Risk factors for COVID-19 hospitalization or death during the first Omicron surge in adults: a large population-based case-control study (preprint)

Background: Description of risk factors of severe acute COVID-19 outcomes with the consideration of vaccination status in the era of the Omicron variant of concern are limited. Objectives: To examine the association of age, sex, underlying medical conditions, and COVID-19 vaccination with hospitalization, intensive-care unit (ICU) admission, or death due to the disease, using data from a period when Omicron was the dominant strain. Methods: A population-based case-control study based on administrative health data, that included confirmed COVID-19 patients during January (2022) in Alberta, Canada. Patients who were non-residents, without the provincial healthcare insurance coverage, or <=18 years of age were excluded. Patients with any severe outcome were the cases; and those without any hospitalization, ICU admission, or death were controls. Adjusted odds ratios, of the explanatory factors of a severe outcome, were estimated using a logistic regression model. Results: There were 90,989 COVID-19 patients included in the analysis; 2% had severe outcomes and 98% were included in the control group. Overall, more COVID patients were found in the younger age-groups (72.0% <=49 years old), females (56.5%), with no underlying conditions (59.5%), and fully vaccinated patients (90.4%). However, the adjusted odds ratios were highest in the 70-79 age group (28.32; 95% CI 20.6-38.9) or among >=80 years old (29.8; 21.6-41.0), males (1.4; 1.3-1.6); unvaccinated (16.1; 13.8-18.8), or patients with >=3 underlying conditions (13.1; 10.9-15.8). Conclusion: Higher risk of severe acute COVID-19 outcomes were associated with older age, the male sex, and increased number of underlying medical conditions. Unvaccination or undervaccination remained as the greatest modifiable risk factor in prevention of severe COVID outcomes. These findings help inform medical decisions and allocation of scarce healthcare resources.

LESSONS FROM THE COVID-19 THIRD WAVE IN CANADA: THE IMPACT OF VARIANTS OF CONCERN AND SHIFTING DEMOGRAPHICS (preprint)

ImportanceWith the emergence of more transmissible SARS-CoV-2 variants of concern (VOC), there is an urgent need for evidence about disease severity and the health care impacts of VOC in North America, particularly since a substantial proportion of the population have declined vaccination thus far. ObjectiveTo examine 30-day outcomes in Canadians infected with SARS-CoV-2 in the first year of the pandemic and to compare event rates in those with VOC versus wild-type infection. DesignRetrospective cohort study using linked healthcare administrative datasets. SettingAlberta and Ontario, the two Canadian provinces that experienced the largest third wave in the spring of 2021. ParticipantsAll individuals with a positive SARS-CoV-2 reverse transcriptase polymerase chain reaction swab from March 1, 2020 until March 31, 2021, with genomic confirmation of VOC screen-positive tests during February and March 2021 (wave 3). Exposure of InterestVOC versus wild type SARS-CoV-2 Main Outcomes and MeasuresAll-cause hospitalizations or death within 30 days after a positive SARS-CoV-2 swab. ResultsCompared to the 372,741 individuals with SARS-CoV-2 infection between March 2020 and January 2021 (waves 1 and 2 in Canada), there was a shift in transmission towards younger patients in the 104,232 COVID-19 cases identified in wave 3. As a result, although third wave patients were more likely to be hospitalized (aOR 1.34 [1.29-1.39] in Ontario and aOR 1.53 [95%CI 1.41-1.65] in Alberta), they had shorter lengths of stay (median 5 vs. 7 days, p<0.001) and were less likely to die within 30 days (aOR 0.66 [0.60-0.71] in Ontario and aOR 0.74 [0.62-0.89] in Alberta). However, within the third wave, patients infected with VOC (91% Alpha) exhibited higher risks of death (aOR 1.52 [1.27-1.81] in Ontario and aOR 1.67 [1.13-2.48] in Alberta) and hospitalization (aOR 1.57 [1.47-1.69] in Ontario and aOR 1.88 [1.74-2.02] in Alberta) than those with wild-type SARS-CoV-2 infections during the same timeframe. Conclusions and RelevanceOn a population basis, the shift towards younger age groups as the COVID-19 pandemic has evolved translates into more hospitalizations but shorter lengths of stay and lower mortality risk than seen in the first 10 months of the pandemic in Canada. However, on an individual basis, infection with a VOC is associated with a higher risk of hospitalization or death than the original wild-type SARS-CoV-2 - this is important information to address vaccine hesitancy given the increasing frequency of VOC infections now.

Transmissibility of COVID-19 among Vaccinated Individuals: A Rapid Literature Review (preprint)

