RESUMEN
The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued, enabling the virus to escape from host immunity by changing its spike antigen, while biased toward the receptor-binding domain and N-terminal domain. Here, we isolated a novel pan-SARS-CoV-2 neutralizing antibody (which we named MO11) for even the recent dominators XBB.1.16 and EG.5.1, from a convalescent patient who had received three doses of an original mRNA COVID-19 vaccination. A cryo-electron microscopy analysis of the spike-MO11 complex at 2.3 Å atomic resolution revealed that it recognizes a conserved epitope hidden behind a glycan shield at N331 on subdomain 1 (SD1), holding both the N- and C-terminal segments comprising SD1. Our identification of MO11 unveiled the functional importance of SD1 for the spike's function, and we discuss the potential availability of a novel common epitope among the SARS-CoV-2 variants.IMPORTANCENovel severe acute respiratory syndrome coronavirus 2 variants with immune evasion ability are still repeatedly emerging, nonetheless, a part of immunity developed in responding to the antigen of earlier variants retains efficacy against recent variants irrespective of the numerous mutations. In exploration for the broadly effective antibodies, we identified a cross-neutralizing antibody, named MO11, from the B cells of the convalescent patient. MO11 targets a novel epitope in subdomain 1 (SD1) and was effective against all emerging variants including XBB.1.16 and EG.5.1. The neutralizing activity covering from D614G to EG.5.1 variants was explained by the conservation of the epitope, and it revealed the importance of the subdomain on regulating the function of the antigen for viral infection. Demonstrated identification of the neutralizing antibody that recognizes a conserved epitope implies basal contribution of such group of antibodies for prophylaxis against COVID-19.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/química , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Humanos , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/virología , Epítopos/inmunología , Microscopía por Crioelectrón , Dominios Proteicos , Vacunas contra la COVID-19/inmunologíaRESUMEN
As the world continues to confront severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV) is also causing severe respiratory illness in millions of infants, elderly individuals, and immunocompromised people globally. Exacerbating the situation is the fact that co-infection with multiple viruses is occurring, something which has greatly increased the clinical severity of the infections. Thus, our team developed a bivalent vaccine that delivered mRNAs encoding SARS-CoV-2 Omicron spike (S) and RSV fusion (F) proteins simultaneously, SF-LNP, which induced S and F protein-specific binding antibodies and cellular immune responses in BALB/c mice. Moreover, SF-LNP immunization effectively protected BALB/c mice from RSV infection and hamsters from SARS-CoV-2 Omicron infection. Notably, our study pointed out the antigenic competition problem of bivalent vaccines and provided a solution. Overall, our results demonstrated the potential of preventing two infectious diseases with a single vaccine and provided a paradigm for the subsequent design of multivalent vaccines.
Asunto(s)
COVID-19 , Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Humanos , Ratones , Lactante , Cricetinae , Animales , Anciano , Vacunas de ARNm , Vacunas Combinadas , Anticuerpos Antivirales , Vacunas contra Virus Sincitial Respiratorio/genética , Proteínas Virales de Fusión/genética , COVID-19/prevención & control , SARS-CoV-2/genética , Virus Sincitial Respiratorio Humano/genética , Infecciones por Virus Sincitial Respiratorio/prevención & control , Anticuerpos NeutralizantesRESUMEN
Coronaviruses are evolutionarily successful RNA viruses, common to multiple avian, amphibian and mammalian hosts. Despite their ubiquity and potential impact, knowledge of host immunity to coronaviruses remains incomplete, partly owing to the lack of overt pathogenicity of endemic human coronaviruses (HCoVs), which typically cause common colds. However, the need for deeper understanding became pressing with the zoonotic introduction of three novel coronaviruses in the past two decades, causing severe acute respiratory syndromes in humans, and the unfolding pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This renewed interest not only triggered the discovery of two of the four HCoVs, but also uncovered substantial cellular and humoral cross-reactivity with shared or related coronaviral antigens. Here, we review the evidence for cross-reactive B cell memory elicited by HCoVs and its potential impact on the puzzlingly variable outcome of SARS-CoV-2 infection. The available data indicate targeting of highly conserved regions primarily in the S2 subunits of the spike glycoproteins of HCoVs and SARS-CoV-2 by cross-reactive B cells and antibodies. Rare monoclonal antibodies reactive with conserved S2 epitopes and with potent virus neutralising activity have been cloned, underscoring the potential functional relevance of cross-reactivity. We discuss B cell and antibody cross-reactivity in the broader context of heterologous humoral immunity to coronaviruses, as well as the limits of protective immune memory against homologous re-infection. Given the bidirectional nature of cross-reactivity, the unprecedented current vaccination campaign against SARS-CoV-2 is expected to impact HCoVs, as well as future zoonotic coronaviruses attempting to cross the species barrier. However, emerging SARS-CoV-2 variants with resistance to neutralisation by vaccine-induced antibodies highlight a need for targeting more constrained, less mutable parts of the spike. The delineation of such cross-reactive areas, which humoral immunity can be trained to attack, may offer the key to permanently shifting the balance of our interaction with current and future coronaviruses in our favour.
