Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 BA.2.86 and FLip variants.

Evolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and XBB-derived variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, and EG.5.1 by sera from 3-dose-vaccinated and bivalent-vaccinated healthcare workers, XBB.1.5-wave-infected first responders, and monoclonal antibody (mAb) S309. We assessed the biology of the variant spikes by measuring viral infectivity and membrane fusogenicity. BA.2.86 is less immune evasive compared to FLip and other XBB variants, consistent with antigenic distances. Importantly, distinct from XBB variants, mAb S309 was unable to neutralize BA.2.86, likely due to a D339H mutation based on modeling. BA.2.86 had relatively high fusogenicity and infectivity in CaLu-3 cells but low fusion and infectivity in 293T-ACE2 cells compared to some XBB variants, suggesting a potentially different conformational stability of BA.2.86 spike. Overall, our study underscores the importance of SARS-CoV-2 variant surveillance and the need for updated COVID-19 vaccines.

SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency.

BA.2.86, a recently identified descendant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sublineage, contains ∼35 mutations in the spike (S) protein and spreads in multiple countries. Here, we investigated whether the virus exhibits altered biological traits, focusing on S protein-driven viral entry. Employing pseudotyped particles, we show that BA.2.86, unlike other Omicron sublineages, enters Calu-3 lung cells with high efficiency and in a serine- but not cysteine-protease-dependent manner. Robust lung cell infection was confirmed with authentic BA.2.86, but the virus exhibited low specific infectivity. Further, BA.2.86 was highly resistant against all therapeutic antibodies tested, efficiently evading neutralization by antibodies induced by non-adapted vaccines. In contrast, BA.2.86 and the currently circulating EG.5.1 sublineage were appreciably neutralized by antibodies induced by the XBB.1.5-adapted vaccine. Collectively, BA.2.86 has regained a trait characteristic of early SARS-CoV-2 lineages, robust lung cell entry, and evades neutralizing antibodies. However, BA.2.86 exhibits low specific infectivity, which might limit transmissibility.

Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5.

After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2.

Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike.

Soon after the emergence and global spread of the SARS-CoV-2 Omicron lineage BA.1, another Omicron lineage, BA.2, began outcompeting BA.1. The results of statistical analysis showed that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralization experiments revealed that immunity induced by COVID vaccines widely administered to human populations is not effective against BA.2, similar to BA.1, and that the antigenicity of BA.2 is notably different from that of BA.1. Cell culture experiments showed that the BA.2 spike confers higher replication efficacy in human nasal epithelial cells and is more efficient in mediating syncytia formation than the BA.1 spike. Furthermore, infection experiments using hamsters indicated that the BA.2 spike-bearing virus is more pathogenic than the BA.1 spike-bearing virus. Altogether, the results of our multiscale investigations suggest that the risk of BA.2 to global health is potentially higher than that of BA.1.

Potent cross-reactive antibodies following Omicron breakthrough in vaccinees.

Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1, and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site; however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. In-depth structure-and-function analyses of 27 potent RBD-binding mAbs isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focused in two main clusters within the RBD, with potent right-shoulder antibodies showing increased prevalence. Selection and somatic maturation have optimized antibody potency in less-mutated epitopes and recovered potency in highly mutated epitopes. All 27 mAbs potently neutralize early pandemic strains, and many show broad reactivity with variants of concern.

Atlas of currently available human neutralizing antibodies against SARS-CoV-2 and escape by Omicron sub-variants BA.1/BA.1.1/BA.2/BA.3.

SARS-CoV-2 Omicron variant has presented significant challenges to current antibodies and vaccines. Herein, we systematically compared the efficacy of 50 human monoclonal antibodies (mAbs), covering the seven identified epitope classes of the SARS-CoV-2 RBD, against Omicron sub-variants BA.1, BA.1.1, BA.2, and BA.3. Binding and pseudovirus-based neutralizing assays revealed that 37 of the 50 mAbs lost neutralizing activities, whereas the others displayed variably decreased activities against the four Omicron sub-variants. BA.2 was found to be more sensitive to RBD-5 antibodies than the other sub-variants. Furthermore, a quaternary complex structure of BA.1 RBD with three mAbs showing different neutralizing potencies against Omicron provided a basis for understanding the immune evasion of Omicron sub-variants and revealed the lack of G446S mutation accounting for the sensitivity of BA.2 to RBD-5 mAbs. Our results may guide the application of the available mAbs and facilitate the development of universal therapeutic antibodies and vaccines against COVID-19.

