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BackgroundSymptoms after COVID-19 recovery by SARS-CoV-2 strains are unspecified.MethodsThis self-administered questionnaire-based study was conducted to investigate symptoms after COVID-19 recovery at one of the main hospitals for COVID-19 treatment in Hiroshima, Japan, from September 2020 to March 2022 for patients who visited follow-up consultations after COVID-19. Study subjects were divided into four groups (Wild-type, Alpha, Delta, and Omicron periods) according to COVID-19 onset date. Hierarchical cluster analysis was performed to determine symptom clusters and investigate risk factors for each symptom cluster using multivariate analysis.ResultsAmong 385 patients who enrolled in this study, 249 patients had any persistent symptoms at a median of 23.5 [IQR, 20-31] days after COVID-19 onset. Among patients with any persistent symptoms, symptom clusters including olfactory or taste disorders, respiratory symptoms, and cardiac symptoms were found. Respiratory symptoms were more frequent among patients infected in the Omicron period compared to the Wild-type period (AOR, 3.13; 95% CI, 1.31-7.48; p=0.0101). Compared to patients who recovered from mild COVID-19, patients who needed for oxygen or ventilation support suffered fewer post-COVID-19 respiratory symptoms (AOR, 0.46; 95% CI, 0.22-0.97; p=0.0415) but more post-COID-19 cardiac symptoms among them (AOR, 2.67; 95% CI, 1.26-5.65; p=0.0103). Olfactory or taste disorders were fewer among patients infected in the Omicron period compared to the Wild-type period (AOR, 0.14; 95% CI, 0.04-0.46; p=0.0011).ConclusionThis study revealed that symptoms after COVID-19 may vary depending on the infected strain.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load dynamics in respiratory samples have been studied, but knowledge about changes in serial serum samples of infected patients in relation to their immunological response is lacking. We investigated the dynamics of SARS-CoV-2 viral load and antibody response in sequential serum of coronavirus disease 2019 (COVID-19) patients and attempted to culture the virus in the serum. A total of 81 sequential serum samples from 10 confirmed COVID-19 patients (5 with mild and 5 with moderate symptoms) were analyzed. Samples were collected during hospitalization and after discharge (median follow-up of 35 days). SARS-CoV-2 ribonucleic acid in the serum was detected by real-time polymerase chain reaction. Total antibody and IgG to SARS-CoV-2 Spike protein were analyzed by Chemiluminescent Immunoassays, and neutralizing antibodies were detected using a Surrogate Virus Neutralization Test. Viremia was observed in all cases at admission, and viral copy gradually dropped to undetectable levels in patients with mild symptoms but fluctuated and remained persistent in moderate cases. The viral culture of samples with the highest viral load for each patient did not show any cytopathic change. The antibody response was faster and higher in moderate cases. This study provides a basic clue for infectious severity-dependent immune response, viremia, and antibody acquisition pattern.
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COVID-19/inmunología , COVID-19/virología , Viremia/inmunología , Viremia/virología , Adulto , Anciano , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , ARN Viral/sangre , ARN Viral/genética , SARS-CoV-2/genética , SARS-CoV-2/inmunología , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Carga ViralRESUMEN
INTRODUCTION: The global rise of syphilis infections and the ongoing coronavirus disease 2019 (COVID-19) pandemic are causes for concern. We herein report a rare case of concurrent primary syphilis and COVID-19. CASE REPORT: A 29-year-old man was admitted with a diagnosis of COVID-19. Although COVID-19 pneumonia appeared during ciclesonide and favipiravir treatment, his symptoms improved without developing severe hypoxemia. A small, red ulcer on the left-side of his glans penis was noted and left inguinal lymph node swellings were detected on computed tomography (CT). He reported that his last engagement in sexual intercourse had been 3 months previously, and that his partner had subsequently been diagnosed with syphilis. Although both serum Treponema pallidum (TP) antibody and rapid plasma reagin (RPR) quantitative tests were negative on the day of admission, we clinically diagnosed a suspected case of primary syphilis and started treatment with amoxicillin (1500 mg/day). We subsequently learned that the TP antibody and RPR quantitative tests had been positive 4 days before starting syphilis treatment. Amoxicillin treatment was continued for 61 days, and the ulcer gradually improved. One year later, the RPR quantitative test was negative, and CT revealed a reduction in size of the inguinal lymph nodes and no residual signs of COVID-19 pneumonia. CONCLUSION: The prevalence of syphilis has been increasing even during the COVID-19 pandemic, and the incidence of concurrent syphilis and COVID-19 might be higher than is recognized. Asking patients with COVID-19 about high-risk sexual behavior and genital lesions could help with early diagnosis of syphilis.
