How Omicron BA.5 Exhibits Delta-like Characteristics

The primary difference between Omicron and Delta lies in the severity of the illness they cause; Omicron typically results in milder Covid-19, as it is less adept at infecting lung cells. This results in infections that primarily affect the upper respiratory tract.

However, the BA.5 subvariant has since evolved, surpassing BA.1 and becoming the predominant strain, effectively rendering BA.1 extinct in the United States. BA.5’s ability to outcompete its predecessor underscores its heightened transmissibility:

Research conducted in May 2022 by scientists from the University of Tokyo revealed that BA.5 possesses a superior capacity to evade the immune response compared to BA.1, while also exhibiting virulence traits similar to Delta.

Key findings included:

• Antibodies from vaccinated individuals infected with BA.1 were 2-3 times less effective at neutralizing BA.5 than BA.2.
• BA.5 is 20-30 times more proficient at infecting and replicating in human alveolar lung cells than BA.2.
• Hamsters recovering from BA.2 infections showed no immunity against BA.5.
• Infected hamsters exhibited significant weight loss and a 4-6 times higher SARS-CoV-2 viral load in their lungs compared to those infected with BA.2. Dissections revealed more extensive lung damage from BA.5 infections.
• While BA.2 and BA.5 have comparable binding abilities to the ACE2 receptor, BA.5 can also attach to TMPSSR2, a crucial co-receptor for lung cell infection, a characteristic of Delta.

Later in the month, researchers from the Kirby Institute at the University of New South Wales confirmed that BA.5 infects cells through the TMPSSR2 co-receptor with much greater efficiency than BA.2, nearly matching the level of Delta:

Eric Topol, MD, a molecular medicine expert, noted that the enhanced ability of BA.5 to penetrate cells could explain its troubling impact compared to other Omicron subvariants. He also observed that patients infected with BA.5 often take longer to test negative, frequently exceeding ten days.

The previously seen ability of Delta to bind to TMPSSR2 contributes significantly to its capacity to induce severe Covid-19 compared to other variants. Earlier Omicron subvariants (BA.1/2) had shifted their preference away from TMPSSR2, limiting their ability to infect lung cells.

While BA.5 is not a hybrid of Omicron and Delta resulting from co-infection, it has regained the infectious and virulent characteristics of Delta, while also enhancing its transmissibility and immune evasion from BA.1.

Consequently, Dr. Topol referred to BA.5 as “the most concerning variant of the virus we’ve encountered.”

Nonetheless, whether BA.5 leads to more severe Covid-19 in clinical settings remains unproven. This is complicated by pre-existing immunity from past infections, vaccinations, and boosters, making it difficult to draw definitive conclusions. Currently, we rely on theoretical foundations suggesting that BA.5 could be more severe due to its Delta-like characteristics, supported by laboratory findings and rising hospitalization rates.

As Rochelle Walensky, MD, director of the CDC, stated, “We are uncertain about the clinical severity of BA.4 and BA.5 compared to other Omicron subvariants, but we know they are more transmissible and evade immune defenses more effectively. Individuals with prior infections, even those with BA.1 and BA.2, may still be vulnerable to BA.4 or BA.5.”

The Timing of BA.5's Emergence

Many countries, particularly in Europe and North America, along with nations such as Israel, Japan, and Australia, are currently experiencing a surge in Covid-19 cases and hospitalizations, yet the death toll remains low:

The increase in hospitalizations without a corresponding rise in deaths suggests two possibilities: either we have developed effective treatment protocols for Covid-19 or our existing immunity is diminishing the severity of BA.5. If the latter is true, we are fortunate to have vaccines and that BA.1 had already emerged before BA.5.

Dr. Topol noted, “Had BA.5 emerged without the prior presence of BA.1, it could have resulted in even greater surges than we witnessed globally with the arrival of Omicron. Our immunity wall plays a significant role in how we experience illness from each subsequent variant.”

While immunity from BA.1 infections does little to prevent BA.5 infections, this also holds true for Covid-19 vaccines. Nonetheless, vaccines continue to provide some protection against severe or fatal Covid-19, even against concerning variants.

A recent CDC study reported that:

• During the BA.1 phase, two-dose vaccine effectiveness against Covid-19 hospitalizations was 61%, rising to 85%-92% after a third dose (the first booster).
• For the BA.2 phase, two-dose vaccine effectiveness against hospitalizations dropped to 24%, but increased to 52%-69% with a third dose. In individuals over 50 who received a fourth dose (the second booster), vaccine effectiveness against hospitalizations rose to 80%.

Currently, there is no data on vaccine effectiveness against BA.5. However, given the declining efficacy from BA.1 to BA.2, it is likely that effectiveness against BA.5 will be significantly lower, though not entirely absent.

Dr. Dan Barouch, a professor of medicine and immunology at Harvard Medical School, remarked, “Our data imply that these new Omicron subvariants could potentially lead to spikes in infections even among populations with high levels of vaccine-induced immunity as well as natural immunity from BA.1 and BA.2 infections. Nevertheless, vaccine immunity should still offer substantial protection against severe disease from BA.4 and BA.5.”

Dr. Topol continued, “The perception is that there is a reduced rate of fatalities, ICU admissions, and hospitalizations compared to Omicron BA.1 and earlier variant waves. This is not indicative of a waning pandemic but rather reflects the immunity wall constructed from millions of infections and vaccination doses.”

Had BA.5 appeared earlier, before we had built our immunity defenses, the full impact of this variant would have been much more severe.

However, it is important to recognize that Covid-19 vaccines are becoming less effective with each new variant. While Omicron-specific booster shots are in development, they may not be available in time, particularly in developing countries. By the time they become accessible, public willingness to receive them may be low, and other variants may take precedence.

We are currently engaged in an evolutionary arms race against Covid-19, a scenario we typically lose, as evidenced by influenza and HIV. To change this trajectory, we must explore innovative solutions to combat infectious diseases, such as:

• A universal vaccine that remains effective against all coronavirus variants.
• An intranasal vaccine that provides mucosal immunity in the respiratory tract, potentially halting infection and transmission.
• Widespread installation of ventilation systems indoors to eliminate respiratory viruses.

We must adapt our strategies or risk letting Covid-19 evolve ahead of us.

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