Contraction of Respiratory Viral Infection During air Travel: An Under-Recognized Health Risk for Athletes.

Air travel has an important role in the spread of viral acute respiratory infections (ARIs). Aircraft offer an ideal setting for the transmission of ARI because of a closed environment, crowded conditions, and close-contact setting. Numerous studies have shown that influenza and COVID-19 spread readily in an aircraft with one virus-positive symptomatic or asymptomatic index case. The numbers of secondary cases differ markedly in different studies most probably because of the wide variation of the infectiousness of the infector as well as the susceptibility of the infectees. The primary risk factor is sitting within two rows of an infectious passenger. Elite athletes travel frequently and are thus prone to contracting an ARI during travel. It is anecdotally known in the sport and exercise medicine community that athletes often contract ARI during air travel. The degree to which athletes are infected in an aircraft by respiratory viruses is unclear. Two recent studies suggest that 8% of Team Finland members traveling to major winter sports events contracted the common cold most probably during air travel. Further prospective clinical studies with viral diagnostics are needed to understand the transmission dynamics and to develop effective and socially acceptable preventive measures during air travel.

Respiratory Syncytial Virus-Associated Hospitalizations in Children: A 10-Year Population-Based Analysis in Finland, 2008-2018.

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.

Clinical Outcomes of Acutely Ill Children According to Cycle Threshold Values of Respiratory Viruses Detected by Multiplex PCR Testing.

In this cohort study of 800 children attending a pediatric emergency department at Oulu University Hospital, Finland with fever or respiratory symptoms, the cycle threshold values of point-of-care multiplex polymerase chain reaction testing for respiratory viruses were not associated with hospitalization, respiratory support, or need for intensive care.

Respiratory viral infections - impact on sport and exercise medicine.

Respiratory viruses are the most frequent causative agents of disease in humans and thus also in elite athletes. The COVID-19 pandemic has recently emphasized the entire spectrum of respiratory tract infections worldwide. Understanding the basic elements of respiratory viral infections is a fundamental requirement from the perspective of etiological diagnostics, treatment, and prevention strategy planning, as well as resource allocation.

Coronavirus spike protein-specific antibodies indicate frequent infections and reinfections in infancy and among BNT162b2-vaccinated healthcare workers.

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.

Enterovirus D68 Outbreak in Children, Finland, August-September 2022.

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.

Infectious viruses from transfected SARS-CoV-2 genomic RNA.

SARS-CoV-2 emerged at the end of 2019, and like other novel pathogens causing severe symptoms, WHO recommended heightened biosafety measures for laboratories working with the virus. The positive-stranded genomic RNA of coronaviruses has been known to be infectious since the 1970s, and overall, all experiments with the possibility of SARS-CoV-2 propagation are carried out in higher containment level laboratories. However, as SARS-CoV-2 RNA has been routinely handled in BSL-2 laboratories, the question of the true nature of RNA infectiousness has risen along with discussion of appropriate biosafety measures. Here, we studied the ability of native SARS-CoV-2 genomic RNA to produce infectious viruses when transfected into permissive cells and discussed the biosafety control measures related to these assays. In transfection assays large quantities of genomic vRNA of SARS-CoV-2 was required for a successful production of infectious viruses. However, the quantity of vRNA alone was not the only factor, and especially when the transfected RNA was derived from infected cells, even small amounts of genomic vRNA was enough for an infection. Virus replication was found to start rapidly after transfection, and infectious viruses were detected in the cell culture media at 24 h post-transfection. In addition, silica membrane-based kits were shown to be as good as traditional TRI-reagent based methods in extracting high-quality, 30 kb-long genomic vRNA. Taken together, our data indicates that all transfection experiments with samples containing genomic SARS-CoV-2 RNA should be categorized as a propagative work and the work should be conducted only in a higher containment BSL-3 laboratory.

Biomarkers of viral and bacterial infection in rhinovirus pneumonia.