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COVID-19 , Sífilis , Adulto , Amoxicilina , Anticuerpos Antibacterianos , COVID-19/diagnóstico , Humanos , Masculino , Pandemias , Sífilis/diagnóstico , Sífilis/tratamiento farmacológico , Treponema pallidum , ÚlceraRESUMEN
Standard therapy for idiopathic thrombocytopenic purpura (ITP) has not been established. We are conducting a multicenter, prospective trial to determine the efficacy and safety of short-term, high-dose dexamethasone therapy in ITP patients aged 18-80 years with platelet counts of <20, 000 /µL, or with <50, 000/ µL and bleeding symptoms. The primary endpoints of this trial are the proportion of responses (complete plus partial response) on day 180 (day 46+180) after the completion of the 46-day high-dose dexamethasone therapy. The results of this investigation of the effectiveness and safety of this regimen will be essential for the establishment of standard therapy for ITP.
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Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adulto , Anciano , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Dexametasona/administración & dosificación , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Glucocorticoides/administración & dosificación , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/aislamiento & purificación , Hepatitis B/complicaciones , Hepatitis B/tratamiento farmacológico , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Humanos , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/uso terapéutico , Adulto JovenRESUMEN
A 61-year-old woman with rheumatoid arthritis was diagnosed as having acquired hemophilia A with extensive subcutaneous bleeding. The patient was treated with a corticosteroid, and her symptoms improved temporarily. However, these recurred during the tapering of her corticosteroid dose, and neither the re-increase in the dose nor the addition of cyclophosphamide could control her bleeding tendency. After the administration of an anti-IL-6 receptor antibody (tocilizumab), the doses of corticosteroid and cyclophosphamide could be tapered. Tocilizumab combined with another immunosuppression therapy might be effective in the treatment of acquired hemophilia A.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Artritis Reumatoide/etiología , Hemofilia A/tratamiento farmacológico , Hemorragia/etiología , Corticoesteroides/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Ciclofosfamida/administración & dosificación , Combinación de Medicamentos , Femenino , Hemofilia A/complicaciones , Humanos , Persona de Mediana Edad , RecurrenciaRESUMEN
A 58-year-old man was admitted to our hospital because of fever and night sweating. Laboratory examinations showed pancytopenia on admission. Examination of bone marrow smear specimens revealed many myeloblasts, thus the diagnosis of acute myeloid leukemia (AML) was made. In contrast, many central necrotic epithelioid granulomas were found in clot specimens prepared from the same bone marrow sample. Computed tomography showed small lymphadenopathies and hepatosplenomegaly. Mycobacterium tuberculosis was isolated only from the urine culture. These findings of the bone marrow and the urine culture led to the diagnosis of disseminated tuberculosis. Therefore, these results mentioned above led to the diagnosis of AML complicated with disseminated tuberculosis. After disseminated tuberculosis treatment with anti-tuberculosis drugs, induction chemotherapy for AML helped the patient to achieve complete remission (CR). During treatment and CR, he showed a paradoxical reaction with lymph node enlargement without worsening of disseminated tuberculosis. This is a rare case of AML complicated by disseminated tuberculosis.
