Routine Viral Testing Research Articles

A Novel Anti-nucleocapsid Antibody Avidity Method for Identifying SARS-CoV-2 Reinfections.

Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections is challenging with current serology assays and is further complicated by the marked decrease in routine viral testing practices as viral transmission increased during Omicron. Here, we provide proof-of-principle that high-avidity anti-nucleocapsid (N) antibodies detects reinfections after a single infection with higher specificity (85%; 95% confidence interval [95% CI], 80%-90%) compared to anti-N antibody levels (72%; 95% CI, 66%-79%) in a vaccinated cohort. This method could be used to retroactively investigate the epidemiology and incremental long-term health consequences of SARS-CoV-2 reinfections.

Clinical Outcomes of Rapid Respiratory Virus Testing in Emergency Departments

Rapid tests for respiratory viruses, including multiplex panels, are increasingly available in emergency departments (EDs). Their association with patient outcomes remains unclear. To determine if ED rapid respiratory virus testing in patients with suspected acute respiratory infection (ARI) was associated with decreased antibiotic use, ancillary tests, ED length of stay, and ED return visits and hospitalization and increased influenza antiviral treatment. Ovid MEDLINE, Embase (Ovid), Scopus, and Web of Science from 1985 to November 14, 2022. Randomized clinical trials of patients of any age with ARI in an ED. The primary intervention was rapid viral testing. Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines were followed. Two independent reviewers (T.S. and K.W.) extracted data and assessed risk of bias using the Cochrane Risk of Bias, version 2.0. Estimates were pooled using random-effects models. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Antibiotic use and secondary outcomes were pooled separately as risk ratios (RRs) and risk difference estimates with 95% CIs. Of 7157 studies identified, 11 (0.2%; n = 6068 patients) were included in pooled analyses. Routine rapid viral testing was not associated with antibiotic use (RR, 0.99; 95% CI, 0.93-1.05; high certainty) but was associated with higher use of influenza antivirals (RR, 1.33; 95% CI, 1.02-1.75; moderate certainty) and lower use of chest radiography (RR, 0.88; 95% CI, 0.79-0.98; moderate certainty) and blood tests (RR, 0.81; 95% CI, 0.69-0.97; moderate certainty). There was no association with urine testing (RR, 0.95; 95% CI, 0.77-1.17; low certainty), ED length of stay (0 hours; 95% CI, -0.17 to 0.16; moderate certainty), return visits (RR, 0.93; 95%, CI 0.79-1.08; moderate certainty) or hospitalization (RR, 1.01; 95% CI, 0.95-1.08; high certainty). Adults represented 963 participants (16%). There was no association of viral testing with antibiotic use in any prespecified subgroup by age, test method, publication date, number of viral targets, risk of bias, or industry funding. The results of this systematic review and meta-analysis suggest that there are limited benefits of routine viral testing in EDs for patients with ARI. Further studies in adults, especially those with high-risk conditions, are warranted.

Congenital heart surgery outcomes in patients with positive respiratory viral swabs

ObjectiveTo examine whether or not viral positive patients experienced worse outcomes and assess differences in surgical outcomes between viral-positive patients with and without viral symptoms within 30 days of surgery. MethodsThis retrospective study reviewed charts of pediatric patients who underwent congenital heart surgery and routine viral testing at a single institution over a consecutive 3-year period (2017-2019). Patients with a history of heart transplants, pacemaker changes, or implants, and mediastinal washouts were excluded from the study. Surgical outcomes were compared by viral status and viral symptoms, using the Fisher exact and Wilcoxon rank sum tests. ResultsAmong 1041 patients, 374 patients underwent routine preoperative viral testing, with 107 patients testing positive and 267 testing negative for viral swabs before surgery. There were no significant differences observed in surgical outcomes by viral status, including no differences in mortality. Among the 107 patients with positive viral swabs before surgery, comparisons between 24 patients with viral symptoms and 83 without symptoms within 30 days of surgery detected no significant differences in mortality or complication rates. However, symptomatic versus asymptomatic patients had significantly longer postoperative stay (23.4 vs 13.4 days; P = .02) and intubation time (9.8 vs 4.9 hours; P = .004). ConclusionsPatients who test positive before congenital heart surgery and are asymptomatic beyond the incubation period may proceed to surgery with no further delay. Patients who are viral positive and symptomatic have a longer postoperative stay and intubation time. A prospective study is needed to assess the importance of routine viral testing.

