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BACKGROUND: Prompt differentiation of viral from bacterial infections in febrile children is pivotal in reducing antibiotic overuse. Myxovirus resistance protein A (MxA) is a promising viral biomarker. METHODS: We evaluated the accuracy of a point-of-care (POC) measurement for blood MxA level compared to the reference enzyme immunoassay in 228 febrile children aged between 4 weeks and 16 years, enrolled primarily at the emergency department (ED). Furthermore, we analyzed the ability of MxA to differentiate viral from bacterial infections. RESULTS: The mean difference between POC and reference MxA level was -76 µg/L (95% limits of agreement from -409 to 257 µg/L). Using a cutoff of 200 µg/L, POC results were uniform with the reference assay in 199 (87.3%) children. In ED-collected samples, the median POC MxA levels (interquartile range) were 571 [240-955] µg/L in children with viral infections, 555 (103-889) µg/L in children with viral-bacterial co-infections, and 25 (25-54) µg/L in children with bacterial infections (P < 0.001). MxA cutoff of 101 µg/L differentiated between viral and bacterial infections with 92% sensitivity and 91% specificity. CONCLUSIONS: POC MxA measurement demonstrated acceptable analytical accuracy compared to the reference method, and good diagnostic accuracy as a biomarker for viral infections.
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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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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 , Infecções por Enterovirus , Enterovirus , Infecções Respiratórias , Humanos , Criança , Lactente , Enterovirus Humano D/genética , Finlândia/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções por Enterovirus/epidemiologia , Surtos de DoençasRESUMO
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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Faringite , Infecções Estreptocócicas , Viroses , Humanos , Criança , Lactente , Pré-Escolar , Adolescente , Antivirais/uso terapêutico , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes , Faringite/diagnóstico , Febre , Imunidade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Differences in the functioning of the immune system and the anatomical proportions of the neck between children and adults lead to different manifestations of deep neck infections. Magnetic resonance imaging (MRI) may serve as an alternative to computed tomography (CT) as the primary imaging modality. OBJECTIVE: To study characteristic MRI findings and the diagnostic accuracy of MRI in pediatric deep neck infections. MATERIALS AND METHODS: We retrospectively studied a cohort of pediatric patients who underwent a neck 3-tesla MRI study over a five-year period. Inclusion criteria were: 1) emergency MRI findings indicating an infection, 2) infection as the final clinical diagnosis, 3) diagnostic image quality verified by the radiologist reading the study and 4) age under 18 years. Patient record data, including surgery reports, were compared with the MRI findings. RESULTS: Data of 45 children were included and analysed. Compared to adults, children had a higher incidence of retropharyngeal infection and lymphadenitis, and a lower incidence of peritonsillar/parapharyngeal infection. MRI showed evidence of an abscess in 34 children. Of these 34 patients, 24 underwent surgery, which confirmed an abscess in 21 but no abscess in three patients. In addition, three patients underwent surgery without MRI evidence of abscess, and an abscess was found in one of these cases. The measures of diagnostic accuracy among the children were sensitivity 0.96, specificity 0.77, positive predictive value 0.89, negative predictive value 0.91 and accuracy 0.89. Compared with adults, children had lower C-reactive protein, but a similar proportion of them had an abscess, and abscess size and rate of surgery were similar. CONCLUSION: Despite the differences in the infection foci, emergency MRI in children had equal diagnostic accuracy to that in adults.
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Abscesso , Pescoço , Adolescente , Adulto , Dor no Peito , Criança , Humanos , Imageamento por Ressonância Magnética/métodos , Pescoço/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Blood myxovirus resistance protein A (MxA) has broad antiviral activity, and it is a potential biomarker for symptomatic virus infections. Limited data is available of MxA in coinciding viral and bacterial infections. We investigated blood MxA levels in children hospitalized with a febrile urinary tract infection (UTI) with or without simultaneous respiratory virus infection. We conducted a prospective observational study of 43 children hospitalized with febrile UTI. Nasopharyngeal swab samples were collected at admission and tested for 16 respiratory viruses by nucleic acid detection methods. Respiratory symptoms were recorded, and blood MxA levels were determined. The median age of study children was 4 months (interquartile range, 2-14 months). A respiratory virus was detected in 17 (40%) children with febrile UTI. Of the virus-positive children with febrile UTI, 7 (41%) had simultaneous respiratory symptoms. Blood MxA levels were higher in virus-positive children with respiratory symptoms (median, 778 [interquartile range, 535-2538] µg/L) compared to either virus-negative (155 [94-301] µg/L, P < 0.001) or virus-positive (171 [112-331] µg/L, P = 0.006) children without respiratory symptoms at presentation with febrile UTI. MxA differentiated virus-positive children with respiratory symptoms from virus-negative without symptoms by an area under the receiver operating characteristic curve of 0.96. Respiratory viruses were frequently detected in children with febrile UTI. In UTI with simultaneous respiratory symptoms, host antiviral immune response was demonstrated by elevated blood MxA protein levels. MxA protein could be a robust biomarker of symptomatic viral infection in children with febrile UTI.
