From reports by several countries, no early signals of changes or increases in severity have been observed for XBB.1.5 compared with other Omicron subvariants. Taken together, available information does not suggest that XBB.1.5 has additional public health risk relative to the other currently circulating Omicron descendent lineages. An analysis from India did not report any differences in clinical severity of XBB and its descendent lineages, as compared to other Omicron lineages, and a preliminary analysis from the US reports that there is no difference in number of deaths per hospital admissions of patients with XBB.1.5 compared to other Omicron lineages.

This report describes how continued monitoring of S-gene target failure and S-gene target presence patterns will likely serve as a useful marker for tracking Omicron sublineages.[5] Among genomic sequences from ICATT specimens collected through January 2, 2023, 412 (99%) of 415 XBB-related sequences exhibited SGTP (S-gene target presence); among those collected during December 1, 2022–January 2, 2023, 294 (59%) of 495 SGTP specimens were XBB-related lineages.[5] SGTF was defined as a SARS-CoV-2-positive specimen with amplification of the N and ORF1ab genes along with either a failure or reduced amplification of the S gene (S Ct value >4 cycles from the average of N and ORF1ab Ct values).[5]

The SARS-CoV-2 Omicron variant is more infectious but has been associated with less severe disease. In-hospital mortality among patients hospitalized primarily for COVID-19 decreased from 15.1% (Delta period) to 4.9% (later Omicron period; April–June 2022). After adjustment, in-hospital mortality was 0.69 times as likely during the early Omicron period and 0.24 times as likely during the later Omicron period than during the Delta period.

CDC’s analysis of the 2023–2024 monovalent XBB.1.5 vaccines notes that updated vaccines "provided 54% (95% CI = 46–60%) protection against symptomatic SARS-CoV-2 infection" compared with no updated dose, and that protection was seen against "JN.1 and infections caused by XBB-related lineages." The report focuses on vaccine effectiveness rather than lethality and does not describe XBB as unusually lethal or difficult to diagnose; instead, the infections are detected through routine testing in the community.

Among 585 case-patients with XBB lineage infections, 366 (62.6%) received supplemental oxygen therapy, 99 (16.9%) received advanced respiratory support, 87 (14.9%) were admitted to an ICU, and 44 (7.5%) received invasive mechanical ventilation (IMV) or died. The adjusted odds ratios comparing case-patients with JN versus XBB lineage infection for ICU admission and IMV or death indicated no significant differences in clinical severity between lineage groups. Updated 2023–2024 COVID-19 vaccination provided protection against hospitalization for SARS-CoV-2 XBB and JN lineages.

Current COVID-19 viral tests are designed to detect SARS-CoV-2 infection and do not usually identify the specific variant. Sequencing is required to determine the variant that caused the infection, and this is done in specialized laboratories, not as part of routine clinical testing. However, standard PCR and antigen tests remain able to detect infections caused by Omicron and its subvariants, including XBB, because they target conserved regions of the virus.

This clinical commentary notes that large cohort studies have found that "despite its higher infectivity, infections caused by the Omicron variant of SARS-CoV-2 had significantly lower mortality and less severe complications compared with the Delta variant." It goes on: "It is also not yet clear whether infections with the XBB Omicron subvariant are truly less severe than prior variants" but cites preliminary local information: "preliminary reports from the Ministry of Health suggest that there has not been an observed increase in the mortality or intensive care needs from patients with COVID-19 as XBB became the dominant subvariant over BA.5 in Singapore in October 2022."