Asunto(s)
COVID-19 , SARS-CoV-2 , Animales , Anticuerpos Antivirales , Humanos , Inmunidad HumoralRESUMEN
BACKGROUND: The long-term pulmonary sequelae of mild coronavirus disease 2019 (COVID-19) remains unknown. In this study, we aimed to characterize lung function trajectories in individuals with mild COVID-19 from preinfection to 2 years postinfection. METHODS: We reinvited participants 2 years after infection from our matched cohort study of the Copenhagen General Population who had initially been examined 5.4 months after infection. We repeated lung tests and questionnaires. Linear mixed models were used to estimate dynamics in lung volumes in individuals with COVID-19 patients versus uninfected controls over two intervals: from pre-infection to 6 months postinfection and 6 months postinfection to 2 years postinfection. RESULTS: 52 individuals (48.6%) attended the 2-year examination at median 1.9 years (interquartile range, 1.8-2.4) after COVID-19, all with mild infection. Individuals with COVID-19 had an adjusted excess decline in forced expiratory volume in 1 second (FEV1) of 13.0â mL per year (95% confidence interval [CI], -23.5 to -2.5; P = .02) from before infection to 6 months after infection compared to uninfected controls. From 6 to 24 months after infection, they had an excess decline of 7.5â mL per year (95% CI, -25.6-9.6; P = .40). A similar pattern was observed for forced vital capacity (FVC). Participants had a mean increase in diffusing capacity for carbon monoxide (DLco) of 3.33 (SD 7.97) between the 6- and 24-month examination. CONCLUSIONS: Our results indicate that mild COVID-19 infection affects lung function at the time of infection with limited recovery 2 years after infection.
Asunto(s)
COVID-19 , Pulmón , Pruebas de Función Respiratoria , SARS-CoV-2 , Humanos , COVID-19/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Pulmón/fisiopatología , Adulto , Estudios de Seguimiento , Volumen Espiratorio Forzado , Dinamarca/epidemiología , Anciano , Estudios de Cohortes , Capacidad Vital/fisiologíaRESUMEN
Understanding SARS-CoV-2 infection in populations at increased risk for poor health is critical to reducing disease. We describe the epidemiology of SARS-CoV-2 infection in Kakuma Refugee Camp Complex, Kenya. We performed descriptive analyses of SARS-CoV-2 infection in the camp and surrounding community during March 16, 2020âDecember 31, 2021. We identified cases in accordance with national guidelines.We estimated fatality ratios and attack rates over time using locally weighted scatterplot smoothing for refugees, host community members, and national population. Of the 18,864 SARS-CoV-2 tests performed, 1,024 were positive, collected from 664 refugees and 360 host community members. Attack rates were 325.0/100,000 population (CFR 2.9%) for refugees,150.2/100,000 population (CFR 1.11%) for community, and 628.8/100,000 population (CFR 1.83%) nationwide. During 2020-2021, refugees experienced a lower attack rate but higher CFR than the national population, underscoring the need to prioritize SARS-CoV-2 mitigation measures, including vaccination.
