mteb/CovidQA huggingface dataset:
Concurrently, advancements in molecular identification methods have enabled studies regarding the emergence and epidemiology of ARI viruses in many locations (e.g. novel polyomaviruses in Australia [16, 17] , human coronavirus Erasmus Medical Center (HCoV-EMC) in the Middle East and United Kingdom [18, 19] , SARS in Canada and China [20] [21] [22] ), yet research regarding the molecular epidemiology of ARI viruses in Nigeria is limited. Diagnostic methods available and other constraints have limited studies there to serological surveys of only a few of these viruses and only in clinical populations [23, 24] . Thus, the utility of community-based surveillance may be appropriate in contexts such as in Nigeria, and the purpose of this pilot study was to investigate if clinical cases may describe the entire picture of ARI among children in Nigeria.
We performed a cross-sectional study in three community centers and one clinical in Ilorin, Nigeria. Ilorin is in Kwara state and is the 6th largest city in Nigeria by population [25] . Three Local Government Areas (Ilorin East, Ilorin South and Ilorin West LGAs) were the community sites and Children's Specialist Hospital, Ilorin the clinical site. Convenience sampling was used for the purposes of this pilot study, and samples were obtained from March 28 to April 5 2017. Inclusion criteria were: children less than 14 years old who had visible symptoms of ARI within the communities or those confirmed at the hospital with ARI. Exclusion criteria were: children who were 14 and above, not showing signs of ARI and subjects whose parents did not give consent. Twenty-five children with symptoms were selected each from the three community locations while 16 symptomatic children were sampled from the hospital. The total sample size (n = 91) was arrived at based on materials and processing cost
constraints, as well as to provide enough samples to enable descriptive understanding of viral circulation patterns estimated from other community-based studies [10] .
Disease Surveillance and Notification Officers, who are employed by the State Ministry of Health and familiar with the communities in this study, performed specimen and data collection. Symptoms considered were derived in accordance with other ARI surveillance efforts: sore throat, fever, couch, running nose, vomiting, body ache, leg pain, nausea, chills, shortness of breath [10, 26] . Gender and age, type of residential area (rural/urban), education level, proximity of residence to livestock, proximity to an untarred road and number of people who sleep in same room, were all recorded. The general difference between the two settings was that those from the hospital had severe illnesses, while those from the community were generally "healthy" but exhibiting ARI symptoms (i.e. mild illness).
Nasal swabs were collected from the subjects and stored in DNA/RNA shield (Zymo Research, Irvine, California). Collected samples were spinned and the swab removed. Residues containing the nasal samples were stored at -20 °C prior to molecular analysis.

Viral RNA was isolated using ZR Viral RNA ™ Kit (Zymo Research, Irvine, California) per manufacturer instructions (http://www.zymoresearch.com/downloads/dl/file/ id/147/r1034i.pdf ). Real-time PCR (polymerase chain reaction), commonly used in ARI studies [10, 19, 27] , was then carried out using RV15 One Step ACE Detection Kit, catalogue numbers RV0716K01008007 and RV0717B01008001 (Seegene, Seoul, South Korea) for detection of 15 human viruses: parainfluenza virus 1, 2, 3 and 4 (PIV1-4), respiratory syncytial virus (RSV) A and B, influenza A and B (FLUA, FLUB), rhinovirus type A-C, adenovirus (ADV), coronavirus (OC 229 E/NL63, OC43), enterovirus (HEV), metapneumovirus (hMPV) and bocavirus (BoV).
Reagents were validated in the experimental location using an inbuilt validation protocol to confirm issues of false negative and false positive results were not of concern. Amplification reaction was carried out as described by the manufacturer: reverse transcription 50 °C-30′, initial activation 94°-15′, 45 cycles: denaturation 94°-30″, annealing 60°-1′ 30″, extension 72°-1, final extension 72°-10′, hold 4°. Visualization was performed using electrophoresis on a 2% agarose gel in TBE 1X with EtBr, in presence of RV15 OneStep A/B/C Markers; molecular weight marker. Specimen processing was not blinded as there was no risk of experimental bias. Standardized procedures were used for community and clinic sampling.