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Proteínas de Resistência a Myxovirus/sangue , Infecções Respiratórias/sangue , Infecções Respiratórias/epidemiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/virologia , Biomarcadores/sangue , Feminino , Febre , Humanos , Lactente , Masculino , Prevalência , Estudos Prospectivos , Curva ROC , Infecções Respiratórias/patologia , Infecções Respiratórias/virologia , Infecções Urinárias/microbiologia , Infecções Urinárias/patologiaRESUMO
Dermacoccus spp. have rarely been reported as human pathogens. We describe a case of a 4-year-old boy with congenital heart disease who was diagnosed with a brain abscess. The abscess was drained and the sample grew Streptococcus intermedius, Aggregatibacter aphrophilus and Dermacoccus sp.. Dermacoccus grew after 5 days of incubation and the patient was treated with meropenem.
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Actinobacteria/isolamento & purificação , Antibacterianos/uso terapêutico , Abscesso Encefálico/microbiologia , Coinfecção/microbiologia , Cardiopatias Congênitas/complicações , Meropeném/uso terapêutico , Aggregatibacter aphrophilus/isolamento & purificação , Abscesso Encefálico/diagnóstico , Abscesso Encefálico/terapia , Pré-Escolar , Coinfecção/diagnóstico , Coinfecção/terapia , Drenagem , Humanos , Masculino , Infecções por Pasteurellaceae/diagnóstico , Infecções por Pasteurellaceae/microbiologia , Infecções por Pasteurellaceae/terapia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/terapia , Streptococcus intermedius/isolamento & purificação , Resultado do TratamentoRESUMO
AIM: Procalcitonin (PCT) and C-reactive protein (CRP) are biomarkers of bacterial infection with distinct clinical qualities. This study aimed to determine the occurrence and significance of discrepancies in plasma PCT and CRP levels in hospitalised children. METHODS: This was a single centre, retrospective analysis of simultaneous PCT and CRP measurements. Clinical characteristics, microbiological findings and diagnoses were compared between cases in which only PCT or CRP levels were elevated. RESULTS: We studied 635 pairs of PCT and CRP measurements and found discrepancies in 29% of these. In the group with increased PCT and low CRP, there were more children with hypoxia or haemodynamic stress (14 versus 0, p < 0.001) and more bacteraemic patients (eight versus zero, p = 0.001) than in the group with low PCT and increased CRP. The latter group was associated with focal bacterial infections (three versus 18, p = 0.009), inflammatory conditions (one versus 12, p = 0.016) and postoperative setting (one versus 19, p = 0.001). Diabetic ketoacidosis was associated with a marked elevation of PCT. CONCLUSION: Discrepancies in plasma PCT and CRP levels occurred in 29% of acutely ill children. Both biomarkers can increase in the absence of bacterial infection, but PCT may offer an advantage over CRP in the diagnosis of bacteraemia.
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Infecções Bacterianas/diagnóstico , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Cetoacidose Diabética/diagnóstico , Viroses/diagnóstico , Doença Aguda , Bacteriemia/sangue , Bacteriemia/diagnóstico , Infecções Bacterianas/sangue , Biomarcadores/sangue , Criança , Pré-Escolar , Cetoacidose Diabética/sangue , Hospitalização , Humanos , Lactente , Modelos Logísticos , Estudos Retrospectivos , Viroses/sangueRESUMO
Diagnostic tools to differentiate between community-acquired bacterial and viral meningitis are essential to target the potentially lifesaving antibiotic treatment to those at greatest risk and concurrently spare patients with viral meningitis from the disadvantages of antibiotics. In addition, excluding bacterial meningitis and thus decreasing antibiotic consumption would be important to help reduce antimicrobial resistance and healthcare expenses. The available diagnostic laboratory tests for differentiating bacterial and viral meningitis can be divided microbiological pathogen-focussed methods and biomarkers of the host response. Bacterial culture-independent microbiological methods, such as highly multiplexed nucleic acid amplification tests, are rapidly making their way into the clinical practice. At the same time, more conventional host protein biomarkers, such as procalcitonin and C-reactive protein, are supplemented by newer proteomic and transcriptomic signatures. This review aims to summarise the current state and the recent advances in diagnostic methods to differentiate bacterial from viral meningitis.