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Leucemia Mieloide Aguda/complicaciones , Tuberculosis/complicaciones , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia due to accelerated platelet destruction and impaired platelet production. Diagnosis of ITP is still challenging because ITP has been diagnosed by exclusion. Exclusion of thrombocytopenia due to bone marrow failure is especially important in Japan because of high prevalence of aplastic anemia compared to Western countries. Hence, we propose a new diagnostic criteria involving the measurement of plasma thrombopoietin (TPO) levels and percentage of immature platelet fraction (RP% or IPF%); 1) isolated thrombocytopenia with no morphological evidence of dysplasia in any blood cell type in a blood smear, 2) normal or slightly increased plasma TPO level (< cutoff), 3) elevated RP% or IPF% (> upper limit of normal), and 4) absence of other conditions that potentially cause thrombocytopenia including secondary ITP. A diagnosis of ITP is made if conditions 1-4 are all met. Cases in which criterion 2 or 3 is not met or unavailable are defined as "possible ITP," and diagnosis of ITP can be made mainly by typical clinical course. These new criteria enable us to clearly differentiate ITP from aplastic anemia and other forms of hypoplastic thrombocytopenia and can be highly useful in clinical practice for avoiding unnecessary bone marrow examination as well as for appropriate selection of treatments.
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Anemia Aplásica , Leucopenia , Púrpura Trombocitopénica Idiopática , Trombocitopenia , Adulto , Humanos , Anemia Aplásica/diagnóstico , Plaquetas , Trombocitopenia/diagnóstico , Recuento de Plaquetas , TrombopoyetinaRESUMEN
More than 200 million COVID-19 survivors have lasting symptoms after recovering, but the duration and related risk factors remain uncertain. This study focused on all 6551 patients diagnosed with COVID-19 at a medical institution in Hiroshima from March 2020 to July 2022. In November 2022, a questionnaire survey was conducted regarding post-COVID symptoms and their duration. The prevalence and duration of post-COVID symptoms were illustrated using the Kaplan-Meier method. Risk factors for symptoms lasting over 3 months and interfering with daily life were assessed via multivariate logistic regression. A total of 2421 survivors responded: 1391 adults, 1030 children, median age 34 years (IQR 9-55), 51·2% male, 36·7% hospitalized, median time from infection to the survey was 295 days (IQR 201-538). Upon their initial recovery, the prevalence of post-COVID symptoms was 78·4% in adults and 34·6% in children. Three months later, the rates were 47·6% and 10·8%. After over one year, they were 31·0% and 6·8%. Regarding symptoms interfere with daily life, 304 people (12.6%) experienced symptoms lasting for over three months, with independent risk factors including age, being female, diabetes mellitus, infection during the Delta period, and current smoking. There was no significant association between vaccination history and post-COVID symptoms.
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COVID-19 , Adulto , Niño , Humanos , Femenino , Masculino , COVID-19/epidemiología , Instituciones de Salud , Factores de Riesgo , Fumar , SobrevivientesRESUMEN
The filamins are cytoplasmic proteins that regulate the structure and activity of the cytoskeleton by cross-linking actin into three-dimensional networks, linking the cell membrane to the cytoskeleton and serving as scaffolds on which intracellular signaling and protein trafficking pathways are organized (reviewed in refs. 1,2). We identified mutations in the gene encoding filamin B in four human skeletal disorders. We found homozygosity or compound heterozygosity with respect to stop-codon mutations in autosomal recessive spondylocarpotarsal syndrome (SCT, OMIM 272460) and missense mutations in individuals with autosomal dominant Larsen syndrome (OMIM 150250) and the perinatal lethal atelosteogenesis I and III phenotypes (AOI, OMIM 108720; AOIII, OMIM 108721). We found that filamin B is expressed in human growth plate chondrocytes and in the developing vertebral bodies in the mouse. These data indicate an unexpected role in vertebral segmentation, joint formation and endochondral ossification for this ubiquitously expressed cytoskeletal protein.
