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BA.2.86, a recently identified descendant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sublineage, contains â¼35 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.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , SARS-CoV-2 , Humanos , Anticuerpos Neutralizantes/metabolismo , Anticuerpos Antivirales/metabolismo , Caspasas/metabolismo , COVID-19/inmunología , COVID-19/virología , Pulmón/virología , SARS-CoV-2/clasificación , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , SARS-CoV-2/fisiología , Internalización del Virus , Glicoproteína de la Espiga del Coronavirus/genéticaRESUMEN
The rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodies but remained susceptible to inhibition by sotrovimab. Similarly, the Omicron spike evaded neutralization by antibodies from convalescent patients or individuals vaccinated with the BioNTech-Pfizer vaccine (BNT162b2) with 12- to 44-fold higher efficiency than the spike of the Delta variant. Neutralization of the Omicron spike by antibodies induced upon heterologous ChAdOx1 (Astra Zeneca-Oxford)/BNT162b2 vaccination or vaccination with three doses of BNT162b2 was more efficient, but the Omicron spike still evaded neutralization more efficiently than the Delta spike. These findings indicate that most therapeutic antibodies will be ineffective against the Omicron variant and that double immunization with BNT162b2 might not adequately protect against severe disease induced by this variant.
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Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Neutralizantes/inmunología , COVID-19/inmunología , COVID-19/virología , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Inmunidad Adaptativa , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , Anticuerpos Neutralizantes/farmacología , Anticuerpos Antivirales/inmunología , Vacuna BNT162/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Línea Celular , Chlorocebus aethiops , Femenino , Humanos , Masculino , Unión Proteica , SARS-CoV-2/química , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Vacunación , Células VeroRESUMEN
Patients undergoing chronic hemodialysis were among the first to receive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations because of their increased risk for severe coronavirus disease and high case-fatality rates. By using a previously reported cohort from Germany of at-risk hemodialysis patients and healthy donors, where antibody responses were examined 3 weeks after the second vaccination, we assessed systemic cellular and humoral immune responses in serum and saliva 4 months after vaccination with the Pfizer-BioNTech BNT162b2 vaccine using an interferon-γ release assay and multiplex-based IgG measurements. We further compared neutralization capacity of vaccination-induced IgG against 4 SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Delta) by angiotensin-converting enzyme 2 receptor-binding domain competition assay. Sixteen weeks after second vaccination, compared with 3 weeks after, cellular and humoral responses against the original SARS-CoV-2 isolate and variants of concern were substantially reduced. Some dialysis patients even had no detectable B- or T-cell responses.
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COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/virología , Vacunas contra la COVID-19 , Humanos , Inmunidad Humoral , ARN Mensajero , Diálisis Renal , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , VacunaciónRESUMEN
OBJECTIVES: People living with HIV (PLWH) with low CD4 T-cell counts may be at a higher risk for severe coronavirus disease 2019 (COVID-19) outcomes and in need of efficient vaccination. The World Health Organization (WHO) now recommends prioritizing PLHIV for COVID-19 vaccination. Data on immune responses after messenger RNA (mRNA) vaccination in PLHIV in relation to CD4 counts are scarce. We aimed at assessing the humoral immune response in PLHIV after mRNA vaccination against COVID-19. METHODS: We examined a cohort of PLHIV after prime (n = 88) and boost (n = 52) vaccination with BNT162b2. We assessed levels of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein-specific immunoglobulin G (IgG)/IgA and circulating neutralizing antibodies in plasma and correlated results to the cellular immune status. BNT162b2-vaccinated health care workers served as controls. RESULTS: All PLWH had a viral load of ≤ 200 HIV-1 RNA copies/mL and 96.5% had a viral load of < 50 copies/mL. Anti-S IgG and neutralizing antibody responses after BNT162b2 priming were significantly lower in PLHIV having a CD4:CD8 T-cell ratio of < 0.5. However, we observed robust humoral immunity in the majority of PLWH receiving antiretroviral therapy (ART) irrespective of CD4 T-cell nadir, current CD4 count or CD4:CD8 ratio after full BNT162b2 vaccination. Nevertheless, HIV-negative controls produced significantly higher mean anti-S IgG concentrations with less variability. CONCLUSIONS: The majority of PLWH mounted robust responses after complete BNT162b2 vaccination but overall amounts of antibodies directed against the SARS-CoV-2 receptor-binding domain were variable. The impact on clinical efficacy remains unclear.
