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Cytomegalovirus (CMV) infection has a life-long impact on the immune system, particularly on memory T cells. However, the effect of early life CMV infection on the phenotype and functionality of T cells in infants and especially longitudinal changes occurring during childhood have not been explored in detail. The phenotype and functionality of peripheral blood CD8+ and CD4+ T cells from children infected with CMV in early life (< 6 months of age) was analyzed using high-dimensional flow cytometry. Samples from CMV IgG-seropositive (CMV+) children were collected at 6 months and 6 years of age and compared to samples from CMV-seronegative (CMV-) children. Early life CMV infection caused multiple alterations within T cells. These include downregulation of CD28 expression and upregulation of CD57 expression within both CD27+ early and CD27- late effector memory CD8+ and CD4+ T-cells at 6 months of age. Of these changes, only alterations within the highly differentiated late effector memory compartment persisted at the age of 6 years. Early life CMV-infection has a distinct impact on developing CD8+ and CD4+ memory T cell compartments. It appears to induce both temporary as well as longer-lasting alterations, which may affect the functionality of the immune system throughout life.
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Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Infecciones por Citomegalovirus , Humanos , Infecciones por Citomegalovirus/inmunología , Linfocitos T CD8-positivos/inmunología , Lactante , Niño , Linfocitos T CD4-Positivos/inmunología , Femenino , Masculino , Citomegalovirus/inmunología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/metabolismo , Células T de Memoria/inmunología , Antígenos CD28/inmunología , Antígenos CD28/metabolismo , Citometría de Flujo , Antígenos CD57/inmunología , Antígenos CD57/metabolismo , Memoria Inmunológica/inmunología , Preescolar , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangreRESUMEN
Wheezing children infected with rhinovirus (RV) have a markedly increased risk of subsequently developing recurrencies and asthma. No previous studies have assessed the association between cytokine response and the severity of acute illness in the first wheezing episode in children infected with RV. Forty-seven children treated both as inpatients and as outpatients infected with RV only, aged 3-23 months, with severe first wheezing episodes were recruited. During acute illness, peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with anti-CD3/anti-CD28 in vitro. A multiplex ELISA was used to quantitatively identify 56 different cytokines. The mean age of the children was 17 months, 74% were males, 79% were hospitalized, and 33% were sensitized. In adjusted analyses, the inpatient group was characterized by decreased expressions of interferon gamma (IFN-γ), interleukin 10 (IL-10), macrophage inflammatory protein 1 alpha (MIP-1α), RANTES (CCL5), and tumor necrosis factor-alpha (TNF-α) and an increased expression of ENA-78 (CXCL5) compared to the outpatient group. The cytokine response profiles from the PBMCs were different between the inpatient and outpatient groups. Our results support that firmly controlled interplay between pro-inflammatory and anti-inflammatory responses are required during acute viral infection to absolve the initial infection leading, to less severe illness.
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Citocinas , Leucocitos Mononucleares , Infecciones por Picornaviridae , Ruidos Respiratorios , Rhinovirus , Humanos , Masculino , Rhinovirus/inmunología , Femenino , Citocinas/metabolismo , Lactante , Ruidos Respiratorios/etiología , Infecciones por Picornaviridae/inmunología , Infecciones por Picornaviridae/virología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/virología , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Comparative data on the transmission of respiratory infections positive and negative for SARS-CoV-2 in households with children are limited. METHODS: In June-August 2020, we recruited 700 participants (175 households, 376 children, 324 adults) to be prospectively followed for all respiratory tract infections. Follow-up lasted from recruitment till April 2022. Daily symptoms were monitored by weekly electronic questionnaires. SARS-CoV-2 PCR testing from nasopharyngeal specimens was performed for symptomatic participants and twice (one-week interval) for the household members of positive participants. Clinical features and secondary attack rates (SARs), based on the onset of symptoms, were compared between SARS-CoV-2-positive and -negative respiratory infections. RESULTS: Most (90%) SARS-CoV-2 infections occurred from January to April 2022 when Omicron BA.1 and BA.2 were the dominant variants. SARS-CoV-2-positive infections were transmitted more often than SARS-CoV-2-negative infections (SAR, 41% vs 24%; P < .001). SARS-CoV-2 transmission was similar for child and adult index cases (SAR, 40% vs 43%; P = .47), but the transmission of SARS-CoV-2-negative infections was higher for child index cases (SAR, 27% vs 18%; P < .001). CONCLUSIONS: Our findings demonstrate that SARS-CoV-2 Omicron viruses spread more effectively within households compared to other respiratory infections.
