IMPORTANCE The coronavirus disease 2019 (COVID-19) pandemic has been particularly severe among individuals residing in long-term care (LTC) facilities. As of April 10, 2020, half of Canada's COVID-19 deaths had occurred in LTC facilities. OBJECTIVE To better understand trends and risk factors associated with COVID-19 death in LTC facilities in Ontario, Canada. DESIGN, SETTING, AND PARTICIPANTS This cohort study of 627 LTC facilities included 269 total individuals who died of COVID-19 in Ontario to April 11, 2020, and 83 individuals who died of COVID-19 in Ontario LTC facilities to April 7, 2020. Because population denominators were not available for LTC residents, they were approximated as the total number of LTC facility beds in Ontario (79 498), assuming complete occupancy. EXPOSURES Confirmed or suspected COVID-19 outbreaks; confirmed COVID-19 infection among residents and staff, diagnosed by real-time polymerase chain reaction testing. MAIN OUTCOMES AND MEASURES COVID-19-specific mortality incidence rate ratios (IRRs) for LTC residents were calculated with community-living Ontarians older than 69 years as the comparator group. Count-based regression methods were used to model temporal trends and to identify associations of infection risk among staff and residents with subsequent LTC resident death. Model-derived IRRs for COVID-19-specific mortality were generated through bootstrap resampling (1000 replicates) to generate median and 95% credible intervals for IRR over time. RESULTS Of 627 LTC facilities, 272 (43.4%) reported COVID-19 infection in residents or staff. Of 1 731 315 total individuals older than 69 years living in Ontario during the study period, 229 (<0.1%) died; of 79 498 potential residents in LTC facilities, 83 (0.1%) died. The IRR for COVID-19-related death in LTC residents was 13.1 (95% CI, 9.9-17.3) compared with community-living adults older than 69 years. The IRR increased sharply over time and was 87.3 (95% credible interval, 6.4-769.8) by April 11, 2020. Infection among LTC staff was associated with death among residents with a 6-day lag (eg, adjusted IRR for death per infected staff member, 1.17; 95% CI, 1.11-1.26). CONCLUSIONS AND RELEVANCE In this cohort study of COVID-19-related deaths during the pandemic in Ontario, Canada, mortality risk was concentrated in LTC residents and increased during a short period. Early identification of risk requires a focus on testing, providing personal protective equipment to staff, and restructuring the LTC workforce to prevent the movement of COVID-19 between facilities.

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. MethodsIn 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 computergenerated 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.

Widely available and easily accessible testing for COVID-19 is a cornerstone of pandemic containment strategies. Nasopharyngeal swabs (NPS) are the currently accepted standard for sample collection but are limited by their need for collection devices and sampling by trained healthcare professionals. The aim of this study was to compare the performance of saliva to NPS in an outpatient setting. This was a prospective study conducted at three centers, which compared the performance of saliva and NPS samples collected at the time of assessment center visit. Samples were tested by real-time reverse transcription polymerase chain reaction and sensitivity and overall agreement determined between saliva and NPS. Clinical data was abstracted by chart review for select study participants. Of the 432 paired samples, 46 were positive for SARS-CoV-2, with seven discordant observed between the two sample types (four individuals testing positive only by NPS and three by saliva only). The observed agreement was 98.4% (kappa coefficient 0.91) and a composite reference standard demonstrated sensitivity of 0.91 and 0.93 for saliva and NPS samples, respectively. On average, the Ct values obtained from saliva as compared to NPS were higher by 2.76. This study demonstrates that saliva performs comparably to NPS for the detection of SARS-CoV-2. Saliva was simple to collect, did not require transport media, and could be tested with equipment readily available at most laboratories. The use of saliva as an acceptable alternative to NPS could support the use of widespread surveillance testing for SARS-CoV-2.

Background: Widespread testing for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) is necessary to curb the spread of coronavirus disease 2019 (COVID-19), but testing is undermined when the only option is a nasopharyngeal swab. Self-collected swab techniques can overcome many of the disadvantages of a nasopharyngeal swab, but they require evaluation. Methods: Three self-collected non-nasopharyngeal swab techniques (saline gargle, oral swab and combined oral-anterior nasal swab) were compared to a nasopharyngeal swab for SARS-CoV-2 detection at multiple COVID-19 assessment centers in Toronto, Canada. The performance characteristics of each test were assessed. Results: The adjusted sensitivity of the saline gargle was 0.90 (95% CI 0.86-0.94), the oral swab was 0.82 (95% CI, 0.72–0.89) and the combined oral–anterior nasal swab was 0.87 (95% CI, 0.77–0.93) compared to a nasopharyngeal swab, which demonstrated a sensitivity of ˜90% when all positive tests were the reference standard. The median cycle threshold values for the SARS-CoV-2 E-gene for concordant and discordant saline gargle specimens were 17 and 31 (P < .001), for the oral swabs these values were 17 and 28 (P < .001), and for oral–anterior nasal swabs these values were 18 and 31 (P = .007). Conclusions: Self-collected saline gargle and an oral–anterior nasal swab have a similar sensitivity to a nasopharyngeal swab for the detection of SARS-CoV-2. These alternative collection techniques are cheap and can eliminate barriers to testing, particularly in underserved populations.