Respiratory Virus Co-infection Research Articles

The Complexity of Co-Infections in the Era of COVID-19.

The current frequency of COVID-19 in a pandemic era ensures that co-infections with a variety of co-pathogens will occur. Generally, there is a low rate of bonafide co-infections in early COVID-19 pulmonary infection as currently appreciated. Reports of high co-infection rates must be tempered by limitations in current diagnostic methods since amplification technologies do not necessarily confirm live pathogen and may be subject to considerable laboratory variation. Some laboratory methods may not exclude commensal microbes. Concurrent serodiagnoses have long been of concern for accuracy in these contexts. Presumed virus co-infections are not specific to COVID-19. The association of influenza viruses and SARS-CoV-2 in co-infection has been considerably variable during influenza season. Other respiratory virus co-infections have generally occurred in less than 10% of COVID-19 patients. Early COVID-19 disease is more commonly associated with bacterial co-pathogens that typically represent usual respiratory micro-organisms. Late infections, especially among severe clinical presentations, are more likely to be associated with nosocomial or opportunistic pathogens given the influence of treatments that can include antibiotics, antivirals, immunomodulating agents, blood products, immunotherapy, steroids, and invasive procedures. As anticipated, hospital care carries risk for multi-resistant bacteria. Overall, co-pathogen identification is linked with longer hospital stay, greater patient complexity, and adverse outcomes. As for other viral infections, a general reduction in the use of empiric antibiotic treatment is warranted. Further insight into co-infections with COVID-19 will contribute overall to effective antimicrobial therapies and disease control.

Attenuation of porcine deltacoronavirus disease severity by porcine reproductive and respiratory syndrome virus coinfection in a weaning pig model

ABSTRACT Porcine deltacoronavirus (PDCoV) is a potentially emerging zoonotic pathogen that causes severe diarrhea in young pigs, with a risk of fatal dehydration. Its pathogenicity on neonatal piglet has been previously reported, however, it is less known if the coinfection with immunosuppressive pathogens can influence PDCoV disease manifestation. Here, a coinfection model of PDCoV and porcine reproductive and respiratory syndrome virus (PRRSV), a global-spread immunosuppressive virus, was set to study their interaction. Weaning pigs in the coinfection group were intranasally inoculated with PRRSV NADC30-like virus and latterly orally inoculated with PDCoV at three day-post-inoculation (DPI). Unexpectedly, compared with pigs in the PDCoV single-infected group, the coinfected pigs did not show any obvious diarrhea, as PDCoV fecal shedding, average daily weight gain (ADWG), gross and microscopic lesions and PDCoV IHC scores consistently indicated that PRRSV coinfection lessened PDCoV caused diarrhea. Additionally, three proinflammatory cytokines TNF-α, IL-1 and IL-6, which can be secreted by PRRSV infected macrophages, were detected to be highly expressed at the intestine from both PRRSV infected groups. By adding to PDCoV-infected cells, these three cytokines were further confirmed to be able to inhibit the PDCoV replication post its cellular entry. Meanwhile, the inhibition effect of the supernatant from PRRSV-infected PAMs could be obviously blocked by the antagonist of these three cytokines. In conclusion, PRRSV coinfection increased TNF-α, IL-1, and IL-6 in the microenvironment of intestines, which inhibits the PDCoV proliferation, leading to lessened severity of diarrhea. The findings provide some new insight into the pathogenesis and replication regulation of PDCoV.

Predictive Factors of the Responses to Treatment of Mycoplasma pneumoniae Pneumonia.

