Laboratory-confirmed Viral Respiratory Infections Research Articles

Facemask against viral respiratory infections among Hajj pilgrims: A challenging cluster-randomized trial.

BackgroundIn this large-scale cluster-randomized controlled trial (cRCT) we sought to assess the effectiveness of facemasks against viral respiratory infections.Methods and resultsOver three consecutive Hajj seasons (2013, 2014, 2015) pilgrims’ tents in Makkah were allocated to ‘facemask’ or ‘no facemask’ group. Fifty facemasks were offered to participants in intervention tents, to be worn over four days, and none were offered to participants in control tents. All participants recorded facemask use and respiratory symptoms in health diaries. Nasal swabs were collected from the symptomatic for virus detection by reverse transcription polymerase chain reaction. Clinical symptoms and laboratory results were analyzed by ‘intention- to-treat’ and ‘per-protocol’. A total of 7687 adult participants from 318 tents were randomized: 3864 from 149 tents to the intervention group, and 3823 from 169 tents to the control group. Participants were aged 18 to 95 (median 34, mean 37) years, with a male to female ratio of 1:1.2. Overall, respiratory viruses were detected in 277 of 650 (43%) nasal/pharyngeal swabs collected from symptomatic pilgrims. Common viruses were rhinovirus (35.1%), influenza (4.5%) and parainfluenza (1.7%). In the intervention arm, respectively 954 (24.7%) and 1842 (47.7%) participants used facemasks daily and intermittently, while in the control arm, respectively 546 (14.3%) and 1334 (34.9%) used facemasks daily and intermittently. By intention-to-treat analysis, facemask use did not seem to be effective against laboratory-confirmed viral respiratory infections (odds ratio [OR], 1.4; 95% confidence interval [CI], 0.9 to 2.1, p = 0.18) nor against clinical respiratory infection (OR, 1.1; 95% CI, 0.9 to 1.4, p = 0.40). Similarly, in a per-protocol analysis, facemask use did not seem to be effective against laboratory-confirmed viral respiratory infections (OR 1.2, 95% CI 0.9–1.7, p = 0.26) nor against clinical respiratory infection (OR 1.3, 95% CI 1.0–1.8, p = 0.06).ConclusionThis trial was unable to provide conclusive evidence on facemask efficacy against viral respiratory infections most likely due to poor adherence to protocol.

Medical masks vs N95 respirators for preventing COVID-19 in healthcare workers: A systematic review and meta-analysis of randomized trials

