Evaluation of Prenatal Hepatitis C Virus Prevalence Using Universal Screening, and Linkage to Care in a Real-World Setting in Ontario.

OBJECTIVES: International infectious disease/obstetrical societies have recently recommended universal hepatitis C virus (HCV) prenatal screening and these same recommendations are forthcoming in Canada. At present, there is no formal analysis of universal HCV screening or linkage to care of pregnant people in Ontario. The objectives of our study were to determine the seroprevalence of HCV using 2 different methods to evaluate universal screening, as well as identify opportunities that may improve linkage to care. METHODS: To assess seroprevalence in a large urban area, we aimed to test 12 000 de-identified samples submitted for prenatal HIV testing in the catchment area of Toronto Public Health for HCV antibodies. Then, to assess the seroprevalence as well as the operational impact and follow-up in a real-world setting, we completed a Quality Improvement Project (QIP) for 1 year at a large tertiary care obstetrical centre in London, Ontario. RESULTS: From 2019 to 2021, 11 999 de-identified samples were screened from Toronto with a seroprevalence of 0.40 (95% CI 0.29-0.53). In London, 5771 people were screened in 2021 with a seroprevalence of 0.55% (95% CI 0.38-0.78). Taken together, those aged 26-35 years had the highest positivity; in the QIP, 9% had no documented risk factor, and 59% of individuals were not linked to the next step in HCV care. CONCLUSIONS: HCV prenatal seroprevalence in Ontario is comparable to hepatitis B virus, and ∼15-30-fold higher than HIV. Diagnosis in pregnancy is critical to facilitate referrals for treatment between pregnancies and could increase screening among children born to positive women.

Ebola Virus Encodes Two microRNAs in Huh7-Infected Cells.

MicroRNAs (miRNAs) are important gene regulatory molecules involved in a broad range of cellular activities. Although the existence and functions of miRNAs are clearly defined and well established in eukaryotes, this is not always the case for those of viral origin. Indeed, the existence of viral miRNAs is the subject of intense controversy, especially those of RNA viruses. Here, we characterized the miRNA transcriptome of cultured human liver cells infected or not with either of the two Ebola virus (EBOV) variants: Mayinga or Makona; or with Reston virus (RESTV). Bioinformatic analyses revealed the presence of two EBOV-encoded miRNAs, miR-MAY-251 and miR-MAK-403, originating from the EBOV Mayinga and Makona variants, respectively. From the miRDB database, miR-MAY-251 and miR-MAK-403 displayed on average more than 700 potential human host target candidates, 25% of which had a confidence score higher than 80%. By RT-qPCR and dual luciferase assays, we assessed the potential regulatory effect of these two EBOV miRNAs on selected host mRNA targets. Further analysis of Panther pathways unveiled that these two EBOV miRNAs, in addition to general regulatory functions, can potentially target genes involved in the hemorrhagic phenotype, regulation of viral replication and modulation of host immune defense.

Isolation, Sequence, Infectivity, and Replication Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2.

Since its emergence in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected ≈6 million persons worldwide. As SARS-CoV-2 spreads across the planet, we explored the range of human cells that can be infected by this virus. We isolated SARS-CoV-2 from 2 infected patients in Toronto, Canada; determined the genomic sequences; and identified single-nucleotide changes in representative populations of our virus stocks. We also tested a wide range of human immune cells for productive infection with SARS-CoV-2. We confirm that human primary peripheral blood mononuclear cells are not permissive for SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor single-nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine viral genotype and phenotype by using in vitro and in vivo infection models.

Molecular characterization of pathogenic and nonpathogenic fowl aviadenovirus serotype 11 isolates.

Fowl aviadenoviruses, many of which are of importance in veterinary medicine, are classified into 5 species. In this study, a pathogenic isolate and a nonpathogenic isolate of fowl aviadenovirus serotype 11 (FAdV-11) of species Fowl aviadenovirus D were characterized. Growth rates were analyzed for the 2 isolates, showing notable differences. The complete genomic sequences of the viruses were fully determined and were analyzed. The genomes of the 2 isolates showed 98.1% sequence identity and revealed 6 nonsynonymous mutations between the Ontario isolates. Two of the 6 mutations were also found in the sequences of recently published pathogenic Chinese fowl aviadenovirus 11 isolates, suggesting potential molecular markers that could be associated with pathogenesis. Deletions were found in the L5 region within the overlapping coding sequences for the 100, 22, and 33 kDa proteins, and these were found in only the nonpathogenic isolates. This molecular pattern was identified in FAdV-9, another nonpathogenic FAdV-D species virus. Furthermore, the tandem repeat regions varied dramatically; the pathogenic isolates contained a reduced number of tandem repeats compared with the nonpathogenic isolates. Lastly, a protein produced early in infection was analyzed using bioinformatics to determine its role in disease. This study highlights several candidate molecular determinants of avian adenovirus genomes related to pathogenicity.