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BACKGROUND: The risk of respiratory syncytial virus (RSV) hospitalization is highest during the first months of life, but few studies have assessed the population-based rates of hospitalization in monthly age groups of infants. METHODS: We determined the average population-based rates of hospitalization with virologically confirmed RSV infections in children ≤15 years of age admitted during the 10-year period of 2008-2018. Testing for RSV was routine in all children hospitalized with respiratory infections, and all RSV-positive children admitted at any time during the study period were included in the analyses. RESULTS: The annual population-based rate of RSV hospitalization was highest in infants 1 month of age (52.0 per 1000 children; 95% CI, 45.2-59.7), followed by infants <1 month of age (34.8 per 1000; 95% CI, 29.2-41.1) and those 2 months of age (32.2 per 1000; 95% CI, 26.9-38.4). In cumulative age groups, the rate of hospitalization was 39.7 per 1000 (95% CI, 36.2-43.4) among infants <3 months of age, 26.8 per 1000 (95% CI, 24.8-29.0) in infants aged <6 months, and 15.8 per 1000 (95% CI, 14.7-17.0) in those <12 months of age. CONCLUSION: In monthly age groups of infants, the incidence rates of virologically confirmed RSV hospitalization in all infants up to 3 months of age were substantially higher than those reported in earlier studies. These data may be important for improving the estimates of the cost-effectiveness of various interventions to reduce the burden of RSV in young infants.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Lactante , Niño , Humanos , Adulto , Adolescente , Finlandia , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , HospitalizaciónRESUMEN
PURPOSE: In clinical practice, we observed an apparent overrepresentation of COVID-19 patients on anti-CD20 monoclonal antibody therapy. The aim of this study was to characterize the clinical picture of COVID-19 in these patients. METHODS: All adult patients from Turku University Hospital, Turku, Finland, with COVID-19 diagnosis and/or positive SARS-CoV-2 PCR test result up to March 2023, and with anti-CD20 therapy within 12 months before COVID-19 were included. Data was retrospectively obtained from electronic patient records. RESULTS: Ninety-eight patients were identified. 44/93 patients (47.3%) were hospitalized due to COVID-19. Patients with demyelinating disorder (n = 20) were youngest (median age 36.5 years, interquartile range 33-45 years), had less comorbidities, and were least likely to be hospitalized (2/20; 10.0%) or die (n = 0). COVID-19 mortality was 13.3% in the whole group, with age and male sex as independent risk factors. Persistent symptoms were documented in 33/94 patients (35.1%) alive by day 30, in 21/89 patients (23.6%) after 60 days, and in 15/85 after 90 days (17.6%), mostly in patients with haematological malignancy or connective tissue disease. Prolonged symptoms after 60 days predisposed to persistent radiological findings (odds ratio 64.0; 95% confidence interval 6.3-711; p < 0.0001) and persistently positive PCR (odds ratio 45.5, 95% confidence interval 4.0-535; p < 0.0001). Several patients displayed rapid response to late antiviral therapy. CONCLUSION: Anti-CD20 monoclonal antibody therapy is associated with high COVID-19 mortality and with a phenotype consistent with prolonged viral pneumonia. Our study provides rationale for retesting of immunocompromised patients with prolonged COVID-19 symptoms and considering antiviral therapy.