The prevalence of refractory Mycoplasma pneumoniae (MP) pneumonia is increasing. The present study aimed to identify the predictive factors of responses to treatment of MP pneumonia in children. A total of 149 children were diagnosed with MP pneumonia, of whom 56 were included in the good response group, 75 children in the slow response group, and 18 children in no response or progression group. Data on the clinical, laboratory, and radiologic features were retrospectively obtained through medical chart reviews. The severity of pneumonia, based on the extent of pneumonic lesions on chest x-ray (adjusted odds ratio (aOR), 10.573; 95% confidence intervals (CIs), 2.303−48.543), and lactate dehydrogenase (LDH) levels (aOR, 1.002; 95% CIs, 1.000–1.004) at the time of admission were associated with slow response to treatment of MP pneumonia. Pleural effusion (aOR, 5.127; 95% CIs, 1.404–18.727), respiratory virus co-infection (aOR, 4.354; 95% CIs, 1.374–13.800), and higher LDH levels (aOR, 1.005; 95% CIs, 1.002–1.007) as well as MP-specific IgM titer (aOR, 1.309; 95% CIs, 1.095–1.564) were associated with no response or progression of MP pneumonia. The area under the curve for the prediction of no or poor response in MP pneumonia using pleural effusion, respiratory virus co-infection, LDH levels, and MP-specific IgM titer at the time of admission was 0.8547. This study identified the predictive factors of responses to treatment of MP pneumonia in children, which would be helpful in establishing a therapeutic plan and predicting the clinical course of MP pneumonia in children.

Respiratory viral co-infections among SARS-CoV-2 cases confirmed by virome capture sequencing

Accumulating evidence supports the high prevalence of co-infections among Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients, and their potential to worsen the clinical outcome of COVID-19. However, there are few data on Southern Hemisphere populations, and most studies to date have investigated a narrow spectrum of viruses using targeted qRT-PCR. Here we assessed respiratory viral co-infections among SARS-CoV-2 patients in Australia, through respiratory virome characterization. Nasopharyngeal swabs of 92 SARS-CoV-2-positive cases were sequenced using pan-viral hybrid-capture and the Twist Respiratory Virus Panel. In total, 8% of cases were co-infected, with rhinovirus (6%) or influenzavirus (2%). Twist capture also achieved near-complete sequencing (> 90% coverage, > tenfold depth) of the SARS-CoV-2 genome in 95% of specimens with Ct < 30. Our results highlight the importance of assessing all pathogens in symptomatic patients, and the dual-functionality of Twist hybrid-capture, for SARS-CoV-2 whole-genome sequencing without amplicon generation and the simultaneous identification of viral co-infections with ease.

Prevalence of Co-Infections with Respiratory Viruses in Individuals Investigated for SARS-CoV-2 in Ontario, Canada.

Background: Co-infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with respiratory viruses, bacteria and fungi have been reported to cause a wide range of illness. Objectives: We assess the prevalence of co-infection of SARS-CoV-2 with seasonal respiratory viruses, document the respiratory viruses detected among individuals tested for SARS-CoV-2, and describe characteristics of individuals with respiratory virus co-infection detected. Methods: Specimens included in this study were submitted as part of routine clinical testing to Public Health Ontario Laboratory from individuals requiring testing for SARS-CoV-2 and/or seasonal respiratory viruses. Results: Co-infection was detected in a smaller proportion (2.5%) of individuals with laboratory confirmed SARS-CoV-2 than those with seasonal respiratory viruses (4.3%); this difference was not significant. Individuals with any respiratory virus co-infection were more likely to be younger than 65 years of age and male than those with single infection. Those with SARS-CoV-2 co-infection manifested mostly mild respiratory symptoms. Conclusions: Findings of this study may not support routine testing for seasonal respiratory viruses among all individuals tested for SARS-CoV-2, as they were rare during the study period nor associated with severe disease. However, testing for seasonal respiratory viruses should be performed in severely ill individuals, in which detection of other viruses may assist with patient management.

SARS-CoV-2 and Respiratory Syncytial Virus Coinfection in Hospitalized Pediatric Patients.

In this study, children under 24 months of age hospitalized with respiratory compromise due to COVID-19 were retrospectively analyzed according to the event of coinfection with respiratory syncytial virus. Of 32 patients, 18.7% had coinfection and these had a significantly longer length of stay. There were no differences regarding need for intensive care, mechanical ventilation or mortality rates.

COVID-19 and respiratory tract viral co-infections: Choosing the screening method

COVID-19 and respiratory tract viral co-infections: Choosing the screening method

Prevalence of Co-infection at the Time of Hospital Admission in COVID-19 Patients, A Multicenter Study.

