease.

The interaction of the spiky protein SARS-CoV-2 and TMPRSS2 is also involved in mediating the fusion of infected human cells with neighboring uninfected cells.

The reduced ability of the Omicron spike protein to utilize the enzyme TMPRSS2 also limits its ability to infect neighboring cells. This could further contribute to the lower severity of lower respiratory tract infection due to COVID-19.

These results are from cell cultures and animal studies. Therefore, research in humans is necessary to determine that such a change in Omicron is responsible for its reduced ability to infect lung cells.

MBL spoke with Dr. Peter Casson, a professor at the University of Virginia at Charlottesville. He said:

“The Omicron variant is interesting in that it seems to change entry route preferences compared to Delta and previous variants. As a result, it is less effective in infecting lung cells, but more effective in infecting many upper respiratory tract cells. ”

“This correlates with the disease pattern observed in Omicron – while lower lung pathology is observed, upper respiratory tract disease is often more common,” he concluded.

Increased portability

In addition to causing less severe disease, the Omicron variant is also transmissible. Animal and cell culture studies also suggest that Omicron may be more effective in infecting the upper respiratory tract.

Studies conducted during the early phase of the pandemic show an association between SARS-CoV-2 levels in the upper respiratory tract and increased transmission.

Faster replication of Omicron in the upper respiratory tract may therefore explain its increased infectivity.

“[These studies] encourage attractive speculation that increased replication in upper airway tissues may contribute to increased portability, potentially by increasing expiratory viral load and reducing the number of viral particles required for infection, although, as far as I know, this has not been conclusively proven, ”explained Dr. Casson.

The increased infectivity of the Omicron variant may also be due to its ability to avoid antibody detection.

Previous SARS-CoV-2 infections and immunization with COVID-19 vaccines lead to the production of antibodies that neutralize the virus. This neutralizing antibody prone to predict level of protection against SARS-CoV-2 infection.

COVID-19 vaccines are designed to elicit an immune response against the wild-type wild-type SARS-CoV-2 strain protein.

The presence of mutations in the spike protein variant of Omicron suggests that this variant may avoid neutralization by antibodies.

A study led by researchers from the Center for Virus Research at the University of Glasgow MRC in the United Kingdom showed that the Omicron variant can avoid neutralizing antibodies in people immunized with AstraZeneca COVID-19. This could be another reason for the high portability of the Omicron variant.

Although scientists need to conduct additional research before we can draw firm conclusions, the characteristics of this new variant are slowly being revealed.

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