Background: Rhinovirus (RV) is often detected in children hospitalized with pneumonia, but the role of RV in causing pneumonia is still unclear. Methods: White blood cell count, C-reactive protein, procalcitonin, and myxovirus resistance protein A (MxA) levels were determined from blood samples in children (n = 24) hospitalized with radiologically verified pneumonia. Respiratory viruses were identified from nasal swabs by using reverse transcription polymerase chain reaction assays. Among RV-positive children, the cycle threshold value, RV subtyping by sequence analysis, and the clearance of RV by weekly nasal swabs were determined. RV-positive children with pneumonia were compared to other virus-positive children with pneumonia, and to children (n = 13) with RV-positive upper respiratory tract infection from a separate earlier study. Results: RV was detected in 6 children and other viruses in 10 children with pneumonia (viral co-detections excluded). All RV-positive children with pneumonia had high white blood cell counts, plasma C-reactive protein or procalcitonin levels, or alveolar changes in chest radiograph strongly indicating bacterial infection. The median cycle threshold value for RV was low (23.2) indicating a high RV load, and a rapid clearance of RV was observed in all. Blood level of viral biomarker MxA was lower among RV-positive children with pneumonia (median 100 µg/L) than among other virus-positive children with pneumonia (median 495 µg/L, p = 0.034) or children with RV-positive upper respiratory tract infection (median 620 µg/L, p = 0.011). Conclusions: Our observations suggest a true viral-bacterial coinfection in RV-positive pneumonia. Low MxA levels in RV-associated pneumonia need further studies.

Diagnostic Performance and Tolerability of Saliva and Nasopharyngeal Swab Specimens in the Detection of SARS-CoV-2 by RT-PCR.

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.

Association of Asthma Risk Alleles With Acute Respiratory Tract Infections and Wheezing Illnesses in Young Children.

BACKGROUND: Genome-wide association studies have identified several risk alleles for early childhood asthma, particularly in the 17q21 locus and in the cadherin-related family member 3 (CDHR3) gene. Contribution of these alleles to the risk of acute respiratory tract infections (ARI) in early childhood is unclear. METHODS: We analyzed data from the STEPS birth-cohort study of unselected children and the VINKU and VINKU2 studies on children with severe wheezing illness. Genome-wide genotyping was performed on 1011 children. We analyzed the association between 11 preselected asthma risk alleles and the risk of ARIs and wheezing illnesses of various viral etiologies. RESULTS: The asthma risk alleles in CDHR3, GSDMA, and GSDMB were associated with an increased rate of ARIs (for CDHR3, incidence rate ratio [IRR], 1.06; 95% confidence interval [CI], 1.01-1.12; P = .02), and risk allele in CDHR3 gene with rhinovirus infections (IRR, 1.10; 95% CI, 1.01-1.20, P = .03). Asthma risk alleles in GSDMA, GSDMB, IKZF3, ZPBP2, and ORMDL3 genes were associated with wheezing illnesses in early childhood, especially rhinovirus-positive wheezing illnesses. CONCLUSIONS: Asthma risk alleles were associated with an increased rate of ARIs and an increased risk of viral wheezing illnesses. Nonwheezing and wheezing ARIs and asthma may have shared genetic risk factors. Clinical Trials Registration. NCT00494624 and NCT00731575.

Influenza A Outbreaks in Two Professional Ice Hockey Teams during COVID-19 Epidemic.

Influenza A outbreaks occurred in two professional hockey teams just after two games they played against each other. Thirteen players and two staff members fell ill during 17-20 April 2022, while COVID-19 was prevalent. Altogether, seven players missed an important game due to influenza. The rapid diagnosis permitted effective pharmaceutical and nonpharmaceutical control of the outbreaks.

Non-SARS-CoV-2 Respiratory Viruses in Athletes at Major Winter Sport Events, 2021 and 2022.

We performed prospective studies on respiratory viral infections among Team Finland participants during the 2021 Oberstdorf World Ski Championships and the 2022 Beijing Olympic Games. We enrolled 73 athletes and 110 staff members. Compared with similar studies we conducted before the COVID-19 pandemic, illnesses and virus detections dropped by 10-fold.

Association of human myxovirus resistance protein A with severity of COVID-19.

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.

Detection of group A streptococcus in children with confirmed viral pharyngitis and antiviral host response.

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: •The frequency and significance of GAS-virus co-detection are poorly characterised in children with pharyngitis. •Detection of a virus and the antiviral host response likely indicates symptomatic infection. WHAT IS NEW: •Group A streptococcus (GAS) was detected in 17-43% of the children with confirmed viral pharyngitis depending on the GAS diagnostic method. •Our results emphasize the risk of detecting and treating incidental pharyngeal carriage of GAS in children with viral pharyngitis.

Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children - The TREND study.