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COVID-19 , Infecciones por VIH , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Infecciones por VIH/tratamiento farmacológico , Humanos , Inmunidad Humoral , Inmunoglobulina G , ARN Mensajero , SARS-CoV-2 , VacunaciónRESUMEN
BACKGROUND: Immunogenicity of SARS-CoV-2 vaccines is modestly impaired in cancer patients due to a generally weakened immune system. Immune checkpoint inhibitors (ICI) are expected to enhance immune response. This has already been described to be the case in influenza vaccines, and first data about COVID-19 vaccines show a trend in this direction. AIM: We aimed to investigate the immune response of patients with melanoma under ICI therapy after COVID-19 vaccination. PATIENTS AND METHODS: In the Skin Cancer Center Hanover (Germany), we recruited 60 patients with advanced melanoma who either received ICI therapy during or before the vaccination period. Serological blood analysis was performed using quantitative ELISA for Anti-SARS-CoV-2 spike protein 1 IgG antibodies. RESULTS: We did not observe an enhanced humoral immune response in patients under active or past ICI therapy after COVID-19 vaccination. Nevertheless, there is a tendency of higher antibody levels when ICI therapy was received within the last 6 months before vaccination. Subgroup analysis revealed that patients in our study population under ongoing targeted therapy during vaccination period had significantly higher median antibody levels than patients without any active antitumor treatment. CONCLUSION: Melanoma patients under ICI therapy show comparable antibody response after SARS-CoV-2 vaccination to healthy health care professionals. This finding is independent of the timing of ICI therapy.
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COVID-19 , Melanoma , Anticuerpos Antivirales/metabolismo , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Melanoma/tratamiento farmacológico , SARS-CoV-2 , VacunaciónRESUMEN
BACKGROUND: Immunocompromised people (ICP) and elderly individuals (older than 80 years) are at increased risk for severe coronavirus infections. To protect against serious infection with SARS-CoV-2, ICP are taking precautions that may include a reduction of social contacts and participation in activities which they normally enjoy. Furthermore, for these people, there is an uncertainty regarding the effectiveness of the vaccination. The COVID-19 Contact (CoCo) Immune study strives to characterize the immune response to COVID-19 vaccination in immunocompromised, elderly people, and patients with hematological or oncological diseases. The study uses blood-based screenings to monitor the humoral and cellular immune response in these groups after vaccination. Questionnaires and qualitative interviews are used to describe the level of social participation. METHODS: The CoCo Immune Study is a mixed methods prospective, longitudinal, observational study at two large university hospitals in Northern Germany. Starting in March 2021, it monitors anti-SARS-CoV-2 immune responses and collects information on social participation in more than 600 participants, at least 18 years old. Inclusion criteria and subcohorts: Participants with (1) regularly intake of immunosuppressive medication (ICP-cohort) or (2) age ≥ 80 years (80 + -cohort). Additionally, patients with current or former (3) myeloid, (4) lymphatic disease or (5) solid tumor under checkpoint inhibition (3-5: HO-cohort). EXCLUSION CRITERIA: (1) refusal to give informed consent, (2) contraindication to blood testing, (3) inability to declare consent. Participants complete a questionnaire at four different time points: prior to full vaccination, and 1, 6 and 12 months after completed vaccination. In addition, participants draw blood samples themselves or through a local health care provider and send them with their questionnaires per post at the respective time points after vaccination. Patients of the HO cohort dispense additional blood samples at week 3 to 12 and at month 6 to 9 after 2nd vaccination to gain additional knowledge in B and T cell responses. Selected participants are invited to qualitative interviews about social participation. DISCUSSION: This observational study is designed to gain insight into the immune response of people with weakened immune systems and to find out how social participation is affected after COVID-19 vaccination. TRIAL REGISTRATION: This study was registered with German Clinical Trial Registry (registration number: DRKS00023972) on 30th December 2020.