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Proteínas Contráctiles/genética , Articulaciones/crecimiento & desarrollo , Proteínas de Microfilamentos/genética , Mutación Puntual , Columna Vertebral/crecimiento & desarrollo , Codón de Terminación , Filaminas , Técnica del Anticuerpo Fluorescente , Heterocigoto , Homocigoto , Linaje , Transporte de Proteínas , Transducción de SeñalRESUMEN
Background: Vaccination against severe acute respiratory syndrome coronavirus type 2 is highly effective in preventing infection and reducing the severity of coronavirus disease (COVID-19). However, acquired humoral immunity wanes within six months. Focusing on the different tempo of acquisition and attenuation of specific antibody titers in individuals, we investigated the impact of genetic polymorphisms on antibody production after COVID-19 vaccination. Methods: In total 236 healthcare workers from a Japanese municipal hospital, who received two doses of the vaccine were recruited. We employed a candidate gene approach to identify the target genetic polymorphisms affecting antibody production after vaccination. DNA samples from the study populations were genotyped for 33 polymorphisms in 15 distinct candidate genes encoding proteins involved in antigen-presenting cell activation, T cell activation, T-B interaction, and B cell survival. We measured total anti-SARS-Cov2 spike IgG antibody titers and analyzed the association with genetic polymorphisms at several time points after vaccination using an unbiased statistical method, and stepwise logistic regression following multivariate regression. Results: Significant associations were observed between seven SNPs in NLRP3, OAS1, IL12B, CTLA4, and IL4, and antibody titers at 3 weeks after the first vaccination as an initial response. Six SNPs in NLRP3, TNF, OAS1, IL12B, and CTLA4 were associated with high responders with serum antibody titer > 4000 BAU/ml as boosting effect at 3 weeks after the second vaccination. Analysis of long-term maintenance showed the significance of the three SNPs in IL12B, IL7R, and MIF for the maintenance of antibody titers and that in BAFF for attenuation of neutralizing antibodies. Finally, we proposed a predictive model composed of gene profiles to identify the individuals with rapid antibody attenuation by receiver operating characteristic (ROC) analysis (area under the curve (AUC)= 0.76, sensitivity = 82.5%, specificity=67.8%). Conclusions: The candidate gene approach successfully showed shifting responsible gene profiles and initial and boosting effect mainly related to the priming phase into antibody maintenance including B cell survival, which traces the phase of immune reactions. These gene profiles provide valuable information for further investigation of humoral immunity against COVID-19 and for building a strategy for personalized vaccine schedules.
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Formación de Anticuerpos , COVID-19 , Humanos , Formación de Anticuerpos/genética , Vacunas contra la COVID-19 , Antígeno CTLA-4 , Pueblos del Este de Asia , Proteína con Dominio Pirina 3 de la Familia NLR , COVID-19/genética , COVID-19/prevención & control , Vacunación , Anticuerpos Neutralizantes , Polimorfismo de Nucleótido SimpleRESUMEN
A 40-year-old man was admitted with a diagnosis of COVID-19 pneumonia. Although most of multiple ground-glass opacities and consolidations on computed tomography improved, a round ground-glass opacity with consolidation remained unchanged and was suspected to be a part-solid nodule of lung adenocarcinoma. Pathologic diagnosis of resected tumor was papillary adenocarcinoma.