BackgroundBacterial infections may complicate viral pneumonias. Recent reports suggest that bacterial co-infection at time of presentation is uncommon in coronavirus disease 2019 (COVID-19); however, estimates were based on microbiology tests alone. We sought to develop and apply consensus definitions, incorporating clinical criteria to better understand the rate of co-infections and antibiotic use in COVID-19.MethodsA total of 1016 adult patients admitted to 5 hospitals in the Johns Hopkins Health System between March 1, 2020, and May 31, 2020, with COVID-19 were evaluated. Adjudication of co-infection using definitions developed by a multidisciplinary team for this study was performed. Both respiratory and common nonrespiratory co-infections were assessed. The definition of bacterial community-acquired pneumonia (bCAP) included proven (clinical, laboratory, and radiographic criteria plus microbiologic diagnosis), probable (clinical, laboratory, and radiographic criteria without microbiologic diagnosis), and possible (not all clinical, laboratory, and radiographic criteria met) categories. Clinical characteristics and antimicrobial use were assessed in the context of the consensus definitions.ResultsBacterial respiratory co-infections were infrequent (1.2%); 1 patient had proven bCAP, and 11 (1.1%) had probable bCAP. Two patients (0.2%) had viral respiratory co-infections. Although 69% of patients received antibiotics for pneumonia, the majority were stopped within 48 hours in patients with possible or no evidence of bCAP. The most common nonrespiratory infection was urinary tract infection (present in 3% of the cohort).ConclusionsUsing multidisciplinary consensus definitions, proven or probable bCAP was uncommon in adults hospitalized due to COVID-19, as were other nonrespiratory bacterial infections. Empiric antibiotic use was high, highlighting the need to enhance antibiotic stewardship in the treatment of viral pneumonias.

Gene editing and RNAi approaches for COVID-19 diagnostics and therapeutics.

The novel coronavirus pneumonia (COVID-19) is a highly infectious acute respiratory disease caused by Severe Acute Respiratory Syndrome-Related Coronavirus (SARS-CoV-2) (Prec Clin Med 2020;3:9–13, Lancet 2020;395:497–506, N. Engl J Med 2020a;382:1199–207, Nature 2020;579:270–3). SARS-CoV-2 surveillance is essential to controlling widespread transmission. However, there are several challenges associated with the diagnostic of the COVID-19 during the current outbreak (Liu and Li (2019), Nature 2020;579:265–9, N. Engl J Med 2020;382:727–33). Firstly, the high number of cases overwhelms diagnostic test capacity and proposes the need for a rapid solution for sample processing (Science 2018;360:444–8). Secondly, SARS-CoV-2 is closely related to other important coronavirus species and subspecies, so detection assays can give false-positive results if they are not efficiently specific to SARS-CoV-2. Thirdly, patients with suspected SARS-CoV-2 infection sometimes have a different respiratory viral infection or co-infections with SARS-CoV-2 and other respiratory viruses (MedRxiv 2020a;1–18). Confirmation of the COVID-19 is performed mainly by virus isolation followed by RT-PCR and sequencing (N. Engl J Med 2020;382:727–33, MedRxiv 2020a, Turkish J Biol 2020;44:192–202). The emergence and outbreak of the novel coronavirus highlighted the urgent need for new therapeutic technologies that are fast, precise, stable, easy to manufacture, and target-specific for surveillance and treatment. Molecular biology tools that include gene-editing approaches such as CRISPR-Cas12/13-based SHERLOCK, DETECTR, CARVER and PAC-MAN, antisense oligonucleotides, antisense peptide nucleic acids, ribozymes, aptamers, and RNAi silencing approaches produced with cutting-edge scientific advances compared to conventional diagnostic or treatment methods could be vital in COVID-19 and other future outbreaks. Thus, in this review, we will discuss potent the molecular biology approaches that can revolutionize diagnostic of viral infections and therapies to fight COVID-19 in a highly specific, stable, and efficient way.