Contribution of a mutational bias in hepatitis C virus replication to the genetic barrier in the development of drug resistance.

The development of resistance to direct-acting antivirals (DAAs) targeting the hepatitis C virus (HCV) can compromise therapy. However, mechanisms that determine prevalence and frequency of resistance-conferring mutations remain elusive. Here, we studied the fidelity of the HCV RNA-dependent RNA polymerase NS5B in an attempt to link the efficiency of mismatch formation with genotypic changes observed in vivo. Enzyme kinetic measurements revealed unexpectedly high error rates (approximately 10(-3) per site) for G:U/U:G mismatches. The strong preference for G:U/U:G mismatches over all other mistakes correlates with a mutational bias in favor of transitions over transversions. Deep sequencing of HCV RNA samples isolated from 20 treatment-naïve patients revealed an approximately 75-fold difference in frequencies of the two classes of mutations. A stochastic model based on these results suggests that the bias toward transitions can also affect the selection of resistance-conferring mutations. Collectively, the data provide strong evidence to suggest that the nature of the nucleotide change can contribute to the genetic barrier in the development of resistance to DAAs.

Characterization of Laboratory-Confirmed Creutzfeldt-Jakob Disease From 3 Ontario Tertiary Care Centers Between 2012 and 2022: A Retrospective Cohort Study.

Background: Globally, Creutzfeldt-Jakob disease (CJD) affects one in one million people annually, but there is a paucity of recent Canadian data. This study summarizes epidemiology trends and diagnostic timelines of laboratory-confirmed CJD cases in three tertiary Ontario hospitals. Method: Using laboratory information systems, we identified 30 patients with a laboratory-confirmed CJD diagnosis between 2012 and 2022 at three major tertiary hospitals in Ontario. Retrospective chart reviews were then completed. Results: Patients had a mean of 2.2 hospital visits (SD, 1.2) prior to being admitted for testing. The most common symptom presentations included loss of coordination (63.3%), behavioral changes (60%), progressive mobility loss (53.4%), memory loss (50.0%), and involuntary movements (50.0%). Magnetic resonance imaging findings showed potential CJD in 76.7% of cases, and 56.7% exhibited periodic sharp wave complexes characteristic of CJD on electroencephalogram. The mean duration from symptom onset to microbiologic testing was 91 days (SD, 90.7). End-point quaking-induced conversion (EP-QuIC) testing of cerebrospinal fluid was positive in 90.0% of patients, while 83.3% tested positive for 14-3-3 on enzyme-linked immunosorbent assay. Elevated cerebrospinal fluid 14-3-3 levels significantly correlated with shorter duration from symptom onset to death (R 2 = 0.71, F = 19.55, P = .0022). Post-diagnosis, 46.7% of patients were discharged home, 16.6% were transferred to external palliative care or hospice facilities, and 36.7% died during admission. The mean time from symptom onset to death was 121 days (SD, 120.7), and from diagnosis to death 35 days (SD, 83.9). Conclusions: This study highlights the importance of early CJD consideration and laboratory testing when appropriate neurologic symptoms are present.

Verification, Analytical Sensitivity, Cost-effectiveness, and Comparison of 4 Candida auris Screening Methods.

In this verification study, we compare and contrast the performance characteristics of chromogenic agar culture, direct polymerase chain reaction (PCR), and broth enrichment followed by culture or PCR for the detection of Candida auris colonization. We find that culture and PCR both offer excellent performance, with broth enrichment offering little performance advantage given its cost.

Implementation of point-of-care molecular testing for respiratory viruses in congregate living settings.