Informing the Need for a SARS-CoV-2 Booster Based on the Immune Responses Among Young Healthy Adults to Variants Circulating in Late 2023.

BACKGROUND: COVID-19 remains a global public health challenge due to new immune-evasive SARS-CoV-2 variants and heterogeneous immunity. METHODS: In this cross-sectional study, we evaluated the adaptive immune responses in US active duty personnel who completed a COVID-19 primary vaccine series and had heterogenous SARS-CoV-2 vaccination and infection histories to 3 previously dominant variants (ancestral, Delta, BA.5) and 3 circulating variants (XBB.1.5, EG.5, and BA.2.86) in late 2023. Analyses were based on the most recent exposure in terms of timing (within or beyond 12 months) and type (vaccine or infection). RESULTS: Significant reduction was observed in binding antibodies, neutralization antibodies, memory B cells, and CD8+ T cells against circulating variants when compared with previous variants. The reduction in antibody response was more pronounced in those whose most recent exposure was >12 months from enrollment. In contrast, the CD4+ T-cell response was largely consistent across all tested variants. The type of most recent exposure was not a significant factor in determining the magnitude of current immune responses. CONCLUSIONS: Administration of the XBB.1.5-based booster is likely to enhance cross-reactive humoral responses against SARS-CoV-2 circulating lineages. Ongoing surveillance of immune responses to emerging variants is needed for informing vaccine composition and timing.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity-IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

BACKGROUND: Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages. METHODS: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. RESULTS: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. CONCLUSIONS: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.

Vaccine Effectiveness against SARS-CoV-2 among Household Contacts during Omicron BA.2-Dominant Period, Japan.

We calculated attack rates for household contacts of COVID-19 patients during the SARS-CoV-2 Omicron BA.2-dominant period in Japan. Attack rates among household contacts without recent (<3 months) vaccination was lower for contacts of index patients with complete vaccination than for contacts of index patients without complete vaccination, demonstrating indirect vaccine effectiveness.

Multiple mutations of SARS-CoV-2 Omicron BA.2 variant orchestrate its virological characteristics.

IMPORTANCE: Most studies investigating the characteristics of emerging SARS-CoV-2 variants have been focusing on mutations in the spike proteins that affect viral infectivity, fusogenicity, and pathogenicity. However, few studies have addressed how naturally occurring mutations in the non-spike regions of the SARS-CoV-2 genome impact virological properties. In this study, we proved that multiple SARS-CoV-2 Omicron BA.2 mutations, one in the spike protein and another downstream of the spike gene, orchestrally characterize this variant, shedding light on the importance of Omicron BA.2 mutations out of the spike protein.

Differential pathogenic and molecular features in neurological infection of SARS-CoV-2 Omicron BA.5.2 and BA.2.75 and Delta.

The Coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global threat, exacerbated by the emergence of viral variants. Two variants of SARS-CoV-2, Omicron BA.2.75 and BA.5, led to global infection peaks between May 2022 and May 2023, yet their precise characteristics in pathogenesis are not well understood. In this study, we compared these two Omicron sublineages with the previously dominant Delta variant using a human angiotensin-converting enzyme 2 knock-in mouse model. As expected, Delta exhibited higher viral replication in the lung and brain than both Omicron sublineages which induced less severe lung damage and immune activation. In contrast, the Omicron variants especially BA.5.2 showed a propensity for cellular proliferation and developmental pathways. Both Delta and BA.5.2 variants, but not BA.2.75, led to decreased pulmonary lymphocytes, indicating differential adaptive immune response. Neuroinvasiveness was shared with all strains, accompanied by vascular abnormalities, synaptic injury, and loss of astrocytes. However, Immunostaining assays and transcriptomic analysis showed that BA.5.2 displayed stronger immune suppression and neurodegeneration, while BA.2.75 exhibited more similar characteristics to Delta in the cortex. Such differentially infectious features could be partially attributed to the weakened interaction between Omicron Spike protein and host proteomes decoded via co-immunoprecipitation followed by mass spectrometry in neuronal cells. Our present study supports attenuated replication and pathogenicity of Omicron variants but also highlights their newly infectious characteristics in the lung and brain, especially with BA.5.2 demonstrating enhanced immune evasion and neural damage that could exacerbate neurological sequelae.

Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 subvariant predominance: a systematic literature review.

PURPOSE: Emerging SARS-CoV-2 variants have impacted the in vitro activity of sotrovimab, with variable fold changes in neutralization potency for the Omicron BA.2 sublineage and onward. The correlation between reduced in vitro activity and clinical efficacy outcomes is unknown. A systematic literature review (SLR) evaluated the effectiveness of sotrovimab on severe clinical outcomes during Omicron BA.2 predominance. METHODS: Electronic databases were searched for peer-reviewed journals, preprint articles, and conference abstracts published from January 1-November 3, 2022. RESULTS: Five studies were included, which displayed heterogeneity in study design and population. Two UK studies had large samples of patients during BA.2 predominance: one demonstrated clinical effectiveness vs molnupiravir during BA.1 (adjusted hazard ratio [aHR] 0.54, 95% CI 0.33-0.88; p = 0.014) and BA.2 (aHR 0.44, 95% CI 0.27-0.71; p = 0.001); the other reported no difference in the clinical outcomes of sotrovimab-treated patients when directly comparing sequencing-confirmed BA.1 and BA.2 cases (HR 1.17, 95% CI 0.74-1.86). One US study showed a lower risk of 30-day all-cause hospitalization/mortality for sotrovimab compared with no treatment during the BA.2 surge in March (adjusted relative risk [aRR] 0.41, 95% CI 0.27-0.62) and April 2022 (aRR 0.54, 95% CI 0.08-3.54). Two studies from Italy and Qatar reported low progression rates but were either single-arm descriptive or not sufficiently powered to draw conclusions on the effectiveness of sotrovimab. CONCLUSION: This SLR showed that the effectiveness of sotrovimab was maintained against Omicron BA.2 in both ecological and sequencing-confirmed studies, by demonstrating low/comparable clinical outcomes between BA.1 and BA.2 periods or comparing against an active/untreated comparator.

Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 and BA.5 subvariant predominance: a systematic literature review.

PURPOSE: To evaluate clinical outcomes associated with sotrovimab use during Omicron BA.2 and BA.5 predominance. METHODS: Electronic databases were searched for observational studies published in peer-reviewed journals, preprint articles and conference abstracts from January 1, 2022 to February 27, 2023. RESULTS: The 14 studies identified were heterogeneous in terms of study design, population, endpoints and definitions. They included > 1.7 million high-risk patients with COVID-19, of whom approximately 41,000 received sotrovimab (range n = 20-5979 during BA.2 and n = 76-1383 during BA.5 predominance). Four studies compared the effectiveness of sotrovimab with untreated or no monoclonal antibody treatment controls, two compared sotrovimab with other treatments, and three single-arm studies compared outcomes during BA.2 and/or BA.5 versus BA.1. Five studies descriptively reported rates of clinical outcomes in patients treated with sotrovimab. Rates of COVID-19-related hospitalization or mortality (0.95-4.0% during BA.2; 0.5-2.0% during BA.5) and all-cause mortality (1.7-2.0% during BA.2; 3.4% during combined BA.2 and BA.5 periods) among sotrovimab-treated patients were consistently low. During BA.2, a lower risk of all-cause hospitalization or mortality was reported across studies with sotrovimab versus untreated cohorts. Compared with other treatments, sotrovimab was associated with a lower (molnupiravir) or similar (nirmatrelvir/ritonavir) risk of COVID-19-related hospitalization or mortality during BA.2 and BA.5. There was no significant difference in outcomes between the BA.1, BA.2 and BA.5 periods. CONCLUSIONS: This systematic literature review suggests continued effectiveness of sotrovimab in preventing severe clinical outcomes during BA.2 and BA.5 predominance, both against active/untreated comparators and compared with BA.1 predominance.

EG.5 (Eris) and BA.2.86 (Pirola) two new subvariants of SARS-CoV-2: a new face of old COVID-19.