12: Utility of Testing for Respiratory Viral Co-Infections With SARS-CoV-2 at Time of Initial Diagnosis

Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

High burden of viral respiratory co-infections in a cohort of children with suspected pulmonary tuberculosis

BackgroundThe presentation of pulmonary tuberculosis (PTB) in young children is often clinically indistinguishable from other common respiratory illnesses, which are frequently infections of viral aetiology. As little is known about the role of viruses in children with PTB, we investigated the prevalence of respiratory viruses in children with suspected PTB at presentation and follow-up.MethodsIn an observational cohort study, children < 13 years were routinely investigated for suspected PTB in Cape Town, South Africa between December 2015 and September 2017 and followed up for 24 weeks. Nasopharyngeal aspirates (NPAs) were tested for respiratory viruses using multiplex PCR at enrolment, week 4 and 8.ResultsSeventy-three children were enrolled [median age 22.0 months; (interquartile range 10.0–48.0); 56.2% male and 17.8% HIV-infected. Anti-tuberculosis treatment was initiated in 54.8%; of these 50.0% had bacteriologically confirmed TB. At enrolment, ≥1 virus were detected in 95.9% (70/73) children; most commonly human rhinovirus (HRV) (74.0%). HRV was more frequently detected in TB cases (85%) compared to ill controls (60.6%) (p = 0.02). Multiple viruses were detected in 71.2% of all children; 80% of TB cases and 60.6% of ill controls (p = 0.07). At follow-up, ≥1 respiratory virus was detected in 92.2% (47/51) at week 4, and 94.2% (49/52) at week 8.ConclusionsWe found a high prevalence of viral respiratory co-infections in children investigated for PTB, irrespective of final PTB diagnosis, which remained high during follow up. Future work should include investigating the whole respiratory ecosystem in combination with pathogen- specific immune responses.

Does respiratory co-infection facilitate dispersal of SARS-CoV-2? investigation of a super-spreading event in an open-space office

BackgroundSuper-spreaders are individuals infecting disproportionately large numbers of contacts. They probably play a crucial role in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe a super-spreading event within a team working in an open-space office and investigate factors potentially having facilitated SARS-CoV-2 transmission.MethodsIn this retrospective cohort study, semi-structured telephone interviews with all team members were carried out to identify symptoms, contacts, and adherence to basic hygiene measures. During site visits, we gathered information about workplace and seating arrangements. The secondary attack rate in office and households was calculated. Potential respiratory viral co-infections were assessed by multiplex PCR. SARS-CoV-2 whole-genome sequencing was performed using a tiled-amplicon sequencing approach.ResultsOf 13 team members, 11 fell ill with Coronavirus disease 2019 (COVID-19). Due to the sequence of events and full genome sequence data, one person was considered the index case for this outbreak, directly infecting 67 to 83% of the teammates. All team members reported repetitive close contacts among themselves during joint computer work, team meetings and a “Happy Birthday” serenade. Two individuals shared nuts and dates. The arrangement of the office and meeting rooms precluded sufficient adherence to physical distancing. The index case and a further individual were diagnosed with an adenovirus serotype 4 co-infection.ConclusionWe identified several environmental and behavioral factors that probably have facilitated the transmission of SARS-CoV-2. The relevance of the adenovirus co-infection remains unclear and merits further investigation.

Severity of influenza virus and respiratory syncytial virus coinfections in hospitalized adult patients

Abstract Background With the introduction of molecular diagnostic techniques over the past decades, different kinds of viral pathogens in the same sample are detected simultaneously more frequently. Nevertheless, influenza virus (Flu) and respiratory syncytial virus (RSV) coinfection in adults was reported only occasionally. Moreover, the clinical implications of Flu/RSV coinfection in the respiratory tract of adults remain unclear. Methods This retrospective study analyzed adult patients with acute respiratory infection from January 2017 to June 2019 in China-Japan Friendship Hospital. Results A total of 574, 235 and 113 patients were positive for influenza A-only (FA-only), influenza B-only (FB-only) and RSV-only in influenza seasons (from Nov 2017 to Mar 2018 and from Nov 2018 to Mar 2019), respectively. Of these, 19 cases were coinfected by Flu and RSV and admitted to this hospital. Compared with 809 Flu-only infected patients and 113 RSV-only infected patients, both the rates of intensive care unit(ICU) admission and use of invasive mechanical ventilation in Flu/RSV coinfected patients were higher (ICU admission: 47.4% vs. 20.1%, P=0.004; 47.4% vs. 22.1%, P=0.020; invasive mechanical ventilation: 47.4% vs.13.2%, P Conclusion The findings of this study suggest that coinfection of Flu/RSV in adults is associated with a high adverse outcome. Thus, Flu/RSV coinfections should be increasingly appreciated and given appropriate management.