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Antineoplásicos , COVID-19 , Neumonía Viral , Adulto , Humanos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Prueba de COVID-19 , Estudios Retrospectivos , Neumonía Viral/diagnóstico , Antineoplásicos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Antivirales/uso terapéuticoRESUMEN
BACKGROUND: Rhinovirus (RV)-induced first wheezing episodes in children are associated with a markedly increased risk of asthma. Previous studies have suggested that human bocavirus 1 (HBoV1) may modify RV-induced immune responses in young children. We investigated cytokine profiles of sole RV- and dual RV-HBoV1-induced first wheezing episodes, and their association with severity and prognosis. METHODS: Fifty-two children infected with only RV and nine children infected with dual RV-HBoV1, aged 3-23 months, with severe first wheezing episodes were recruited. At acute illness and 2 weeks later, peripheral blood mononuclear cells were isolated, and stimulated with anti-CD3/anti-CD28 in vitro. Multiplex ELISA was used to quantitatively identify 56 different cytokines at both study points. Patients were prospectively followed for 4 years. RESULTS: The mean age of the children was 14.3 months, and 30% were sensitized. During the acute illness, the adjusted analyses revealed a decrease in the expression of IL-1b, MIP-1b, Regulated upon activation, normal T cell expressed and presumably secreted (CCL5), TNF-a, TARC, and ENA-78 in the RV-HBoV1 group compared with the RV group. In the convalescence phase, the RV-HBoV1 group was characterized by decreased expression of Fractalkine, MCP-3, and IL-8 compared to the RV group. Furthermore, the hospitalization time was associated with the virus group and cytokine response (interaction p < 0.05), signifying that increased levels of epidermal growth factor and MIP-1b were related with a shorter duration of hospitalization in the RV-HBoV1 coinfection group but not in the RV group. CONCLUSIONS: Different cytokine response profiles were detected between the RV and the RV-HBoV1 groups. Our results show the idea that RV-induced immune responses may be suppressed by HBoV1.
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Asthma development and exacerbation is linked to respiratory virus infections. There is limited information regarding the presence of viruses during non-exacerbation/infection periods. We investigated the nasopharyngeal/nasal virome during a period of asymptomatic state, in a subset of 21 healthy and 35 asthmatic preschool children from the Predicta cohort. Using metagenomics, we described the virome ecology and the cross-species interactions within the microbiome. The virome was dominated by eukaryotic viruses, while prokaryotic viruses (bacteriophages) were independently observed with low abundance. Rhinovirus B species consistently dominated the virome in asthma. Anelloviridae were the most abundant and rich family in both health and asthma. However, their richness and alpha diversity were increased in asthma, along with the co-occurrence of different Anellovirus genera. Bacteriophages were richer and more diverse in healthy individuals. Unsupervised clustering identified three virome profiles that were correlated to asthma severity and control and were independent of treatment, suggesting a link between the respiratory virome and asthma. Finally, we observed different cross-species ecological associations in the healthy versus the asthmatic virus-bacterial interactome, and an expanded interactome of eukaryotic viruses in asthma. Upper respiratory virome "dysbiosis" appears to be a novel feature of pre-school asthma during asymptomatic/non-infectious states and merits further investigation.
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Anelloviridae , Asma , Bacteriófagos , Niño , Humanos , Preescolar , Eucariontes , Viroma , Células Eucariotas , Enfermedades AsintomáticasRESUMEN
We observed an intense enterovirus D68 outbreak in children in southwest Finland in August-September 2022. We confirmed enterovirus D68 infection in 56 children hospitalized for respiratory illnesses and in 1 child with encephalitis but were not able to test all suspected patients. Continuing surveillance for enterovirus D68 is needed.