On March 11, 2020, Novel 2019 coronavirus disease (COVID-19) was declared a global pandemic and has steadily depleted healthcare organizations of essential personal protective equipment (PPE). Transmission of SARS-CoV-2 to healthcare workers is a serious threat with an early case series from Wuhan, China suggesting that 29% of hospitalized patients were healthcare workers. Although there is consensus on the use of N95 respirators for all aerosol-generating procedures to reduce transmission risk, guidelines have diverged in recommending N95 vs medical masks for non-aerosol-generating patient care. Evidence supporting non-inferiority of medical masks compared to N95 for routine care would allow preservation of diminishing N95 products, as well as provide reassurance that healthcare workers practicing such a protocol are safe. Authors searched multiple literature databases for English-language, randomized controlled trials (RCTs) from January 1, 2014 to March 9, 2020. This updated search was conducted by two independent reviewers and combined with the previous review completed on December 9, 2014. Eligible studies were RCTs, including cluster randomized trials, that compared medical masks with N95 respirators in healthcare workers at risk of exposure to acute respiratory illness. Included studies reported outcomes on laboratory confirmed viral infections (via PCR, serology or viral culture), laboratory-confirmed coronavirus infection, laboratory-confirmed influenza infection, influenza-like illness, clinical respiratory illness or work-place absenteeism. The primary outcome for the meta-analysis was reported laboratory confirmed viral infections. Data was extracted by a single reviewer and assessed by a second reviewer for quality control. Bias was assessed using a modified Cochrane risk of bias tool which evaluated selection bias, performance bias, detection bias, attrition bias and reporting bias. The grading of recommendations, assessment, development and evaluation (GRADE) approach was used to evaluate for certainty of the evidence. Data analysis included pooled odds ratios (ORs) with 95% confidence intervals (CIs) and evaluation of data heterogeneity. Authors used adjusted meta-analysis to account for the clustered nature of the included RCTs. Of 389 screened titles and abstracts and 12 full texts, the systematic review yielded 1 additional RCT (n = 5180). The combination of this study with the three trials from a 2016 systematic review resulted in a total of four randomized controlled trials examining medical masks (n = 3957) vs N95 respirators (n = 4779) in healthcare workers treating patients with acute respiratory illness. Although PCR testing for viruses in the Coronavidiae family was completed in all studies, data specifically on coronavirus was limited to a single study. Additionally, only a single study reported workplace absenteeism. Comparison of medical masks vs N95 respirators for laboratory-confirmed viral respiratory infection yield a pooled OR 1.06 (95% CI 0.90-1.25), I2 = 0%. Results for laboratory-confirmed influenza infection and influenza-like illness were OR 0.94 (95% CI 0.73-1.20), I2 = 0% and OR 1.31 (95% CI 0.94-1.85), I2 = 5%, respectively. In the study which specifically reported coronavirus, there were infections rates of 4.3% (9/212) and 5.7% (12/210) in the medical mask vs N95 respirator groups, respectively (p = 0.49). Work-related absenteeism was 19.8% and 18.6% for medical masks vs N95 respirators, respectively (p = 0.75). Although risk of selection bias, attrition bias and reporting bias were low amongst all RCTs, the risk of detection bias was high for non-laboratory confirmed outcomes. There was also high risk of performance bias given the absence of participant blinding. Additionally, evidence was low for laboratory-confirmed outcomes and very low for non-laboratory confirmed outcomes. The authors state that the current evidence supporting either inferiority or non-inferiority of medical masks to N95 respirators for routine care (i.e., non-aerosol generating procedures) is insufficient. Additionally, there are no quality studies specifically evaluating medical masks vs N95 respirators in the treatment of COVID-19. A limitation of this systematic review and meta-analysis includes that only a single trial examined coronavirus infection individually and therefore, generalizability to SARS-CoV-2 is unclear. The fact that the meta-analysis was performed on aggregate data is an additional limitation. Accounting for cluster randomization should be viewed as a strength which was not done in the previous meta-analysis. Due to concern for N95 respirator availability with the current pandemic, use of medical masks should be considered. However, certainty of evidence is low and additional studies are needed. Comment: Healthcare workers have been forced into an area of uncertainty with regard to appropriate PPE due to conflicting and ever-changing guidelines. Although data is limited, hopefully they can find solace in the current literature that at least suggests medical masks may be sufficient for routine patient care. Funding for further research should be a priority given the high rates of transmission to healthcare workers with the current COVID-19 pandemic. Additionally, such research will hopefully further prepare the healthcare system for future pandemics.

Sources of viral respiratory infections in Canadian acute care hospital healthcare personnel

SummaryBackgroundViral respiratory illnesses are common causes of outbreaks and can be fatal to some patients.AimTo investigate the association between laboratory-confirmed viral respiratory infections and potential sources of exposure during the previous 7 days.MethodsIn this nested case–control analysis, healthcare personnel from nine Canadian hospitals who developed acute respiratory illnesses during the winters of 2010/11–2013/14 submitted swabs that were tested for viral pathogens. Associated illness diaries and the weekly diaries of non-ill participants provided information on contact with people displaying symptoms of acute respiratory illness in the previous week. Conditional logistic regression assessed the association between cases, who were matched by study week and site with controls with no respiratory symptoms.FindingsThere were 814 laboratory-confirmed viral respiratory illnesses. The adjusted odds ratio (aOR) of a viral illness was higher for healthcare personnel reporting exposures to ill household members [7.0, 95% confidence interval (CI) 5.4–9.1], co-workers (3.4, 95% CI 2.4–4.7) or other social contacts (5.1, 95% CI 3.6–7.1). Exposures to patients with respiratory illness were not associated with infection (aOR 0.9, 95% CI 0.7–1.2); however, healthcare personnel with direct patient contact did have higher odds (aOR 1.3, 95% CI 1.1–1.6). The aORs for exposure and for direct patient contact were similar for illnesses caused by influenza.ConclusionCommunity and co-worker contacts are important sources of viral respiratory illness in healthcare personnel, while exposure to patients with recognized respiratory infections is not associated. The comparatively low risk associated with direct patient contact may reflect transmission related to asymptomatic patients or unrecognized infections.

