An inventory of COVID-19 related research projects

To date, COVID-19 infection has been diagnosed solely through laboratory tests that detect viral RNA. These diagnostic tests reveal whether someone is currently infected but do not reveal critical information about the development of immunity, which requires analysis of the antibodies generated by the immune system after infection. More information is urgently needed about the development, duration, and strength of the antibody responses that lead to immunity following infection with SARS-CoV-2. This project will evaluate four new commercial antibody detection platforms to identify suitable genomic tests, known as assays, to reliably detect different types of antibodies that can provide clues about immune response. These assays will be used to profile antibody production against SARS-CoV-2 in both newly infected and previously infected Health Care Workers (HCW) over three months. Findings will reveal how quickly HCW develop an immune response to SARS-CoV-2 and how robust this protection is against subsequent exposures they will likely encounter after recovery. This antibody data can be used to immediately inform guidelines for HCW at high risk of SARS-CoV-2 exposure, including return to work policies and front-line deployment strategies.

The purpose of this study is to identify proteins produced by all human coronaviruses that bind to antibodies. Specifically, this study will identify similar proteins that are recognized by common antibodies and how they may interfere with the results of antibody detection by commercial assays. The study outcomes will be used to guide antibody detection against SARS-CoV-2.

"Purpose: To estimate diagnostic accuracy of molecular testing for patients under investigation for COVID-19 admitted to acute care hospital Hypothesis: This is a diagnostic accuracy study, we hypothesize that our diagnostic testing will be 90% sensitive Justification: Molecular assays for SARS-CoV-2 detection have undergone testing of their analytical performance such as analytic sensitivity, specificity, reproducibility etc. However, little is published on molecular test performance in a clinical setting. Knowledge of diagnostic capabilities and limitations will further guide development of testing and infection control strategies particularly in hospitalized patients, as well have effect on public health measures to limit further spread by contact tracing in the community"

This study aims to definitively determine whether or not convalescent plasma is effective at treatment patients significantly ill with COVID-19. Patients who have recovered from COVID-19 will be identified and recruited to donate their plasma. We will then randomly select certain hospitalized COVID-19 patients to receive this convalescent plasma, and compare their health outcomes with similar patients who did not receive this treatment.

"1. Assess the incidence of transmission of SARS-CoV-2 among exposed nocturnal HD patients 2. Assess the incidence of transmission of SARS-CoV-2 among exposed nocturnal HD staff Methods: A retrospective chart review will be conducted for patients exposed to the index case of SARS-CoV-2 in nocturnal hemodialysis (March 24 - April 23, 2020). Data to be collected are included on the data collection spreadsheet. Information to be collected include age, symptoms of COVID-19 (fever, cough, shortness of breath/chest heaviness, fatigue/malaise, myalgias/body aches, headache, rhinorrhea, sore throat, anosmia, ageusia, nausea/vomiting, diarrhea, abdominal pain and loss of appetite), results of SARS-CoV-2 PCR tests, and results of SARS-CoV serology testing. A retrospective review will also be done with staff collecting the same information, in collaboration with the HD unit leads and Occupational Health and Safety."

"1. Assess the incidence of transmission of SARS-CoV-2 among exposed nocturnal HD patients 2. Assess the incidence of transmission of SARS-CoV-2 among exposed nocturnal HD staff Methods: A retrospective chart review will be conducted for patients exposed to the index case of SARS-CoV-2 in nocturnal hemodialysis (March 24 - April 23, 2020). Data to be collected are included on the data collection spreadsheet. Information to be collected include age, symptoms of COVID-19 (fever, cough, shortness of breath/chest heaviness, fatigue/malaise, myalgias/body aches, headache, rhinorrhea, sore throat, anosmia, ageusia, nausea/vomiting, diarrhea, abdominal pain and loss of appetite), results of SARS-CoV-2 PCR tests, and results of SARS-CoV serology testing. A retrospective review will also be done with staff collecting the same information, in collaboration with the HD unit leads and Occupational Health and Safety."

This study will validate the use of dried blood spots for COVID19 serology testing. Dried blood spot collection is a simple, minimally invasive, process whereby a drop of blood is deposited on filter paper and dried. It may therefore be an extremely useful test method with simplified sample collection, which could be applied to assess the prevalence of COVID19 antibodies among the population.

The UBC COVID Biobank will be established in 2020 in response to the COVID-19 Pandemic. The biobank will be established specifically to support COVID research which is defined as research related to the diagnosis, treatment and cure of COVID-19.