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Enterovirus Humano D , Infecciones por Enterovirus , Enterovirus , Infecciones del Sistema Respiratorio , Humanos , Niño , Lactante , Enterovirus Humano D/genética , Finlandia/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones por Enterovirus/epidemiología , Brotes de EnfermedadesRESUMEN
Saliva is a promising alternative for a nasopharyngeal swab (NPS) in specimen collection to detect SARS-CoV-2. We compared the diagnostic performance and tolerability of saliva collection versus NPS in a clinical setting. Paired NPS and saliva specimens were collected sequentially from participants (n = 250) at the Turku University Hospital drive-in coronavirus testing station in the spring of 2022, with Omicron BA.2 as the dominant SARS-CoV-2 variant. Discomfort and preference for the sampling method were assessed. The specimens were analyzed for SARS-CoV-2 using real-time multiplex reverse transcriptase PCR (RT-PCR) with a laboratory-developed test (LDT) and two commercial kits (PerkinElmer SARS-CoV-2 and PerkinElmer SARS-CoV-2 Plus) for several target genes. Among the 250 participants, 246 had respiratory symptoms. With LDT, SARS-CoV-2 was detected in 135 and 134 participants from NPS and saliva, respectively. Of the 250 specimens, 11 gave a discordant outcome, resulting in excellent agreement between the specimen types (Cohen's kappa coefficient of 0.911; P = 0.763). The cycle threshold (CT) values of LDT and commercial kit target genes were significantly lower from NPS than from saliva. A total of 172 (69%) participants assessed saliva sampling as more tolerable than NPS (P < 0.0001). Our findings present saliva as an applicable alternative for SARS-CoV-2 diagnostics. However, the lower CT values obtained from NPS indicate that NPS may be a slightly more sensitive specimen type. Participants preferred saliva sampling, although delivering an adequate volume of saliva was challenging for some participants. IMPORTANCE The extensive testing of SARS-CoV-2 is vital in controlling the spread of COVID-19. The reference standard for specimen collection is a nasopharyngeal swab (NPS). However, the discomfort of NPS sampling, the risk of nosocomial infections, and global material shortages have accelerated the development of alternative testing methods. Our study demonstrates that patients tolerate saliva sampling better than NPS. Of importance, although the RT-PCR qualitative test results seem to correspond between NPS and saliva, we show significantly lower CT values for NPS, compared to saliva, thus contradicting the suggested superiority of the saliva specimen over NPS in the detection of the Omicron variants of SARS-CoV-2. Future research is still required to enable individual planning for specimen collection and to determine the effects of different SARS-CoV-2 variants on the sensitivity of the saliva matrix.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Saliva , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Prueba de COVID-19 , NasofaringeRESUMEN
BACKGROUND: Limited long-term data are available on potential changes in the demographics and management of children hospitalized with influenza. METHODS: We identified all children ≤15 years old hospitalized with virologically confirmed influenza at Turku University Hospital, Finland, during the 25-year period of July 1993-June 2018. Data on clinical variables, comorbidities and management were retrieved directly from the medical records. Population-based rates of hospitalization were calculated using official annual databases of children living in the hospital catchment area. RESULTS: Between 1993-1998 and 2013-2018, the median age of children increased from 1.3 years to 3.3 years ( P < 0.0001). The proportion of children <2 years of age decreased from 65.2% to 36.8%, whereas the proportion of children 6-15-year-old increased from 13.0% to 36.2% ( P < 0.0001 for both). The population-based rates of hospitalization decreased by 49% in children 1 year of age (incidence rate ratio, 0.51; 95% confidence interval: 0.27-0.92; P = 0.018) and increased by 194% in children 6-15 years old (incidence rate ratio, 2.94; 95% confidence interval: 1.70-5.32; P < 0.0001). The median duration of hospitalization shortened from 2.0 days (interquartile range [IQR], 1.0-4.0) to 1.0 day (IQR, 1.0-2.0; P < 0.0001). CONCLUSIONS: During the 25 years, the median age of hospitalized children increased by 2 years, while the duration of hospitalization shortened.