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BACKGROUND: This study aimed to compare the performance of Sanger-based SARS-CoV-2 spike gene sequencing and Next Generation Sequencing (NGS)-based full-genome sequencing for variant identification in saliva samples with low viral titer. METHODS: Using 241 stocked saliva samples collected from confirmed COVID-19 patients between November 2020 and March 2022 in Hiroshima, SARS-CoV-2 spike gene sequencing (nt22735-nt23532) was performed by nested RT-PCR and Sanger platform using in-house primers. The same samples underwent full-genome sequencing by NGS using Illumina NextSeq2000. RESULTS: Among 241 samples, 147 were amplified by both the Sanger and the Illumina NextSeq2000 NGS, 86 by Sanger only, and 8 were not amplified at all. The overall amplification rates of Illumina NextSeq2000 NGS and Sanger were 61% and 96.7%, respectively. At low viral titer (< 103 copies/mL), Illumina NextSeq2000 NGS provided 19.2% amplification, while Sanger was 89.7% (p < 0.0001). Both platforms identified 38 wild type, 54 Alpha variants, 84 Delta variants, and 57 Omicron variants. CONCLUSIONS: Our study provided evidence to expand the capacity of Sanger-based SARS-CoV-2 spike gene sequencing for variants identification over full-genome by Illumina NextSeq2000 NGS for mass screening. Therefore, the feasible and simple Sanger-based SARS-CoV-2 spike gene sequencing is practical for the initial variants screening, which might reduce the gap between the rapid evolution of SARS-CoV-2 and its molecular surveillance.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Saliva , Mapeo CromosómicoRESUMEN
BACKGROUND: Casirivimab and imdevimab are effective in preventing hospitalization in outpatients with coronavirus disease 2019 (COVID-19); however, disease progression after casirivimab and imdevimab administration has been reported. This study aimed to elucidate the risk factors for disease progression after casirivimab and imdevimab administration. METHODS: This retrospective study included patients with COVID-19 who received casirivimab and imdevimab at Hiroshima City Funairi Citizens Hospital between August 6, 2021, and October 10, 2021. All patients had at least one risk factor for severe disease and were treated on admission. The patients' background characteristics and test results at the first visit were analyzed. The patients were divided into two groups (progressed and improved) based on whether they progressed to acute respiratory failure during hospitalization. RESULTS: Sixty-seven patients were included: 9 patients in the progressed group (median age, 56 years) and 58 patients in the improved group (median age, 51 years). Age, coexistence rate of diabetes, cycle threshold value of polymerase chain reaction test, rate of detectable pneumonia on chest radiographs or chest computed tomography images, lymphocyte count, and the levels of C-reactive protein, interleukin-6, glucose, and glycated hemoglobin were significantly different between the two groups. Multivariate logistic regression analysis revealed that the coexistence of diabetes and the presence of detectable pneumonia on chest radiographs were independent factors predicting the progression to acute respiratory failure. CONCLUSION: Acute respiratory failure after antibody therapy with casirivimab and imdevimab may develop in patients with diabetes or detectable pneumonia on chest radiographs at the first visit.
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Tratamiento Farmacológico de COVID-19 , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Anticuerpos Monoclonales Humanizados , Progresión de la Enfermedad , Humanos , Persona de Mediana Edad , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The Omicron variant (B.1.1.529) of coronavirus disease 2019 (COVID-19) has rapidly spread worldwide since December 2021. In daily medical practice, pneumonia does not often appear as a complication of the Omicron variant. We present a case of COVID-19 pneumonia by the Omicron variant in young patients without obvious risk factors.
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BACKGROUND: The characteristics of coronavirus disease 2019 (COVID-19) pneumonia caused by the severe acute respiratory syndrome coronavirus 2 Omicron variant have not been fully described. Unlike other variants, the Omicron variant replicates rapidly in the bronchus. Therefore, we hypothesized that it would have different computed tomography (CT) findings from non-Omicron variants. METHODS: We enrolled patients with COVID-19 who visited our hospital and underwent chest CT during the first month of the Omicron wave (January 2022; N = 231) and the previous non-Omicron wave (July 2021; N = 87). We retrospectively evaluated the differences in the prevalence rate and CT characteristics of COVID-19 pneumonia between the two waves. RESULTS: The prevalence of pneumonia was significantly lower in the Omicron wave group (79/231, 34.2%) compared to the previous wave group (67/87, 77.0%) (P < 0.001). For the predominant distribution pattern of pneumonia, the Omicron wave group revealed a significantly lower rate of the peripheral pattern and a higher rate of the random pattern than the previous wave group. In addition, the Omicron wave group had a significantly lower rate of consolidation than the previous wave group. The ground-glass opacities (GGOs) rate was similar between the two wave groups. For GGOs patterns, cluster-like GGOs along the bronchi on chest CT were more frequently observed during the Omicron wave than during the previous wave. CONCLUSION: The Omicron wave group had a lower COVID-19 pneumonia prevalence than the previous wave group. Cluster-like GGOs should be noted as a characteristic CT finding of pneumonia during the Omicron wave.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Estudios Retrospectivos , Pulmón/diagnóstico por imagenRESUMEN