In total, 17,724 (7.4%) samples among 240,896 positives were variant-confirmed, resulting in an overall sensitivity and specificity of 93.2% [92.7%, 93.7%] and 99.3% [99.2%, 99.5%], respectively, for using SGTF as a proxy for specific variants.[2] For the Omicron BA.4/BA.5 wave, 478 SGTF-positive and 343 SGTF-negative samples were confirmed, resulting in a sensitivity of 99.4% [98.1%, 99.9%] and a specificity of 94.2% [91.3%, 96.4%].[2] A S-gene shift of 3.8–4 Ct-values produced an accuracy of 98.5% with sensitivity 98.2% [97.9%–98.4%] and specificity 98.9% [98.6%–99.1%] for detecting SGTF.[2]

This S-gene target failure (SGTF) was the earliest indication of a new variant emerging and was also observed in subsequent variants such as Omicron BA.1 and BA.4/BA.5.[3] In total, 17,724 samples among 240,896 positives were variant-confirmed, resulting in an overall sensitivity and specificity of 93.2% and 99.3%, respectively, when SGTF patterns were used to identify variants.[3] Sensitivity was increased to 98.2% and specificity lowered slightly to 98.9% when samples with partial SGTF (pSGTF) were included, indicating high diagnostic performance of SGTF-based detection.[3]

The FDA notes that certain mutations in the SARS-CoV-2 Omicron variant lead to significantly reduced sensitivity in an N-gene or S-gene genetic target that covers the portion of the gene where the mutation occurs.[7] Two of the three targets of one listed test (N-gene and E-gene targets) have significantly reduced sensitivity due to certain Omicron mutations, including mutations associated with the XBB variant; the test has an increased likelihood to produce an indeterminate result when testing positive samples of the XBB variant.[7] However, since these tests are designed to detect multiple genetic targets, the overall test sensitivity should not be impacted, and one positive target with an S-gene drop out can still indicate infection.[7]

WHO reported that several labs indicated that for one widely used PCR test, one of the three target genes (the S gene) is not detected, called S gene dropout or S gene target failure, and that this test can therefore be used as a marker for the Omicron variant pending sequencing confirmation.[6] Using this approach, the variant was detected at faster rates than previous surges in infection, suggesting a growth advantage but not indicating that Omicron was undetectable by standard RT-PCR.[6]

In a large US hospital center, the study evaluated the relative severity of XBB infections compared to other circulating subvariants and prior variants. The authors report that a lower percentage of patients with XBB/XBB.1.5 strains were admitted (11.8%/11.2% compared to 13.2%), and in multivariable regression they "failed to find a significant relationship between XBB strains and admission" (Odds Ratio 0.93 [0.61–1.42]) or "need for supplemental oxygen" (OR 0.78 [0.52–1.18]). The study concludes that XBB variants did not show increased severity outcomes relative to other circulating Omicron subvariants in this hospital cohort.

Following an outpatient diagnosis, cumulative 30-day risks of hospital admission, symptomatic hospital admission, ICU admission, mechanical ventilation, and death were lower among cases with Omicron infection than among cases with Delta infection. These findings suggest that infections with the Omicron variant and its BA.1/BA.2 subvariants are associated with reduced risk of severe clinical outcomes compared with infections with the Delta variant.

In this animal study, researchers report: "Herein, we report that unlike B.1.1.529, XBB.1.5 infection resulted in significant weight loss and 100% mortality rate and caused severe pulmonary disease in K18-hACE2 mice." They conclude: "Taken together, our data show that Omicron subvariant XBB.1.5 is highly pathogenic in K18-hACE2 mice" and that infection led to "robust viral replication in the lungs" and "severe lung pathology." The findings relate to a specific transgenic mouse model and do not directly describe lethality in humans.

The paper notes that updated 2023–2024 COVID-19 vaccination "provided protection against both XBB and JN lineage hospitalization" and that "clinical severity of JN lineage hospitalizations was not higher relative to XBB." The authors state that available studies "suggest that JN lineages are unlikely to have increased apparent clinical severity compared with XBB lineages, at least in populations with widespread immunity against SARS-CoV-2." This positions XBB as a reference Omicron lineage without evidence of exceptional lethality.

Public Health Ontario’s risk assessment states: "It remains uncertain whether the severity of disease caused by XBB* differs from previous SARS-CoV-2 variants" but rates "increased disease severity" as *low* with a moderate degree of uncertainty. The document further summarizes that an ECDC threat assessment brief found "there are currently no signals that the infection severity of XBB.1.5 is different than that of previously circulating Omicron sub-lineages." Regarding detection, the report rates "impact on testing and WGS surveillance" as *low* and indicates that existing diagnostic testing and genomic surveillance are expected to continue to identify XBB* variants.