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COVID-19 , Campos de Refugiados , Refugiados , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/mortalidad , Kenia/epidemiología , Adulto , Masculino , Femenino , Adulto Joven , Persona de Mediana Edad , Adolescente , Niño , Refugiados/estadística & datos numéricos , Preescolar , Lactante , Anciano , IncidenciaRESUMEN
SARS-CoV-2 can infect wildlife, and SARS-CoV-2 variants of concern might expand into novel animal reservoirs, potentially by reverse zoonosis. White-tailed deer and mule deer of North America are the only deer species in which SARS-CoV-2 has been documented, raising the question of whether other reservoir species exist. We report cases of SARS-CoV-2 seropositivity in a fallow deer population located in Dublin, Ireland. Sampled deer were seronegative in 2020 when the Alpha variant was circulating in humans, 1 deer was seropositive for the Delta variant in 2021, and 12/21 (57%) sampled deer were seropositive for the Omicron variant in 2022, suggesting host tropism expansion as new variants emerged in humans. Omicron BA.1 was capable of infecting fallow deer lung type-2 pneumocytes and type-1-like pneumocytes or endothelial cells ex vivo. Ongoing surveillance to identify novel SARS-CoV-2 reservoirs is needed to prevent public health risks during human-animal interactions in periurban settings.
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COVID-19 , Ciervos , SARS-CoV-2 , Animales , SARS-CoV-2/inmunología , SARS-CoV-2/genética , COVID-19/epidemiología , COVID-19/veterinaria , Humanos , Ciervos/virología , Irlanda/epidemiología , Estudios Seroepidemiológicos , Población Urbana , Reservorios de Enfermedades/virología , Reservorios de Enfermedades/veterinaria , Animales Salvajes/virología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Femenino , MasculinoRESUMEN
Using the GISAID EpiCoV database, we identified 256 COVID-19 patients in Japan during March 31-December 31, 2023, who had mutations in the SARS-CoV-2 nonstructural protein 5 conferring ensitrelvir resistance. Ongoing genomic surveillance is required to monitor emergence of SARS-CoV-2 mutations that are resistant to anticoronaviral drugs.
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Antivirales , COVID-19 , Farmacorresistencia Viral , Mutación , SARS-CoV-2 , Humanos , Japón/epidemiología , SARS-CoV-2/genética , COVID-19/epidemiología , COVID-19/virología , Farmacorresistencia Viral/genética , Antivirales/uso terapéutico , Antivirales/farmacología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Proteínas no Estructurales Virales/genética , Tratamiento Farmacológico de COVID-19 , Indazoles , Triazinas , TriazolesRESUMEN
Because novel SARS-CoV-2 variants continue to emerge, immunogenicity of XBB.1.5 monovalent vaccines against live clinical isolates needs to be evaluated. We report boosting of IgG (2.1×), IgA (1.5×), and total IgG/A/M (1.7×) targeting the spike receptor-binding domain and neutralizing titers against WA1 (2.2×), XBB.1.5 (7.4×), EG.5.1 (10.5×), and JN.1 (4.7×) variants.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Humoral , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , SARS-CoV-2/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Glicoproteína de la Espiga del Coronavirus/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Femenino , Inmunogenicidad Vacunal , AdultoRESUMEN
Few precise estimates of hospitalization and fatality rates from COVID-19 exist for naive populations, especially within demographic subgroups. We estimated rates among persons with SARS-CoV-2 infection in the United States during May 1-December 1, 2020, before vaccines became available. Both rates generally increased with age; fatality rates were highest for persons >85 years of age (24%) and lowest for children 1-14 years of age (0.01%). Age-adjusted case hospitalization rates were highest for African American or Black, not Hispanic persons (14%), and case-fatality rates were highest for Asian or Pacific Islander, not Hispanic persons (4.4%). Eighteen percent of hospitalized patients and 44.2% of those admitted to an intensive care unit died. Male patients had higher hospitalization (6.2% vs. 5.2%) and fatality rates (1.9% vs. 1.5%) than female patients. These findings highlight the importance of collecting surveillance data to devise appropriate control measures for persons in underserved racial/ethnic groups and older adults.
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COVID-19 , Hospitalización , SARS-CoV-2 , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , Hospitalización/estadística & datos numéricos , Masculino , Femenino , Adolescente , Anciano , Niño , Preescolar , Persona de Mediana Edad , Adulto , Lactante , Estados Unidos/epidemiología , Anciano de 80 o más Años , Adulto Joven , Recién Nacido , Vacunas contra la COVID-19/administración & dosificación , Etnicidad/estadística & datos numéricosRESUMEN
We conducted a serologic and molecular study to assess exposure of captive nonhuman primates (NHPs) to SARS-CoV-2 in Spain during the 2020-2023 COVID-19 pandemic. We found limited exposure of NHPs to SARS-CoV-2. Biosafety measures must be strictly maintained to avoid SARS-CoV-2 reverse-zoonotic transmission in the human-NHP interface.