This study aimed to exercise the Sanger sequencing strategy for screening of variants among confirmed COVID-19 cases and validate our strategy against NGS strains in Hiroshima retrieved from GISAID. A total of 660 samples from confirmed COVID-19 cases underwent screening for variants by Sanger-based partial sequencing to the targeted spike gene (nt22,735~nt23,532) using an in-house-developed primer set. The identification of variants was done by unique checkpoints of base nucleotide changes in the targeted spike gene. Moreover, we amplified one full-length genome using Sanger method and an in-house-developed primer library. Using NGS strains of the same sampling period from GISAID, a phylogenetic tree was constructed to examine the distribution pattern of variants in Hiroshima and to validate our Sanger method. The modified primer set provided 100% validation and 99.2% amplification. PANGO Lineage R.1 was detected in late in the third wave, followed by Alpha (B.1.1.7) domination in the fourth wave, Delta (B.1.617.2) domination in the fifth wave, and Omicron (B.1.1.529) domination in the sixth wave, and there was no significant difference in viral copies between variants (p = 0.09). The variants showed different transmission patterns, but the distribution of variants is consistent to that shown by the phylogenetic tree. The Sanger method also provided successful amplification of the full-length genome of the SARS-CoV-2 virus. Our Sanger sequencing strategy was useful for the screening of SASR-CoV-2 variants without the need for full-genome amplification. The modified primer set was validated to use universally, which allows an understanding of the variants' distribution in real time and provides the evidence for policy-making and the formulation or modification of preventive strategies.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Brotes de Enfermedades , Humanos , Mutación , Filogenia , SARS-CoV-2/genéticaRESUMEN
Perceived discrimination and work impairment are commonly observed in COVID-19 survivors, but their relationship has not been well understood. We aimed to evaluate the role of discrimination in the development of psychological distress and work impairment in COVID-19 survivors. From April 2020 to November 2021, 309 patients were recruited at two designated COVID-19 hospitals in Japan. Participants completed a standardized questionnaire including COVID-19 sequelae, psychological distress, impairments in work performance and perceived discrimination. The majority of participants (62.5%) experienced one or more COVID-19 sequelae. Psychological distress was observed in 36.9% and work impairment in 37.9%. In multivariate logistic regression analyses, COVID-19 sequelae and discrimination were associated with both psychological distress and work impairment. Mediation analysis demonstrated that the direct effect of sequelae on work impairment was non-significant after accounting for psychological distress, suggesting that the effect of sequelae on work impairment was mainly mediated through psychological distress. These findings were replicated in a subgroup analysis limited to patients with mild COVID-19. We conclude that discrimination plays an important role in the development of psychological distress and work impairment, and that both discrimination and psychological distress should be targets of intervention in COVID-19 survivors.
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COVID-19 , Distrés Psicológico , Humanos , COVID-19/complicaciones , Sobrevivientes/psicología , Japón/epidemiología , Estrés Psicológico/psicologíaRESUMEN
This cross-sectional study aimed to investigate the post-acute consequences of COVID-19. We conducted a self-administered questionnaire survey on sequelae, psychological distress (K6), impairments in work performance (WFun), and COVID-19-related experiences of stigma and discrimination in two designated COVID-19 hospitals in Hiroshima Prefecture, Japan, between August 2020 and March 2021. The prevalence of sequelae was calculated by age and COVID-19 severity. Factors independently associated with sequelae or psychological distress were identified using logistic regression analysis. Among 127 patients who had recovered from COVID-19, 52.0% had persistent symptoms at a median of 29 days [IQR 23-128] after COVID-19 onset. Among patients with mild COVID-19, 49.5% had sequelae. The most frequent symptoms were olfactory disorders (15.0%), taste disorders (14.2%), and cough (14.2%). Multivariate analysis showed that age was an independent risk factor for sequelae (adjusted odds ratios [AOR] for ≥ 60 years vs. < 40 years 3.63, p = 0.0165). Possible psychological distress was noted in 30.7% (17.9% of males and 45.0% of females). Female sex and the presence of sequelae were independent risk factors for psychological distress. Of all participants, 29.1% had possible impairments in work performance. Experiences of stigma and discrimination were reported by 43.3% of participants. This study revealed the significant impacts of Long COVID on health in local communities. A large-scale, long-term cohort study is desired.