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COVID-19 , Enfermedades Hematológicas , Neoplasias , Adolescente , Anciano , Anciano de 80 o más Años , Vacunas contra la COVID-19 , Cocos , Humanos , Inmunidad , Estudios Observacionales como Asunto , Estudios Prospectivos , SARS-CoV-2 , Resultado del TratamientoRESUMEN
Recently, a recombinant SARS-CoV-2 lineage, XD, emerged that harbors a spike gene that is largely derived from the Omicron variant BA.1 in the genetic background of the Delta variant. This finding raised concerns that the recombinant virus might exhibit altered biological properties as compared to the parental viruses and might pose an elevated threat to human health. Here, using pseudotyped particles, we show that ACE2 binding and cell tropism of XD mimics that of BA.1. Further, XD and BA.1 displayed comparable sensitivity to neutralization by antibodies induced upon vaccination with BNT162b2/Comirnaty (BNT) or BNT vaccination followed by breakthrough infection. Our findings reveal important biological commonalities between XD and Omicron BA.1 host cell entry and its inhibition by antibodies.
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COVID-19 , Glicoproteína de la Espiga del Coronavirus , Humanos , Glicoproteína de la Espiga del Coronavirus/genética , SARS-CoV-2/genética , Proteínas del Envoltorio Viral/genética , Vacuna BNT162 , Glicoproteínas de Membrana/metabolismoRESUMEN
BACKGROUND: Telemedicine was implemented in outpatient care during the lockdown between March and May 2020. The aim of the study was to assess patients from a private practice and the university outpatient department with respect to patient satisfaction with telemedicine, COVID-19 worries and vaccination behavior and to compare the teleconsultation by a medical assistant for rheumatology (RFA) and a physician. METHODS: Patients with rheumatoid arthritis, psoriatric arthropathy or spondylarthritis without treatment modifications since the previous presentation were offered a telemedical replacement appointment within the framework of this study in the case of appointment cancellation by the treating center. Participants were randomized to a telemedicine appointment by a physician or an RFA (RFA university only). The patient history was carried out by telephone and standardized using a questionnaire. The disease activity was determined using the modified clinical disease activity score (CDAI) and the BASDAI. Subsequently, all patients received a pseudonymized evaluation questionnaire. RESULTS: In total 112/116 (96%) patients participated. Of these 88/112 (79%) returned the questionnaire. The RFAs conducted 19/112 (17%) of the telephone calls. The treatment was modified in 19/112 (17%) patients. Concerns about contracting COVID-19 correlated with high disease activity (pâ¯= 0.031) including the presence of painful joints (pâ¯= 0.001) and high pain levels (VAS ≥7, pâ¯= 0.009). These patients would have also cancelled their appointment themselves (pâ¯= 0.015). Patient satisfaction with the consultation was good (mean 4.3/5.0 modified FAPI) independent of the institution, the duration of the consultation and the consultation partner. Patients with a high pain intensity were the least satisfied (pâ¯= 0.036). Only 42/100 (38.2%) of the patients had been vaccinated against pneumococci and 59/100 (53.6%) against influenza. CONCLUSION: Telemedical care within the framework of a telephone consultation is well-suited for selected patients. With respect to patient satisfaction the delegation of a telemedical consultation to an RFA is possible. There is a need for improvement with respect to the vaccination behavior.
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COVID-19 , Consulta Remota , Reumatología , Telemedicina , COVID-19/epidemiología , COVID-19/prevención & control , Control de Enfermedades Transmisibles , Humanos , Satisfacción del Paciente , SARS-CoV-2 , Telemedicina/métodos , Teléfono , VacunaciónRESUMEN
BACKGROUND: Vaccine-induced neutralizing antibodies are key in combating the coronavirus disease 2019 (COVID-19) pandemic. However, delays of boost immunization due to limited availability of vaccines may leave individuals vulnerable to infection and prolonged or severe disease courses. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC)-B.1.1.7 (United Kingdom), B.1.351 (South Africa), and P.1 (Brazil)-may exacerbate this issue, as the latter two are able to evade control by antibodies. METHODS: We assessed humoral and T-cell responses against SARS-CoV-2 wild-type (WT), VOC, and endemic human coronaviruses (hCoVs) that were induced after single and double vaccination with BNT162b2. RESULTS: Despite readily detectable immunoglobulin G (IgG) against the receptor-binding domain of the SARS-CoV-2 S protein at day 14 after a single vaccination, inhibition of SARS-CoV-2 S-driven host cell entry was weak and particularly low for the B.1.351 variant. Frequencies of SARS-CoV-2 WT and VOC-specific T cells were low in many vaccinees after application of a single dose and influenced by immunity against endemic hCoV. The second vaccination significantly boosted T-cell frequencies reactive for WT and B.1.1.7 and B.1.351 variants. CONCLUSIONS: These results call into question whether neutralizing antibodies significantly contribute to protection against COVID-19 upon single vaccination and suggest that cellular immunity is central for the early defenses against COVID-19.