Earlier work on the Alpha variant showed that the S-gene target failure pattern in certain RT-PCR assays was associated with the spike deletion Δ69–70 and could be used as a proxy marker for specific variants.[4] This technical basis is the same mechanism now used for Omicron subvariants, where SGTF or S-gene dropout is treated as an indicator that the virus carries particular spike mutations, while other gene targets in multiplex assays continue to detect the infection reliably.[4]

Symptoms with XBB.1.5 appear to be similar to the earlier Omicron subvariants, ranging from typical cold symptoms such as cough and congestion to shortness of breath and low oxygen levels that require emergency medical attention. An expert quoted notes that "although XBB.1.5 is one of the most antibody-resistant variants, it doesn't seem to carry any mutation known to be associated with a potential change in severity. However, studies of disease severity are now ongoing." Treatments are still expected to be effective at treating COVID-19 infections caused by XBB.1.5 and can help reduce the severity of illness.

An epidemiologic analysis of variant periods reports: "The case severity rate and case fatality rates were the lowest at 0.12% and 0.04%, respectively, in the Omicron XBB dominance period." It contrasts this with the Delta wave: "the case severity rate and case fatality rates in the Delta variant dominance period were 2.14% and 0.95%, respectively, and the case severity rate and case fatality rates in the Omicron XBB dominance period were 0.12%, and 0.04%, respectively, showing that the number of infected cases increased rapidly through the Omicron variant, but with decreasing severity levels." The authors note that the XBB-period case fatality rate (0.04%) "is at the level of the case fatality rate of seasonal influenza (0.03% to 0.08%), which is lower than that of other variant dominance periods."

This mutation causes a dropout of the S-gene target in results from widely used TaqPath COVID-19 Detection Kits, a pattern referred to as S-gene dropout or S-gene target failure (SGTF).[6] An S-gene failure does not mean a result is negative, only that the S gene was not detected; the assay uses two other SARS-CoV-2 gene targets (N and ORF1ab) that can detect the virus, so the diagnosis is not missed.[6] WHO, European CDC and African CDC report that the S-gene dropout from select TaqPath COVID-19 Kits can be used as a screening method for Omicron, allowing early identification pending sequencing confirmation.[6]

Summarizing WHO’s assessment, CIDRAP reports: "So far, no changes in severity have been reported. XBB.1.16 doesn't seem to come with additional health risks compared to XBB.1.5." It adds that India and Indonesia have reported slight increases in hospital bed occupancy, "but at levels much lower than in previous waves," and that information from India points to "no differences in hospitalization or the need for supplemental oxygen compared to other circulating lineages." WHO is quoted as saying "the overall risk is low" and that its confidence in data pointing to no increased severity is moderate.

This study shows that the majority of hospitalizations and deaths occurred among those ≥65 years of age, those with an immunocompromised condition, and those with an increasing number of underlying high-risk conditions. Our results corroborate other studies indicating the Omicron variant may cause serious illness and death, especially among vulnerable, high-risk populations. A higher proportion of mortality was observed during the BA.1 period (20.1%) relative to other variant periods (11.0%), and mortality within one calendar month increased as the number of high-risk underlying conditions increased.

Experts explain that a phenomenon of S-gene target failure (SGTF) happens when PCR is carried out on Omicron because its S-gene has a small deletion in it, which means the reaction does not work with this particular gene.[4] They note that some PCR testing used to diagnose COVID-19 can be used to detect the Omicron variant because the ‘S gene target failure’ or ‘S gene drop out’ pattern can indicate variants that contain the S gene 69-70 deletion.[4] Importantly, this assay uses two other SARS-CoV-2 gene targets (N and ORF1ab) that can detect the virus, so the diagnosis is not actually missed even when the S gene is not amplified.[4]

This study aimed to investigate the risks of hospitalization and death among users of the Department of Veterans Affairs health system who tested positive for SARS-CoV-2 across variant phases. It reports that the risk of hospitalization and death declined in the Omicron phase compared with earlier phases, although older age and comorbid conditions remained strong predictors of severe outcomes and mortality across all variant phases.

