Omicron Xbb.1.5

[Nickie Koskinen]

This latest variant should be a reminder that we have tools to fight off COVID infection and minimize severe disease: The vaccines are still protecting against severe disease, and antivirals are still capable of treating infection from XBB.1.5. We just have to use these tools more effectively than we have over the last six months.

Lab studies suggest that the bivalent vaccine is still effective in protecting against severe disease, though perhaps not as much against infection. XBB.1.5 is derived from the omicron variant BA.2, and while the current bivalent vaccine was developed for the BA.5 variant, it has been shown to generate antibodies that recognize BA.2.

There is no guidance yet for if or when a second bivalent booster would be recommended. As of now, only about 15% of eligible individuals have received their bivalent booster, so the bigger concern is for people who have not yet gotten one to go out and get it.

With current available data, the symptoms are similar to the prior strains with no evidence of more severe infection. Recent mutations of COVID-19 have led to less severe disease. This is because the virus must give up something, in this case its ability to do harm, to survive.

A perspective from Paul Offit, director of the Vaccine Education Center and attending physician in the Division of Infectious Diseases at Children's Hospital of Philadelphia, showed that the updated bivalent booster may not be more effective as compared the original, monovalent vaccine. This included the new booster not showing an appreciably greater antibody response against the newer omicron variants including BQ.1, BQ1.1, XBB, and XBB.1.5.

This is NOT to say that the vaccine is not effective, just that the bivalent boosters may not be more effective than the original monovalent booster vaccine. That said, the bivalent booster would still be important for people at highest risk of getting severe disease. This includes those ages 65 and older and those who are immunocompromised. Even small, additional increases in antibody production are critically important for them.

In addition, if more people get seriously ill, it could place an unnecessary strain on an already overwhelmed hospital system. Current strains are also better at evading our immune defenses as compared to prior strains. Therefore, your risk of reinfection is higher. Getting infected also puts vulnerable populations at unnecessary risk of infection including severe illness, hospitalization and death.

Last, you could end up with long COVID. There are currently too many unknowns regarding who is more likely to get long COVID, but the risk of developing this chronic condition after infection is very real. Millions of people have developed this and suffer for many months, including time and money lost by the inability to work.

In prior epidemics, viruses eventually reach a saturation threshold, meaning most of the population will be or has already been infected. At this point, when the virus has fewer people to infect, the epidemic will decrease naturally.

Hopefully, this will equate to an endemic instead of a pandemic. Endemic is a disease that is still around but at a more manageable level, without causing spikes in deaths, for example. Instead, the disease is more manageable in terms of not overwhelming the system. The hope is that if COVID-19 is not eliminated, it would become more like the common cold.

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Based on what is known about the XBB variants, someone who has been infected with an earlier omicron variant may continue to be susceptible to reinfection with XBB.1.5. The variant is more transmissible than other omicron variants, according to the CDC. We are still learning if it will cause more severe illness than past sub-variants, but we do know that people with compromised immune systems are still at greater risk of potential serious illness.

The symptoms of XBB.1.5 infection include many of the same symptoms as infection with an earlier version of the coronavirus. Anyone with symptoms should take a COVID-19 test. It is the only way to be certain whether the infection is caused by COVID-19 or by a different germ, such as the flu virus.

Despite the three years spent navigating the COVID-19 pandemic, scientists are still having to react to the disease due to the constant evolution of novel variants/subvariants. Over the last few months, a global plummet in COVID-19 cases has suggested we are transitioning towards endemic COVID-19. However, the new omicron offshoots (XBB variants) are driving a new surge of cases around the world. A few preliminary research findings suggest that the XBB.1.5 subvariant is more immune-evasive and displays higher binding to ACE2 human receptor than its other related omicron subvariants in circulation. In this first-of-its-kind report, we discuss a few XBB.1.5 cases and its clinical characteristics reported in Delhi State, North India.

Figure 1 The lineage prevalence in India over the past 6 months (Comparison shown only for XBB.1.5 and XBB.1.16 and other Omicron lineages). The x-axis is time and y-axis is the relative frequencies of the lineages. The less frequent lineages are not depicted in the figure for the sake of comparison between these three lineages only. Currently, XBB.1.16 is the most predominant lineage in India, surpassing other Omicron lineages by a huge margin. The data are taken from the public repository, The time period is from the 1st week November, 2022 till the last week of March, 2023.

Copyright 2023 Samal, Bhugra, Suroliya, Gautam, Agarwal, Bihari and Gupta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Understanding the evolutionary strategies of the SARS-CoV-2 omicron variant is crucial for comprehending the COVID-19 pandemic and preventing future coronavirus pandemics. In this study, we determined the crystal structures of the receptor-binding domains (RBDs) from currently circulating omicron subvariants XBB.1 and XBB.1.5 (also the emerging XBB.1.9.1), each complexed with human ACE2. We studied how individual RBD residues evolved structurally in omicron subvariants, specifically how they adapted to human ACE2. Our findings revealed that residues 493 and 496, which exhibited good human ACE2 adaptation in pre-omicron variants, evolved to poor adaptation in early omicron subvariants (but with good adaption to mouse ACE2) and then reverted to good adaptation in recent omicron subvariants. This result is consistent with the hypothesis that non-human animals facilitated the evolution of early omicron subvariants. Additionally, residue 486, which exhibited good human ACE2 adaptation in early omicron subvariants, evolved to poor adaptation in later omicron subvariants and then returned to good adaptation in recent omicron subvariants. This result is consistent with the hypothesis that immune evasion facilitated the evolution of later omicron subvariants. Thus, our study suggests that both non-human animals and immune evasion may have contributed to driving omicron evolution at different stages of the pandemic. IMPORTANCE The sudden emergence and continued evolution of the SARS-CoV-2 omicron variant have left many mysteries unanswered, such as the origin of early omicron subvariants and the factors driving omicron evolution. To address these questions, we studied the crystal structures of human ACE2-bound receptor-binding domains (RBDs) from omicron subvariants XBB.1 and XBB.1.5 (XBB.1.9.1). Our in-depth structural analysis sheds light on how specific RBD mutations adapt to either human or mouse ACE2 and suggests non-human animals and immune evasion may have influenced omicron evolution during different stages of the pandemic. These findings provide valuable insights into the mechanisms underlying omicron evolution, deepen our understanding of the COVID-19 pandemic, and have significant implications for preventing future coronavirus pandemics.

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.

Update: The COVID-19 omicron subvariant XBB.1.5 has been identified in Austin-Travis County on Jan. 11. The latest data from the Centers for Disease Control and Prevention shows that XBB.1.5 accounts for 27.6% of COVID-19 cases in the U.S. XBB.1.5 contains more mutations capable of evading immunity than any other variant.

While antivirals do appear to offer protection against the XBB family of variants, the Food and Drug Administration (FDA) does not expect that to be the case for monoclonal antibody treatments such as Evusheld. XBB.1.5 is like other subvariants that are not neutralized by Evusheld, which means we have fewer tools available to help prevent serious illness from COVID-19.

APH has not detected omicron subvariant XBB.1.5 in Travis County wastewater samples, though it has been reported in other parts of Texas and throughout the country. Considering the rate of spread, detection is expected in Travis County soon.

"We need to avoid another surge," said APH Director Adrienne Sturrup. "Our hospitals are treating patients with COVID-19, flu and various upper respiratory illnesses right now. If you have already resolved to prioritize your health with a healthier diet, or more physical activity in this new year, add getting vaccinated to your list. If you are already vaccinated, get your booster. Protect yourself and loved ones who are at high risk of severe illness."

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