The true severity of infection due to COVID-19 is under-represented because it is based on only those who are tested. Although nucleic acid amplifications tests (NAAT) are the gold standard for ...COVID-19 diagnostic testing, serological assays provide better population-level SARS-CoV-2 prevalence estimates. Implementing large sero-surveys present several logistical challenges within Canada due its unique geography including rural and remote communities. Dried blood spot (DBS) sampling is a practical solution but comparative performance data on SARS-CoV-2 serological tests using DBS is currently lacking. Here we present test performance data from a well-characterized SARS-CoV-2 DBS panel sent to laboratories across Canada representing 10 commercial and 2 in-house developed tests for SARS-CoV-2 antibodies. Three commercial assays identified all positive and negative DBS correctly corresponding to a sensitivity, specificity, positive predictive value, and negative predictive value of 100% (95% CI = 72.2, 100). Two in-house assays also performed equally well. In contrast, several commercial assays could not achieve a sensitivity greater than 40% or a negative predictive value greater than 60%. Our findings represent the foundation for future validation studies on DBS specimens that will play a central role in strengthening Canada's public health policy in response to COVID-19.
The novel coronavirus, SARS-CoV-2, has spread into a pandemic since its emergence in Wuhan, China in December of 2019. This has been facilitated by its high transmissibility within the human ...population and its ability to remain viable on inanimate surfaces for an extended period. To address the latter, we examined the effect of simulated sunlight on the viability of SARS-CoV-2 spiked into tissue culture medium or mucus. The study revealed that inactivation took 37 minutes in medium and 107 minutes in mucus. These times-to-inactivation were unexpected since they are longer than have been observed in other studies. From this work, we demonstrate that sunlight represents an effective decontamination method but the speed of decontamination is variable based on the underlying matrix. This information has an important impact on the development of infection prevention and control protocols to reduce the spread of this deadly pathogen.
Because of the global spread of Zika virus, accurate and high-throughput diagnostic immunoassays are needed. We compared the sensitivity and specificity of 5 commercially available Zika virus ...serologic assays to the recommended protocol of Zika virus IgM-capture ELISA and plaque-reduction neutralization tests. Most commercial immunoassays showed low sensitivity, which can be increased.
Use of the vesicular stomatitis virus (VSV)-based Ebola virus vaccine during outbreaks and the potential use of a similar VSV-based Lassa virus vaccine has raised questions about the vaccines' ...stability should the cold chain fail. We demonstrated that current cold chain conditions might tolerate significant variances without affecting efficacy.
With the emerging Zika virus (ZIKV) epidemic, serologic diagnosis relies on a labor-intensive IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) and confirmation by a plaque reduction ...neutralization test (PRNT). To streamline serologic testing, several commercial assays have been developed. Our aim was to compare the commercial Euroimmun anti-ZIKV IgM and IgG assays to the reference MAC-ELISA and PRNT currently in use. Serum specimens submitted to Public Health Ontario Laboratory, Canada, were tested for IgM and IgG using the Euroimmun assays and the results were compared with those from MAC-ELISA. The PRNT was performed on positive or equivocal specimens using either MAC-ELISA or Euroimmun assays, MAC-ELISA-inconclusive specimens, and a convenience sample of specimens negative by both assays (cohort 1). Another set of specimens selected on the basis of PRNT results was subsequently tested by the Euroimmun assays (cohort 2). MAC-ELISA was positive, equivocal, negative, and inconclusive in 57/223, 15/223, 147/223, and 4/223 specimens, respectively. Among the 76 specimens that were MAC-ELISA positive, equivocal, or inconclusive, 30 (39.5%) were Euroimmun IgM and/or IgG positive or equivocal. Among the 147 MAC-ELISA-negative specimens, 136 (92.5%) were Euroimmun IgM and IgG negative. The sensitivity of the combined Euroimmun IgM/IgG against the PRNT was 83% (cohort 1) and 92% (cohort 2), whereas the specificity was 81% (cohort 1) and 65% (cohort 2). The combined Euroimmun IgM/IgG showed good specificity (92.5%) but suboptimal sensitivity (39.5%) compared with that of the MAC-ELISA. However, the sensitivity of the combined Euroimmun IgM/IgG against the PRNT was significantly higher (83 to 92%). More studies are needed before commercial assays are implemented for routine ZIKV serologic diagnosis.
Abstract
The use of antibody-based therapies for the treatment of high consequence viral pathogens has gained interest over the last fifteen years. Here, we sought to evaluate the use of unique ...camelid-based IgG antibodies to prevent lethal hantavirus pulmonary syndrome (HPS) in Syrian hamsters. Using purified, polyclonal IgG antibodies generated in DNA-immunized alpacas, we demonstrate that post-exposure treatments reduced viral burdens and organ-specific pathology associated with lethal HPS. Antibody treated animals did not exhibit signs of disease and were completely protected. The unique structures and properties, particularly the reduced size, distinct paratope formation and increased solubility of camelid antibodies, in combination with this study support further pre-clinical evaluation of heavy-chain only antibodies for treatment of severe respiratory diseases, including HPS.
