The WE SENSE study protocol: A controlled, longitudinal clinical trial on the use of wearable sensors for early detection and tracking of viral respiratory tract infections

Background Viral respiratory tract infections (VRTI) are extremely common. Considering the profound social and economic impact of COVID-19, it is imperative to identify novel mechanisms for early detection and prevention of VRTIs, to prevent future pandemics. Wearable biosensor technology may facilitate this. Early asymptomatic detection of VRTIs could reduce stress on the healthcare system by reducing transmission and decreasing the overall number of cases. The aim of the current study is to define a sensitive set of physiological and immunological signature patterns of VRTI through machine learning (ML) to analyze physiological data collected continuously using wearable vital signs sensors. Methods A controlled, prospective longitudinal study with an induced low grade viral challenge, coupled with 12 days of continuous wearable biosensors monitoring surrounding viral induction. We aim to recruit and simulate a low grade VRTI in 60 healthy adults aged 18–59 years via administration of live attenuated influenza vaccine (LAIV). Continuous monitoring with wearable biosensors will include 7 days pre (baseline) and 5 days post LAIV administration, during which vital signs and activity-monitoring biosensors (embedded in a shirt, wristwatch and ring) will continuously monitor physiological and activity parameters. Novel infection detection techniques will be developed based on inflammatory biomarker mapping, PCR testing, and app-based VRTI symptom tracking. Subtle patterns of change will be assessed via ML algorithms developed to analyze large datasets and generate a predictive algorithm. Conclusion This study presents an infrastructure to test wearables for the detection of asymptomatic VRTI using multimodal biosensors, based on immune host response signature. CliniclTrials.govregistration:NCT05290792

Importance of occupation for SARS-CoV-2 seroprevalence and COVID-19 vaccination among correctional workers in Quebec, Canada: A cross-sectional study.

Background: Correctional workers are at increased risk of SARS-CoV-2 infection. We examined the seroprevalence of SARS-CoV-2, determined the effects of carceral and occupational exposures on seropositivity, and explored predictors of COVID-19 vaccine uptake among correctional workers in Quebec, Canada. Methods: We conducted a cross-sectional seroprevalence study in three provincial prisons. The primary and secondary outcomes were SARS-CoV-2 antibody seropositivity (Roche Elecsys® serology test) and self-reported COVID-19 vaccination status ("fully vaccinated" defined as two doses or prior infection plus one dose), respectively. Poisson regression models with robust standard error were used to examine the effect of occupational variables with SARS-CoV-2 seropositivity and predictors of COVID-19 vaccine uptake. Estimates are presented as crude and adjusted prevalence ratios (aPR) with 95% confidence intervals (95% CI). Results: From 14 July to 15 November 2021, 105/600 (18%) correctional workers tested positive across three prisons (range 11-21%); 76% were fully vaccinated. Seropositivity was affected by prison occupation (aPR 1.59, 95% CI 1.11-2.27 for correctional officers vs. all other occupations) and low perceived concern of SARS-CoV-2 acquisition (aPR 1.62, 95% CI 1.11-2.38 for not/hardly worried vs. somewhat/extremely worried). Predictors of being fully vaccinated included race/ethnicity (aPR 0.86, 95% CI 0.76-0.99 for visible minority vs. White), presence of comorbidities (aPR 1.14, 95% CI 1.02-1.28 for > 2 vs. none), and prison occupation (aPR 0.82, 95% CI 0.73-0.92 for correctional officers vs. all other occupations). Conclusions: Correctional officers were most likely to have acquired SARS-CoV-2, but least likely to be vaccinated, underscoring the importance of addressing both occupational risks and COVID-19 vaccine hesitancy to mitigate future outbreaks.

Global SARS-CoV-2 seroprevalence from January 2020 to April 2022: A systematic review and meta-analysis of standardized population-based studies.