OBJECTIVE: To implement and evaluate a point-of-care (POC) molecular testing platform for respiratory viruses in congregate living settings (CLS). DESIGN: Prospective quality improvement study. SETTING: Seven CLS, including three nursing homes and four independent-living facilities. PARTICIPANTS: Residents of CLS. METHODS: A POC platform for COVID-19, influenza A and B, and respiratory syncytial virus was implemented at participating CLS from December 1, 2022 to April 15, 2023. Residents with respiratory symptoms underwent paired testing, with respiratory specimens tested first with the POC platform and then delivered to an off-site laboratory for multiplex respiratory virus panel (MRVP) polymerase chain reaction (PCR) as per standard protocol. Turn-around time and diagnostic accuracy of the POC platform were compared against MRVP PCR. In an exploratory analysis, time to outbreak declaration among participating CLS was compared against a convenience sample of 19 CLS that did not use the POC platform. RESULTS: A total of 290 specimens that underwent paired testing were included. Turn-around time to result was significantly shorter with the POC platform compared to MRVP PCR, with median difference of 36.2 hours (interquartile range 21.8-46.4 hours). The POC platform had excellent diagnostic accuracy compared to MRVP PCR, with area under the curve statistic of .96. Time to outbreak declaration was shorter in CLS that used the POC platform compared to CLS that did not. CONCLUSION: Rapid POC testing platforms for respiratory viruses can be implemented in CLS, with high diagnostic accuracy, expedited turn-around times, and shorter time to outbreak declaration.

Differential Gene Expression in the Upper Respiratory Tract following Acute COVID-19 Infection in Ambulatory Patients That Develop Long COVID.

Background: Post-acute sequelae of COVID-19, or long COVID, is a condition characterized by persistent COVID-19 symptoms. As long COVID is defined by clinical criteria after an elapsed period, an opportunity for early intervention may aid in future prophylactic approaches; however, at present, the pathobiological mechanisms are multifactorial. By analyzing early virally infected upper respiratory tract tissue prior to eventual clinical diagnosis, it may be possible to identify biomarkers of altered immune response to facilitate future studies and interventions. Methods: This is a sub-group analysis of samples collected from those with confirmed COVID-19. RNA extraction from nasopharyngeal/mid-turbinate samples, sequencing, and bioinformatic analysis were performed to analyze long COVID and non-long COVID cohorts at day 14 post infection. Differences in mean viral load at various timepoints were analyzed as well as serological data. Results: We identified 26 upregulated genes in patients experiencing long COVID. Dysregulated pathways including complement and fibrinolysis pathways and IL-7 upregulation. Additionally, genes involved in neurotransmission were dysregulated, and the long COVID group had a significantly higher viral load and slower viral clearance. Conclusions: Uncovering early gene pathway abnormalities associated with eventual long COVID diagnosis may aid in early identification. We show that, post acute infection, in situ pathogenic deviations in viral response are associated with patients destined to meet consensus long COVID diagnosis that is entirely dependent on clinical factors. These results identify an important biological temporal window in the natural history of COVID-19 infection and long COVID pathogenesis amenable to testing from standard-of-care upper respiratory tract specimens.

Altered microRNA Transcriptome in Cultured Human Airway Cells upon Infection with SARS-CoV-2.

Numerous proteomic and transcriptomic studies have been carried out to better understand the current multi-variant SARS-CoV-2 virus mechanisms of action and effects. However, they are mostly centered on mRNAs and proteins. The effect of the virus on human post-transcriptional regulatory agents such as microRNAs (miRNAs), which are involved in the regulation of 60% of human gene activity, remains poorly explored. Similar to research we have previously undertaken with other viruses such as Ebola and HIV, in this study we investigated the miRNA profile of lung epithelial cells following infection with SARS-CoV-2. At the 24 and 72 h post-infection time points, SARS-CoV-2 did not drastically alter the miRNome. About 90% of the miRNAs remained non-differentially expressed. The results revealed that miR-1246, miR-1290 and miR-4728-5p were the most upregulated over time. miR-196b-5p and miR-196a-5p were the most downregulated at 24 h, whereas at 72 h, miR-3924, miR-30e-5p and miR-145-3p showed the highest level of downregulation. In the top significantly enriched KEGG pathways of genes targeted by differentially expressed miRNAs we found, among others, MAPK, RAS, P13K-Akt and renin secretion signaling pathways. Using RT-qPCR, we also showed that SARS-CoV-2 may regulate several predicted host mRNA targets involved in the entry of the virus into host cells (ACE2, TMPRSS2, ADAM17, FURIN), renin-angiotensin system (RAS) (Renin, Angiotensinogen, ACE), innate immune response (IL-6, IFN1ß, CXCL10, SOCS4) and fundamental cellular processes (AKT, NOTCH, WNT). Finally, we demonstrated by dual-luciferase assay a direct interaction between miR-1246 and ACE-2 mRNA. This study highlights the modulatory role of miRNAs in the pathogenesis of SARS-CoV-2.