"We propose to apply PDT using methylene blue directed at the nasopharynx on patients with known COVID-19. After obtaining consent, VGH inpatients will receive a pretreatment anterior nares and/or nasopharyngeal (NP) swab, and then randomized to receive either a) Anterior nares or Nasopharyngeal PDT using methylene blue and the appropriate wavelength of light delivered by NP cannula as per manufacturer's instructions OR b) Nasopharyngeal methylene blue without light delivery (sham arm) OR c) No treatment (control) All patients will then receive a post-treatment anterior nares or NP swab. One operator will be responsible for administration of PDT to the anterior nares and/or nasopharynx."

The purpose of this study is to assess how patients infected with COVID-19 shed viral particles as well as to assess the degree of contamination of patient room surfaces and air with the virus. This information will help inform the infection prevention community when making decisions regarding the necessary infection prevention and control measures (e.g. personal protective equipment, requirements for hospital room ventilation) . We will collect demographic and clinical data from COVID-19 positive patients and ask our inpatient participants for regular swab samples (daily or every 2 days from nose and throat) from the time of consent until two samples are negative for the virus (serial swabs until negative is part of our hospital's "deisolation" protocol, however we will start these swabs immediatley after admission rather than wait for clinical improvement).

To identify the outcomes of patients with chronic kidney disease (CKD) who have symptoms of COVID-19 requiring testings and determine how these outcomes differ by patient characteristics.

This project aims to identify antibodies against SARS-CoV-2, with the potential for use as diagnostic, prophylactic or therapeutic tools. To perform this work, we will obtain blood samples from individuals who have recovered from COVID-19. These samples contain the immune cells we study. We will isolate and analyze the cells that naturally produce antibodies (B cells), recover the sequences encoding those antibodies using molecular biology techniques, assess the function of those antibodies, and their suitability for synthetic, large-scale manufacturing. We will also sequence the viral genome of the SARS-CoV-2 virus from each study participant's clinical sample, to track the emergence of escape mutations, and the evolution of the virus.

Scientific evidence suggested that SARS-CoV-2 is not limited to infected cells but causes systemic changes in the physiology of the human host. Wide spread tissue damage, abnormal blood clotting and aberrant immune response, alongside sex and age differences are among the key effects that are not yet fully understood. In this project, we will investigate changes in the protein and metabolite composition of human cells and body fluids in response to an active or resolved infection with SARS-CoV-2. This data will provide further mechanistic insights for SARS-CoV-2.

We aim to examine the possible impact of the COVID-19 pandemic on the diagnosis of melanoma in British Columbians.

"Accurate COVID-19 diagnosis is critical to a successful clinical and public health response. Recent research from our group however indicates that suboptimal biological sampling by nasopharyngeal swab can cause false-negative SARS-CoV-2 diagnostic test results. Thus, there is a need to further refine nasopharyngeal swab collection technique for COVID-19 diagnosis. In addition, there is a need to evaluate alternative sample types for COVID-19 diagnosis, particularly those that can be self-collected. The overarching goal of this study is to refine specimen collection techniques for COVID-19 diagnosis using different types of biological samples collected from healthy volunteers."

The research team is seeking to understand how many passengers, if any, departing from YVR are asymptomatic, but have the virus, meaning that they are infected and could be potentially contagious but don’t have symptoms. Read more...

For more information, including some recent news media interviews with Dr. Romney, on this study, visit:

• UBC - New study to determine the impact of COVID-19 vaccines in residents of long-term care facilities in B.C.
• CITF - Two studies to determine the impact of COVID-19 vaccines in residents of long-term care facilities in BC and Alberta
• Global TV - Top B.C. researchers to study effects of COVID-19 on the elderly
• CBC - Researchers study COVID-19 vaccine's impact on long-term care residents and staff in B.C., Alberta
• Medicinematters.ca - How long will vaccines protect us from COVID 19? Vancouver researchers get grant to find out
• Pique News Magazine / Vancouver Sun - Why does COVID-19 kill so many seniors in long-term care?
• Vancouver Sun - COVID-19: As care home residents get second vaccine doses, study aims to track their antibody levels
• PHC COVID-19 Staff Bulletin

Senior people living in long-term care facilities are among high-risk individuals with the highest rate of mortality when affected by COVID-19. A non-invasive, rapid and sensitive method for regular screening allows early detection of the high-risk individuals infected with COVID-19 helping to reduce the rate of viral transmission in long-term care facilities. Moreover, data indicate better outcomes when treatment protocols start earlier. We aim to develop and test a novel, non-invasive, sensitive and accurate biosensing device and a simple-to-operate method for regular screening and early diagnosis of patients who are affected by COVID-19 in long-term care facilities. Prof. Andrew Macnab, Dr. Jordan Guenette, Dr. Kevin Afra, Dr. Eric Sayre, Dr. Reza Alemi and Dr. Amir Gandjbakhche are key collaborators in this multidisciplinary project.