Facemask versus No Facemask in Preventing Viral Respiratory Infections During Hajj: A Cluster Randomised Open Label Trial

Background: This large-scale cluster-randomised controlled trial (cRCT) evaluated use of facemasks against laboratory-confirmed viral respiratory tract infections (vRTIs) and clinical respiratory infection (CRI) because previous studies have been inconclusive. Methods: An open label cRCT, conducted in Makkah compared the offer and use of 50 surgical facemasks worn over five days versus no facemasks among pilgrims. Cluster-randomisation was by accommodation tents stratified by country and gender. Tents were allocated to groups by coin-tossing. Neither participants nor recruiting investigators could be blinded to the intervention. Facemask use and respiratory symptoms were recorded daily and nasal/pharyngeal swabs were collected from symptomatic participants for detection of respiratory viruses. Clinical and laboratory data were analysed for facemask efficacy against laboratory-confirmed vRTIs and CRI. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12613001018707. Findings: From October 13 to 17 in 2013, October 2 to 6 in 2014, and September 22 to 26 in 2015, 7,687 adult participants from 318 tents were randomised to facemasks or no facemasks; 3,864 participants from 149 tents were assigned to the Facemask group and 3,823 participants from 169 tents to the Control group. In the Facemask arm, respectively 27% and 51% participants used facemasks daily and intermittently, 22% did not; in the Control arm, respectively 15% and 38% participants used facemasks daily and intermittently, 47% did not. Respiratory viruses were detected in 277 of 650 (43%) nasal/pharyngeal swabs from symptomatic pilgrims. In intention-to-treat analysis, facemask use was neither effective against laboratory-confirmed vRTIs (OR 1.35, 95% CI 0.88-2.07) nor against CRI (OR 1.1, 95% CI 0.88-1.39), not even in per-protocol analysis (OR 1.2, 95% CI 0.87-1.69; OR 1.3, 95% CI 0.99-1.83). Interpretation: Facemask use does not prevent clinical or laboratory-confirmed viral respiratory infections among Hajj pilgrims. Funding: Qatar National Research Fund (number: NPRP 6-1505-3-358). Declaration of Interest: Professor Robert Booy has received funding from Baxter, CSL, GSK, Merck, Novartis, Pfizer, Roche, Romark and Sanofi Pasteur for conducting this research, travel to conferences or consultancy work; all funding received is directed to research accounts at The Children’s Hospital at Westmead. Dr Harunor Rashid has received fees from Pfizer, Sanofi Pasteur and Novartis for consulting or serving on an advisory board. The other authors have no competing interests to declare. Ethical Approval: The trial has received approval from an Australian Human Research Ethics Committee (NSW HREC Ref: HREC/13/HNE/265), and the Joint Institutional Review Board (J-IRB) of Hamad Medical Corporation - Weill Cornell Medical College in Qatar (IRB Number: 13-00039).

Temporal relationship between occurrences of hand, foot and mouth disease, respiratory virus detection and febrile seizures in children in tropical Singapore: a time-series analysis.

Febrile seizure (FS) in children is a common complication of infections with respiratory viruses and hand, foot and mouth disease (HFMD). We conducted a retrospective ecological time-series analysis to determine the temporal relationship between hospital attendances for FS and HFMD or respiratory virus infections. Epilepsy attendance was used as a control. Data from 2004 to 2012 FS and epilepsy hospital attendance, HFMD notifications to the Ministry of Health and from laboratory-confirmed viral respiratory infections among KK Women's and Children's Hospital inpatients were used. A multivariate linear regression analysis was conducted to evaluate the relationship between FS and the virus time series. Relative risks of FS by age were calculated using Bayesian statistical methods. Paediatric accident and emergency (A&E) attendances for FS were found to be associated with influenza A (extra 0.47 FS per influenza A case), B (extra 0.32 per influenza B case) and parainfluenza 3 (extra 0.35 per parainfluenza type 3 case). However, other viruses were not significantly associated with FS. None of the viruses were associated with epileptic seizure attendance. Influenza A, B and parainfluenza 3 viruses contributed to the burden of FS resulting in A&E attendance. Children at risk of FS should be advised to receive seasonal influenza vaccination.

Laboratory-Confirmed Respiratory Infections as Predictors of Hospital Admission for Myocardial Infarction and Stroke: Time-Series Analysis of English Data for 2004-2015.