Province-to-province variability in hepatitis C testing, care, and treatment across Canada.

Background: Few countries have implemented the necessary policy changes to reduce the number of steps in the cascade of care to achieve hepatitis C virus (HCV) elimination, including Canada. The aim of this study was to describe and compare legislation, scope of practice, and policy as it relates to the provision of HCV care in each province. Methods: We reviewed grey literature and regulatory and legislative documents which affect various aspects of the HCV cascade of care. Findings were verified by content experts. Results: HCV RNA reflex testing ensures those that are antibody positive get an HCV RNA test; however only 80% of provinces have reflex test. Point-of-care antibody testing can be offered in most community non-health care settings, yet many types of health care providers are unable to do this independently. Following a positive test, it may not be feasible to complete venipuncture; however only a single province processes HCV RNA dried blood spot cards. In many provinces, training and verification are required for novice prescribers, and in some provinces prescribing continues to be restricted to specialists. Only a single province has task-shifted treatment to a non-physician non-nurse practitioner model, where pharmacists can prescribe treatment. Finally, 80% of provinces require authorization forms, and 30% require proof of investigations for treatment. Conclusions: No single province is optimizing the use of diagnostic tools and task shifting and decreasing paperwork to expedite treatment initiation. Collaboration between provinces is needed to streamline practice, update policy, and promote equity in HCV diagnosis, care, and treatment.

Host Expression Profiling From Diagnostic Coronavirus Disease 2019 Swabs Associates Upper Respiratory Tract Immune Responses With Radiologic Lung Pathology and Clinical Severity.

Background: COVID-19 presents with a breadth of symptomatology including a spectrum of clinical severity requiring intensive care unit (ICU) admission. We investigated the mucosal host gene response at the time of gold standard COVID-19 diagnosis using clinical surplus RNA from upper respiratory tract swabs. Methods: Host response was evaluated by RNA-sequencing, and transcriptomic profiles of 44 unvaccinated patients including outpatients and in-patients with varying levels of oxygen supplementation were included. Additionally, chest X-rays were reviewed and scored for patients in each group. Results: Host transcriptomics revealed significant changes in the immune and inflammatory response. Patients destined for the ICU were distinguished by the significant upregulation of immune response pathways and inflammatory chemokines, including cxcl2 which has been linked to monocyte subsets associated with COVID-19 related lung damage. In order to temporally associate gene expression profiles in the upper respiratory tract at diagnosis of COVID-19 with lower respiratory tract sequalae, we correlated our findings with chest radiography scoring, showing nasopharygeal or mid-turbinate sampling can be a relevant surrogate for downstream COVID-19 pneumonia/ICU severity. Conclusions: This study demonstrates the potential and relevance for ongoing study of the mucosal site of infection of SARS-CoV-2 using a single sampling that remains standard of care in hospital settings. We highlight also the archival value of high quality clinical surplus specimens, especially with rapidly evolving COVID-19 variants and changing public health/vaccination measures.

Streptococcus pyogenes secondary impetigo due to loofah sponge use.

Loofah sponges have been implicated in skin and soft tissue infections due to their ability to harbor bacteria and cause microtrauma to the skin. In this case report, we describe a case of impetigo and cellulitis due to Streptococcus pyogenes complicated by secondary spread through loofah sponge use. The same organism was cultured from the infected body sites and loofah sponge, and a comparative genomic analysis confirmed that the isolates were identical.

Development and Evaluation of a Molecular Hepatitis A Virus Assay for Serum and Stool Specimens.

Hepatitis A virus (HAV) is an emerging public health concern and there is an urgent need for ways to rapidly identify cases so that outbreaks can be managed effectively. Conventional testing for HAV relies on anti-HAV IgM seropositivity. However, studies estimate that 10-30% of patients may not be diagnosed by serology. Molecular assays that can directly detect viral nucleic acids have the potential to improve diagnosis, which is key to prevent the spread of infections. In this study, we developed a real-time PCR (RT-PCR) assay to detect HAV RNA for the identification of acute HAV infection. Primers were designed to target the conserved 5'-untranslated region (5'-UTR) of HAV, and the assay was optimized on both the Qiagen Rotor-Gene and the BD MAX. We successfully detected HAV from patient serum and stool samples with moderate differences in sensitivity and specificity depending on the platform used. Our results highlight the clinical utility of using a molecular assay to detect HAV from various specimen types that can be implemented in hospitals to assist with diagnostics, treatment and prevention.

Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B.

Safe and effective vaccines are needed to end the COVID-19 pandemic. Here, we report the preclinical development of a lipid nanoparticle­formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern, including the Alpha, Beta, Gamma, and Delta lineages. No adverse effects were induced by PTX-COVID19-B in either mice or hamsters. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 2 clinical trial ongoing.

Region of difference 2 contributes to virulence of Mycobacterium tuberculosis.

Mycobacterium bovis BCG strains are live, attenuated vaccines generated through decades of in vitro passage. Because in vitro growth does not select for interaction with the host, it has been hypothesized that genetic loci lost from BCG code for virulence determinants that are dispensable for growth in the laboratory, as exemplified by Region of Difference 1 (RD1), which was lost during the original derivation of BCG between 1908 and 1921. Region of Difference 2 (RD2) was lost during the ongoing propagation of BCG between 1927 and 1931, a time that coincides with reports of the ongoing attenuation of the vaccine. In this study, RD2 has been disrupted in M. tuberculosis H37Rv to test whether its loss contributed to the further attenuation of BCG. The deletion of RD2 did not affect in vitro growth; in contrast, the mutant manifested a decrease in pulmonary and splenic bacterial burdens and reduced pathology in C57BL/6 mice at early time points. This attenuated phenotype was complemented by reintroducing the genes Rv1979c to Rv1982 (including mpt64) but not Rv1985c to Rv1986. In RAW 264.7 macrophages, H37Rv:ΔRD2 showed a decreased proliferation and impaired modulation of the host innate immune response; both observations were complemented with Rv1979c to Rv1982. To test the effect of RD2 disruption on innate immunity, Rag(-/-) mice were infected; H37Rv:ΔRD2 had increased survival times compared those of H37Rv. These findings support the notion that the safety profile of certain BCG vaccines stems from multiple attenuating mutations, with the RD2 deletion resulting in a less-virulent organism through the impaired bacterial manipulation of the host innate immune response.

An exploratory assessment of the attitudes of Chinese wood products manufacturers towards forest certification.

Interviews with Chinese forest products manufacturers were conducted to explore their attitudes towards forest certification and related issues. Participants comprised owners, CEOs, and managers in 20 Chinese wood products companies, including producers of furniture, doors, flooring, and various engineered wood products. The interviews were used to analyze the extent to which participants were considering adopting forest certification and what might motivate such a decision. This was done by assessing their awareness and knowledge of certification. The results indicated that participants' understanding of forest certification was extremely low, despite major efforts in China to raise awareness of the issue. Potential economic benefits were the most frequently cited reason to adopt certification, including gaining or maintaining competitive advantage over their industry counterparts, improved access to both domestic and export markets, better customer recognition, and enhanced corporate responsibility practices. Some interviewees (3 out of 20) considered that certification would become a mandatory requirement or industry standard, and that this would be the only viable motivation for certification given that the financial benefits were potentially limited. According to the participants, the main differences between certified and uncertified wood products operations related to improved market access and public image. Interviewees felt that cooperation between and support from governments and the forest industry would enable the enhanced awareness of certification amongst manufacturers and the general public. This, in turn, could serve to stimulate demand for certified products.

Framing community forestry challenges with a broader lens: case studies from the Brazilian Amazon.

Community forestry initiatives have been shown to reduce rural poverty while promoting the conservation and sustainable use of forests. However, a number of challenges face communities wanting to initiate or maintain formal, community-based forest management. Through a grounded theory approach, this paper uses three case studies of community forest management models in the eastern Amazon to create a framework showing challenges faced by communities at different phases of formal management. The framework shows that, in the development phase, four root problems (land ownership, knowledge acquisition, community organization, and adequate capital) need to be addressed to obtain legal management permission. With this permission in hand, further challenges to operationalization are presented (deterring illegal loggers, maintaining infrastructure, obtaining necessary managerial skills and accessing markets). The interrelatedness of these challenges emphasizes that all challenges need to be addressed in a holistic manner for communities to maintain a profitable and self-sufficient operation. This contradicts current development approaches that only address part of this framework. The framework proposed here can be used as a starting point for community forestry initiatives in other regions.