Routine Asymptomatic Testing Strategies for Airline Travel During the COVID-19 Pandemic: A Simulation Analysis

Background: Airline travel has been significantly reduced during the COVID-19 pandemic due to concern for individual risk of SARS-CoV-2 infection and population-level transmission risk from importation. Routine viral testing strategies for COVID-19 may facilitate safe airline travel through reduction of individual and/or population-level risk, although the effectiveness and optimal design of these “test-and-travel” strategies remain unclear.Methods: We developed a microsimulation of SARS-CoV-2 transmission in a cohort of airline travelers to evaluate the effectiveness of various testing strategies to reduce individual risk of infection and population-level risk of transmission. We evaluated five testing strategies in asymptomatic passengers: i) anterior nasal polymerase chain reaction (PCR) within 3 days of departure; ii) PCR within 3 days of departure and PCR 5 days after arrival; iii) rapid antigen test on the day of travel (assuming 90% of the sensitivity of PCR during active infection); iv) rapid antigen test on the day of travel and PCR 5 days after arrival; and v) PCR within 3 days of arrival alone. The travel period was defined as three days prior to the day of travel and two weeks following the day of travel, and we assumed passengers followed guidance on mask wearing during this period. The primary study outcome was cumulative number of infectious days in the cohort over the travel period (population-level transmission risk); the secondary outcome was the proportion of infectious persons detected on the day of travel (individual-level risk of infection). Sensitivity analyses were conducted.Findings: Assuming a community SARS-CoV-2 incidence of 50 daily infections, we estimated that in a cohort of 100,000 airline travelers followed over the travel period, there would be a total of 2,796 (95% UI: 2,031, 4,336) infectious days with 229 (95% UI: 170, 336) actively infectious passengers on the day of travel. The pre-travel PCR test (within 3 days prior to departure) reduced the number of infectious days by 35% (95% UI: 27, 42) and identified 88% (95% UI: 76, 94) of the actively infectious travelers on the day of flight; the addition of PCR 5 days after arrival reduced the number of infectious days by 79% (95% UI: 71, 84). The rapid antigen test on the day of travel reduced the number of infectious days by 32% (95% UI: 25, 39) and identified 87% (95% UI: 81, 92) of the actively infectious travelers; the addition of PCR 5 days after arrival reduced the number of infectious days by 70% (95% UI: 65, 75). The post-travel PCR test alone (within 3 days of landing) reduced the number of infectious days by 42% (95% UI: 31, 51). The ratio of true positives to false positives varied with the incidence of infection. The overall study conclusions were robust in sensitivity analysis.Interpretation: Routine asymptomatic testing for COVID-19 prior to travel can be an effective strategy to reduce individual risk of COVID-19 infection during travel, although post-travel testing with abbreviated quarantine is likely needed to reduce population-level transmission due to importation of infection when traveling from a high to low incidence setting.Funding: NCL is supported by the University of California, San Francisco (Department of Medicine). MVK is supported in part by the National Institute on Drug Abuse of the National Institutes of Health (K99DA051534).Conflict of Interest: NCL has received grants and personal fees from the World Health Organization and the California Department of Public Health unrelated to the current study. GWR has received funding from the San Francisco Department of Public Health and the California Department of Public Health for COVID-19-related work unrelated to the current study.

Characteristics of COVID-19 in Homeless Shelters : A Community-Based Surveillance Study.

Homeless shelters are a high-risk setting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission because of crowding and shared hygiene facilities. To investigate SARS-CoV-2 case counts across several adult and family homeless shelters in a major metropolitan area. Cross-sectional, community-based surveillance study. (ClinicalTrials.gov: NCT04141917). 14 homeless shelters in King County, Washington. A total of 1434 study encounters were done in shelter residents and staff, regardless of symptoms. 2 strategies were used for SARS-CoV-2 testing: routine surveillance and contact tracing ("surge testing") events. The primary outcome measure was test positivity rate of SARS-CoV-2 infection at shelters, determined by dividing the number of positive cases by the total number of participant encounters, regardless of symptoms. Sociodemographic, clinical, and virologic variables were assessed as correlates of viral positivity. Among 1434 encounters, 29 (2% [95% CI, 1.4% to 2.9%]) cases of SARS-CoV-2 infection were detected across 5 shelters. Most (n = 21 [72.4%]) were detected during surge testing events rather than routine surveillance, and most (n = 21 [72.4% {CI, 52.8% to 87.3%}]) were asymptomatic at the time of sample collection. Persons who were positive for SARS-CoV-2 were more frequently aged 60 years or older than those without SARS-CoV-2 (44.8% vs. 15.9%). Eighty-six percent of persons with positive test results slept in a communal space rather than in a private or shared room. Selection bias due to voluntary participation and a relatively small case count. Active surveillance and surge testing were used to detect multiple cases of asymptomatic and symptomatic SARS-CoV-2 infection in homeless shelters. The findings suggest an unmet need for routine viral testing outside of clinical settings for homeless populations. Gates Ventures.

Respiratory syncytial virus: diagnosis, prevention and management.