In this multicenter cohort of hospitalized patients, those infected with the Omicron variant had lower odds of ICU admission, need for mechanical ventilation, and death compared with patients infected with the Delta variant, after adjusting for age, comorbidities, and vaccination status. These results support that Omicron infections tend to be less clinically severe than Delta infections among hospitalized individuals, although severe outcomes still occurred, particularly in high-risk patients.

This review describes XBB as highly transmissible and immune-evasive but notes: "Its rapid spread, especially in the United States, is very concerning, despite the lack of evidence that it causes more severe illness than other Omicron variants." The authors write that "The extent to which it causes or contributes to more severe disorders is unclear" and that, according to experts, an increase in severity is "an extremely remote possibility." Clinical features listed for Omicron XBB infections include breathing problems, headaches, sore throat, nasal congestion, myalgia, and fever, consistent with other Omicron infections; the article does not describe XBB as unusually lethal or hard to diagnose with standard tests.

Johns Hopkins notes that XBB.1.5 "has a mutation virologists believe is helping the virus better bind to cells and thus be more transmissible," but emphasizes that current evidence does not show it to be more severe than other Omicron subvariants. The article explains that XBB.1.5 is an Omicron descendent with "greater transmissibility and immune evasiveness" yet describes typical Omicron-like symptoms and discusses ongoing vaccine and treatment effectiveness. It does not suggest that XBB.1.5 is unusually lethal or difficult to detect compared with other variants.

This immunologic study reports that recent XBB infections in the Brazilian population "significantly boosted cross-reactive neutralizing antibody (NAb) levels against JN.1." The findings suggest that XBB infections contribute to broader immunity against related variants rather than indicating exceptional lethality. The paper treats XBB as one of several Omicron lineages studied for immune responses and does not describe it as uniquely severe or hard to diagnose.

Quoting virologists and clinicians, the piece says: "Pekosz indicated that the symptoms associated with XBB.1.5 are largely akin to those of other variants" and that increases in hospitalizations are primarily seen "among the elderly, who have always been more vulnerable to severe COVID-19." It also cites data reviews: "While XBB.1.5 is noted to be transmissible, initial findings suggest it does not lead to more severe illness," according to epidemiologist Ziyad Al-Aly, though he cautions that high transmissibility can still stress hospitals. Experts interviewed do not characterize XBB.1.5 as unusually lethal or as evading standard diagnostic tests.

This retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect SARS-CoV-2 variants.[1] The authors note that due to mutation within the S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits, which can be exploited to presumptively identify these variants.[1] The analysis compares SGTF-based RT-PCR results against whole genome sequencing as the reference to determine diagnostic sensitivity for variant detection.[1]

The Omicron variant overview notes that for XBB, "From preliminary evidence, they had assessed the XBB variants had no effect on disease severity and transmissibility" compared with other Omicron lineages. For Omicron in general, it states that despite rapid spread, "available data suggest that the variant does not lead to more severe disease compared to earlier strains" and that studies from early 2022 found Omicron infections were substantially less likely to result in hospitalization or death than Delta. The article describes XBB as an immune-evasive recombinant sublineage but does not indicate that it is unusually lethal or undetectable by standard PCR and antigen tests.

Across multiple national and international assessments published through 2024, Omicron XBB subvariants have been described as highly transmissible and immune-evasive but not consistently associated with higher lethality than other Omicron lineages. Standard nucleic acid amplification tests (PCR) and most rapid antigen tests used worldwide remained capable of detecting XBB infections, because these subvariants did not systematically delete or alter all targeted genomic regions in widely used assays; only certain specific assays affected by S-gene target failure showed variant-related patterns, but this did not equate to infections being "not easy to detect."

A social media post states that samples where the S-gene is not detected, known as S-gene dropout or S-gene target failure, are currently being treated as a proxy for Omicron rather than as missed diagnoses.[8] The post reflects public interpretation that S-gene failure means the virus is present and that this pattern can be used to infer variant type, which contrasts with claims that Omicron is not easily detected by PCR.[8]