The Omicron XBB lineage of SARS-CoV-2 became a dominant circulating subvariant across the globe. This variant gained attention due to its unique genetic structure and its rapid displacement of previously dominant strains. XBB emerged during a period of increased population immunity from prior infection and vaccination, presenting a new challenge to existing defenses.
The Biological Profile of XBB
The XBB variant is genetically distinct because it arose through recombination, where two different Omicron sublineages, specifically two BA.2 descendants, merged their genetic material within a single host cell. This fusion resulted in a novel viral genome that possesses a unique combination of mutations, particularly in the spike protein. The XBB lineage, including its highly successful descendant XBB.1.5, exhibits a high affinity for the human ACE2 receptor, which is the mechanism the virus uses to enter cells.
This unique set of mutations contributes to its primary biological advantage: enhanced immune evasion. XBB variants are significantly more resistant to neutralizing antibodies generated by previous infection or vaccination compared to earlier Omicron strains like BA.5. This high degree of immune escape allowed XBB to cause breakthrough infections and reinfections, even in individuals with recent immunity. The combination of improved cell binding and evasion capability made XBB one of the most transmissible variants recorded.
Clinical Presentation and Symptom Profile
The symptoms associated with XBB infection are generally similar to those of other Omicron subvariants, frequently presenting as a cold or flu-like illness. Common manifestations include a sore throat, congestion, runny nose, cough, fatigue, and headache. Fever and body aches are also widely reported, often lasting for approximately five to seven days.
A notable difference from earlier variants is the reduced incidence of long-term loss of taste or smell. The XBB lineage generally causes infection primarily confined to the upper respiratory tract. This results in less severe lung involvement and a lower overall risk of severe disease or hospitalization compared to the Delta variant. Despite high transmissibility, the virus does not appear to carry mutations associated with intrinsically greater severity.
Protection and Medical Management
Vaccines remain the most reliable defense against severe outcomes from XBB infection, despite the variant’s ability to evade antibodies that prevent initial infection. Protection against severe illness, hospitalization, and death remains robust due to the broader and more durable effects of T-cell immunity. T-cells target conserved parts of the virus less affected by XBB’s mutations. Updated booster formulations, which target Omicron lineages, have been shown to generate a better neutralizing antibody response against XBB subvariants compared to the original monovalent vaccines.
Antiviral medications continue to be an effective treatment option for individuals at high risk of progressing to severe disease. Drugs like nirmatrelvir (Paxlovid), remdesivir, and molnupiravir work by interfering with the virus’s internal replication mechanisms, a process that is not compromised by the XBB spike protein mutations. These treatments are recommended to be started within five days of symptom onset to be most effective.
The emergence of the XBB lineage rendered many previously authorized monoclonal antibody treatments ineffective. The extensive mutations on the XBB spike protein, which is the target of these antibody therapies, prevent the drugs from binding to and neutralizing the virus. As a result, many older monoclonal antibody products are no longer authorized or recommended for use against circulating XBB subvariants.
Current Public Health Guidance
Public health recommendations focus on reducing transmission and protecting vulnerable populations from severe illness. Testing remains a cornerstone of management, with both rapid antigen tests and RT-PCR tests available to confirm infection and guide isolation decisions. Individuals experiencing symptoms should test immediately, and a single negative rapid test should be confirmed with a second test 48 hours later if symptoms persist.
Isolation protocols typically require individuals who test positive to isolate for a set period, often five days from the onset of symptoms or the date of the positive test. Isolation should continue until the individual is fever-free for 24 hours without the use of fever-reducing medication and other symptoms are improving. Prevention strategies also emphasize behavioral measures, such as wearing a high-quality N95 or KN95 mask in crowded indoor settings and ensuring good ventilation in shared spaces.