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Vacuna BNT162/inmunología , COVID-19 , Inmunidad Celular , Inmunidad Humoral , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/inmunología , COVID-19/prevención & control , Humanos , Inmunoglobulina G/sangre , Glicoproteína de la Espiga del Coronavirus/inmunología , Linfocitos T/inmunología , VacunaciónRESUMEN
There have been concerns about high rates of thus far undiagnosed SARS-CoV-2 infections in the health-care system. The COVID-19 Contact (CoCo) Study follows 217 frontline health-care professionals at a university hospital with weekly SARS-CoV-2-specific serology (IgA/IgG). Study participants estimated their personal likelihood of having had a SARS-CoV-2 infection with a mean of 21% [median 15%, interquartile range (IQR) 5-30%]. In contrast, anti-SARS-CoV-2 IgG prevalence was about 1-2% at baseline. Regular anti-SARS-CoV-2 IgG testing of health-care professionals may aid in directing resources for protective measures and care of COVID-19 patients in the long run.
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Anticuerpos Antivirales/sangre , Infecciones por Coronavirus/inmunología , Personal de Salud , Neumonía Viral/inmunología , Adolescente , Adulto , Anciano , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/diagnóstico , Femenino , Alemania , Hospitales Universitarios , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico , Prevalencia , SARS-CoV-2 , Estudios Seroepidemiológicos , Pruebas Serológicas , Adulto JovenRESUMEN
Transmissibility and immune evasion of the recently emerged, highly mutated SARS-CoV-2 BA.2.87.1 are unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for efficient spread in the population.
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In July/August 2023, the highly mutated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2.86 lineage emerged and its descendant JN.1 is on track to become the dominant SARS-CoV-2 lineage globally. Compared to the spike (S) protein of the parental BA.2.86 lineage, the JN.1 S protein contains one mutation, L455S, which may affect receptor binding and antibody evasion. Here, we performed a virological assessment of the JN.1 lineage employing pseudovirus particles bearing diverse SARS-CoV-2 S proteins. Using this strategy, it was found that S protein mutation L455S confers increased neutralization resistance but reduces ACE2 binding capacity and S protein-driven cell entry efficiency. Altogether, these data suggest that the benefit of increased antibody evasion outweighs the reduced ACE2 binding capacity and further enabled the JN.1 lineage to effectively spread in the human population.