The impact of SARS-Cov-2 infection on neurodegenerative disease is unknown. Although most first wave patients were elderly, subsequent waves affect younger people and the differential risk for neurodegeneration is not known. This project expands an ongoing prospective observational cohort study of critically ill COVID-19 patients in three British Columbia Intensive Care Units (ICU) to assess the acute and chronic neurological and neuropsychiatric consequences of COVID-19. A wealth of clinical and blood biomarker data are collected in the ICU and we propose to use clinical, blood biomarker and neuroimaging tests in follow-up visits planned for 8-12 weeks, 6, 12, 24 and 36 months after discharge. This study is expected to have a major impact on assessing risk of new or exacerbated neurological dysfunction in COVID-19 patients.

There is an urgent need to quickly and accurately identify cases of COVID-19, as this information can be used to help stop the spread of the virus, both in the community and in the hospital (or other settings, like long-term care facilities). Current COVID-19 tests detect viral RNA using a tool called PCR. In general, PCR is considered a very sensitive way to diagnose infections. Sometimes, tests do not perform as expected, and this can due to many different factors (e.g. the way the specimen is collected, transport issues, the technology used in the laboratory). This work will help us understand which factors play a role in PCR testing for COVID-19 specifically.It will also allow us to potentially identify any pitfalls with the current testing process, and improve upon them. It is also important to develop a method for researchers to better measure viral load in patients. This will help medical professionals determine which therapeutic interventions are effective during the course of infection. In the management of other viral infections such as HIV, information around viral load has been invaluable. Ultimately, this project will be able to examine the diagnostic performance of COVID-19 tests and determine viral loads of patients which will improve the way that people are treated. This project will leverage local expertise in viral quantification and precision medicine to help control the current COVID-19 pandemic.

As the COVID-19 pandemic expands around the world, the BC Centre for Disease Control and other testing sites are facing two dire problems: a shortage in reagents and the personnel needed to ramp-up diagnostic testing. In the immediate term the project team will ensure that BC can maintain and expand its capacity for COVID-19 testing by making sure that reagent sources can be sourced locally. In the medium term, these reagents will be further validated, and production scaled up to meet the accelerating testing demands in BC. The establishment of molecular resources, protocols and formulations will also ensure that BC and Canada are prepared to meet future pandemics in the face of disrupted global supply chains. Ultimately, a stable supply of reagents, produced locally, will allow expansion of testing to mild/asymptomatic cases, resulting in enhanced contact tracing and isolation that will limit onward transmission.

A growing number of young and/or otherwise healthy COVID-19 patients are progressing to symptoms serious enough to require hospital admission and intubation for breathing assistance. This project aims to better understand how and why these patients become so unwell so quickly; this information will be critical to ensuring this growing patient population gets effective care. Researchers will study a large collection of viral samples, from the BC Centre for Disease Control, collected from patients' upper and lower respiratory tract, divided into study groups based on whether patients required hospital admission and breathing assistance. Genetic information from these samples will help the researchers identify biological markers of projected disease severity and progression. Future COVID-19 patients could then be tested for these same markers so that high risk patients can be quickly identified for targeted interventions.

There are many unanswered questions regarding the virus, how it spreads and the disease that it causes. This information is needed for a data-driven response to this outbreak. We aim to use two types of next-generation data (next-gen genomics data and next-gen human data), along with a data integration tool called PLOVER 2.0, to answer these unknowns. The research team will 1)Carry out rapid genomic sequencing on patient samples to study the virus, how it spreads, how it evolves and predict which drugs will work 2)Develop knowledge of how the virus characteristics, along with a patient's previous health conditions, impact the severity of illness and how they recover from the illness 3)Develop a software tool (PLOVER 2.0) that will allow us to carry out this research and will also make the data viewable by key stakeholders such as Medical Health Officers. This work will not only generate critical knowledge about the SARS-CoV-2 virus but will also help develop a better understanding of health outcomes for infected patients. The knowledge generated and tools developed by this research can ensure an evidence-based and cohesive response to this public health emergency, here in Canada and internationally.