All statistical analyses were performed using R version 3.2.4. Univariate statistics [mean and 95% confidence interval (CI)] are described. Bivariate statistics (difference in proportions) were assessed using a two-proportion z-test. A p value < 0.001 was considered significant. No observations used in this study had any missing data for analyses in this study.
Basic participant demographics are summarized in PCR results showed that ten different viruses (influenza A, coronavirus OC 229 E/NL63, RSVA, RSV B, parainfluenza 1-4) were detected. Figure 1 shows how these infections were distributed across virus types as well as in the community versus clinic samples. In sum, a total of 33 of the 91 subjects surveyed had one or more respiratory tract virus (36.3%, 95% CI 26.6-47.0%, Fig. 1 ). Furthermore, 10 of those cases were triple infections and 5 were quadruple infections (illustrated by color of bars in Fig. 1 ). Figure 2 indicates how frequently each pair of viruses were found in the same participant; co-infections were most common among enterovirus and parainfluenza virus 4 (Fig. 2) .
We also compared and contrasted the clinical and community results. Parainfluenza virus 4, respiratory syncytial virus B and enterovirus were the most common viruses found in the clinical sample. These three infections resulted in 41 viruses detected in 15 subjects clinically, and eight infections detected in five people in the community. Together they infected 94% (15/16, 95% CI 67.7-99.7%) of clinical subjects, and 7% (5/75, 95% CI 2.5-15.5%) in the community (significant difference, p < 0.001). The most common virus detected in community samples was Coronavirus OC43; this virus was detected in 13.3% (95% CI 6.9-23.6%) people in the community and not in any of the clinical samples. However a different strain, coronavirus OC 229 E/NL63 was detected in 12.5% of the clinical subjects (2/16, 95% CI 2.2-39.6%) and not detected in the community. Double, triple and quadruple infections were another common feature of note.
We identified ten different respiratory tract viruses among the subjects as shown in Fig. 1 . Samples collected from the Children's specialist hospital showed 100% prevalence rate of infection with one or more viruses. This might not be surprising, as the basic difference between the community and clinic samples was an increased severity of illness in the clinical sample. This may also explain the high level of co-infection found among the clinical subjects. The most prevalent virus in the clinical sample (coronavirus OC43) was not detected in the community sample. Further, there was a significant difference between prevalence of the most common viruses in the clinical sample (parainfluenza virus 4, respiratory syncytial virus B and enterovirus) and their prevalence in the community. Finally, some of the viruses detected in this study have not been detected and implicated with ARIs in Nigeria. There is no report, to the best of our knowledge, implicating coronavirus in ARIs in
Nigeria, and it was detected in 12 subjects in this study. Although cases of double and triple infections were observed in a study in Nigeria in 2011 [28] , as far as we are aware, reports of quadruple infections are rare and have not been reported in Nigeria previously.
Due to the unique nature of the data generated in this study and novelty of work in the setting, it is not possible to exactly compare results to other studies. For example, though we found a similar study regarding ARIs in clinical subjects in Burkina Faso [27] , due to the small sample size from this study it would not be feasible to infer or compare prevalence rates. Studies of ARI etiology have mostly been generally focused in areas of the world that are more developed [29] , and it is important to note that the availability of molecular diagnostic methods as employed in this study substantially improve the ability to detect viruses which hitherto have not been detected in Nigeria. Further, findings from this work also add to the growing body of research that shows value of community-data in infectious disease surveillance [8] . As most of the work to-date has been in higher resource areas of the world this study adds perspective from an area where healthcare resources are lower.
In conclusion, results of this study provide evidence for active community surveillance to enhance public health surveillance and scientific understanding of ARIs. This is not only because a minority of children with severe infection are admitted to the hospital in areas such this in Nigeria, but also findings from this pilot study which indicate that viral circulation in the community may not get detected clinically [29] . This pilot study indicates that in areas of Nigeria, etiology of ARIs ascertained from clinical samples may not represent all of the ARIs circulating in the community.