OBJECTIVE: Discriminating between viral and bacterial lower respiratory tract infection (LRTI) in children is challenging, leading to an excessive use of antibiotics. Myxovirus resistance protein A (MxA) is a promising biomarker for viral infections. The primary aim of the study was to assess differences in blood MxA levels between children with viral and bacterial LRTI. Secondary aims were to assess differences in blood MxA levels between children with viral LRTI and asymptomatic controls and to assess MxA levels in relation to different respiratory viruses. METHODS: Children with LRTI were enrolled as cases at Sachs' Children and Youth Hospital, Stockholm, Sweden. Nasopharyngeal aspirates and blood samples for analysis of viral PCR, MxA, and C-reactive protein were systematically collected from all study subjects in addition to standard laboratory/radiology assessment. Aetiology was defined according to an algorithm based on laboratory and radiological findings. Asymptomatic children with minor surgical disease were enrolled as controls. RESULTS: MxA levels were higher in children with viral LRTI (n = 242) as compared to both bacterial (n = 5) LRTI (p <0.01, area under the curve (AUC) 0.90, 95% CI: 0.81 to 0.99), and controls (AUC 0.92, 95% CI: 0.88 to 0.95). In the subgroup of children with pneumonia diagnosis, a cutoff of MxA 430 µg/l discriminated between viral (n = 29) and bacterial (n = 4) aetiology with 93% (95% CI: 78-99%) sensitivity and 100% (95% CI: 51-100%) specificity (AUC 0.98, 95% CI: 0.94 to 1.00). The highest MxA levels were seen in cases PCR positive for influenza (median MxA 1699 µg/l, interquartile range: 732 to 2996) and respiratory syncytial virus (median MxA 1115 µg/l, interquartile range: 679 to 2489). DISCUSSION: MxA accurately discriminated between viral and bacterial aetiology in children with LRTI, particularly in the group of children with pneumonia diagnosis, but the number of children with bacterial LRTI was low.

Gut Microbiota and Serum Metabolome in Elite Cross-Country Skiers: A Controlled Study.

Exercise has been shown to affect gut the microbiome and metabolic health, with athletes typically displaying a higher microbial diversity. However, research on the gut microbiota and systemic metabolism in elite athletes remains scarce. In this study, we compared the gut microbiota profiles and serum metabolome of national team cross-country skiers at the end of an exhausting training and competitive season to those of normally physically-active controls. The gut microbiota were analyzed using 16S rRNA amplicon sequencing. Serum metabolites were analyzed using nuclear magnetic resonance. Phylogenetic diversity and the abundance of several mucin-degrading gut microbial taxa, including Akkermansia, were lower in the athletes. The athletes had a healthier serum lipid profile than the controls, which was only partly explained by body mass index. Butyricicoccus associated positively with HDL cholesterol, HDL2 cholesterol and HDL particle size. The Ruminococcus torques group was less abundant in the athlete group and positively associated with total cholesterol and VLDL and LDL particles. We found the healthier lipid profile of elite athletes to co-occur with known health-beneficial gut microbes. Further studies should elucidate these links and whether athletes are prone to mucin depletion related microbial changes during the competitive season.

Serological Follow-Up Study Indicates High Seasonal Coronavirus Infection and Reinfection Rates in Early Childhood.

Seasonal human coronaviruses (HCoVs) cause respiratory infections, especially in children. Currently, the knowledge on early childhood seasonal coronavirus infections and the duration of antibody levels following the first infections is limited. Here we analyzed serological follow-up samples to estimate the rate of primary infection and reinfection(s) caused by seasonal coronaviruses in early childhood. Serum specimens were collected from 140 children at ages of 13, 24, and 36 months (1, 2, and 3 years), and IgG antibody levels against recombinant HCoV nucleoproteins (N) were measured by enzyme immunoassay (EIA). Altogether, 84% (118/140) of the children were seropositive for at least one seasonal coronavirus N by the age of 3 years. Cumulative seroprevalences for HCoVs 229E, HKU1, NL63, and OC43 increased by age, and they were 45%, 27%, 70%, and 44%, respectively, at the age of 3 years. Increased antibody levels between yearly samples indicated reinfections by 229E, NL63, and OC43 viruses in 20-48% of previously seropositive children by the age of 3 years. Antibody levels declined 54-73% or 31-77% during the year after seropositivity in children initially seropositive at 1 or 2 years of age, respectively, in case there was no reinfection. The correlation of 229E and NL63, and OC43 and HKU1 EIA results, suggested potential cross-reactivity between the N specific antibodies inside the coronavirus genera. The data shows that seasonal coronavirus infections and reinfections are common in early childhood and the antibody levels decline relatively rapidly. IMPORTANCE The rapid spread of COVID-19 requires better knowledge on the rate of coronavirus infections and coronavirus specific antibody responses in different population groups. In this work we analyzed changes in seasonal human coronavirus specific antibodies in young children participating in a prospective 3-year serological follow-up study. We show that based on seropositivity and changes in serum coronavirus antibody levels, coronavirus infections and reinfections are common in early childhood and the antibodies elicited by the infection decline relatively rapidly. These observations provide further information on the characteristics of humoral immune responses of coronavirus infections in children.