Respiratory syncytial virus (RSV) is responsible for a large burden of disease globally and can present as a variety of clinical syndromes in children of all ages. Bronchiolitis in infants under 1 year of age is the most common clinical presentation hospitalizing 24.2 per 1000 infants each year in the United Kingdom. RSV has been shown to account for 22% of all episodes of acute lower respiratory tract infection in children globally. RSV hospitalization, that is, RSV severe disease, has also been associated with subsequent chronic respiratory morbidity. Routine viral testing in all children is not currently recommended by the United Kingdom National Institute for Health and Care Excellence (NICE) or the American Academy of Pediatrics (AAP) guidance and management is largely supportive. There is some evidence for the use of ribavirin in severely immunocompromised children. Emphasis is placed on prevention of RSV infection through infection control measures both in hospital and in the community, and the use of the RSV-specific monoclonal antibody, palivizumab, for certain high-risk groups of infants. New RSV antivirals and vaccines are currently in development. Ongoing work is needed to improve the prevention of RSV infection, not only because of the acute morbidity and mortality, but also to reduce the associated chronic respiratory morbidity after severe infection.

Reducing the Use of Routine Viral Testing in Pediatric Patients Admitted with Bronchiolitis

Bronchiolitis is a common condition among patients presenting to the emergency department (ED). Current American Academy of Pediatrics bronchiolitis clinical practice guidelines recommend against the routine use of viral testing for diagnosis, instead favoring the use of clinical criteria for diagnosis. At our institution, we identified an excess of viral testing in this population as compared to national benchmarks. This variation increased the cost of care for this condition locally. Among children admitted to the general …

Reducing the Use of Routine Viral Testing in Pediatric Patients Admitted with Bronchiolitis

Reducing the Use of Routine Viral Testing in Pediatric Patients Admitted with Bronchiolitis

Can Analysis of Routine Viral Testing Provide Accurate Estimates of Respiratory Syncytial Virus Disease Burden in Adults?

Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of adult respiratory illness. We evaluated routine viral testing and discharge diagnoses for identifying RSV and influenza burden. Polymerase chain reaction results performed in adults during emergency room visits or hospitalizations were reviewed. Peak RSV activity preceded influenza activity by 8 weeks. The ratio of total number of viral tests performed divided by total number of respiratory visits was higher during influenza than RSV peaks (1.31 vs 0.72; P = .0001). Influenza and RSV were listed primary diagnoses in 56 (30%) vs 7 (6%), respectively (P < .0001). Routine viral testing to estimate adult RSV disease burden has limitations.

Can Analysis of Routine Viral Testing Provide Accurate Estimates of Respiratory Syncytial Virus (RSV) Disease Burden in Adults?

Can Analysis of Routine Viral Testing Provide Accurate Estimates of Respiratory Syncytial Virus (RSV) Disease Burden in Adults?

Prevalence of human parechoviruses in central nervous system infections in children: A retrospective study in Shanghai, China

Human parechoviruses (HPeV) are associated with central nervous system (CNS) infections and sepsis-like illnesses. However, data from China are not available. The aim of this study was to determine the prevalence, age, and seasonal distributions and genotypes of HPeV infections in children with CNS related disease in Shanghai, China. Of 776 cerebrospinal fluid (CSF) samples collected from children with CNS-related diseases under the age of 16 years during the years 2008-2011, 68 (9%) were identified to be HPeV positive. The annual prevalence varied remarkably: 1% (2/153) in 2008, 7% (12/177) in 2009, 15% (23/153) in 2010, and 11% (31/293) in 2011. The virus was detected in all age groups of children ranging from 2 days to 13 years and the median age was 14 months. Of the 31 positive samples that were genotyped successfully, 28 were HPeV1 and 3 were HPeV3. This study provided data on the molecular epidemiology of HPeV infections in CNS-related diseases in Shanghai, China and suggest that the screening for HPeV by PCR should be included in the routine viral testing of CSF.

Is routine viral screening useful in patients with recent‐onset polyarthritis of a duration of at least 6 weeks? Results from a nationwide longitudinal prospective cohort study