The main limitation of the study is the sample size. In particular, the sample is not equally representative across all ages. However, the sample size was big enough to ascertain significant differences in community and clinic sourced viruses, and provides a qualitative understanding of viral etiology in samples from the community and clinic. Moreover, the sample was largely concentrated on subjects under 6 years, who are amongst the groups at highest risk of ARIs. Despite the small sample size, samples here indicate that circulation patterns in the community may differ from those in the clinic. In addition, this study resulted in unique findings Given that resources are limited for research and practice, we hope these pilot results may motivate further systematic investigations into how community-generated data can best be used in ARI surveillance. Results of this study can inform a larger study, representative across demographic and locations to systematically assess the etiology of
infection and differences in clinical and community cohorts. A larger study will also enable accounting for potential confounders such as environmental risk factors. Finally, while it may be intuitive, findings from this pilot study shed light on the scope of differences in ARI patterns including different types and strains of circulating viruses. Also, because PCR was used for viral detection, the study was limited to detection of viruses in the primer sets. Given that these are the most up-to-date and common viruses, this approach was deemed sufficient for this initial investigation.
The study was conceived by RC and OK. RC and OK, MO and TD were involved in the design of the study, which was conducted by MO and TD. RC and OK analyzed the data. RC and OK wrote and revised the manuscript. All authors read and approved the final manuscript.
Aetiology of Acute Respiratory Tract Infections in Hospitalised Children in Cyprus

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720120/

SHA: efd27ff0ac04dd60838266386aaebb5df80f4fa9

Authors: Richter, Jan; Panayiotou, Christakis; Tryfonos, Christina; Koptides, Dana; Koliou, Maria; Kalogirou, Nikolas; Georgiou, Eleni; Christodoulou, Christina
Date: 2016-01-13
DOI: 10.1371/journal.pone.0147041
License: cc-by
Abstract: In order to improve clinical management and prevention of viral infections in hospitalised children improved etiological insight is needed. The aim of the present study was to assess the spectrum of respiratory viral pathogens in children admitted to hospital with acute respiratory tract infections in Cyprus. For this purpose nasopharyngeal swab samples from 424 children less than 12 years of age with acute respiratory tract infections were collected over three epidemic seasons and were analysed for the presence of the most common 15 respiratory viruses. A viral pathogen was identified in 86% of the samples, with multiple infections being observed in almost 20% of the samples. The most frequently detected viruses were RSV (30.4%) and Rhinovirus (27.4%). RSV exhibited a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. While RSV and PIV3 incidence decreased
significantly with age, the opposite was observed for influenza A and B as well as adenovirus infections. The data presented expand our understanding of the epidemiology of viral respiratory tract infections in Cypriot children and will be helpful to the clinicians and researchers interested in the treatment and control of viral respiratory tract infections.
Text: Viral Respiratory tract infections (RTI) represent a major public health problem because of their world-wide occurrence, ease of transmission and considerable morbidity and mortality effecting people of all ages. Children are on average infected two to three times more frequently than adults, with acute RTIs being the most common infection in childhood [1, 2] . Illnesses caused by respiratory viruses include, among others, common colds, pharyngitis, croup, bronchiolitis, viral pneumonia and otitis media. Rapid diagnosis is important not only for timely therapeutic intervention but also for the identification of a beginning influenza epidemic and the avoidance of unnecessary antibiotic treatment [3, 4] .
RTIs are a major cause of morbidity and mortality worldwide. Acute RTI is most common in children under five years of age, and represents 30-50% of the paediatric medical admissions, as well as 20-40% of hospitalizations in children. Respiratory infections cluster during winter and early spring months. The leading viral agents include respiratory syncytial virus (RSV), influenza A and B (INF-A, INF-B) viruses, parainfluenza viruses (PIVs), and human adenoviruses (HAdVs). In addition, there is a continuously increasing list of new respiratory viruses that contribute significantly to the burden of acute respiratory infections, such as the recently identified human metapneumovirus (HMPV) and human Bocavirus (HBoV) [5] .
Acute RTIs are classified as upper (UTRIs) and lower RTI (LRTIs), according to the involved anatomic localization. URTIs cause non-severe but widespread epidemics that are responsible for continuous circulation of pathogens in the community. LRTIs have been classified as frank pneumonia and bronchiolitis with clinical, radiological and etiological features that usually overlap [6, 7] . Viruses are again the foremost agents of LRTIs often misdiagnosed as bacterial in origin and hence treated with antibiotics unnecessarily [8] .