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BACKGROUND: Human immune responses to COVID-19 vaccines display a large heterogeneity of induced immunity and the underlying immune mechanisms for this remain largely unknown. METHODS: Using a systems biology approach, we longitudinally profiled a unique cohort of female high and low responders to the BNT162b vaccine, who were known from previous COVID-19 vaccinations to develop maximum and minimum immune responses to the vaccine. We utilized high dimensional flow cytometry, bulk and single cell mRNA sequencing and 48-plex serum cytokine analyses. FINDINGS: We revealed early, transient immunological and molecular signatures that distinguished high from low responders and correlated with B and T cell responses measured 14 days later. High responders featured a distinct transcriptional activity of interferon-driven genes and genes connected to enhanced antigen presentation. This was accompanied by a robust cytokine response related to Th1 differentiation. Both transcriptome and serum cytokine signatures were confirmed in two independent confirmatory cohorts. INTERPRETATION: Collectively, our data contribute to a better understanding of the immunogenicity of mRNA-based COVID-19 vaccines, which might lead to the optimization of vaccine designs for individuals with poor vaccine responses. FUNDING: German Center for Infection Research, German Center for Lung Research, German Research Foundation, Excellence Strategy EXC 2155 "RESIST" and European Regional Development Fund.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Femenino , COVID-19/prevención & control , Citocinas/genética , Vacunación , Biología de Sistemas/métodos , ARN Mensajero , Anticuerpos AntiviralesRESUMEN
Introduction: Migrant healthcare workers played an important role during the COVID-19 pandemic, but data are lacking especially for high-resourced European healthcare systems. This study aims to research migrant healthcare workers through an intersectional health system-related approach, using Germany as a case study. Methods: An intersectional research framework was created and a rapid scoping study performed. Secondary analysis of selected items taken from two COVID-19 surveys was undertaken to compare perceptions of national and foreign-born healthcare workers, using descriptive statistics. Results: Available research is focused on worst-case pandemic scenarios of Brazil and the United Kingdom, highlighting racialised discrimination and higher risks of migrant healthcare workers. The German data did not reveal significant differences between national-born and foreign-born healthcare workers for items related to health status including SARS-CoV-2 infection and vaccination, and perception of infection risk, protective workplace measures, and government measures, but items related to social participation and work conditions with higher infection risk indicate a higher burden of migrant healthcare workers. Conclusions: COVID-19 pandemic policy must include migrant healthcare workers, but simply adding the migration status is not enough. We introduce an intersectional health systems-related approach to understand how pandemic policies create social inequalities and how the protection of migrant healthcare workers may be improved.
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COVID-19 , Migrantes , Humanos , COVID-19/epidemiología , Pandemias/prevención & control , SARS-CoV-2 , Personal de Salud , Atención a la SaludRESUMEN
Since early 2022, various Omicron variants have dominated the SARS-CoV-2 pandemic in most countries. All Omicron variants are B-cell immune escape variants, and antibodies induced by first-generation COVID-19 vaccines or by infection with earlier SARS-CoV-2 variants largely fail to protect individuals from Omicron infection. In the present study, we investigated the effect of Omicron infections in triple-vaccinated and in antigen-naive individuals. We show that Omicron breakthrough infections occurring 2-3.5 months after the third vaccination restore B-cell and T-cell immune responses to levels similar to or higher than those measured 14 days after the third vaccination, including the induction of Omicron-neutralizing antibodies. Antibody responses in breakthrough infection derived mostly from cross-reacting B cells, initially induced by vaccination, whereas Omicron infections in antigen-naive individuals primarily generated B cells binding to the Omicron but not the Wuhan spike protein. Although antigen-naive individuals mounted considerable T-cell responses after infection, B-cell responses were low, and neutralizing antibodies were frequently below the limit of detection. In summary, the detection of Omicron-associated B-cell responses in primed and in antigen-naive individuals supports the application of Omicron-adapted COVID-19 vaccines, but calls into question their suitability if they also contain/encode antigens of the original Wuhan virus.
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COVID-19 , Humanos , Vacunas contra la COVID-19 , SARS-CoV-2 , Anticuerpos Neutralizantes , Infección IrruptivaRESUMEN
Introduction: This study analyses how healthcare workers (HCWs) perceived risks, protection and preventive measures during the COVID-19 pandemic in relation to medically approved risks and organizational measures. The aim is to explore "blind spots" of pandemic protection and make mental health needs of HCWs visible. Methods: We have chosen an "optimal-case" scenario of a high-income country with a well-resourced hospital sector and low HCW infection rate at the organizational level to explore governance gaps in HCW protection. A German multi-method hospital study at Hannover Medical School served as empirical case; document analysis, expert information and survey data (n = 1,163) were collected as part of a clinical study into SARS-CoV-2 serology testing during the second wave of the pandemic (November 2020-February 2021). Selected survey items included perceptions of risks, protection and preventive measures. Descriptive statistical analysis and regression were undertaken for gender, profession and COVID-19 patient care. Results: The results reveal a low risk of 1% medically approved infections among participants, but a much higher mean personal risk estimate of 15%. The majority (68.4%) expressed "some" to "very strong" fear of acquiring infection at the workplace. Individual protective behavior and compliance with protective workplace measures were estimated as very high. Yet only about half of the respondents felt strongly protected by the employer; 12% even perceived "no" or "little" protection. Gender and contact with COVID-19 patients had no significant effect on the estimations of infection risks and protective workplace behavior, but nursing was correlated with higher levels of personal risk estimations and fear of infection. Conclusions: A strong mismatch between low medically approved risk and personal risk perceptions of HCWs brings stressors and threats into view, that may be preventable through better information, training/education and risk communication and through investment in mental health and inclusion in pandemic preparedness plans.