Risk factors for the development of post-infectious bronchiolitis obliterans after Mycoplasma pneumoniae pneumonia in the era of increasing macrolide resistance

BackgroundThe prevalence of macrolide-resistant Mycoplasma pneumoniae (MP) pneumonia has been rapidly increased. MP pneumonia is a risk factor for the development of post-infectious bronchiolitis obliterans (PIBO). The aim of the present study was to identify the risk factors for the development of PIBO after MP pneumonia in the era of increasing macrolide resistance of MP. Materials and methodsThis retrospective study enrolled 150 children with a mean age of 6.0 years admitted to the hospital due to MP pneumonia between May 2019 and February 2020 at a tertiary hospital. The clinical, radiologic, and laboratory data were obtained using retrospective chart review. ResultsEighteen children (12%) were diagnosed with PIBO after MP pneumonia. PIBO was diagnosed after a mean duration of 100.0 days (range, 6–268 days) from symptom onset. The respiratory virus co-infection (adjusted odds ratio [aOR], 4.069; 95% confidence interval [95% CI], 1.224–13.523), adenovirus co-infection (aOR, 5.607; 95% CI, 1.801–17.454), longer duration between symptom onset and admission (aOR, 1.150; 95% CI, 1.020–1.298), higher levels of serum lactate dehydrogenase (LDH) at the time of admission (aOR, 1.001; 95% CI, 1.000–1.003), and poor response to stepwise treatment increased the risk for development of PIBO after MP pneumonia. However, macrolide resistance of MP was not associated with development of PIBO after MP pneumonia. ConclusionThe present study suggests that respiratory virus co-infection, including adenovirus, poor response to the treatment of MP pneumonia, and higher levels of serum LDH, but not macrolide resistance of MP, are risk factors of PIBO after MP pneumonia.

Clinical Impact of Combined Viral and Bacterial Infection in Pediatric Mycoplasmal Community-Acquired Pneumonia in Western China

Community-acquired pneumonia (CAP) refers to an infection contracted outside the hospital that leads to lung parenchyma inflammation. The clinical characteristics of Mycoplasma pneumoniae (M. pneumoniae) infection in CAP patients were rarely reported. The aim of this study was to describe the clinical characteristic and the impact of co-infections of M. pneumoniae with viral and bacterial pathogens in hospitalized children with CAP in Liuzhou, China. This study retrospects children diagnosed with CAP due to M. pneumoniae infection at a tertiary maternal and child health care hospital. Data related to co-infection pathogens, demographics, clinical characteristics, and hospitalization cost were collected from the electronic medical system in this hospital. A total of 983 children were diagnosed with mycoplasmal CAP in 2017. Among them, 18.2% had a bacterial-M. pneumoniae co-infection and 11.3% had a viral-M. pneumoniae co-infection. The highest infection rate of M. pneumoniae was 19.1% in February and March, while the highest rates of bacterial-M. pneumoniae and viral-M. pneumoniae co-infections were 3.6% in December and 2.3% in January, respectively. The prevalence of coughing and wheezing had significant differences between the bacterial- or viral-M. pneumoniae co-infections and the mono-infection groups. Furthermore, the chest X-ray progression, pleural effusions, respiratory failure, and ventilation rates were higher in the respiratory viral- and bacterial-M. pneumoniae co-infection groups than in the mono-infection group. Children with a bacterial or respiratory viral co-infection had a longer hospitalization and spent more on treatment fees than those with a M. pneumoniae mono-infection (P value &lt;0.001). We conclude that children with mycoplasmal CAP, either with a bacterial or viral co-infection, who show signs of coughing and wheezing and have a radiographic progression, will have a severe disease progression and should be specifically treated and managed.