The main aim of this study was to determine the aetiology of acute respiratory tract infections in Cypriot children and assess the epidemiology of the identified viral pathogens over three epidemic seasons.
The study was approved by the Cyprus National Bioethics Committee. Accordingly, written informed consent was obtained from parents prior to sample taking. Between November 2010 and October 2013, 485 nasopharyngeal swab samples were collected from children up to 12 years of age, who had been hospitalized with acute respiratory tract infection at the Archbishop Makarios III hospital, Nicosia. Clinical and demographic information including symptoms, duration of hospitalisation, diagnosis and treatment were recorded. Nasal swab samples were collected using the BD Universal Viral Transport Collection Kit. Viral RNA/DNA was extracted from 400 μl sample using the iPrep PureLink Virus Kit on an iPrep purification instrument (Invitrogen).
A set of four multiplex Real-Time RT-PCR assays was established and validated for the detection of the 15 most common respiratory viruses as follows: assay 1: influenzaviruses A and B, RSV, assay 2: parainfluenzaviruses 1-4, assay 3: HAdV, enteroviruses, HMPV and HBoV and assay 4: rhinoviruses and the human coronaviruses OC43, NL63 and 229E (Table 1) .
Published primer and probe sets were used as a basis for designing the assays, however, all primer/probe sequences were checked against newly build sequence alignments of all viruses tested and were modified, if necessary, to account for possible sequence variations. For this purpose, all available complete genome sequences were obtained for each virus from GenBank, imported into the BioEdit Sequence Alignment Editor v7.1.7 and aligned using ClustalX. In case of mismatches between published primers/probe and target sequences, modifications were applied, as indicated in Table 1 . The alignments for the viruses, which necessitated changes to the primers/probe are available in Fasta-Format as supplement S1-S4 Files.
Primer concentrations and reaction conditions for the four assays were subsequently optimised for multiplexing. In order to assess the sensitivity and specificity of the assays, the laboratory enrolled for two consecutive years in Quality Control for Molecular Diagnostics (QCMD) external quality assessment schemes for all viruses, except Bocavirus, which was unavailable. In summary, the established assays were able to correctly identify all viruses tested, proving their suitability for diagnostic application.
A possible correlation of virus prevalence and age of infection was assessed using univariate analyses. The Fisher's exact test was used where cell counts below 5 were encountered; otherwise, the chi-squared test was performed. The same statistical tests were used to compare the frequency of subjects with single or multiple infections between age groups. In addition, Pearson correlation was used to examine co-infections of different viruses. All statistical analyses were performed using StataSE 12 (StatCorp. 2007. College Station, TX, USA).

The present study was a prospective investigation of children hospitalized with acute respiratory tract infections between November 2010 and October 2013 in Cyprus. The median age of the children was 15 months (range: 0-140 months) with 243 being male and 181 female (male/ female ratio 1.34). The age distribution is shown in Fig 1.
Out of the 424 samples analysed, 364 (85.8%) were positive for one or more viruses. Results are summarized in Table 2 .The most commonly detected viruses were RSV, which was found in 129 (30.4%) patients and rhinoviruses in 116 (27.4%) accounting together for almost 60% of all detections. With moderate frequency have been detected HAdV in 31(7.3%) patients, influenza A in 28 (6.6%), HBoV in 24 (5.7%), enteroviruses and PIV 3 in 23 (5.4%) of patients respectively, and Influenza B in 21 (5.0%). A low frequency was exhibited by HMPV with 16 (3.8%) positive samples, human coronavirus OC43 with 13 (3.1%), PIV 1 with 12 (2.8%), PIV 4 with 9 (2.1%), PIV 2 with 7 (1.7%) and HCoV NL63 with 6 (1.4%). Coronavirus 229E could be detected only in a single sample.