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Meningites Bacterianas , Meningite Viral , Humanos , Proteômica , Diagnóstico Diferencial , Meningite Viral/diagnóstico , Biomarcadores , Meningites Bacterianas/diagnóstico , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: Vaccinations against the SARS-CoV-2 are still crucial in combating the ongoing pandemic that has caused more than 700 million infections and claimed almost 7 million lives in the past four years. Omicron (B.1.1.529) variants have incurred mutations that challenge the protection against infection and severe disease by the current vaccines, potentially compromising vaccination efforts. METHODS: We analyzed serum samples taken up to 9 months post third dose from 432 healthcare workers. Enzyme-linked immunosorbent assays (ELISA) and microneutralization tests (MNT) were used to assess the prevalence of vaccine-induced neutralizing antibodies against various SARS-CoV-2 Omicron variants. RESULTS: In this serological analysis we show that SARS-CoV-2 vaccine combinations of BNT162b2, mRNA-1273, and ChAdOx1 mount SARS-CoV-2 binding and neutralizing antibodies with similar kinetics, but with differing neutralization capabilities. The most recent Omicron variants, BQ.1.1 and XBB.1.5, show a significant increase in the ability to escape vaccine and infection-induced antibody responses. Breakthrough infections in thrice vaccinated adults were seen in over 50% of the vaccinees, resulting in a stronger antibody response than without infection. CONCLUSIONS: Different three-dose vaccine combinations seem to induce considerable levels of neutralizing antibodies against most SARS-CoV-2 variants. However, the ability of the newer variants BQ1.1 and XBB 1.5 to escape vaccine-induced neutralizing antibody responses underlines the importance of updating vaccines as new variants emerge.
During the COVID-19 pandemic, mass vaccination efforts against SARS-CoV-2 infection have provided effective protection against the virus and helped reduce the severity of symptoms in infected individuals. However, it is not well established whether the existing vaccines can provide the same protection against new and emerging SARS-CoV-2 variants that develop over time as the virus evolves. In this study, we tested combinations of three-dose COVID-19 vaccines given in random order to protect against all SARS-CoV-2 variants in circulation including the newest being Omicron variants. We demonstrate that more than half of the population who received the three-dose vaccine combinations were infected with SARS-CoV-2 Omicron variants after receiving the last vaccine dose. These findings indicate the need to develop new vaccine candidates against emerging SARS-CoV-2 variants.
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Immunization during pregnancy (IP) against pertussis is recommended in many countries to protect infants. Although maternal antibodies can influence the infants' antibody responses to primary vaccinations, their effect on the development of functional antibodies and B cells remain poorly studied. We investigated the maternal immune response to IP and the effect of IP and pre-existing antibodies on infants' primary vaccine responses in an open-label, non-randomized trial. Forty-seven mothers received tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy, and 22 mothers were included as controls. Sixty-nine infants received primary doses of DTaP at three and five months of age. Geometric mean concentrations of antibodies to pertussis toxin, filamentous haemagglutinin, pertactin, diphtheria, and tetanus toxins, pertussis toxin neutralizing antibodies (PTNAs), and plasma and memory B-cell frequencies were studied at delivery, and at three, five and six months. Levels of antibodies, PTNAs, and frequencies of memory B-cells were significantly increased at delivery and up to six months after in mothers with IP compared to those without IP (all p < 0.05, except for PT-specific memory B-cells). In vaccinated pregnant women, high pre-existing antibody levels were positively correlated with higher antibody responses after IP. IP blunted the infants' antibody and plasma B-cell responses to all vaccine antigens, except for tetanus toxin. This blunting effect was the strongest in infants with high concentrations of maternal antibodies. In conclusion, IP resulted in significantly higher concentrations of antibodies in infants up to three months of age (all p < 0.05); but was associated with blunting of various infants' vaccine responses.