BACKGROUND: Our understanding of the global scale of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains incomplete: Routine surveillance data underestimate infection and cannot infer on population immunity; there is a predominance of asymptomatic infections, and uneven access to diagnostics. We meta-analyzed SARS-CoV-2 seroprevalence studies, standardized to those described in the World Health Organization's Unity protocol (WHO Unity) for general population seroepidemiological studies, to estimate the extent of population infection and seropositivity to the virus 2 years into the pandemic. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis, searching MEDLINE, Embase, Web of Science, preprints, and grey literature for SARS-CoV-2 seroprevalence published between January 1, 2020 and May 20, 2022. The review protocol is registered with PROSPERO (CRD42020183634). We included general population cross-sectional and cohort studies meeting an assay quality threshold (90% sensitivity, 97% specificity; exceptions for humanitarian settings). We excluded studies with an unclear or closed population sample frame. Eligible studies-those aligned with the WHO Unity protocol-were extracted and critically appraised in duplicate, with risk of bias evaluated using a modified Joanna Briggs Institute checklist. We meta-analyzed seroprevalence by country and month, pooling to estimate regional and global seroprevalence over time; compared seroprevalence from infection to confirmed cases to estimate underascertainment; meta-analyzed differences in seroprevalence between demographic subgroups such as age and sex; and identified national factors associated with seroprevalence using meta-regression. We identified 513 full texts reporting 965 distinct seroprevalence studies (41% low- and middle-income countries [LMICs]) sampling 5,346,069 participants between January 2020 and April 2022, including 459 low/moderate risk of bias studies with national/subnational scope in further analysis. By September 2021, global SARS-CoV-2 seroprevalence from infection or vaccination was 59.2%, 95% CI [56.1% to 62.2%]. Overall seroprevalence rose steeply in 2021 due to infection in some regions (e.g., 26.6% [24.6 to 28.8] to 86.7% [84.6% to 88.5%] in Africa in December 2021) and vaccination and infection in others (e.g., 9.6% [8.3% to 11.0%] in June 2020 to 95.9% [92.6% to 97.8%] in December 2021, in European high-income countries [HICs]). After the emergence of Omicron in March 2022, infection-induced seroprevalence rose to 47.9% [41.0% to 54.9%] in Europe HIC and 33.7% [31.6% to 36.0%] in Americas HIC. In 2021 Quarter Three (July to September), median seroprevalence to cumulative incidence ratios ranged from around 2:1 in the Americas and Europe HICs to over 100:1 in Africa (LMICs). Children 0 to 9 years and adults 60+ were at lower risk of seropositivity than adults 20 to 29 (p < 0.001 and p = 0.005, respectively). In a multivariable model using prevaccination data, stringent public health and social measures were associated with lower seroprevalence (p = 0.02). The main limitations of our methodology include that some estimates were driven by certain countries or populations being overrepresented. CONCLUSIONS: In this study, we observed that global seroprevalence has risen considerably over time and with regional variation; however, over one-third of the global population are seronegative to the SARS-CoV-2 virus. Our estimates of infections based on seroprevalence far exceed reported Coronavirus Disease 2019 (COVID-19) cases. Quality and standardized seroprevalence studies are essential to inform COVID-19 response, particularly in resource-limited regions.

Durability and cross-reactivity of immune responses induced by a plant-based virus-like particle vaccine for COVID-19.

As the SARS-CoV-2 pandemic evolves, vaccine evaluation needs to include consideration of both durability and cross-reactivity. This report expands on previously reported results from a Phase 1 trial of an AS03-adjuvanted, plant-based coronavirus-like particle (CoVLP) displaying the spike (S) glycoprotein of the ancestral SARS-CoV-2 virus in healthy adults (NCT04450004). Humoral and cellular responses against the ancestral strain were evaluated 6 months post-second dose (D201) as secondary outcomes. Independent of dose, all vaccinated individuals retain binding antibodies, and ~95% retain neutralizing antibodies (NAb). Interferon gamma and interleukin-4 responses remain detectable in ~94% and ~92% of vaccinees respectively. In post-hoc analyses, variant-specific (Alpha, Beta, Delta, Gamma and Omicron) NAb were assessed at D42 and D201. Using a live virus neutralization assay, broad cross-reactivity is detectable against all variants at D42. At D201, cross-reactive antibodies are detectable in almost all participants against Alpha, Gamma and Delta variants (94%) and the Beta variant (83%) and in a smaller proportion against Omicron (44%). Results are similar with the pseudovirion assay. These data suggest that two doses of 3.75 µg CoVLP+AS03 elicit a durable and cross-reactive response that persists for at least 6 months post-vaccination.

Safety and immunogenicity of an AS03-adjuvanted plant-based SARS-CoV-2 vaccine in Adults with and without Comorbidities.