Co-infections with two or more viruses were observed in 84 out of the 364 positive samples (see Table 2 ). Dual infections accounted for 17% of all positive samples and three viruses were detected in 2.7% of samples). A single patient sample displayed a quadruple infection being simultaneously positive for RSV, rhinovirus, HBoV and influenza B. Table 3 summarizes the frequency of each virus in single vs. multiple infections as well as the number of co-occurrences of viruses for each possible virus combination. In absolute terms the most common combination observed was RSV/rhinovirus. As a percentage, however, the virus appearing most often in co- infections was HBoV, which was found in more than 70% of cases together with another virus, followed by coronaviruses HCoV OC43 and HCoV NL63 with 61% and 67%, respectively. On the other hand, the viruses most rarely seen in co-infections were influenza viruses A and B as well as RSV. Pearson correlation coefficients were calculated to
examine the likelihood of co-infections of different viruses. The results of the analysis are summarized in Table 1 in S1 Table. Significant correlation (P-value < 0.05) was seen mostly for co-infections with RSV, however correlations were very weak (r<0.3) and negative. This finding can probably be explained by the fact that RSV infections occurred predominantly in the very young, where co-infections were less frequently observed. On the other hand, a significant positive correlation was observed for enterovirus and rhinovirus co-infection hinting maybe at similarities in circulation patterns and/or transmission modes.
Regarding seasonality, different patterns of circulations could be observed for RSV, rhinoviruses and influenzaviruses (A and B combined) (Fig 2) , with RSV and influenza exhibiting a clear seasonality with marked peaks in January/February, while rhinovirus infections did not exhibit a pronounced seasonality being detected almost throughout the year. However, as more than 100 different rhinovirus strains have been identified to be circulating worldwide in parallel and successively, a potential seasonality of individual rhinovirus serotypes may be masked by overlapping patterns [18, 19] .
The data was further analysed with regard to the age distribution of virus infection (see Table 2 ). In infants up to 3 months old, RSV was by far the most common pathogen (58.1%), followed by rhinovirus (20.3%) and PIV3 with 8.1% each. The incidence of RSV, however, decreases significantly with increasing age (p-value < 0.0001) dropping to 13% in children older than 3 years old, while the reverse relationship is observed for Influenza A and B and HAdV. Rhinoviruses, HBoV and enteroviruses are most frequently observed in children from 4 months to 3 years of age. The age dependency of the virus incidence is visualized in Fig 3 for the seven most frequently observed viruses. The positivity rate also showed a trend according to the age group dropping from 90.5% in the under 3-month old to 78.3% in the 4-12 years old (p-value = 0.020). This may point to an increasing role of pathogens not included in the assays, such as bacterial infections in older children.
Regarding multiple infections, children less than 3 month of age and those older than 4 years had a significantly smaller risk to present with multiple infections as compared to the other two age groups (p-value = 0.014).

A reason for this could be that very young children have limited contact to others reducing thereby the chance for a co-infection, whereas children older than 3 years already established immunity to an increasing number of viruses encountered previously.
This study for the first time examined the aetiology of acute respiratory tract infections in hospitalised children in Cyprus. Four multiplex Real-Time RT-PCR assays were developed in order to detect the most common respiratory viral pathogens in a fast and cost-effective way. The high rate of positive samples (85.8%) is evidence of the high sensitivity of the Multiplex-assays used and that the range of viruses included in the analysis is comprehensive. Many previous studies have shown detection rates ranging from below 50% to 75% [20] [21] [22] [23] [24] .

The most common viruses detected were RSV and rhinovirus accounting for almost 60% of all cases. Both viruses were reported previously by others as the major aetiology for respiratory viral infections in young children with rhinoviruses being recognized increasingly for their role in lower respiratory tract infections [20, [25] [26] [27] [28] [29] [30] .
Our data support the results of similar studies performed in the Middle East region. A recently published study found that RSV was the most commonly detected virus in nasopharyngeal swabs from children presenting symptoms of RTIs and in addition to that it also showed that RSV infections follow a similar circulation pattern peaking from December to March [31] . Another study has revealed that RSV and PIV3 incidence decreases significantly with age, whereas the opposite is observed for influenza and adenovirus infections, a trend that was also observed in our study [26] .