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Vacinas contra Difteria, Tétano e Coqueluche Acelular , Difteria , Coqueluche , Humanos , Lactente , Feminino , Gravidez , Coqueluche/prevenção & controle , Toxina Pertussis , Anticorpos Antibacterianos , Vacinação/métodos , ImunizaçãoRESUMO
Pediatric neck infections and their complications, such as abscesses extending to deep neck compartments, are potentially life-threatening acute conditions. Medical imaging aims to verify abscesses and their extensions and exclude other complications. Magnetic resonance imaging (MRI) has proven to be a useful and highly accurate imaging method in acute neck infections in children. Children and adults differ in terms of the types of acute infections and the anatomy and function of the neck. This pictorial review summarizes typical findings in pediatric patients with neck infections and discusses some difficulties related to image interpretation.
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The prevalence of seasonal human coronavirus (HCoV) infections in early childhood and adults has not been well analyzed in longitudinal serological studies. Here we analyzed the changes in HCoV (229E, HKU1, NL63, OC43, MERS, and SARS-CoV-2) spike-specific antibody levels in follow-up serum specimens of 140 children at the age of 1, 2, and 3 years, and of 113 healthcare workers vaccinated for Covid-19 with BNT162b2-vaccine. IgG antibody levels against six recombinant HCoV spike subunit 1 (S1) proteins were measured by enzyme immunoassay. We show that by the age of three years the cumulative seropositivity for seasonal HCoVs increased to 38-81% depending on virus type. BNT162b2 vaccinations increased anti-SARS-CoV-2 S1 antibodies, but no increase in seasonal coronavirus antibodies associated with vaccinations. In healthcare workers (HCWs), during a 1-year follow-up, diagnostic antibody rises were seen in 5, 4 and 14% of the cases against 229E, NL63 and OC43 viruses, respectively, correlating well with the circulating HCoVs. In 6% of the HCWs, a diagnostic antibody rise was seen against S1 of HKU1, however, these rises coincided with anti-OC43 S1 antibody rises. Rabbit and guinea pig immune sera against HCoV S1 proteins indicated immunological cross-reactivity within alpha-CoV (229E and NL63) and beta-CoV (HKU1 and OC43) genera.
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Antígenos de Grupos Sanguíneos , COVID-19 , Coronavirus Humano 229E , Adulto , Criança , Humanos , Pré-Escolar , Lactente , Animais , Cobaias , Coelhos , Reinfecção , Vacina BNT162 , Glicoproteína da Espícula de Coronavírus , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Anticorpos Antivirais , Pessoal de SaúdeRESUMO
Introduction: The prime-boost COVID-19 mRNA vaccination strategy has proven to be effective against severe COVID-19 disease and death. However, concerns have been raised due to decreasing neutralizing antibody levels after COVID-19 vaccination and due to the emergence of new immuno-evasive SARS-CoV-2 variants that may require additional booster vaccinations. Methods: In this study, we analyzed the humoral and cell-mediated immune responses against the Omicron BA.1 and BA.2 subvariants in Finnish healthcare workers (HCWs) vaccinated with three doses of COVID-19 mRNA vaccines. We used enzyme immunoassay and microneutralization test to analyze the levels of SARS-CoV-2 specific IgG antibodies in the sera of the vaccinees and the in vitro neutralization capacity of the sera. Activation induced marker assay together with flow cytometry and extracellular cytokine analysis was used to determine responses in SARS-CoV-2 spike protein stimulated PBMCs. Results: Here we show that within the HCWs, the third mRNA vaccine dose recalls both humoral and T cell-mediated immune responses and induces high levels of neutralizing antibodies against Omicron BA.1 and BA.2 variants. Three weeks after the third vaccine dose, SARS-CoV-2 wild type spike protein-specific CD4+ and CD8+ T cells are observed in 82% and 71% of HCWs, respectively, and the T cells cross-recognize both Omicron BA.1 and BA.2 spike peptides. Although the levels of neutralizing antibodies against Omicron BA.1 and BA.2 decline 2.5 to 3.8-fold three months after the third dose, memory CD4+ T cell responses are maintained for at least eight months post the second dose and three months post the third vaccine dose. Discussion: We show that after the administration of the third mRNA vaccine dose the levels of both humoral and cell-mediated immune responses are effectively activated, and the levels of the spike-specific antibodies are further elevated compared to the levels after the second vaccine dose. Even though at three months after the third vaccine dose antibody levels in sera decrease at a similar rate as after the second vaccine dose, the levels of spike-specific CD4+ and CD8+ T cells remain relatively stable. Additionally, the T cells retain efficiency in cross-recognizing spike protein peptide pools derived from Omicron BA.1 and BA.2 subvariants. Altogether our results suggest durable cellmediated immunity and protection against SARS-CoV-2.
