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SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States and South Africa, respectively 1 , 2 . These new subvariants carrying further mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain 3 . The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies. Findings from a systematic antigenic analysis of these surging Omicron subvariants that this lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.

The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single and combination therapies with monoclonal antibodies have received emergency use authorization 1 – 3 , and more treatments are under development 4 – 7 . Furthermore, multiple vaccine constructs have shown promise 8 , including two that have an approximately 95% protective efficacy against COVID-19 9 , 10 . However, these interventions were directed against the initial SARS-CoV-2 virus that emerged in 2019. The recent detection of SARS-CoV-2 variants B.1.1.7 in the UK 11 and B.1.351 in South Africa 12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. Here we show that B.1.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclonal antibodies against the receptor-binding domain. It is not more resistant to plasma from individuals who have recovered from COVID-19 or sera from individuals who have been vaccinated against SARS-CoV-2. The B.1.351 variant is not only refractory to neutralization by most monoclonal antibodies against the N-terminal domain but also by multiple individual monoclonal antibodies against the receptor-binding motif of the receptor-binding domain, which is mostly due to a mutation causing an E484K substitution. Moreover, compared to wild-type SARS-CoV-2, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4-fold) and sera from individuals who have been vaccinated (10.3–12.4-fold). B.1.351 and emergent variants 13 , 14 with similar mutations in the spike protein present new challenges for monoclonal antibody therapies and threaten the protective efficacy of current vaccines. The SARS-CoV-2 variant B.1.1.7 can be neutralized by convalescent sera or sera from vaccinated individuals, whereas the B.1.351 variant is resistant to neutralization by these sera and by several monoclonal antibodies that are in clinical use.

The identification of the Omicron (B.1.1.529.1 or BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Botswana in November 2021 1 immediately caused concern owing to the number of alterations in the spike glycoprotein that could lead to antibody evasion. We 2 and others 3 – 6 recently reported results confirming such a concern. Continuing surveillance of the evolution of Omicron has since revealed the rise in prevalence of two sublineages, BA.1 with an R346K alteration (BA.1+R346K, also known as BA.1.1) and B.1.1.529.2 (BA.2), with the latter containing 8 unique spike alterations and lacking 13 spike alterations found in BA.1. Here we extended our studies to include antigenic characterization of these new sublineages. Polyclonal sera from patients infected by wild-type SARS-CoV-2 or recipients of current mRNA vaccines showed a substantial loss in neutralizing activity against both BA.1+R346K and BA.2, with drops comparable to that already reported for BA.1 (refs. 2 , 3 , 5 , 6 ). These findings indicate that these three sublineages of Omicron are antigenically equidistant from the wild-type SARS-CoV-2 and thus similarly threaten the efficacies of current vaccines. BA.2 also exhibited marked resistance to 17 of 19 neutralizing monoclonal antibodies tested, including S309 (sotrovimab) 7 , which had retained appreciable activity against BA.1 and BA.1+R346K (refs. 2 – 4 , 6 ). This finding shows that no authorized monoclonal antibody therapy could adequately cover all sublineages of the Omicron variant, except for the recently authorized LY-CoV1404 (bebtelovimab). A study reports on the antigenic characterization of SARS-CoV-2 BA.1, BA.1.1 and BA.2 and the neutralizing activity of different monoclonal antibodies and sera against them.