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COVID-19 , COVID-19/complicaciones , COVID-19/epidemiología , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Sobrevivientes , Síndrome Post Agudo de COVID-19RESUMEN
This study aimed to develop the feasible and effective universal screening strategy of the notable SARS-CoV-2 variants by Sanger Sequencing Strategy and then practically applied it for mass screening in Hiroshima, Japan. A total of 734 samples from COVID-19 confirmed cases in Hiroshima were screened for the notable SARS-CoV-2 variants (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.1, C.37, B.1.1.529, etc.). The targeted spike region is amplified by nested RT-PCR using in-house designed primer set hCoV-Spike-A and standard amplification protocol. Additionally, randomly selected 96 samples were also amplified using primer sets hCoV-Spike-B and hCoV-Spike-C. The negative amplified samples were repeated for second attempt of amplification by volume-up protocol. Thereafter, the amplified products were assigned for Sanger sequencing using corresponding primers. The positive amplification rate of primer set hCoV-Spike-A, hCoV-Spike-B and hCoV-Spike-C were 87.3%, 83.3% and 93.8% respectively for standard protocol and increased to 99.6%, 95.8% and 96.9% after second attempt by volume-up protocol. The readiness of genome sequences was 96.9%, 100% and 100% respectively. Among 48 mutant isolates, 26 were B.1.1.7 (Alpha), 7 were E484K single mutation and the rest were other types of mutation. Moreover, 5 cluster cases with single mutation at N501S were firstly reported in Hiroshima. This study indicates the reliability and effectiveness of Sanger sequencing to screen large number of samples for the notable SARS-CoV-2 variants. Compared to the Next Generation Sequencing (NGS), our method introduces the feasible, universally applicable, and practically useful tool for identification of the emerging variants with less expensive and time consuming especially in those countries where the NGS is not practically available. Our method allows not only to identify the pre-existing variants but also to examine other rare type of mutation or newly emerged variants and is crucial for prevention and control of pandemic.
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COVID-19/diagnóstico , Tamizaje Masivo/métodos , SARS-CoV-2/genética , Análisis de Secuencia de ADN/métodos , Glicoproteína de la Espiga del Coronavirus/genética , Secuencia de Aminoácidos , COVID-19/epidemiología , COVID-19/virología , Estudios de Factibilidad , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Japón/epidemiología , Pandemias/prevención & control , Reproducibilidad de los Resultados , SARS-CoV-2/fisiología , Sensibilidad y Especificidad , Homología de Secuencia de AminoácidoRESUMEN
Actin-binding proteins filamin A (FLNA) and B (FLNB) are expressed in endothelial cells and play an essential role during vascular development. In order to investigate their role in adult endothelial cell function, we initially confirmed their expression pattern in different adult mouse tissues and cultured cell lines and found that FLNB expression is concentrated mainly in endothelial cells, whereas FLNA is more ubiquitously expressed. Functionally, small interfering RNA knockdown of endogenous FLNB in human umbilical vein endothelial cells inhibited vascular endothelial growth factor (VEGF)-induced in vitro angiogenesis by decreasing endothelial cell migration capacity, whereas FLNA ablation did not alter these parameters. Moreover, FLNB-depleted cells increased their substrate adhesion with more focal adhesions. The molecular mechanism underlying this effect implicates modulation of small GTP-binding protein Rac-1 localization and activity, with altered activation of its downstream effectors p21 protein Cdc42/Rac-activated kinase (PAK)-4/5/6 and its activating guanine nucleotide exchange factor Vav-2. Moreover, our results suggest the existence of a signaling complex, including FLNB, Rac-1, and Vav-2, under basal conditions that would further interact with VEGFR2 and integrin alphavbeta5 after VEGF stimulation. In conclusion, our results reveal a crucial role for FLNB in endothelial cell migration and in the angiogenic process in adult endothelial cells.