The rapid spread of SARS-CoV-2 continues to impact humanity on a global scale with rising total morbidity and mortality. Despite the development of several effective vaccines, new products are needed to supply ongoing demand and to fight variants. We report herein a pre-specified interim analysis of the phase 2 portion of a Phase 2/3, randomized, placebo-controlled trial of a coronavirus virus-like particle (CoVLP) vaccine candidate, produced in plants that displays the SARS-CoV-2 spike glycoprotein, adjuvanted with AS03 (NCT04636697). A total of 753 participants were recruited between 25th November 2020 and 24th March 2021 into three groups: Healthy Adults (18-64 years: N = 306), Older Adults (≥65 years: N = 282) and Adults with Comorbidities (≥18 years: N = 165) and randomized 5:1 to receive two intramuscular doses of either vaccine (3.75 µg CoVLP/dose+AS03) or placebo, 21 days apart. This report presents safety, tolerability and immunogenicity data up to 6 months post-vaccination. The immune outcomes presented include neutralizing antibody (NAb) titres as measured by pseudovirion assay at days 21 and 42 as well as neutralizing antibody cross-reactivity to several variants of concern (VOCs): Alpha, Beta, Gamma, Delta, and Omicron (BA.1), up to 201 days post-immunization. Cellular (IFN-γ and IL-4 ELISpot) response data in day 21 and 42 peripheral blood are also presented. In this study, CoVLP+AS03 was well-tolerated and adverse events (AE) after each dose were generally mild to moderate and transient. Solicited AEs in Older Adults and Adults with Comorbidities were generally less frequent than in Healthy Adults and the reactogenicity was higher after the second dose. CoVLP+AS03 induced seroconversion in >35% of participants in each group after the first dose and in ~98% of participants, 21 days after the second dose. In all cohorts, 21-days after the second dose, NAb levels in sera against the vaccine strain were ~10-times those in a panel of convalescent sera. Cross-reactivity to Alpha, Beta and Delta variants was generally retained to day 201 (>80%) while cross-reactivity to the Gamma variant was reduced but still substantial at day 201 (73%). Cross-reactivity to the Omicron variant fell from 72% at day 42 to 20% at day 201. Almost all participants in all groups (>88%) had detectable cellular responses (IFN-γ, IL-4 or both) at 21 days after the second dose. A Th1-biased response was most evident after the first dose and was still present after the second dose. These data demonstrated that CoVLP+AS03 is well-tolerated and highly immunogenic, generating a durable (at least 6 months) immune response against different VOCs, in adults ≥18 years of age, with and without comorbidities.

Symptomatology during previous SARS-CoV-2 infection and serostatus before vaccination influence the immunogenicity of BNT162b2 COVID-19 mRNA vaccine.

Public health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. This study presents detailed immunological evidence to clarify the requirements for one- or two-dose primary vaccination series for naturally primed individuals. The main objective was to evaluate the immune response to COVID-19 mRNA vaccination to establish the most appropriate vaccination regimen to induce robust immune responses in individuals with prior SARS-CoV-2 infection. The main outcome measure was a functional immunity score (zero to three) before and after vaccination, based on anti-RBD IgG levels, serum capacity to neutralize live virus and IFN-γ secretion capacity in response to SARS-CoV-2 peptide pools. One point was attributed for each of these three functional assays with response above the positivity threshold. The immunity score was compared based on subjects' symptoms at diagnosis and/or serostatus prior to vaccination. None of the naïve participants (n=14) showed a maximal immunity score of three following one dose of vaccine compared to 84% of the previously infected participants (n=55). All recovered individuals who did not have an immunity score of three were seronegative prior to vaccination, and 67% had not reported symptoms resulting from their initial infection. Following one dose of vaccine, their immune responses were comparable to naïve individuals, with significantly weaker responses than individuals who were symptomatic during infection. These results indicate that the absence of symptoms during initial infection and negative serostatus prior to vaccination predict the strength of immune responses to COVID-19 mRNA vaccine. Altogether, these findings highlight the importance of administering the complete two-dose primary regimen and following boosters of mRNA vaccines to individuals who experienced asymptomatic SARS-CoV-2 infection.

Cost-effectiveness of remdesivir plus usual care versus usual care alone for hospitalized patients with COVID-19: an economic evaluation as part of the Canadian Treatments for COVID-19 (CATCO) randomized clinical trial.