One swab, two tests: Validation of dual SARS-CoV-2 testing on the Abbott ID NOW™.

BACKGROUND: Point-of-care tests (POCT) are promising tools to detect SARS-CoV-2 in specific settings. Initial reports suggest the ID NOW™ COVID-19 assay (Abbott Diagnostics Inc, USA) is less sensitive than standard real-time reverse transcription polymerase chain reaction (rRT-PCR) assays. This has raised concern over false negatives in SARS-CoV-2 POCT. OBJECTIVES: We compared the performance of the ID NOW™ COVID-19 assay to our in-house rRT-PCR assay to assess whether dry swabs used in ID NOW™ testing could be stored in transport media and be re-tested by rRT-PCR for redundancy and to provide material for further investigation. METHODS: Paired respiratory swabs collected from patients at three acute care hospitals were used. One swab in transport media (McMaster Molecular Media (MMM)) was tested for SARS-CoV-2 by a laboratory-developed two-target rRT-PCR assay. The second was stored dry in a sterile container and tested by the ID NOW™ COVID-19 assay. Following ID NOW™ testing, dry swabs were stored in MMM for up to 48 h and re-tested by rRT-PCR. Serially diluted SARS-CoV-2 particles were used to assess the impact of heat inactivation and storage time. RESULTS: Respiratory swabs (n = 343) from 179 individuals were included. Using rRT-PCR results as the comparator, the ID NOW™ COVID-19 assay had positive (PPA) and negative (NPA) percent agreements of 87.0% (95% CI:0.74-0.94) and 99.7% (95% CI:0.98-0.99). Re-tested swabs placed in MMM following ID NOW testing had PPA and NPA of 88.8% (95% CI:0.76-0.95) and 99.7% (95% CI:0.98-0.99), respectively. CONCLUSIONS: Storing spent dry swabs in transport media for redundancy rRT-PCR testing is a potential approach to address possible false negatives with the ID NOW™ COVID-19 assay.

Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial.

BACKGROUND: To date, only monoclonal antibodies have been shown to be effective for outpatients with COVID-19. Interferon lambda-1 is a type III interferon involved in innate antiviral responses with activity against respiratory pathogens. We aimed to investigate the safety and efficacy of peginterferon lambda in the treatment of outpatients with mild-to-moderate COVID-19. METHODS: In this double-blind, placebo-controlled trial, outpatients with laboratory-confirmed COVID-19 were randomly assigned to a single subcutaneous injection of peginterferon lambda 180 µg or placebo within 7 days of symptom onset or first positive swab if asymptomatic. Participants were randomly assigned (1:1) using a computer-generated randomisation list created with a randomisation schedule in blocks of four. At the time of administration, study nurses received a sealed opaque envelope with the treatment allocation number. The primary endpoint was the proportion of patients who were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on day 7 after the injection, analysed by a χ2 test following an intention-to-treat principle. Prespecified analysis of the primary endpoint, adjusted for baseline viral load, using bivariate logistic regression was done. The trial is now complete. This trial is registered with ClinicalTrials.gov, NCT04354259. FINDINGS: Between May 18, and Sept 4, 2020, we recruited 30 patients per group. The decline in SARS-CoV-2 RNA was greater in those treated with peginterferon lambda than placebo from day 3 onwards, with a difference of 2·42 log copies per mL at day 7 (p=0·0041). By day 7, 24 (80%) participants in the peginterferon lambda group had an undetectable viral load, compared with 19 (63%) in the placebo group (p=0·15). After controlling for baseline viral load, patients in the peginterferon lambda group were more likely to have undetectable virus by day 7 than were those in the placebo group (odds ratio [OR] 4·12 [95% CI 1·15-16·73; p=0·029). Of those with baseline viral load above 106 copies per mL, 15 (79%) of 19 patients in the peginterferon lambda group had undetectable virus on day 7, compared with six (38%) of 16 in the placebo group (OR 6·25 [95% CI 1·49-31·06]; p=0·012). Peginterferon lambda was well tolerated, and adverse events were similar between groups with mild and transient aminotransferase, concentration increases more frequently observed in the peginterferon lambda group. Two individuals met the threshold of grade 3 increase, one in each group, and no other grade 3 or 4 laboratory adverse events were reported. INTERPRETATION: Peginterferon lambda accelerated viral decline in outpatients with COVID-19, increasing the proportion of patients with viral clearance by day 7, particularly in those with high baseline viral load. Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding. FUNDING: The Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.