An additional critical dimension of information for outbreak response can be revealed by genomic analysis and will be piloted in this Genome BC-funded project by three BCCDC-affiliated investigators at UBC, Dr. Mel Krajden, Dr. Richard Harrigan, and Dr. Natalie Prystajecky. Sequencing the whole genome of viruses can enable researchers to determine how strains of a virus between patients are related, an approach called phylogenetic analysis. This type of analysis of the evolutionary relationships between viruses can provide important insights into how a virus is spreading, including revealing "clusters" of closely related viruses and whether new infections represent new introductions of the virus into BC or the spread of existing strains. These insights are essential for guiding targeted interventions to stop further transmission and evaluating the efficacy of existing infection control measures. By developing these tools on a rapid sequencing platform, the BCCDC will improve its agility and potentially be mobile in its analysis of viral transmission. This work will not only help the BCCDC respond to this emergency, but also to other current and future epidemics.

We propose to undertake a laboratory investigation into real-time PCR sensitivity for COVID-19 detection by testing remnant clinical specimens using two other molecular tests that, at least in theory, should have higher analytical sensitivity to detect low levels of virus in clinical samples. If false-negative test results are occurring in the current COVID-19 pandemic, this would have important clinical and public health implications for COVID-19 management. It is therefore important to investigate, in as timely a way possible, whether assay sensitivity issues in BC's testing pipeline may be occurring.

1) Purpose. To generate complete genomic information for patients who have tested positive for a COVID-19 infection. This will allow the determination of any genetic determinants that influence the severity of the disease and the response to intervention. 2) Objectives. To create a database of genetic variants that can be correlated with features of coronavirus infection and patient phenotype information. 3) Research Method. Eligibility will be restricted to patients that have tested positive for COVID-19. Residual material remaining from COVID-19 testing will be used to isolate genomic DNA, which will then be subjected to whole genome sequencing. Where sufficient material exists, the sequence of the COVID-19 coronavirus may also be generated. There will be no blinding or randomization. 4) Statistical Analysis. It is likely, that data from British Columbia alone will be insufficient to robustly determine relevant genetic features (at least initially) and that insights will more likely be gained through data-sharing and interactions with international research consortia. For example, similar projects are being planned across Canada (Ontario and Quebec) and data would likely initially be shared with these studies.

Proof of concept pilot project to determine whether anterior nares or nasopharyngeal photo-disinfection using methylene blue will decrease COVID-19 viral load.

To support decision making around relaxing restrictions and managing work environments as society reopens, an inter-sectoral group of industry, academic, and public sector partners in BC is leading a new 15-month, $1.2 million return-to-work study. The data from the “SARS‐CoV‐2 Study for Eased Restrictions in British Columbia” (SAfER) project, collected in controlled settings, will be available in real time to help inform public health decisions that lead to positive outcomes. The SAfER study—supported by Genome BC, Genome Canada, and industry partners—will track and collect data over time on infection, immunity, contacts, and clinical symptoms for 1,500 volunteer employees at BC based biotechnology companies, including Xenon Pharmaceuticals, STEMCELL Technologies and Zymeworks, as well as Simon Fraser University and the University of British Columbia. An employee survey will also collect information about stress and anxiety related to the pandemic.

To validate SARS-CoV-2 antibody assays in development and to evaluate the type, quantity, quality and kinetics of the immune response. To collect blood from confirmed COVID-19 cases to enable validation of antibody assays, guide timing of specimen collection for serological diagnosis and to support future investigation and fuller understanding of the immune response more generally to COVID-19, other coronaviruses and emerging or re-emerging respiratory pathogens.

Most people have had one or more colds due to seasonal coronaviruses (CoV) with the number of prior infections increasing with age. SARS-CoV-2 entered the human population in late 2019, causing the COVID-19 pandemic. Before that no one had immunity yet older males are at higher risk of severe COVID-19 illness. One explanation is that prior antibodies to seasonal CoVs may enhance SARS-CoV-2 risk through a process called antibody dependent enhancement. To assess that hypothesis we first need to know if seasonal CoV antibodies interact with SARS-CoV-2, how common those antibodies are, and if older men have more of them. We will develop a pan-CoV assay to compare prevalence of all human CoVs by age and sex. Findings will inform SARS-CoV-2 sero-surveys, severity profiles and vaccine strategies.

Diagnostic testing is vital to the COVID-19 pandemic response. The current standard is to test nasopharyngeal swabs, but the supply of swabs has been rapidly depleted. At SPH Virology, there is an automated COVID-19 molecular test which enables high-volume testing, but is currently only testing swabs and not other specimens due to concerns regarding compatibility of specimens like saliva on the instrument. As an easier sample to collect, which also minimizing supply chain concerns for swabs, we will be evaluating the potential to do COVID-19 testing on saliva using this high-throughput platform to further increase COVID-19 testing capacity in BC.