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COVID-19 , SARS-CoV-2 , Animales , España/epidemiología , COVID-19/epidemiología , COVID-19/veterinaria , COVID-19/transmisión , COVID-19/prevención & control , Primates , Humanos , Anticuerpos Antivirales/sangre , Animales de Zoológico/virologíaRESUMEN
During 2020-2022, players and staff in the English Premier League in the United Kingdom were tested regularly for SARS-CoV-2 with the aim of creating a biosecure bubble for each team. We found that prevalence and reinfection estimates were consistent with those from other studies and with community infection trends.
RESUMEN
To support the ongoing management of viral respiratory diseases while transitioning out of the acute phase of the COVID-19 pandemic, many countries are moving toward an integrated model of surveillance for SARS-CoV-2, influenza virus, and other respiratory pathogens. Although many surveillance approaches catalyzed by the COVID-19 pandemic provide novel epidemiologic insight, continuing them as implemented during the pandemic is unlikely to be feasible for nonemergency surveillance, and many have already been scaled back. Furthermore, given anticipated cocirculation of SARS-CoV-2 and influenza virus, surveillance activities in place before the pandemic require review and adjustment to ensure their ongoing value for public health. In this report, we highlight key challenges for the development of integrated models of surveillance. We discuss the relative strengths and limitations of different surveillance practices and studies as well as their contribution to epidemiologic assessment, forecasting, and public health decision-making.
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COVID-19 , Virosis , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Pandemias , Salud PúblicaRESUMEN
We devised a model to interpret discordant SARS-CoV-2 test results. We estimate that, during March 2020-May 2022, a patient in the United States who received a positive rapid antigen test result followed by a negative nucleic acid test result had only a 15.4% (95% CI 0.6%-56.7%) chance of being infected.
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COVID-19 , SARS-CoV-2 , Humanos , Estados Unidos/epidemiología , COVID-19/diagnóstico , Prueba de COVID-19 , Pruebas Diagnósticas de Rutina , Sensibilidad y EspecificidadRESUMEN
We report an outbreak of COVID-19 in a beaver farm in Mongolia in 2021. Genomic characterization revealed a unique combination of mutations in the SARS-CoV-2 of the infected beavers. Based on these findings, increased surveillance of farmed beavers should be encouraged.
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COVID-19 , Humanos , COVID-19/epidemiología , Mongolia/epidemiología , SARS-CoV-2/genética , Granjas , Brotes de EnfermedadesRESUMEN
The COVID-19 pandemic disproportionately affected persons held in and working in correctional and detention facilities, causing facilities' traditional priorities to shift when healthcare and public health needs temporarily drove many aspects of operations. During July-August 2022, we interviewed members of health departments and criminal justice organizations to document lessons learned from the COVID-19 response in correctional settings. Participants valued enhanced partnerships, flexibility, and innovation, as well as real-time data and corrections-specific public health guidance. Challenges included cross-sector collaborations, population density, scarcity of equipment and supplies, and mental health. Most participants reported improved relationships between criminal justice and public health organizations during the pandemic. Lessons from COVID-19 can be applied to everyday public health preparedness and emergency response in correctional facilities by ensuring representation of correctional health in public health strategy and practice and providing timely, data-driven, and partner-informed guidance tailored to correctional environments when public health needs arise.
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COVID-19 , Humanos , COVID-19/epidemiología , Pandemias/prevención & control , Prisiones , Salud Pública , Atención a la SaludRESUMEN
We compared the effectiveness and interactions of molnupiravir and nirmatrelvir/ritonavir and 2 vaccines, CoronaVac and Comirnaty, in a large population of inpatients with COVID-19 in Hong Kong. Both the oral antiviral drugs and vaccines were associated with lower risks for all-cause mortality and progression to serious/critical/fatal conditions (study outcomes). No significant interaction effects were observed between the antiviral drugs and vaccinations; their joint effects were additive. If antiviral drugs were prescribed within 5 days of confirmed COVID-19 diagnosis, usage was associated with lower risks for the target outcomes for patients >60, but not <60, years of age; no significant clinical benefit was found if prescribed beyond 5 days. Among patients >80 years of age, 3-4 doses of Comirnaty vaccine were associated with significantly lower risks for target outcomes. Policies should encourage COVID-19 vaccination, and oral antivirals should be made accessible to infected persons within 5 days of confirmed diagnosis.