BACKGROUND: The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir. METHODS: Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Apr. 1, 2021, were randomly assigned to receive remdesivir plus usual care versus usual care alone. Taking a public health care payer's perspective, we collected in-hospital outcomes and health care resource utilization alongside estimated unit costs in 2020 Canadian dollars over a time horizon from randomization to hospital discharge or death. Data from 1281 adults admitted to 52 hospitals in 6 Canadian provinces were analyzed. RESULTS: The total mean cost per patient was $37 918 (standard deviation [SD] $42 413; 95% confidence interval [CI] $34 617 to $41 220) for patients randomly assigned to the remdesivir group and $38 026 (SD $46 021; 95% CI $34 480 to $41 573) for patients receiving usual care (incremental cost -$108 [95% CI -$4953 to $4737], p > 0.9). The difference in proportions of in-hospital deaths between remdesivir and usual care groups was -3.9% (18.7% v. 22.6%, 95% CI -8.3% to 1.0%, p = 0.09). The difference in proportions of incident invasive mechanical ventilation events between groups was -7.0% (8.0% v. 15.0%, 95% CI -10.6% to -3.4%, p = 0.006), whereas the difference in proportions of total mechanical ventilation events between groups was -5.7% (16.4% v. 22.1%, 95% CI -10.0% to -1.4%, p = 0.01). Remdesivir was the dominant intervention (but only marginally less costly, with mildly lower mortality) with an incalculable incremental cost effectiveness ratio; we report results of incremental costs and incremental effects separately. For willingness-to-pay thresholds of $0, $20 000, $50 000 and $100 000 per death averted, a strategy using remdesivir was cost-effective in 60%, 67%, 74% and 79% of simulations, respectively. The remdesivir costs were the fifth highest cost driver, offset by shorter lengths of stay and less mechanical ventilation. INTERPRETATION: From a health care payer perspective, treating patients hospitalized with COVID-19 with remdesivir and usual care appears to be preferrable to treating with usual care alone, albeit with marginal incremental cost and small clinical effects. The added cost of remdesivir was offset by shorter lengths of stay in the intensive care unit and less need for ventilation. STUDY REGISTRATION: ClinicalTrials. gov, no. NCT04330690.

More than a 'Hundred Days War': Persistent SARS-CoV-2 infection in a patient with ANCA-associated vasculitis.

BACKGROUND: Few reports exist on the characteristics and outcomes of persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in immunocompromised hosts. METHODS: A 49-year-old patient with granulomatosis with polyangiitis (GPA) and a renal transplant experienced multiple hospitalizations for coronavirus disease 2019 (COVID-19) pneumonia and relapses between October 2020 and February 2021. Careful chart review of medical history, hospitalizations, and microbiological testing including SARS-CoV-2 cycle threshold values, therapies, and imaging was undertaken. SARS-CoV-2 genome sequencing was performed in five viral samples to distinguish persistent infection from re-infection with a different strain. RESULTS: Sequencing confirmed that all samples tested were from the same viral lineage, indicating a long-term, persistent infection rather than re-infection with a new strain. The patient ultimately stabilized after two courses of remdesivir plus dexamethasone, replacement intravenous immunoglobulin, and bamlanivimab. Rituximab maintenance therapy for vasculitis remains on hold. CONCLUSIONS: SARS-CoV-2 may persist for several months in immunocompromised hosts and may go unrecognized as an ongoing active infection. More studies are needed to determine how to optimize COVID-19 treatment in this vulnerable population.

HISTORIQUE: Il existe peu de rapports sur les caractéristiques et les issues de l'infection par le coronavirus 2 du syndrome respiratoire aigu sévère (SRAS-CoV-2) chez les hôtes immunodéprimés. MÉTHODOLOGIE: UNE PATIENTE de 49 ans receveuse d'une transplantation rénale atteinte d'une granulomatose avec polyangéite a été hospitalisée à de multiples reprises à cause d'une pneumonie à maladie à coronavirus 2019 (COVID-19) et de récidives entre octobre 2020 et février 2021. Les chercheurs ont exécuté une analyse attentive du dossier pour connaître l'histoire médicale de la patiente, les hospitalisations et les tests microbiologiques effectués, y compris les valeurs seuils du cycle du SRAS-CoV-2, les traitements et les techniques d'imagerie. Ils ont procédé au séquençage du génome du SRAS-CoV-2 dans cinq prélèvements viraux pour distinguer l'infection persistante de la réinfection par une souche différente. RÉSULTATS : Le séquençage a confirmé que tous les prélèvements effectués provenaient de la même lignée virale, ce qui détermine une infection persistante prolongée plutôt qu'une réinfection par une nouvelle souche. L'état de la patiente a fini par se stabiliser après deux traitements au remdésivir combiné à de la dexaméthasone, une thérapie de substitution par immunoglobuline intraveineuse et du bamlanivimab. Un traitement d'entretien de la vasculite au rituximab demeure en suspens. CONCLUSIONS: Le SRAS-CoV-2 peut persister plusieurs mois chez les hôtes immunodéprimés, et un état d'infection active continue peut passer inaperçu. Plus d'études devront être réalisées pour déterminer le moyen d'optimiser le traitement de la COVID-19 dans cette population vulnérable.