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COVID-19 , Pandemias , COVID-19/epidemiología , Personal de Salud/psicología , Hospitales , Humanos , Salud Mental , Pandemias/prevención & control , SARS-CoV-2RESUMEN
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitates viral entry into host cells and is the key target for neutralizing antibodies. The SARS-CoV-2 lineage B.1.620 carries fifteen mutations in the S protein and is spread in Africa, the US and Europe, while lineage R.1 harbors four mutations in S and infections were observed in several countries, particularly Japan and the US. However, the impact of the mutations in B.1.620 and R.1 S proteins on antibody-mediated neutralization and host cell entry are largely unknown. Here, we report that these mutations are compatible with robust ACE2 binding and entry into cell lines, and they markedly reduce neutralization by vaccine-induced antibodies. Our results reveal evasion of neutralizing antibodies by B.1.620 and R.1, which might have contributed to the spread of these lineages.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus , Enzima Convertidora de Angiotensina 2 , Internalización del Virus , Peptidil-Dipeptidasa A/metabolismo , Anticuerpos Neutralizantes , Anticuerpos Antivirales , MutaciónRESUMEN
The Omicron variant of SARS-CoV-2 evades antibody-mediated neutralization with unprecedented efficiency. At least three Omicron sublineages have been identified-BA.1, BA.2, and BA.3-and BA.2 exhibits increased transmissibility. However, it is currently unknown whether BA.2 differs from the other sublineages regarding cell entry and antibody-mediated inhibition. Here, we show that BA.1, BA.2, and BA.3 enter and fuse target cells with similar efficiency and in an ACE2-dependent manner. However, BA.2 was not efficiently neutralized by seven of eight antibodies used for COVID-19 therapy, including Sotrovimab, which robustly neutralized BA.1. In contrast, BA.2 and BA.3 (but not BA.1) were appreciably neutralized by Cilgavimab, which could constitute a treatment option. Finally, all sublineages were comparably and efficiently neutralized by antibodies induced by BNT162b2 booster vaccination after previous two-dose homologous or heterologous vaccination. Collectively, the Omicron sublineages show comparable cell entry and neutralization by vaccine-induced antibodies but differ in susceptibility to therapeutic antibodies.
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Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Anticuerpos Monoclonales , Anticuerpos Monoclonales Humanizados , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/uso terapéutico , Vacuna BNT162 , Humanos , Internalización del VirusRESUMEN
BACKGROUND: With population-wide vaccination availability, the global COVID-19 pandemic entered a new phase. Despite vaccination status, some people who were infected with SARS-CoV-2 experience long-term symptoms. OBJECTIVE: In this study, we aim to characterize the long-term effects of SARS-CoV-2 infection and the pandemic. We also aim to build symptom clusters and determine risk factors for developing long COVID symptoms. Furthermore, we assess social participation and health-related quality of life in patients with long COVID and in the general population during a global pandemic. METHODS: With a mixed-methods, web-based approach, we aim to recruit 2000 people in Germany who are older than 18 years and can provide informed consent. In the quantitative arm of the study, we identify symptoms of and predictive factors for long COVID manifestations with cluster analysis and assess social participation during the pandemic with standardized questionnaires. The qualitative arm of the study uses individual interviews and focus group discussions to better understand the illness experience of persons who experience long COVID. RESULTS: Recruitment started in September 2021. Up until July 2022, we recruited approximately 4500 participants via our web-based database. CONCLUSIONS: This study aims to build an innovative, patient-centered, web-based research platform appropriate for the pandemic by minimizing physical contact between study personnel and participants. All study activities are designed to better understand the long COVID syndrome, social participation during the pandemic, and the illness experiences of persons affected by long COVID. TRIAL REGISTRATION: German Clinical Trial Registry DRKS00026007; https://tinyurl.com/yh282fkt. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38718.