Acute respiratory infections are associated with increased risk of myocardial infarction (MI) and stroke; however, the role of different organisms is poorly characterized. Time-series analysis of English hospital admissions for MI and stroke (age-stratified: 45-64, 65-74, ≥75 years), laboratory-confirmed viral respiratory infections, and environmental data for 2004-2015. Weekly counts of admissions were modeled using multivariable Poisson regression with weekly counts of respiratory viruses (influenza, parainfluenza, rhinovirus, respiratory syncytial virus [RSV], adenovirus, or human metapneumovirus [HMPV]) investigated as predictors. We controlled for seasonality, long-term trends, and environmental factors. Weekly hospital admissions in adults aged ≥45 years averaged 1347 (interquartile range [IQR], 1217-1541) for MI and 1175 (IQR, 1023-1395) for stroke. Respiratory infections ranged from 11 cases per week (IQR, 5-53) for influenza to 55 (IQR, 7-127) for rhinovirus. In the adjusted models, all viruses except parainfluenza were significantly associated with MI and ischemic stroke admissions in those aged ≥75. Among 65- to 74-year-olds, adenovirus, rhinovirus, and RSV were associated with MI but not ischemic stroke admissions. Respiratory infections were not associated with MI or ischemic stroke in people aged 45-64 years, nor with hemorrhagic stroke in any age group. An estimated 0.4%-5.7% of MI and ischemic stroke admissions may be attributable to respiratory infection. We identified small but strongly significant associations in the timing of respiratory infection (with HMPV, RSV, influenza, rhinovirus, and adenovirus) and MI or ischemic stroke hospitalizations in the elderly. NCT02984280.

The Respiratory Protection Effectiveness Clinical Trial (ResPECT): a cluster-randomized comparison of respirator and medical mask effectiveness against respiratory infections in healthcare personnel.

BackgroundAlthough N95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. A lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and experts.MethodsThe Respiratory Protection Effectiveness Clinical Trial (ResPECT) is a prospective comparison of respiratory protective equipment to be conducted at multiple U.S. study sites. Healthcare personnel who work in outpatient settings will be cluster-randomized to wear N95 respirators or medical masks for protection against infections during respiratory virus season. Outcome measures will include laboratory-confirmed viral respiratory infections, acute respiratory illness, and influenza-like illness. Participant exposures to patients, coworkers, and others with symptoms and signs of respiratory infection, both within and beyond the workplace, will be recorded in daily diaries. Adherence to study protocols will be monitored by the study team.DiscussionResPECT is designed to better understand the extent to which N95s and MMs reduce clinical illness among healthcare personnel. A fully successful study would produce clinically relevant results that help clinician-leaders make reasoned decisions about protection of healthcare personnel against occupationally acquired respiratory infections and prevention of spread within healthcare systems.Trial registrationThe trial is registered at clinicaltrials.gov, number NCT01249625 (11/29/2010).

Hospital-acquired viral infection increases mortality in children with severe viral respiratory infection

To investigate the association of method of acquisition (hospital-acquired vs. community-acquired) and mortality in children with severe viral respiratory infection. Retrospective cohort study. : Pediatric intensive care unit at an urban academic tertiary care children's hospital. All patients aged <18 yrs admitted to our pediatric intensive care unit with laboratory-confirmed respiratory syncytial virus, influenza, parainfluenza, or adenovirus infection between October 2002 and September 2008. We stratified patients by method of viral acquisition and identified those patients with chronic medical conditions associated with an increased risk of complications from viral illness. There were 289 patients admitted to the pediatric intensive care unit with laboratory-confirmed viral respiratory infection during the period of study. Fifty-three patients (18%) had hospital-acquired infection and 117 patients (40%) had chronic medical conditions associated with an increased risk of complications from viral illness. Hospital-acquired infection was associated with increased mortality and length of stay (all p < .001). Adjusting for age, chronic medical conditions, severity of illness index, and catheter-associated bloodstream infections, patients with hospital-acquired infection had a 5.8 (95% confidence interval 2.1-15.6) times greater odds (p = .001) of mortality. Our results suggest that in children with severe viral respiratory infection, hospital acquisition of infection is associated with increased mortality even after adjusting for chronic medical conditions that predispose to an increased risk of complications from viral illness.