Renin-Angiotensin System Pathway Therapeutics Associated With Improved Outcomes in Males Hospitalized With COVID-19.

OBJECTIVES: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components. DESIGN: Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup ( n = 46), recorded d -dimer ( n = 967), comparing males with females. SETTING: ARBs CORONA I is a multicenter Canadian observational cohort of patients hospitalized with acute COVID-19. This analysis includes patients admitted to 10 large urban hospitals across the four most populated provinces. PATIENTS: One-thousand six-hundred eighty-six patients with polymerase chain reaction-confirmed COVID-19 (February 2020 to March 2021) for acute COVID-19 illness were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Males on ARBs before admission had decreased use of ventilation (adjusted odds ratio [aOR] = 0.52; p = 0.007) and vasopressors (aOR = 0.55; p = 0.011) compared with males not on ARBs or ACE inhibitors. No significant effects were observed in females for these outcomes. The test for interaction was significant for use of ventilation ( p = 0.006) and vasopressors ( p = 0.044) indicating significantly different responses to ARBs according to sex. Males had significantly higher plasma ACE-1 at baseline and angiotensin II at day 7 and 14 than females. CONCLUSIONS: ARBs use was associated with less ventilation and vasopressors in males but not females. Sex-based differences in RAS dysregulation may contribute to sex-based differences in outcomes and responses to ARBs in COVID-19.

Short Communication: Ongoing Impact of the Social Determinants of Health During the Second and Third Waves of the COVID-19 Pandemic in People Living with HIV Receiving Care in a Montreal-Based Tertiary Care Center.

We performed retrospective chart reviews and described the clinical characteristics, exposure risks, and disease severity of people living with HIV (PLWH) attending the Chronic Viral Illness Service (CVIS) in Montreal, Canada, who developed coronavirus disease 2019 (COVID-19) during September 2020-August 2021, coinciding with the second and third waves of the pandemic. A total of 61 PLWH with a positive COVID-19 polymerase chain reaction were identified, giving a COVID-19 prevalence of 5%. The most common exposure risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during waves two and three was having a family member/close contact with COVID-19 (36%). Similar to what we observed during the first wave, PLWH who acquired COVID-19 during waves two and three of the pandemic often worked or lived in long-term care residences or health care settings, putting them at risk. Five people (8%) were asymptomatic. Nearly all persons had mild disease on initial presentation and most had a full recovery. Two individuals were admitted to hospital with COVID-19, whereas three individuals acquired COVID-19 nosocomially. No individuals died due to COVID-19. Two individuals developed symptoms associated with long COVID-19 syndrome. Findings highlight the ongoing impact of the social determinants of health during the second and third waves of the pandemic in PLWH.

Adequacy of Serial Self-performed SARS-CoV-2 Rapid Antigen Detection Testing for Longitudinal Mass Screening in the Workplace.