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Vacinas contra COVID-19 , COVID-19 , Imunidade Celular , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Linfócitos T CD8-Positivos , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Imunoglobulina G , SARS-CoV-2 , Glicoproteína da Espícula de CoronavírusRESUMO
Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis bacterium. The mainstay of treatment is macrolide antibiotics that reduce transmissibility, shorten the duration of symptoms and decrease mortality in infants. Recently, the macrolide resistance of B. pertussis has been reported globally but is especially widespread in mainland China. In this review, we aim to summarise the current understanding of the epidemiology, resistance mechanisms and clinical implications of B. pertussis macrolide resistance. Since the first appearance of macrolide-resistant B. pertussis in Arizona, USA, in 1994, only sporadic cases have been reported outside China. In certain parts of China, on the other hand, up to 70-100% of the recent clinical isolates have been found to be macrolide resistant. Reasons for macrolide resistance being centred upon China during the last decade can only be speculated on, but the dominant B. pertussis lineage is different between China and most of the high-income countries. It seems evident that efforts to increase awareness, guide molecular epidemiological surveillance and carry out systematic screening of B. pertussis positive samples for macrolide resistance should be implemented globally. In addition, practices to improve the clinical care of infants with pertussis caused by resistant strains should be studied vigorously.
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A biomarker for viral infection could improve the differentiation between viral and bacterial infections and reduce antibiotic overuse. We examined blood myxovirus resistance protein A (MxA) as a biomarker for viral infections in children with an acute infection. We recruited 251 children presenting with a clinical suspicion of serious bacterial infection, determined by need for a blood bacterial culture collection, and 14 children with suspected viral infection at two pediatric emergency departments. All children were aged between 4 weeks and 16 years. We classified cases according to the viral, bacterial, or other etiology of the final diagnosis. The ability of MxA to differentiate between viral and bacterial infections was assessed. The median blood MxA levels were 467 (interquartile range, 235 to 812) µg/L in 39 children with a viral infection, 469 (178 to 827) µg/L in 103 children with viral-bacterial coinfection, 119 (68 to 227) µg/L in 75 children with bacterial infection, and 150 (101 to 212) µg/L in 26 children with bacterial infection and coincidental virus finding (P < 0.001). In a receiver operating characteristics analysis, MxA cutoff level of 256 µg/L differentiated between children with viral and bacterial infections with an area under the curve of 0.81 (95% confidence interval [CI] = 0.73 to 0.90), a sensitivity of 74.4%, and a specificity of 80.0%. In conclusion, MxA protein showed moderate accuracy as a biomarker for symptomatic viral infections in children hospitalized with an acute infection. High prevalence of viral-bacterial coinfections supports the use of MxA in combination with biomarkers of bacterial infection. IMPORTANCE Due to the diagnostic uncertainty concerning the differentiation between viral and bacterial infections, children with viral infections are often treated with antibiotics, predisposing them to adverse effects and contributing to the emerging antibiotic resistance. Since currently available biomarkers only estimate the risk of bacterial infection, a biomarker for viral infection is needed in attempts of reducing antibiotic overuse. Blood MxA protein, which has broad antiviral activity and is rapidly induced in acute, symptomatic viral infections, is a potential biomarker for viral infection. In this diagnostic study of 265 children hospitalized because of an acute infection, blood MxA cutoff level of 256 µg/L discriminated between viral and bacterial infections with a sensitivity of 74% and specificity of 80%. MxA could improve the differential diagnostics of febrile children at the emergency department but, because of frequently detected viral-bacterial coinfections, a combination with biomarkers of bacterial infection may be needed.