Tenofovir disoproxil fumarate can cause renal and bone toxic effects related to high plasma tenofovir concentrations. Tenofovir alafenamide is a novel tenofovir prodrug with a 90% reduction in plasma tenofovir concentrations. Tenofovir alafenamide-containing regimens can have improved renal and bone safety compared with tenofovir disoproxil fumarate-containing regimens. In these two controlled, double-blind phase 3 studies, we recruited treatment-naive HIV-infected patients with an estimated creatinine clearance of 50 mL per min or higher from 178 outpatient centres in 16 countries. Patients were randomly assigned (1:1) to receive once-daily oral tablets containing 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 10 mg tenofovir alafenamide (E/C/F/tenofovir alafenamide) or 300 mg tenofovir disoproxil fumarate (E/C/F/tenofovir disoproxil fumarate) with matching placebo. Randomisation was done by a computer-generated allocation sequence (block size 4) and was stratified by HIV-1 RNA, CD4 count, and region (USA or ex-USA). Investigators, patients, study staff, and those assessing outcomes were masked to treatment group. All participants who received one dose of study drug were included in the primary intention-to-treat efficacy and safety analyses. The main outcomes were the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48 as defined by the the US Food and Drug Adminstration (FDA) snapshot algorithm (pre-specified non-inferiority margin of 12%) and pre-specified renal and bone endpoints at 48 weeks. These studies are registered with ClinicalTrials.gov, numbers NCT01780506 and NCT01797445. We recruited patients from Jan 22, 2013, to Nov 4, 2013 (2175 screened and 1744 randomly assigned), and gave treatment to 1733 patients (866 given E/C/F/tenofovir alafenamide and 867 given E/C/F/tenofovir disoproxil fumarate). E/C/F/tenofovir alafenamide was non-inferior to E/C/F/tenofovir disoproxil fumarate, with 800 (92%) of 866 patients in the tenofovir alafenamide group and 784 (90%) of 867 patients in the tenofovir disoproxil fumarate group having plasma HIV-1 RNA less than 50 copies per mL (adjusted difference 2·0%, 95% CI −0·7 to 4·7). Patients given E/C/F/tenofovir alafenamide had significantly smaller mean serum creatinine increases than those given E/C/F/tenofovir disoproxil fumarate (0·08 vs 0·12 mg/dL; p<0·0001), significantly less proteinuria (median % change −3 vs 20; p<0·0001), and a significantly smaller decrease in bone mineral density at spine (mean % change −1·30 vs –2·86; p<0·0001) and hip (−0·66 vs –2·95; p<0·0001) at 48 weeks. Through 48 weeks, more than 90% of patients given E/C/F/tenofovir alafenamide or E/C/F/tenofovir disoproxil fumarate had virological success. Renal and bone effects were significantly reduced in patients given E/C/F/tenofovir alafenamide. Although these studies do not have the power to assess clinical safety events such as renal failure and fractures, our data suggest that E/C/F/tenofovir alafenamide will have a favourable long-term renal and bone safety profile. Gilead Sciences.

HIV infection has been associated with an increased risk of fragility fracture. We explored whether or not this increased risk persisted in HIV infected and uninfected men when controlling for traditional fragility fracture risk factors. Cox regression models were used to assess the association of HIV infection with the risk for incident hip, vertebral, or upper arm fracture in male Veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC). We calculated adjusted hazard ratios comparing HIV status and controlling for demographics and other established risk factors. The sample consisted of 119,318 men, 33% of whom were HIV infected (34% aged 50 years or older at baseline, and 55% black or Hispanic). Median body mass index (BMI) was lower in HIV infected compared with uninfected men (25 vs. 28 kg/m²; p<0.0001). Unadjusted risk for fracture was higher among HIV infected compared with uninfected men [HR: 1.32 (95% CI: 1.20, 1.47)]. After adjusting for demographics, comorbid disease, smoking and alcohol abuse, HIV infection remained associated with an increased fracture risk [HR: 1.24 (95% CI: 1.11, 1.39)]. However, adjusting for BMI attenuated this association [HR: 1.10 (95% CI: 0.97, 1.25)]. The only HIV-specific factor associated with fragility fracture was current protease inhibitor use [HR: 1.41 (95% CI: 1.16, 1.70)]. HIV infection is associated with fragility fracture risk. This risk is attenuated by BMI.

Background Older persons living with HIV (PLWH) need routine healthcare to manage HIV and other comorbidities. This mixed methods study investigated digital equity, constituted as access, use and quality, of HIV and specialty telehealth services for PLWH > 50 years during the initial wave of the COVID-19 pandemic when services transitioned to remote care. Methods A survey of closed and open-ended questions was administered to 80 English ( N  = 63) and Spanish ( N  = 17) speaking PLWH receiving HIV care at an Academic Medical Center ( N  = 50) or a Federally Qualified Health Center ( N  = 30) in New York State. Quantitative analyses examined characteristics predicting telehealth use and visit quality. Qualitative analyses utilized thematic coding to reveal common experiences. Results were integrated to deepen the interpretation. Results Telehealth access and use were shaped by multiple related and unstable factors including devices and connectivity, technology literacy, and comfort including privacy concerns. Participants demonstrated their substantial effort to achieve the visit. The majority of patients with a telehealth visit perceived it as worse than an in-person visit by describing it as less interpersonal, and resulting in poorer outcomes, particularly participants with less formal education. Technology was not only a barrier to access, but also influenced perceptions of quality. Conclusions In the COVID-19 pandemic initial wave, barriers to using telehealth were unequally distributed to those with more significant access and use challenges. Beyond these barriers, examining the components of equity indicate further challenges replicating in-person care using telehealth formats for older PLWH. Work remains to establish telehealth as both equitable and desirable for this population.

