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Summary: The Omicron variant of SARS-CoV-2 is highly resistant to neutralizing antibodies, which raises concerns about the effectiveness of antibody therapies and vaccines. A study found that individuals who received two or three doses of an inactivated SARS-CoV-2 vaccine had varying rates of seroconversion for neutralizing antibodies. The effectiveness of neutralizing antibodies against Omicron was significantly lower in individuals who received three vaccine doses. However, monoclonal antibodies derived from individuals who received three vaccine doses showed strong neutralizing activity against all variants of concern, including Omicron.
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Summary: Omicron sublineages BA.2.12.1, BA.4 and BA.5 have higher transmissibility and increased evasion of neutralizing antibodies compared to the BA.2 lineage. They exhibit similar binding affinities to the ACE2 receptor as BA.2. BA.1 infection after vaccination boosts humoral immune memory against wild-type SARS-CoV-2, but these antibodies are largely evaded by BA.2 and BA.4/BA.5 variants.
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Summary: Here, researchers successfully screened and isolated a broadly neutralizing antibody ZCB11 that can neutralize all variants of concern of SARS-CoV-2, showing particularly potent activity against the Omicron variant. Further studies demonstrated that ZCB11 predominantly interacts with the receptor-binding domain of the Omicron variant, blocking ACE2 binding. Prophylactic or therapeutic administration of ZCB11 protected against lung infection in animal models challenged with the Omicron variant.
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Summary: The Omicron subvariants of SARS-CoV-2 have caused a global crisis as they are resistant to most approved neutralizing antibodies and evade vaccination-induced antibodies. In this study, researchers describe a mouse model that produces a diverse repertoire of humanized SARS-CoV-2 neutralizing antibodies. Through immunization with SARS-CoV-2 spike protein, they identified a potent and broadly neutralizing antibody, SP1-77, which bound to the receptor-binding domain in a unique way. This antibody showed potential therapeutic value and could inform vaccine strategies. Furthermore, this humanized mouse model may contribute to the development of therapeutic antibodies against future SARS-CoV-2 variants and other pathogens.
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Summary: The newly emerged SARS-CoV-2 Omicron subvariant BA.2.75 exhibits moderate resistance to neutralization by sera from vaccinated/boosted individuals compared to the currently circulating BA.2, but is more sensitive than BA.4/5. BA.2.75 shows heightened resistance to class 1 and class 3 monoclonal antibodies targeting the spike-receptor-binding domain, while gaining sensitivity to class 2 antibodies. The resistance is mainly conferred by two mutations. BA.2.75 also shows slight resistance to a therapeutic antibody with potent activity against all Omicron subvariants. Additionally, BA.2.75 exhibits higher binding affinity to the host receptor ACE2 compared to other Omicron subvariants.
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Dan-Yu Lin et al.
Summary: The study shows that COVID-19 vaccination and prior SARS-CoV-2 infection are associated with the risk of SARS-CoV-2 infection, hospitalization, and death. While vaccination can lower the risk of infection, the protection wanes over time.
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Ewen Callaway
Summary: Descendants of Omicron are spreading rapidly worldwide, and the same mutations are emerging repeatedly.
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Nicole P. Hachmann et al.
Summary: Neutralization titers against omicron subvariant BA.4.6 were lower compared to subvariants BA.4 and BA.5 induced by infection or vaccination against SARS-CoV-2.
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Fiona P. Havers et al.
Summary: Understanding the factors that contribute to hospitalization in vaccinated individuals is crucial for combating COVID-19. This study found that unvaccinated adults were more likely to be hospitalized compared to vaccinated adults, with the lowest hospitalization rates observed in those who had received a booster dose.
JAMA INTERNAL MEDICINE
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Daniel Ayoubkhani et al.
Summary: Vaccination reduces the incidence of long COVID, highlighting the importance of increasing population-level vaccine uptake through public health initiatives.
OPEN FORUM INFECTIOUS DISEASES
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Lei Wang et al.
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Sho Iketani et al.
Summary: The identification of the Omicron variant of SARS-CoV-2 in Botswana in November 2021 sparked concern due to the spike protein alterations that could potentially evade antibodies. Further studies showed that the Omicron sublineages, BA.1+R346K and BA.2, are antigenically similar to the wild-type virus and pose similar risks to the effectiveness of current vaccines. BA.2 also demonstrated resistance to many neutralizing monoclonal antibodies, highlighting the challenges in developing effective therapeutic options.
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Medicine, General & Internal
Mark W. Tenforde et al.
Summary: This study evaluated the association between mRNA COVID-19 vaccines and COVID-19 hospitalization, as well as disease progression to critical illness among hospitalized patients. The results showed that vaccination with mRNA COVID-19 vaccines significantly decreased the likelihood of COVID-19 hospitalization and disease progression to death or mechanical ventilation.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
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Pengfei Wang et al.
Summary: The COVID-19 pandemic has had global repercussions, with promising vaccines and monoclonal antibody therapies. However, newly detected variants of SARS-CoV-2 present challenges to these treatment options.
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Yunlong Cao et al.
Summary: The study found that the diversity of anti-RBD NAbs plays a major role in neutralization against SARS-CoV-2 variants, especially 501Y.V2, with E484K being the dominant cause of neutralization reduction. Specific antibodies respond differently to mutations in RBD variants, with lower diversity observed in NTD antibodies. RBD-subunit vaccinees exhibit higher tolerance to neutralization against variants, while extending the interval between doses of ZF2001 enhances neutralizing activity and tolerance to variants.
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Aine O'Toole et al.
Summary: The global virus genomics community has responded unprecedentedly to the SARS-CoV-2 pandemic, leading to significant advances in 'real-time' generation and sharing of genomic data. The development of new analytical methods, such as pangolin, has been necessary to handle the rapid growth in virus genome data production. Pangolin has processed nearly two million virus genomes, aiding in SARS-CoV-2 genomic epidemiology and providing researchers with valuable information about the pandemic's transmission lineages.
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