High incidence and characteristic of PRRSV and resistant bacterial Co-Infection in pig farms

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and resistant bacterial co-infection is a serious threat to pig farms. This study was aimed to determine the characteristics of the co-infection of PRRSV with resistant bacterial strains in pig farms. The presence of the PRRSV orf5 gene was confirmed by RT-PCR from 395 samples. Bacterial strains were isolated from PRRSV positive samples. Antimicrobial drug susceptibility was determined by the Kirby-Bauer method. Resistant genes were determined by PCR amplification and sequencing. The whole genome of carbapenems resistant E.coli was sequenced and analyse. A total of 75 samples were PRRSV positive, and 45 different orf5 sequences were finally determined. Phylogenetic analysis showed that 45 sequences are clustered into four groups, including JXA1-like, NADC30-like, GD-QY2-like, and CH-1a-like viruses. Twenty-one samples were identified with PRRSV and amoxicillin resistance bacterial co-infection, and 23 were found with amoxicillin resistance (including 15 Escherichia coli, 3 Klebsiella pneumoniae, 2 Haemophilus parasuis, 1 Actinobacillus pleuropneumoniae, 1 Pasteurella multocida, and 1 Proteus mirabilis). All bacterial strains were resistant to the most commonantibiotics and were carriers of a large number of resistance genes. Whole-genome sequencing of E. coli ScEc7 yielded 113 scaffolds of genome DNA, one IncX3 plasmid pScEc7-NDM-5 (46,161 bp) and one IncF plasmid pScEc7-CTX-M (129,978 bp). It carries19 resistance genes, 8 virulence factors, and several mobile genetic elements. The results obtained let us to concluded that: (1) Co-infection is common in pig farms. (2) The orf5 gene continues to undergo its sequences divergence. (3) The bacterial carrying diverse resistance genes were resistant to most of the commonly used antibiotics. (4) Carbapenems resistant isolate has a large number of resistance genes, virulence factors, and MGEs. Therefore, continuous study of the characteristic of PRRSV and resistant bacterial co-infection is necessary for healthy pig aquaculture.

Derivation and Validation of a Predictive Score for Disease Worsening in Patients with COVID-19.

The prospective observational cohort study COMPASS-COVID-19 aimed to develop a risk assessment model for early identification of hospitalized COVID-19 patients at risk for worsening disease. Patients with confirmed COVID-19 ( n = 430) hospitalized between March 18 and April 21, 2020 were divided in derivation ( n = 310) and validation ( n = 120) cohorts. Two groups became evident: (1) good prognosis group (G-group) with patients hospitalized at the conventional COVID-19 ward and (2) Worsening disease group (W-group) with patients admitted to the intensive care unit (ICU) from the emergency departments. The study end point was disease worsening (acute respiratory failure, shock, myocardial dysfunction, bacterial or viral coinfections, and acute kidney injury) requiring ICU admission. All patients were routinely evaluated for full blood count, prothrombin time, fibrinogen, D-dimers, antithrombin (AT), and protein C activity. Data from the first hospitalization day at the conventional ward or the ICU were analyzed. Cardiovascular risk factors and comorbidities were routinely registered. Obesity, hypertension, diabetes and male gender, increased fibrinogen and D-dimers, thrombocytopenia, AT deficiency, lymphopenia, and an International Society on Thrombosis and Haemostasis (ISTH) score for compensated disseminated intravascular coagulation score (cDIC-ISTH) ≥ 5 were significant risk factors for worsening disease. The COMPASS-COVID-19 score was derived from multivariate analyses and includes obesity, gender, hemoglobin, lymphocyte, and the cDIC-ISTH score (including platelet count, prothrombin time, D-dimers, AT, and protein C levels). The score has a very good discriminating capacity to stratify patients at high and low risk for worsening disease, with an area under the receiver operating characteristic curve value of 0.77, a sensitivity of 81%, and a specificity of 60%. Application of the COMPASS-COVID-19 score at the validation cohort showed 96% sensitivity. The COMPASS-COVID-19 score is an accurate clinical decision-making tool for an easy identification of COVID-19 patients being at high risk for disease worsening.