Women experience a higher incidence of oral diseases including periodontal diseases and temporomandibular joint disease (TMD) implicating the role of estrogen signaling in disease pathology. Fluctuating levels of estrogen during childbearing age potentiates facial pain, high estrogen levels during pregnancy promote gingivitis, and low levels of estrogen during menopause predisposes the TMJ to degeneration and increases alveolar bone loss. In this review, an overview of estrogen signaling pathways in vitro and in vivo that regulate pregnancy-related gingivitis, TMJ homeostasis, and alveolar bone remodeling is provided. Deciphering the specific estrogen signaling pathways for individual oral diseases is crucial for potential new drug therapies to promote and maintain healthy tissue.

The coronavirus disease 2019 (COVID-19) pandemic affected people at all ages. Whereas pregnant women seemed to have a worse course of disease than age-matched non-pregnant women, the risk of feto-placental infection is low. Using a cohort of 66 COVID-19-positive women in late pregnancy, we correlated clinical parameters with disease severity, placental histopathology, and the expression of viral entry and Interferon-induced transmembrane (IFITM) antiviral transcripts. All newborns were negative for SARS-CoV-2. None of the demographic parameters or placental histopathological characteristics were associated with disease severity. The fetal-maternal transfer ratio for IgG against the N or S viral proteins was commonly less than one, as recently reported. We found that the expression level of placental ACE2, but not TMPRSS2 or Furin, was higher in women with severe COVID-19. Placental expression of IFITM1 and IFITM3, which have been implicated in antiviral response, was higher in participants with severe disease. We also showed that IFITM3 protein expression, which localized to early and late endosomes, was enhanced in severe COVID-19. Our data suggest an association between disease severity and placental SARS-CoV-2 processing and antiviral pathways, implying a role for these proteins in placental response to SARS-CoV-2.

We studied plasma antibody responses of 35 patients about 1 month after SARS-CoV-2 infection. Titers of antibodies binding to the viral nucleocapsid and spike proteins were significantly higher in patients with severe disease. Likewise, mean antibody neutralization titers against SARS-CoV-2 pseudovirus and live virus were higher in the sicker patients, by ∼5-fold and ∼7-fold, respectively. These findings have important implications for those pursuing plasma therapy, isolation of neutralizing monoclonal antibodies, and determinants of immunity.

Children living with HIV (CLHIV) have decreased bone mineral content (BMC) and density (BMD), increasing risk for fracture and future osteoporosis. While DXA is the gold-standard for bone assessments, it lacks availability in resource-constrained settings (RCS). Quantitative ultrasound (QUS) offers an alternative owing to its portability, low cost, ease of handling, and lack of ionizing radiation. While QUS has detected reduced bone quality in CLHIV, the relationship between QUS and DXA in this population remains unexplored. At baseline and 12 months, BMC and BMD of the whole body, lumbar spine, and radius were measured by DXA in a longitudinal cohort of CLHIV in Johannesburg, South Africa. Calcaneal speed of sound (SOS) and broadband ultrasound attenuation (BUA) and radius SOS were obtained by QUS, and calcaneal stiffness index (SI) was calculated. Spearman correlations, with and without HIV stratification, were performed between QUS and DXA measurements at each visit and for absolute difference in measurements between visits. At baseline and 12-months, calcaneal BUA and SI displayed strong positive correlations with DXA, with only modest correlations between radial QUS and DXA at baseline. Longitudinal measures of QUS did not correlate with DXA. At both baseline and 12-months, individuals with DXA whole-body BMD z -score < -1 displayed significantly lower calcaneal BUA and SI. Cross-sectionally, calcaneal QUS correlates strongly with whole body DXA and may represent a viable diagnostic alternative in RCS. Longitudinally, the two methods do not correlate well, possibly reflecting that each method assesses distinct aspects of bone architecture.