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Gripe Humana , Niño , Humanos , Lactante , Preescolar , Adolescente , Gripe Humana/epidemiología , Finlandia/epidemiología , Hospitalización , Niño Hospitalizado , HospitalesRESUMEN
A novel automated mariPOC SARS-CoV-2 antigen test was evaluated in a Health Care Center Laboratory among symptomatic and asymptomatic individuals seeking SARS-CoV-2 testing. According to the national testing strategy, reverse transcription polymerase chain reaction (RT-PCR) was used as a reference method. A total of 962 subjects were included in this study, 4.8% (46/962) of their samples were SARS-CoV-2 RT-PCR-positive, and 87% (40/46) of these were from symptomatics. Among the symptomatics, the overall sensitivity of the mariPOC SARS-CoV-2 test was 82.5% (33/40), though the sensitivity increased to 97.1% (33/34) in samples with a Ct < 30. The mariPOC SARS-CoV-2 test detected two of six PCR-positive samples among the asymptomatics, four cases that remained antigen test negative had Ct values between 28 and 36. The specificity of the mariPOC SARS-CoV-2 test was 100% (916/916). The evaluation showed that the mariPOC SARS-CoV-2 rapid antigen test is very sensitive and specific for the detection of individuals who most probably are contagious.
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COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Prueba de COVID-19 , Instituciones de Salud , Pruebas Inmunológicas , Sensibilidad y Especificidad , Antígenos ViralesRESUMEN
Rhinovirus (RV) and respiratory syncytial virus (RSV) are common causes of bronchiolitis. Unlike an RSV etiology, an RV etiology is associated with a markedly increased risk of asthma. We investigated the cytokine profiles of RV- and RSV-induced first wheezing episode and their correlation with prognosis. We recruited 52 sole RV- and 11 sole RSV-affected children with a severe first wheezing episode. Peripheral blood mononuclear cells (PBMCs) were isolated during acute illness and 2 weeks later and stimulated in vitro with anti-CD3/anti-CD28. Culture medium samples were analyzed for 56 different cytokines by multiplex ELISA. Recurrences were prospectively followed for 4 years. In adjusted analyses, the cytokine response from PBMCs in the RV group was characterized by decreased expression of interleukin 1 receptor antagonist (IL-1RA), interleukin 1 beta (IL-1ß), and monocyte chemoattractant protein-1 (MCP-1) and increased expression of eosinophil chemotactic protein 2 (eotaxin-2), thymus- and activation-regulated chemokine (TARC), and epithelial-derived neutrophil-activating peptide 78 (ENA-78) in the acute phase and increased expression of fractalkine in the convalescent phase compared to those in the RSV group. An analysis of the change in cytokine expression between study points revealed an increased expression of fractalkine and IL-1ß and decreased expression of I-309 (CCL1) and TARC in the RV group compared to those in the RSV group.. Considering hospitalization time, a significant non-adjusted group × cytokine interaction was observed in the levels of interferon gamma (IFN-γ), macrophage-derived chemokine (MDC), IL-1RA, and vascular endothelial growth factor (VEGF), indicating that a higher expression of cytokine was associated with shorter hospitalization time in the RSV group but not in the RV group. A significant interaction was also found in interleukin 6 (IL-6), but the cytokine response was not associated with hospitalization time in the RSV or RV group. In the RV group, increased expression of I-309 (CCL1) and TARC was associated with fewer relapses within 2 months, and decreased expression of interleukin 13 (IL-13) and increased expression of I-309 (CCL1) were associated with less relapses within 12 months. Differences in cytokine response from PBMCs were observed between RV- and RSV-induced first severe wheezing episode. Our findings also reveal new biomarkers for short- and medium-term prognosis in first-time wheezing children infected with RV or RSV.