Phase 4 of BC’s Restart Plan requires community immunity but seroprevalence studies of people who are street entrenched, in prison, or live in remote or rural communities is challenging. The most accurate serology tests are lab-based Enzyme-Linked Immuno Assays (EIAs) that use blood drawn from veins, but with people who are not engaged into care, or who have collapsed veins due injection drug use or obesity, it's not a viable option. Point-of-care tests (PoCT) that use blood collected through finger prick (like a glucose test) seems to offer a solution but these tests lack specificity and therefore can’t provide an accurate picture. We propose evaluating dried blood spots (DBS), as these seem to offer the accuracy of EIAs and the ease of collection of a PoCT to determine BC seroprevalence. ASSESS-DBS is a cross-sectional study to investigate the seroprevalence of SARS-CoV-2 antibodies among people who are incarcerated in British Columbia (BC) Provincial Correctional Centres, as well as staff that work in these facilities. This will be achieved by collecting paired Dried Blood Spot (‘DBS’) and venous blood samples from 1000 voluntary participants recruited from across all 10 BC Provincial Correctional Centres. Additional specimens will be collected from anyone with COVID-19 symptoms, consistent with standard of care in BC. As such, ASSESS-DBS will also aim to determine prevalence of active SARS-CoV-2 infections among study participants, and evaluate whether Dried Blood Spots (‘DBS’) are as effective for SARS-CoV-2 sero-prevalence estimates as standard venepuncture specimens, what the acceptability of DBS among people in BC Provincial Corrections is, and what the preferences of people who are incarcerated are for blood specimen collection.

Patients with COVID-19 most often suffer from breathing problems, but they also have a high risk of developing dangerous blood clots (thrombosis) in their blood vessels. Indeed, it is the widespread excess clotting of blood that likely causes most of the morbidity and mortality associated with COVID-19. The increased risk of thrombosis in COVID-19 is not well understood, and treatment with traditional anti-clotting drugs (anticoagulants) works only to a limited extent. Therefore, we need to better understand why COVID-19 patients develop the clots so that we can develop/use more effective medicines. Based on recent work, we know that a part of the immune system in the blood, referred to as complement, is over-activated in patients with COVID-19. When over-activated, complement components (there are several) cause the blood clotting system (coagulation) to also become over-activated, increasing the risk of thrombosis. In line with a link between these systems, anti-complement drugs have been used in other diseases to effectively prevent thrombosis. If we confirm a link between complement over-activation and thrombosis in COVID-19, anti-complement drugs could be rapidly evaluated in clinical trials.

COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With no treatment or vaccine currently available, it is imperative that rapid, sensitive, and simple screening technologies be developed that can be fully integrated into near real time medical reporting infrastructure so as to speedily identify viral carriers and slow this and future viral outbreaks. The Unrau laboratory at Simon Fraser University has engineered an isothermal RNA detection kit that reports the presence of RNA template by fluorogenic aptamer (RNA Mango) synthesis in a simple fluorogenic assay (Mango NASBA). This technology, which currently is being commercialised for the detection of pathogens in human tissue culture, can be rapidly adapted for the detection of SARS-CoV_2 and offers several advantages over conventional RT-PCR: 1. Isothermal Mango NASBA viral testing has a considerably simpler work flow than RT-PCR requiring only a simple fixed temperature device capable of detecting fluorescent readout. This offers the potential to implement real time viral testing at venues (i.e. airports, borders, hospitals etc) not normally considered with existing RT-PCR methodologies and that require more costly real-time thermocycler infrastructure to implement. 2. We anticipate that Mango NASBA offers a significant time saving of ~3-4 fold relative to a standard RT-PCR assay (90-120 min) in high viral load samples. Should high sensitivity detection be required, Nested Mango NASBA can be performed subsequently. Nested Mango NASBA has sensitivity directly comparable to RT-PCR and can be performed twice as fast as RT-PCR methodologies. We have assembled a team consisting of biochemists, chemists, virologists, engineers, and clinicians offering deep skills in four highly significant fields to help address this rapidly evolving SARS-CoV_2 crisis. This highly expert team will meet the challenge of detecting and tracking this rapidly evolving viral outbreak.

We are making a blood test that will tell us a lot of information about the body’s response to the COVID-19, including whether a person is likely to get really sick or will easily fight off the virus. The blood test is will be easy to take, using only a drop of blood from the tip of the finger. The test is run using cutting-edge technology so that we can test a lot of people, at low cost, while getting the right results. The test will help prevent people from getting severely sick from COVID-19 by letting doctors know BEFORE things get worse that their patient may need additional care to help fight off the virus. For our citizens most at risk, like the elderly and those with other medical conditions, the results can be used to direct resources and support where they are needed most.