BACKGROUND: The World Health Organization announced the end of the Coronavirus Disease of 2019 (COVID-19) global health emergency on May 5, 2023. However, the reports from different countries indicate an elevation in the number of COVID-19-related hospitalizations and deaths through the last months. The subvariant XBB.1.5 (Kraken) was the cause of 49.1% of COVID-19 cases by the end of January 2023. Although, the subvariant EG.5 (Eris) has surpassed the XBB.1.5 recently. EG.5 is a close subvariant descending from XBB.1.9.2 subvariant of Omicron. EG.5.1 is a sublineage carrying two crucial spike mutations F456L and Q52H. Up to now, it is not well-established whether its infectivity, severity, and immune evasion have shown any change or not. Also, BA.2.86 another subvariant of Omicron descending from BA.2 bears over 30 mutations which could affect its infectivity and transmissibility. METHODS: Scopus, PubMed, Google Scholar, and Google were searched with six keywords up to 20 November 2023 and highly reliable research and reports were selected to refer to in this article. PURPOSE: This brief review aims to overview the most reliable data about EG.5 and BA.2.86 based on scientific evidence. CONCLUSION: Based on the currently available data these two new subvariants have similar features with currently circulating variants of Omicron and are less immune evasive than ancestral SARS-CoV-2.

SARS-CoV-2 Omicron and its current known unknowns: A narrative review.

The emergence of the SARS-CoV-2 Omicron variant (B.1.1.529) has created great global distress. This variant of concern shows multiple sublineages, importantly B.1.1.529.1 (BA.1), BA.1 + R346K (BA.1.1), and B.1.1.529.2 (BA.2), each with unique properties. However, little is known about this new variant, specifically its sub-variants. A narrative review was conducted to summarise the latest findings on transmissibility, clinical manifestations, diagnosis, and efficacy of current vaccines and treatments. Omicron has shown two times higher transmission rates than Delta and above ten times more infectious than other variants over a similar period. With more than 30 mutations in the spike protein's receptor-binding domain, there is reduced detection by conventional RT-PCR and rapid antigen tests. Moreover, the two-dose vaccine effectiveness against Delta and Omicron variants was found to be approximately 21%, suggesting an urgent need for a booster dose to prevent the possibility of breakthrough infections. However, the current vaccines remain highly efficacious against severe disease, hospitalisation, and mortality. Japanese preliminary lab data elucidated that the Omicron sublineage BA.2 shows a higher illness severity than BA.1. To date, the clinical management of Omicron remains unchanged, except for monoclonal antibodies. Thus far, only Bebtelovimab could sufficiently treat all three sub-variants of Omicron. Further studies are warranted to understand the complexity of Omicron and its sub-variants. Such research is necessary to improve the management and prevention of Omicron infection.

Latent and incubation periods of Delta, BA.1, and BA.2 variant cases and associated factors: a cross-sectional study in China.

BACKGROUND: The latent and incubation periods characterize the transmission of infectious viruses and are the basis for the development of outbreak prevention and control strategies. However, systematic studies on the latent period and associated factors with the incubation period for SAS-CoV-2 variants are still lacking. We inferred the two durations of Delta, BA.1, and BA.2 cases and analyzed the associated factors. METHODS: The Delta, BA.1, and BA.2 (and its lineages BA.2.2 and BA.2.76) cases with clear transmission chains and infectors from 10 local SAS-CoV-2 epidemics in China were enrolled. The latent and incubation periods were fitted by the Gamma distribution, and associated factors were analyzed using the accelerated failure time model. RESULTS: The mean latent period for 672 Delta, 208 BA.1, and 677 BA.2 cases was 4.40 (95%CI: 4.24 ~ 4.63), 2.50 (95%CI: 2.27 ~ 2.76), and 2.58 (95%CI: 2.48 ~ 2.69) days, respectively, with 85.65% (95%CI: 83.40 ~ 87.77%), 97.80% (95%CI: 96.35 ~ 98.89%), and 98.87% (95%CI: 98.40 ~ 99.27%) of them starting to shed viruses within 7 days after exposure. In 405 Delta, 75 BA.1, and 345 BA.2 symptomatic cases, the mean latent period was 0.76, 1.07, and 0.79 days shorter than the mean incubation period [5.04 (95%CI: 4.83 ~ 5.33), 3.42 (95%CI: 3.00 ~ 3.89), and 3.39 (95%CI: 3.24 ~ 3.55) days], respectively. No significant difference was observed in the two durations between BA.1 and BA.2 cases. After controlling for the sex, clinical severity, vaccination history, number of infectors, the length of exposure window and shedding window, the latent period [Delta: exp(ß) = 0.81, 95%CI: 0.66 ~ 0.98, p = 0.034; Omicron: exp(ß) = 0.82, 95%CI: 0.71 ~ 0.94, p = 0.004] and incubation period [Delta: exp(ß) = 0.69, 95%CI: 0.55 ~ 0.86, p < 0.001; Omicron: exp(ß) = 0.83, 95%CI: 0.72 ~ 0.96, p = 0.013] were significantly shorter in 18 ~ 49 years but did not change significantly in ≥ 50 years compared with 0 ~ 17 years. CONCLUSION: Pre-symptomatic transmission can occur in Delta, BA.1, and BA.2 cases. The latent and incubation periods between BA.1 and BA.2 were similar but shorter compared with Delta. Age may be associated with the latent and incubation periods of SARS-CoV-2.