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Infecciones por Enterovirus , Pneumovirus , Virus Sincitial Respiratorio Humano , Niño , Humanos , Rhinovirus , Ruidos Respiratorios , Citocinas , Quimiocina CX3CL1 , Leucocitos Mononucleares , Proteína Antagonista del Receptor de Interleucina 1 , Factor A de Crecimiento Endotelial Vascular , Interleucina-6 , RecurrenciaRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in late 2019, and quickly spread to every continent causing the global coronavirus disease 2019 (COVID-19) pandemic. Fast propagation of the disease presented numerous challenges to the health care industry in general and especially placed enormous pressure on laboratory testing. Throughout the pandemic, reverse transcription-PCR (RT-PCR)-based nucleic acid amplification tests have been the primary technique to identify acute infections caused by SARS-CoV-2. Since the start of the pandemic, there has been a constantly growing need for accurate and fast tests to enable timely protective and isolation means, as well as rapid therapeutic interventions. Here we present an evaluation of the GenomEra test for SARS-CoV-2. Analytical and clinical performance was evaluated in a multicenter setting with specimens analyzed using standard-of-care (SOC) techniques. Analytical sensitivity was assessed from spiked respiratory swab samples collected into different viral transport media, and in the best performer eSwab, the limit of detection was found to be 239 IU/mL in a heat processed sample. The GenomEra SARS-CoV-2 Assay Kit did not show specificity/cross-reactivity issues with common micro-organisms or other substances commonly found in respiratory specimens when analyzed both in vitro and in silico. Finally, the clinical performance was assessed in comparison to SOC techniques used at four institutions. Based on the analysis of 274 clinical specimens, the positive agreement of the GenomEra SARS-CoV-2 Assay Kit was 90.7%, and the negative agreement was 100%. The GenomEra SARS-CoV-2 Assay Kit provided accurate detection of SARS-CoV-2 with a short turnaround time in under 90 min.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Bioensayo , Pandemias , Reacciones CruzadasRESUMEN
Our aim was to study the detection of group A streptococcus (GAS) with different diagnostic methods in paediatric pharyngitis patients with and without a confirmed viral infection. In this prospective observational study, throat swabs and blood samples were collected from children (age 1-16 years) presenting to the emergency department with febrile pharyngitis. A confirmed viral infection was defined as a positive virus diagnostic test (nucleic acid amplification test [NAAT] and/or serology) together with an antiviral immune response of the host demonstrated by elevated (≥ 175 µg/L) myxovirus resistance protein A (MxA) blood concentration. Testing for GAS was performed by a throat culture, by 2 rapid antigen detection tests (StrepTop and mariPOC) and by 2 NAATs (Simplexa and Illumigene). Altogether, 83 children were recruited of whom 48 had samples available for GAS testing. Confirmed viral infection was diagnosed in 30/48 (63%) children with febrile pharyngitis. Enteroviruses 11/30 (37%), adenoviruses 9/30 (30%) and rhinoviruses 9/30 (30%) were the most common viruses detected. GAS was detected by throat culture in 5/30 (17%) with and in 6/18 (33%) patients without a confirmed viral infection. Respectively, GAS was detected in 4/30 (13%) and 6/18 (33%) by StrepTop, 13/30 (43%) and 10/18 (56%) by mariPOC, 6/30 (20%) and 9/18 (50%) by Simplexa, and 5/30 (17%) and 6/18 (30%) patients by Illumigene. CONCLUSION: GAS was frequently detected also in paediatric pharyngitis patients with a confirmed viral infection. The presence of antiviral host response and increased GAS detection by sensitive methods suggest incidental throat carriage of GAS in viral pharyngitis. WHAT IS KNOWN: â¢The frequency and significance of GAS-virus co-detection are poorly characterised in children with pharyngitis. â¢Detection of a virus and the antiviral host response likely indicates symptomatic infection. WHAT IS NEW: â¢Group A streptococcus (GAS) was detected in 17-43% of the children with confirmed viral pharyngitis depending on the GAS diagnostic method. â¢Our results emphasize the risk of detecting and treating incidental pharyngeal carriage of GAS in children with viral pharyngitis.