Objectives: This is an update of a previous report that examined literature published up to March 11th, 2021. Sixteen additional studies have been included in this update. The objective of this report is to identify comparative observational studies and randomized controlled trials (RCTs) evaluating the efficacy and effectiveness of COVID-19 vaccination in reducing forward transmission from vaccinated people, and studies examining the biological plausibility of vaccination-induced transmission reduction. Method: A search of databases, MEDLINE, Embase, L-OVE and the Cochrane Central Register of Controlled Trials was conducted to identify RCTs or comparative observational studies evaluating the efficacy and effectiveness of COVID-19 vaccination in the prevention of transmission, asymptomatic infections and transmissibility of COVID-19 among vaccinated persons. An additional search of grey literature was conducted. This search is current to May 4th, 2021. Results: In this update, 16 additional studies, including 9 human and 7 animal studies, were included. Therefore, this review examines a total of 33 included studies: 21 human studies and 12 preclinical animal studies. Evidence from two large household surveillance studies from the UK suggests that a single or full dose of AstraZeneca (AZ) and Pfizer-BioNtech (PfBnT) vaccines may prevent household transmission of COVID-19 after 14 days of vaccination by up to 54%. The AZ vaccine trials in the general population suggest that an initial low dose followed by a standard dose may provide up to 59% protection against asymptomatic or unknown infection, although efficacy against these outcomes was not demonstrated following two standard doses. PfBnT vaccine observational studies in the general population suggest up to 90% effectiveness against asymptomatic infection after seven or more days of full dose vaccination. Up to 75% effectiveness against asymptomatic infection was reported after full-dose in healthcare workers. Across RCTs examining asymptomatic infection in the general population, one dose of Moderna was shown to provide an efficacy of 61.4% against asymptomatic infection 21 days after the first dose; in another trial, the J&J vaccine had an efficacy of 74% 28 days after the first dose. Lastly, seven of eight studies found significantly increased cycle threshold, suggestive of lower viral load, in PfBnT or AZ vaccinated individuals compared with those who were unvaccinated. Conclusion: The AZ and PfBnT vaccines may prevent household transmission of COVID-19 after 14 days of vaccination. More studies have found the vaccines to significantly reduce the risk of asymptomatic infection and significantly increase cycle threshold, suggestive of lower viral load. Further research is needed to evaluate post-vaccination infectivity and transmission of both the wild type COVID-19 virus and the variants of concern from other jurisdictions.

Public Health and Health Systems Impacts of SARS-CoV-2 Variants of Concern: A Rapid Scoping Review (preprint)

BackgroundAs of April 2021, three SARS-CoV-2 variants of concern (VOC: B.1.1.7, B.1.351 and P.1) have been detected in over 132 countries. Increased transmissibility of VOC has implications for public health measures and health system arrangements. This rapid scoping review aims to provide a synthesis of current evidence related to public health measures and health system arrangements associated with VOC. MethodsRapid scoping review. Seven databases were searched up to April 7, 2021 for terms related to VOC, transmission, public health and health systems. A grey literature search was conducted up to April 14, 2021. Title, abstracts and full text were screened independently by two reviewers. Data were double extracted using a standardized form. Studies were included if they reported on at least one of the VOC and public health or health system outcomes. ResultsOf the 2487 articles and 59 grey literature sources retrieved, 37 studies and 21 guidance documents were included. Included studies used a wide range of designs and methods. Most of the studies and guidance documents reported on B.1.1.7, and 18 studies and 4 reports provided data for consideration in relation to public health measures. Public health measures, including lockdowns, physical distancing, testing and contact tracing, were identified as critical adjuncts to a comprehensive vaccination campaign. No studies reported on handwashing or masking procedures related to VOC. For health system arrangements, 17 studies were identified. Some studies found an increase in hospitalization due to B.1.1.7 but no difference in length of stay or ICU admission. Six studies found an increased risk of death ranging from 15-67% with B.1.1.7 compared non-B.1.1.7, but three studies reported no change. One study reported on the effectiveness of personal protective equipment in reducing VOC transmission in the hospital. No studies reported on screening staff and visitors, adjusting service provisions, or adjusting patient accommodations and shared spaces, which is a significant gap in the literature. Guidance documents did not tend to cite any evidence and were thus assumed to be based on expert opinion. ConclusionWhile the findings should be interpreted with caution as most of the sources identified were preprints, findings suggest a combination of non-pharmaceutical interventions (e.g., masking, physical distancing, lockdowns, testing) should be employed alongside a vaccine strategy to improve population and health system outcomes. While the findings are mixed on the impact of VOC on health system arrangements, the evidence is trending towards increased hospitalization and death.

Treatment of Moderate to Severe Respiratory COVID-19--A Cost-Utility Analysis (preprint)

Background: Due to COVID-19's significant morbidity and mortality, identifying the most cost-effective pharmacologic treatment strategy is critical. As such, we determined the most cost-effective strategy for moderate to severe COVID-19 respiratory infections using the United States health care system as a representative model. Methods: A decision analytic model modelled a base case scenario of a 60-year-old patient admitted to hospital with COVID-19. Patients requiring oxygen were considered moderate severity, and patients with severe COVID-19 required intubation with intensive care. Strategies modelled included giving remdesivir to all patients, remdesivir in severe infections, remdesivir in moderate infections, dexamethasone to all patients, dexamethasone in severe infections, remdesivir in moderate/dexamethasone in severe infections, and best supportive care. Data for the model came from the published literature. The time horizon was 28 days; no discounting was performed due to the short duration. The perspective was of the payer in the United States health care system. Results: Supportive care for moderate/severe COVID-19 cost $11,112.98/0.8256 QALY. Remdesivir in moderate/dexamethasone in severe infections was the most cost-effective with an incremental cost-effectiveness ratio of $19,764.56/QALY gained compared to supportive care. Probabilistic sensitivity analyses showed remdesivir for moderate/dexamethasone for severe COVID-19 infection was most cost-effective in 88.6% of scenarios and dexamethasone in moderate-severe infections in 11.4% of scenarios. With lower willingness to pay thresholds ($250-$37,500), dexamethasone for severe infections was favoured. Conclusions: Remdesivir for moderate/dexamethasone for severe COVID-19 infections was the most cost-effective strategy. Further data is required for remdesivir to better assess its cost effectiveness in treatment of COVID-19.