Presumed respiratory syncytial virus and severe acute respiratory syndrome coronavirus-2 co-infection in a critically ill infant: Diagnostic uncertainty and emergency management.

Presumed respiratory syncytial virus and severe acute respiratory syndrome coronavirus-2 co-infection in a critically ill infant: Diagnostic uncertainty and emergency management.

Respiratory viral coinfection in a birth cohort of infants in rural Nepal.

BackgroundAcute respiratory illnesses are a leading cause of global morbidity and mortality in children. Coinfection with multiple respiratory viruses is common. Although the effects of each virus have been studied individually, the impacts of coinfection on disease severity are less understood.MethodsA secondary analysis was performed of a maternal influenza vaccine trial conducted between 2011 and 2014 in Nepal. Prospective weekly household‐based active surveillance of infants was conducted from birth to 180 days of age. Mid‐nasal swabs were collected and tested for respiratory syncytial virus (RSV), rhinovirus, influenza, human metapneumovirus (HMPV), coronavirus, parainfluenza (HPIV), and bocavirus by RT‐PCR. Coinfection was defined as the presence of two or more respiratory viruses detected as part of the same illness episode.ResultsOf 1730 infants with a respiratory illness, 327 (19%) had at least two respiratory viruses detected in their primary illness episode. Of 113 infants with influenza, 23 (20%) had coinfection. Of 214 infants with RSV, 87 (41%) had coinfection. The cohort of infants with coinfection had increased occurrence of fever lasting ≥ 4 days (OR 1.4, 95% CI: 1.1, 2.0), and so did the subset of coinfected infants with influenza (OR 5.8, 95% CI: 1.8, 18.7). Coinfection was not associated with seeking further care (OR 1.1, 95% CI: 0.8, 1.5) or pneumonia (OR 1.2, 95% CI: 0.96, 1.6).ConclusionA high proportion of infants had multiple viruses detected. Coinfection was associated with greater odds of fever lasting for four or more days, but not with increased illness severity by other measures.

Dynamics and predisposition of respiratory viral co-infections in children and adults

ObjectivesThe epidemiology of respiratory co-infection pairings is poorly understood. Here we assess the dynamics of respiratory viral co-infections in children and adults and determine predisposition for or against specific viral pairings. MethodsOver five respiratory seasons from 30 November 2013 through 6 June 2018, the mono-infection and co-infection prevalence of 13 viral pathogens was tabulated at The Cleveland Clinic. Employing a model to proportionally distribute viral pairs using individual virus co-infection rate with prevalence patterns of concurrent co-circulating viruses, we compared predicted occurrence with observed occurrence of 132 viral pairing permutations using binomial analysis. ResultsOf 30 535 respiratory samples, 9843 (32.2%) were positive for at least one virus and 1018 (10.8%) of these were co-infected. Co-infected samples predominantly originated from children. Co-infection rate in paediatric population was 35.0% (2068/5906), compared with only 5.8% (270/4591) in adults. Adenovirus C (ADVC) had the highest co-infection rate (426/623, 68.3%) while influenza virus B had the lowest (55/546, 10.0%). ADVC–rhinovirus (HRV), respiratory syncytial virus A (RSVA)–HRV and RSVB–HRV pairings occurred at significantly higher frequencies than predicted by the proportional distribution model (p < 0.05). Additionally, several viral pairings had fewer co-infections than predicted by our model: notably metapneumovirus (hMPV)–parainfluenza virus 3, hMPV–RSVA and RSVA–RSVB. ConclusionsThis is one of the largest studies on respiratory viral co-infections in children and adults. Co-infections are substantially more common in children, especially under 5 years of age, and the most frequent pairings occurred at a higher frequency than would be expected by random. Specific pairings occur at altered rates compared with those predicted by proportional distribution, suggesting either direct or indirect interactions result between specific viral pathogens.