To study the contribution of routine viral screening tests in patients with early rheumatoid arthritis (RA) or a potential for progressing to RA. Eight hundred thirteen patients with swelling of at least 2 joints for at least 6 weeks and a symptom duration of less than 6 months in the ESPOIR cohort were screened for parvovirus B19 (IgG and IgM anti-parvovirus B19 antibodies), hepatitis B virus (HBV; hepatitis B surface antigen), hepatitis C virus (HCV; anti-HCV antibodies), and human immunodeficiency virus (HIV; anti-HIV-1 and -2 antibodies). Parvovirus B19 testing was performed in 806 patients and showed longstanding immunity in 574 (71.2%) and no antibodies in 223 (27.7%). Among the 9 remaining patients (7 IgG positive/IgM positive, 1 IgG negative/IgM positive, and 1 IgG indeterminate/IgM positive), only 2 (0.25%; 95% confidence interval [95% CI] 0-0.99%) had a positive polymerase chain reaction test for parvovirus B19; these patients (women ages 34 and 40 years) had no extraarticular signs. HIV seroprevalence was 0.12% (n = 1 of 813; 95% CI 0.01-0.8%) and HCV seroprevalence was 0.86% (n = 7 of 808, 95% CI 0.38-1.86%). HCV-related arthritis was diagnosed in 4 patients (0.5%). HCV-seropositive patients had significantly higher transaminase levels than the other patients (P = 0.001), with no significant differences for the other laboratory data. HBV seroprevalence was 0.12% (n = 1 of 808; 95% CI 0.01-0.8%); the positive HBV status was known before study inclusion, and the patient had no diagnosis of HBV-related arthritis. Finally, routine viral testing identified 2 patients with parvovirus B19 infection and 3 with HBV infection (0.6%; 95% CI 0.2-1.5%). Cost was €85.05 per patient (total €68,720). Routine serologic testing did not contribute substantially to the diagnosis in this context.

Attention with virus contaminated cell lines

Although (or probably because) quality control efforts are continuously increasing in animal cell technology, sometimes surprising news on contaminated cell lines are arriving. Recently a Japanese group (Li et al. in J. Virol., doi:10.1128/JVI.00807-07, published on-line ahead of print on 8 August 2007) working on the development of the production of hepatitis E virus-like particles by infecting High Five insect cells (BTI-TN-5B1-4 (Tn5)) with recombinant baculovirus has observed the appearance of unknown viral particles with diameter of 35 nm containing RNA. The study established that these unknown viral particles were nodaviral particles and that they belong to the genus Alphanodavirus. The infection of the Tn5 cells with recombinant baculovirus induced the production of infectious nodaviral particles in parallel to the production of the recombinant protein. The preoccupying fact is that this nodavirus was latently present in the ‘High Five’ cells and that other freshly purchased ampoules equally contained cells with latent nodavirus infection. In principle, the presence of latent virus per se might not be a problem, however, in the case of nodaviruses their presence can be an issue because 1st there is a serious risk of contamination by this virus when virus-like particles for vaccine purposes or recombinant proteins for therapeutic purposes are produced using the mentioned cell system, and 2nd nodaviruses (known as viruses infecting insects and fishes) are unique in being able to infect suckling mice and suckling hamsters (Garzon et al. Arch. Virol. 113 (1990) 165, Scherer & Hurlbut. Am. J. Epidemiol. 86 (1967) 271, Scherer et al. Am. J. Trop. Med. Hyg. 17 (1968) 120) with resulting paralysis and death, although no alphanodavirus infections of humans have been reported. Today nobody knows if the original stock of these cells was contaminated thus we do not know if all established subcultures and all derived subclones of the ‘High Five’ cells also contain latent nodavirus or not. Therefore, the authors (Li et al.) of the paper further indicated that all cell lines derived from the insect Tn5 cell line should be examined for the presence of such nodaviruses, and that, because of the ability of nodaviruses to establish latent and inapparent infections, all insect cell lines should be screened routinely for the presence of virus. What does this mean to the producer of biologicals using ‘High Five’ cells as cell substrate? In the case (the worst case scenario has to be assumed here), that the original stock of the ‘High Five’ cells was already contaminated and that these cells are used for the production of recombinant proteins for human use or virus like particles for vaccination purposes, either the downstream processing protocol has to be able to eliminate any nodavirus present or potentially present, or, as a total elimination cannot unequivocally be proven, a supplementary virus inactivation step should be added to the purification protocol. Else, ‘High Five’ should not be further considered for production of biological substances for human use. How is the situation for other insect cell lines? Schneider’s cell line 1 (Drosophila melanogaster cells): a similar infection by a nodavirus has been reported previously for a sub clone of this cell line (Friesen et al. J. Virol. 35 (1980) 741). Sf9 cells: With respect to Sf9 cells, Li et al. (J. Virol. doi:10.1128/JVI.00807-07) did not find any indication for the presence of a latent nodavirus infection. No information is available for other insect cell lines. And for mammalian cell lines? With respect to mammalian cells, many virus contaminations have been observed during the past and more details can be found in Merten (Cytotechnology 39 (2002) 91). As a conclusion, I would like to ask any ‘cell culturist’ to follow the recommendations of Li et al. (J. Virol. doi:doi:10.1128/JVI.00807-07) and to be cautious because almost any animal cell is a potential virus producer. Although routine virus testing is a must and a valuable means for reducing the risk of using virus contaminated cell lines, it does not provide absolute safety because of the possibility of new emerging viruses and the permanently existing risk of contaminations by adventitious agents and viruses. Thus the users of animal cells as well as the producers of biotech products by using animal cells have to be attentive to this possible threat and they have to assure the absence of adventitious agents/viruses by any means.