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COVID-19 , Vacunas , Humanos , Preescolar , Hong Kong/epidemiología , Vacunas contra la COVID-19 , Vacuna BNT162 , Prueba de COVID-19 , COVID-19/prevención & control , Antivirales/uso terapéuticoRESUMEN
Studies suggest that central venous catheter bloodstream infections (BSIs) increased during the COVID-19 pandemic. We investigated catheter-related BSIs in Switzerland and found peripheral venous catheter (PVC) BSI incidence increased during 2021-2022 compared with 2020. These findings should raise awareness of PVC-associated BSIs and prompt inclusion of PVC BSIs in surveillance systems.
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Bacteriemia , COVID-19 , Cateterismo Periférico , Infección Hospitalaria , Sepsis , Humanos , Suiza/epidemiología , Pandemias , Cateterismo Periférico/efectos adversos , COVID-19/epidemiología , COVID-19/complicaciones , Sepsis/etiología , Catéteres/efectos adversos , Infección Hospitalaria/epidemiología , Bacteriemia/epidemiología , Bacteriemia/complicacionesRESUMEN
We describe 5 children who had Rocky Mountain spotted fever (RMSF) and manifested clinical symptoms similar to multisystem inflammatory syndrome in Sonora, Mexico, where RMSF is hyperendemic. Physicians should consider RMSF in differential diagnoses of hospitalized patients with multisystem inflammatory syndrome to prevent illness and death caused by rickettsial disease.
Asunto(s)
Fiebre Maculosa de las Montañas Rocosas , Síndrome de Respuesta Inflamatoria Sistémica , Humanos , México , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Niño , Masculino , Fiebre Maculosa de las Montañas Rocosas/diagnóstico , Femenino , Diagnóstico Diferencial , Preescolar , Adolescente , HospitalizaciónRESUMEN
Accurate and timely mortality surveillance is crucial for elucidating risk factors, particularly for emerging diseases. We compared use of COVID-19 keywords on death certificates alone to identify COVID-19 deaths in Minnesota, USA, during 2020-2022, with use of a standardized mortality definition incorporating additional clinical data. For analyses, we used likelihood ratio χ2 and median 1-way tests. Death certificates alone identified 96% of COVID-19 deaths confirmed by the standardized definition and an additional 3% of deaths that had been classified as non-COVID-19 deaths by the standardized definition. Agreement between methods was >90% for most groups except children, although agreement among adults varied by demographics and location at death. Overall median time from death to filing of death certificate was 3 days; decedent characteristics and whether autopsy was performed varied. Death certificates are an efficient and timely source of COVID-19 mortality data when paired with SARS-CoV-2 testing data.
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COVID-19 , Certificado de Defunción , SARS-CoV-2 , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , Minnesota/epidemiología , Masculino , Persona de Mediana Edad , Femenino , Adulto , Anciano , Niño , Adolescente , Preescolar , Adulto Joven , Lactante , Anciano de 80 o más Años , Causas de Muerte , Autopsia , Prueba de COVID-19/métodosRESUMEN
The increased risk for post-COVID-19 condition after the Omicron-dominant wave remains unclear. This population-based study included 25,911 persons in Japan 20-69 years of age with confirmed SARS-CoV-2 infection enrolled in the established registry system during July-August 2022 and 25,911 age- and sex-matched noninfected controls who used a self-reported questionnaire in January-February 2023. We compared prevalence and age- and sex-adjusted odds ratios of persistent COVID-19 symptoms (lasting ≥2 months). We evaluated factors associated with post-COVID-19 condition by comparing cases with and without post-COVID-19 condition. We analyzed 14,710 (8,392 cases and 6,318 controls) of 18,183 respondents. Post-COVID-19 condition proportion among cases was 11.8%, higher by 6.3% than 5.5% persistent symptoms among controls. Female sex, underlying medical conditions, mild to moderate acute COVID-19, and vaccination were associated with post-COVID-19 condition. Approximately 12% had post-COVID-19 condition during the Omicron-dominant wave, indicating the need for longer follow-up.