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Faringitis , Infecciones Estreptocócicas , Virosis , Humanos , Niño , Lactante , Preescolar , Adolescente , Antivirales/uso terapéutico , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes , Faringitis/diagnóstico , Fiebre , Inmunidad , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: In this retrospective cohort study, we explored the correlation of blood human myxovirus resistance protein A (MxA) level with severity of disease in hospitalized COVID-19 patients. METHODS: All 304 patients admitted for COVID-19 in our hospital until 30th of April 2021 were included in this study. MxA was measured from peripheral blood samples in 268 cases. Patients were divided into groups based on their level of MxA on admission. We studied baseline characteristics and severity of disease on admission based on clinical parameters and inflammatory biomarker levels in each group. Severity of disease during hospitalization was determined by the applied level of respiratory support, by the usage of corticosteroids and by the duration of hospitalization. RESULTS: Higher MxA levels on admission were associated with a shorter duration of symptoms before admission, and with more severe disease. Adjusted Odds Ratios for any respiratory support were 9.92 (95%CI 2.11-46.58; p = 0.004) in patients with MxA between 400 µg/L and 799 µg/L (p = 0.004) and 20.08 (95%CI 4.51-89.44; p < 0.001) in patients with MxA ≥ 800 µg/L in comparison with patients with initial MxA < 400 µg/L. The usage of corticosteroids was significantly higher in the high-MxA group (77%) in comparison with the intermediate-MxA group (62%, p = 0.013) and low-MxA group (47%, p < 0.001). CONCLUSIONS: Higher initial levels of MxA were associated with more severe COVID-19. MxA may be a helpful additional biomarker to predict the severity of the disease.
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COVID-19 , Orthomyxoviridae , Biomarcadores , Humanos , Proteínas de Resistencia a Mixovirus/genética , Proteínas de Resistencia a Mixovirus/metabolismo , Estudios Retrospectivos , Proteína Estafilocócica ARESUMEN
Sindbis virus (SINV) caused a large outbreak in Finland in 2021 with 566 laboratory-confirmed human cases and a notable geographical expansion. Compared with the last large outbreak in 2002, incidence was higher in several hospital districts but lower in traditionally endemic locations in eastern parts of the country. A high incidence is also expected in 2022. Awareness of SINV should be raised in Finland to increase recognition of the disease and prevent transmission through the promotion of control measures.
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Infecciones por Alphavirus , Virus Sindbis , Infecciones por Alphavirus/diagnóstico , Infecciones por Alphavirus/epidemiología , Brotes de Enfermedades , Finlandia/epidemiología , Geografía , HumanosRESUMEN
The aim was to evaluate the herpes simplex virus (HSV) seroprevalence and seroconversion among 285 pregnant women and their 120 male spouses in Finland during a six-year follow-up (FU) between 1998-2008. We also studied the effect of sexual habits, pregnancy, and other demographic factors on the acquisition of HSV infection. Combined HSV-1 and HSV-2-IgG antibodies were assessed in the first baseline serum samples with an indirect enzyme immunoassay method. The individuals with seronegative or borderline HSV serology at baseline were additionally tested using their latest FU serum sample available. The overall HSV seroprevalence during the FU was 58.9% (168/285) among the women and 53.3% (64/120) among their spouses. The seroconversion rate was 11.4% (15/132) and 12.5% (8/64) among women and their spouses, respectively. Both spouses were HSV seropositive in 39.2% (47/120). To determine the HSV-2 seroprevalence, we also tested all HSV-seropositive participants using HSV-2-specific antigen. HSV-2 seropositivity was detected in 10.9% (44/405) of the participants. The age (p = 0.006) and history of genital warts (p = 0.006) of the women were associated with combined HSV-1 and/or HSV-2 seropositivity, while a younger age was related to HSV seroconversion (p = 0.023). Among the male spouses, HSV seropositivity was associated with the practice of oral sex (p = 0.033). To conclude, women of childbearing age acquire primary HSV infections and the presence of HSV in oral epithelium is common among HSV-seropositive individuals.