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Biomarcadores/sangue , Proteínas de Resistência a Myxovirus , Infecções por Orthomyxoviridae/diagnóstico , Infecções por Orthomyxoviridae/virologia , Orthomyxoviridae/metabolismo , Adolescente , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Febre/diagnóstico , Humanos , Lactente , Masculino , Proteínas de Resistência a Myxovirus/sangue , Orthomyxoviridae/genética , Proteína Estafilocócica A , Viroses/tratamento farmacológico , Viroses/virologiaRESUMO
Background: Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primes the immune system; thus individuals who have recovered from infection have enhanced immune responses to subsequent vaccination (hybrid immunity). However, it remains unclear how well hybrid immunity induced by severe or mild infection can cross-neutralize emerging variants. We aimed to compare the strength and breadth of antibody responses in vaccinated recovered and uninfected subjects. Methods: We measured spike-specific immunoglobulin (Ig)G and neutralizing antibodies (NAbs) from vaccinated subjects including 320 with hybrid immunity and 20 without previous infection. From 29 subjects with a previous severe or mild infection, we also measured NAb responses against Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529/BA.1) variants following vaccination. Results: A single vaccine dose induced 2-fold higher anti-spike IgG concentrations and up to 4-fold higher neutralizing potency of antibodies in subjects with a previous infection compared with vaccinated subjects without a previous infection. Hybrid immunity was more enhanced after a severe than a mild infection, with sequentially decreasing NAb titers against Alpha, Beta, Delta, and Omicron variants. We found similar IgG concentrations in subjects with a previous infection after 1 or 2 vaccine doses. Conclusions: Hybrid immunity induced strong IgG responses, particularly after severe infection. However, the NAb titers were low against heterologous variants, especially against Omicron.
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BACKGROUND: Health care workers are at risk of acquiring SARS-CoV-2 infection. Our aim was to study the prevalence of SARS-CoV-2 nucleoprotein and spike protein specific antibodies in health care workers with occupational exposure to COVID-19 in Turku, Finland, from May to December 2020. METHODS: Health care workers of Turku University Hospital units caring for COVID-19 patients or handling clinical SARS-CoV-2 samples were invited to participate in the study. The presence of SARS-CoV-2 nucleoprotein and spike protein specific IgG antibodies were analysed with in-house enzyme immunoassay. RESULTS: At study enrolment, only one of the 222 (0.5%) study participants was seropositive for SARS-CoV-2 protein specific antibodies. Two additional study participants (2/222, 0.9%) seroconverted during the follow-up. All these participants were diagnosed with a RT-PCR-positive COVID-19 infection before turning seropositive. CONCLUSION: In our study population, the prevalence of SARS-CoV-2 seropositivity remained low. The absence of seropositive cases without previous RT-PCR confirmed infections demonstrate good access to diagnostics. In addition to high vaccine coverage, high standards of infection prevention practices and use of standard personal protective equipment seem sufficient in preventing occupational SARS-CoV-2 infection in a setting with low number of circulating virus. However, it remains unclear whether similar protective practices would also be effective against more transmissible SARS-CoV-2 variants.
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COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Finlândia/epidemiologia , Pessoal de Saúde , Humanos , Nucleoproteínas , Estudos Prospectivos , Estudos Soroepidemiológicos , Glicoproteína da Espícula de Coronavírus , VacinaçãoRESUMO
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.
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COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Vacina BNT162 , Vacinas contra COVID-19 , Humanos , Leucócitos Mononucleares , RNA Mensageiro/genética , Glicoproteína da Espícula de Coronavírus , Linfócitos TRESUMO
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has raised concern about increased transmissibility, infectivity, and immune evasion from a vaccine and infection-induced immune responses. Although COVID-19 mRNA vaccines have proven to be highly effective against severe COVID-19 disease, the decrease in vaccine efficacy against emerged Beta and Delta variants emphasizes the need for constant monitoring of new virus lineages and studies on the persistence of vaccine-induced neutralizing antibodies. To analyze the dynamics of COVID-19 mRNA vaccine-induced antibody responses, we followed 52 health care workers in Finland for 6 months after receiving two doses of BNT162b2 vaccine with a 3-week interval. We demonstrate that, although anti-S1 antibody levels decrease 2.3-fold compared to peak antibody levels, anti-SARS-CoV-2 antibodies persist for months after BNT162b2 vaccination. Variants D614G, Alpha, and Eta are neutralized by sera of 100% of vaccinees, whereas neutralization of Delta is 3.8-fold reduced and neutralization of Beta is 5.8-fold reduced compared to D614G. Despite this reduction, 85% of sera collected 6 months postvaccination neutralizes Delta variant. IMPORTANCE A decrease in vaccine efficacy against emerging SARS-CoV-2 variants has increased the importance of assessing the persistence of SARS-CoV-2 spike protein-specific antibodies and neutralizing antibodies. Our data show that after 6 months post two doses of BNT162b2 vaccine, antibody levels decrease yet remain detectable and capable of neutralizing emerging variants. By monitoring the vaccine-induced antibody responses, vaccination strategies and administration of booster doses can be optimized.