Lassa virus (LASV) is a rodent-borne arenavirus endemic to several West African countries that causes Lassa fever (LF). LF is typically mild but it can cause severe disease characterized by ...hemorrhagic fever and multi-organ failure. A current outbreak of LASV in Nigeria has seen greater than 300 cases with a case fatality rate of 22%. Currently, there are limited treatment options and no vaccine candidates are approved to prevent LASV infection. The Coalition for Epidemic Preparedness Innovations has identified LASV as an emerging pathogen of high consequence and this has resulted in a push for several preclinical vaccine candidates to be advanced toward clinical trials. Here, we discuss several important aspects of LASV infection including immunobiology, immune evasion, and correlates of protection against LF, which have been identified through animal models and human infections. In addition, we discuss several vaccine candidates that have shown efficacy in animal models that could be advanced toward clinical trials. The increased fatality rate seen in the recent LASV outbreak in Nigeria highlights the importance of developing effective treatment and prevention strategies against LF. The spike in LASV cases seen in West Africa has the potential for increased mortality and human-to-human transmission, making the development and testing of effective vaccines for LASV critical.
We compared the seroprevalence of SARS-CoV-2 anti-nucleocapsid antibodies in blood donors across Canadian regions in 2021. The seroprevalence was the highest in Alberta and the Prairies, and it was ...so low in Atlantic Canada that few correlates were observed. Being male and of young age were predictive of seropositivity. Racialization was associated with higher seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. Living in a materially deprived neighborhood predicted higher seroprevalence, but it was more linear across quintiles in Alberta and the Prairies, whereas in British Columbia and Ontario, the most affluent 60% were similarly low and the most deprived 40% similarly elevated. Living in a more socially deprived neighborhood (more single individuals and one parent families) was associated with lower seroprevalence in British Columbia and Ontario but not in Alberta and the Prairies. These data show striking variability in SARS-CoV-2 seroprevalence across regions by social determinants of health.
Canadian blood donors are a healthy adult population that shows clear disparities associated with racialization and material deprivation. This underscores the pervasiveness of the socioeconomic gradient on SARS-CoV-2 infections in Canada. We identify regional differences in the relationship between SARS-CoV-2 seroprevalence and social determinants of health. Cross-Canada studies, such as ours, are rare because health information is under provincial jurisdiction and is not available in sufficient detail in national data sets, whereas other national seroprevalence studies have insufficient sample sizes for regional comparisons. Ours is the largest seroprevalence study in Canada. An important strength of our study is the interpretation input from a public health team that represented multiple Canadian provinces. Our blood donor seroprevalence study has informed Canadian public health policy at national and provincial levels since the start of the SARS-CoV-2 pandemic.
Nigeria experiences annual outbreaks of Lassa fever (LF) with high case numbers. At least three clades of Lassa virus (LASV) have been documented in Nigeria, though recent outbreaks are most often ...associated with clade II or clade III viruses. Using a recently isolated clade III LASV from a case of LF in Nigeria in 2018, we developed and characterized a guinea pig adapted virus capable of causing lethal disease in commercially available Hartley guinea pigs. Uniform lethality was observed after four passages of the virus and was associated with only two dominant genomic changes. The adapted virus was highly virulent with a median lethal dose of 10 median tissue culture infectious doses. Disease was characterized by several hallmarks of LF in similar models including high fever, thrombocytopenia, coagulation disorders, and increased inflammatory immune mediators. High viral loads were noted in all solid organ specimens analyzed. Histological abnormalities were most striking in the lungs and livers of terminal animals and included interstitial inflammation, edema, and steatosis. Overall, this model represents a convenient small animal model for a clade III Nigeria LASV with which evaluation of specific prophylactic vaccines and medical countermeasures can be conducted.
Zika virus (ZIKV) is rapidly spreading throughout the Americas and is associated with significant fetal complications, most notably microcephaly. Treatment with polyclonal antibodies for pregnant ...women at risk of ZIKV-related complications could be a safe alternative to vaccination. We found that large quantities of human polyclonal antibodies could be rapidly produced in transchromosomal bovines (TcB) and successfully used to protect mice from lethal infection. Additionally, antibody treatment eliminated ZIKV induced tissue damage in immunologically privileged sites such as the brain and testes and protected against testicular atrophy. These data indicate that rapid development and deployment of human polyclonal antibodies could be a viable countermeasure against ZIKV.
Display omitted
•Transchromosomal Bovine (TcB) were developed to produce human polyclonal antibody.•Vaccinated TcB produce high-titer neutralizing antibody to Zika virus.•Human ZIKV-TcB antibodies prevent lethal disease in two mouse models.•ZIKV-TcB antibodies prevent tissue damage and testicular atrophy in mice.•Delayed treatment results in significant protection from lethal ZIKV infection.
PDF