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Herpes simplex virus type 1 (HSV-1) is the only FDA- and EMA- approved oncolytic virus, and accordingly, many potential oncolytic HSVs (oHSV) are in clinical development. The utilized oHSV parental strains are, however, mostly based on laboratory reference strains, which may possess a compromised cytolytic capacity in contrast to circulating strains of HSV-1. Here, we assess the phenotype of thirty-six circulating HSV-1 strains from Finland to uncover their potential as oHSV backbones. First, we determined their capacity for cell-to-cell versus extracellular spread, to find strains with replication profiles favorable for each application. Second, to unfold the differences, we studied the genetic diversity of two relevant viral glycoproteins (gB/UL27, gI/US7). Third, we examined the oncolytic potential of the strains in cells representing glioma, lymphoma, and colorectal adenocarcinoma. Our results suggest that the phenotype of a circulating isolate, including the oncolytic potential, is highly related to the host cell type. Nevertheless, we identified isolates with increased oncolytic potential in comparison with the reference viruses across many or all of the studied cancer cell types. Our research emphasizes the need for careful selection of the backbone virus in early vector design, and it highlights the potential of clinical isolates as backbones in oHSV development.
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Herpes Simple , Herpesvirus Humano 1 , Viroterapia Oncolítica , Virus Oncolíticos , Finlandia , Herpes Simple/genética , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/metabolismo , Humanos , Viroterapia Oncolítica/métodos , Virus Oncolíticos/genéticaRESUMEN
The emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made it more difficult to prevent the virus from spreading despite available vaccines. Reports of breakthrough infections and decreased capacity of antibodies to neutralize variants raise the question whether current vaccines can still protect against COVID-19 disease. We studied the dynamics and persistence of T cell responses using activation induced marker (AIM) assay and Th1 type cytokine production in peripheral blood mononuclear cells obtained from BNT162b2 COVID-19 mRNA vaccinated health care workers and COVID-19 patients. We demonstrate that equally high T cell responses following vaccination and infection persist at least for 6 months against Alpha, Beta, Gamma, and Delta variants despite the decline in antibody levels.
Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , Humanos , Leucocitos Mononucleares , ARN Mensajero/genética , Glicoproteína de la Espiga del Coronavirus , Linfocitos TRESUMEN
Adenoids and tonsils have gained interest as a new in vivo model to study local immune functions and virus reservoirs. Especially herpesviruses are interesting because their prevalence and persistence in local lymphoid tissue are incompletely known. Our aim was to study herpesvirus and common respiratory virus infections in nonacutely ill adenotonsillar surgery patients. Adenoid and/or palatine tonsil tissue and nasopharyngeal aspirate (NPA) samples were collected from elective adenoidectomy (n = 45) and adenotonsillectomy (n = 44) patients (median age: 5, range: 1-20). Real-time polymerase chain reaction was used to detect 22 distinct viruses from collected samples. The overall prevalence of herpesviruses was 89% and respiratory viruses 94%. Human herpesviruses 6 (HHV6), 7 (HHV7), and Epstein-Barr virus (EBV) were found, respectively, in adenoids (33%, 26%, 25%), tonsils (45%, 52%, 23%), and NPA (46%, 38%, 25%). Copy numbers of the HHV6 and HHV7 genome were significantly higher in tonsils than in adenoids. Patients with intra-adenoid HHV6 were younger than those without. Detection rates of EBV and HHV7 showed agreement between corresponding sample types. This study shows that adenoid and tonsil tissues commonly harbor human herpes- and respiratory viruses, and it shows the differences in virus findings between sample types.