Characteristics and outcomes of patients with COVID-19 at high risk of disease progression receiving sotrovimab, oral antivirals, or no treatment: a retrospective cohort study.

BACKGROUND: The clinical benefit of coronavirus disease 2019 (COVID-19) treatments against new circulating variants remains unclear. We sought to describe characteristics and clinical outcomes of highest risk patients with COVID-19 receiving early COVID-19 treatments in Scotland. METHODS: Retrospective cohort study of non-hospitalized patients diagnosed with COVID-19 from December 1, 2021-October 25, 2022, using Scottish administrative health data. We included adult patients who met ≥ 1 of the National Health Service highest risk criteria for early COVID-19 treatment and received outpatient treatment with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or no early COVID-19 treatment. Index date was defined as the earliest of COVID-19 diagnosis or early COVID-19 treatment. Baseline characteristics and acute clinical outcomes in the 28 days following index were reported. Values of ≤ 5 were suppressed. RESULTS: In total, 2548 patients were included (492: sotrovimab, 276: nirmatrelvir/ritonavir, 71: molnupiravir, and 1709: eligible highest risk untreated). Patients aged ≥ 75 years accounted for 6.9% (n = 34/492), 21.0% (n = 58/276), 16.9% (n = 12/71) and 13.2% (n = 225/1709) of the cohorts, respectively. Advanced renal disease was reported in 6.7% (n = 33/492) of sotrovimab-treated and 4.7% (n = 81/1709) of untreated patients, and ≤ 5 nirmatrelvir/ritonavir-treated and molnupiravir-treated patients. All-cause hospitalizations were experienced by 5.3% (n = 25/476) of sotrovimab-treated patients, 6.9% (n = 12/175) of nirmatrelvir/ritonavir-treated patients, ≤ 5 (suppressed number) molnupiravir-treated patients and 13.3% (n = 216/1622) of untreated patients. There were no deaths in the treated cohorts; mortality was 4.3% (n = 70/1622) among untreated patients. CONCLUSIONS: Sotrovimab was often used by patients who were aged < 75 years. Among patients receiving early COVID-19 treatment, proportions of 28-day all-cause hospitalization and death were low.

Unveiling the emergence of SARS-CoV-2 JN.1 sub-variant: Insights from the first cases at Charles Nicolle Hospital, Tunisia.

The JN.1 sub-variant is a new variant of the SARS-CoV-2 Omicron strain, derived from the BA.2.86 sub-variant. It was first detected in late 2023 and has quickly spread to many countries, becoming the most prevalent variant in some regions. JN.1 exhibits a unique mutation (L455S) in the spike protein compared to the BA.2.86 lineage, which may affect its transmissibility and immune evasion capabilities. JN.1 has been designated as a "variant of interest" by the World Health Organization due to its rapidly increasing spread and is being closely monitored for its impact on the COVID-19 pandemic. This study describes the emergence of SARS-CoV-2 JN.1 sub-variant in Tunisia, and reports its mutation profiles.Nasopharyngeal samples collected over a four-month period (October 2023 to January 2024) were subjected to RNA extraction and real-time RT-PCR confirmation of SARS-CoV-2 infection. The whole-genome sequencing was performed by an iSeq 100 sequencer and COVIDSeq kit reagents (Illumina, USA).Mutation analysis, using the NextClade platform and GISAID database, revealed the presence of JN.1 in 15 out of 80 positive cases (18.75%) during the study period.The emergence of JN.1 highlights the ongoing evolution of SARS-CoV-2 and the need for continued surveillance and research to better understand the characteristics and impact of emerging variants.

COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 BA.1/BA.2 lineages among adults and adolescents in a multicentre primary care study, Europe, December 2021 to June 2022.

BackgroundScarce European data in early 2021 suggested lower vaccine effectiveness (VE) against SARS-CoV-2 Omicron lineages than previous variants.AimWe aimed to estimate primary series (PS) and first booster VE against symptomatic BA.1/BA.2 infection and investigate potential biases.MethodsThis European test-negative multicentre study tested primary care patients with acute respiratory symptoms for SARS-CoV-2 in the BA.1/BA.2-dominant period. We estimated PS and booster VE among adults and adolescents (PS only) for all products combined and for Comirnaty alone, by time since vaccination, age and chronic condition. We investigated potential bias due to correlation between COVID-19 and influenza vaccination and explored effect modification and confounding by prior SARS-CoV-2 infection.ResultsAmong adults, PS VE was 37% (95% CI: 24-47%) overall and 60% (95% CI: 44-72%), 43% (95% CI: 26-55%) and 29% (95% CI: 13-43%) < 90, 90-179 and ≥ 180 days post vaccination, respectively. Booster VE was 42% (95% CI: 32-51%) overall and 56% (95% CI: 47-64%), 22% (95% CI: 2-38%) and 3% (95% CI: -78% to 48%), respectively. Primary series VE was similar among adolescents. Restricting analyses to Comirnaty had little impact. Vaccine effectiveness was higher among older adults. There was no signal of bias due to correlation between COVID-19 and influenza vaccination. Confounding by previous infection was low, but sample size precluded definite assessment of effect modification.ConclusionPrimary series and booster VE against symptomatic infection with BA.1/BA.2 ranged from 37% to 42%, with similar waning post vaccination. Comprehensive data on previous SARS-CoV-2 infection would help disentangle vaccine- and infection-induced immunity.

A longitudinal study on SARS-CoV-2 seroconversion, reinfection and neutralisation spanning several variant waves and vaccination campaigns, Heinsberg, Germany, April 2020 to November 2022.

BackgroundSince its emergence in December 2019, over 700 million people worldwide have been infected with SARS-CoV-2 up to May 2024. While early rollout of mRNA vaccines against COVID-19 has saved many lives, there was increasing immune escape of new virus variants. Longitudinal monitoring of population-wide SARS-CoV-2 antibody responses from regular sample collection irrespective of symptoms provides representative data on infection and seroconversion/seroreversion rates.AimTo examine adaptive and cellular immune responses of a German SARS-CoV-2 outbreak cohort through several waves of infection with different virus variants.MethodsUtilising a 31-month longitudinal seroepidemiological study (n = 1,446; mean age: 50 years, range: 2-103) initiated during the first SARS-CoV-2 superspreading event (February 2020) in Heinsberg, Germany, we analysed acute infection, seroconversion and virus neutralisation at five follow-up visits between October 2020 and November 2022; cellular and cross-protective immunity against SARS-CoV-2 Omicron variants were also examined.ResultsSARS-CoV-2 spike (S)-specific IgAs decreased shortly after infection, while IgGs remained stable. Both increased significantly after vaccination. We predict an 18-month half-life of S IgGs upon infection. Nucleocapsid (N)-specific responses declined over 12 months post-infection but increased (p < 0.0001) during Omicron. Frequencies of SARS-CoV-2-specific TNF-alpha+/IFN-gamma+ CD4+ T-cells declined over 12 months after infection (p < 0.01). SARS-CoV-2 S antibodies and neutralisation titres were highest in triple-vaccinated participants infected between April 2021 and November 2022 compared with infections between April 2020 and January 2021. Cross neutralisation against Omicron BQ.1.18 and XBB.1.5 was very low in all groups.ConclusionInfection and/or vaccination did not provide the population with cross-protection against Omicron variants.