Importance: Longitudinal mass testing using rapid antigen detection tests (RADT) for serial screening of asymptomatic persons has been proposed for preventing SARS-CoV-2 community transmission. The feasibility of this strategy relies on accurate self-testing. Objective: To quantify the adequacy of serial self-performed SARS-CoV-2 RADT testing in the workplace, in terms of the frequency of correct execution of procedural steps and accurate interpretation of the range of possible RADT results. Design, Setting, and Participants: This prospective repeated cross-sectional study was performed from July to October 2021 at businesses with at least 2 active cases of SARS-CoV-2 infection in Montreal, Canada. Participants included untrained persons in their workplace, not meeting Public Health quarantine criteria (ie, required quarantine for 10 days after a moderate-risk contact with someone infected with SARS-CoV-2). Interpretation and performance were compared between participants who received instructions provided by the manufacturer vs those who received modified instructions that were informed by the most frequent or most critical errors we observed. Data were analyzed from October to November 2021. Exposures: RADT testing using a modified quick reference guide compared with the original manufacturer's instructions. Main Outcomes and Measures: The main outcome was the difference in correctly interpreted RADT results. Secondary outcomes included difference in proportions of correctly performed procedural steps. Additional analyses, assessed among participants with 2 self-testing visits, compared the second self-test visit with the first self-test visit using the same measures. Results: Overall, 1892 tests were performed among 647 participants, of whom 278 participants (median [IQR] age, 43 [31-55] years; 156 [56.1%] men) had at least 1 self-testing visit. For self-test visit 1, significantly better accuracy in test interpretation was observed among participants using the modified quick reference guide than those using the manufacturer's instructions for reading results that were weak positive (64 of 115 participants [55.6%] vs 20 of 163 participants [12.3%]; difference, 43.3 [95% CI, 33.0-53.8] percentage points), positive (103 of 115 participants [89.6%] vs 84 of 163 participants [51.5%]; difference, 38.1 [95% CI, 28.5-47.5] percentage points), strong positive (219 of 229 participants [95.6%] vs 274 of 326 participants [84.0%]; difference, 11.6 [95% CI, 6.8-16.3] percentage points), and invalid (200 of 229 participants [87.3%] vs 252 of 326 participants [77.3%]; difference, 10.0 [95% CI, 3.8-16.3] percentage points). Use of the modified guide was associated with improvements on self-test visit 2 for results that were weak positive (difference, 15.4 [95% CI, 0.7-30.1] percentage points), positive (difference, 19.0 [95% CI, 7.2-30.9] percentage points), and invalid (difference, 8.0 [95% CI, 0.8-15.4] percentage points). For procedural steps identified as critical for test validity, adherence to procedural testing steps did not differ meaningfully according to instructions provided or reader experience. Conclusions and Relevance: In this cross-sectional study of self-performed SARS-CoV-2 RADT in an intended-use setting, a modified quick reference guide was associated with significantly improved accuracy in RADT interpretations.

The REinfection in COVID-19 Estimation of Risk (RECOVER) study: Reinfection and serology dynamics in a cohort of Canadian healthcare workers.

BACKGROUND: Understanding the immune response to natural infection by SARS-CoV-2 is key to pandemic management, especially in the current context of emerging variants. Uncertainty remains regarding the efficacy and duration of natural immunity against reinfection. METHODS: We conducted an observational prospective cohort study in Canadian healthcare workers (HCWs) with a history of PCR-confirmed SARS-CoV-2 infection to (i) measure the average incidence rate of reinfection and (ii) describe the serological immune response to the primary infection. RESULTS: Our cohort comprised 569 HCWs; median duration of individual follow-up was 371 days. We detected six cases of reinfection in absence of vaccination between August 21, 2020, and March 1, 2022, for a reinfection incidence rate of 4.0 per 100 person-years. Median duration of seropositivity was 415 days in symptomatics at primary infection compared with 213 days in asymptomatics (p < 0.0001). Other characteristics associated with prolonged seropositivity for IgG against the spike protein included age over 55 years, obesity, and non-Caucasian ethnicity. CONCLUSIONS: Among unvaccinated healthcare workers, reinfection with SARS-CoV-2 following a primary infection remained rare.

Seroprevalence and Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 Among Incarcerated Adult Men in Quebec, Canada, 2021.

BACKGROUND: People in prison are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We examined the seroprevalence of SARS-CoV-2 and associated carceral risk factors among incarcerated adult men in Quebec, Canada. METHODS: We conducted a cross-sectional seroprevalence study in 2021 across 3 provincial prisons, representing 45% of Quebec's incarcerated male provincial population. The primary outcome was SARS-CoV-2 antibody seropositivity (Roche Elecsys serology test). Participants completed self-administered questionnaires on sociodemographic, clinical, and carceral characteristics. The association of carceral variables with SARS-CoV-2 seropositivity was examined using Poisson regression models with robust standard errors. Crude and adjusted prevalence ratios (aPR) with 95% confidence intervals (95% CIs) were calculated. RESULTS: Between 19 January 2021 and 15 September 2021, 246 of 1100 (22%) recruited individuals tested positive across 3 prisons (range, 15%-27%). Seropositivity increased with time spent in prison since March 2020 (aPR, 2.17; 95% CI, 1.53-3.07 for "all" vs "little time"), employment during incarceration (aPR, 1.64; 95% CI, 1.28-2.11 vs not), shared meal consumption during incarceration ("with cellmates": aPR, 1.46; 95% CI, 1.08-1.97 vs "alone"; "with sector": aPR, 1.34; 95% CI, 1.03-1.74 vs "alone"), and incarceration post-prison outbreak (aPR, 2.32; 95% CI, 1.69-3.18 vs "pre-outbreak"). CONCLUSIONS: The seroprevalence of SARS-CoV-2 among incarcerated individuals was high and varied among prisons. Several carceral factors were associated with seropositivity, underscoring the importance of decarceration and occupational safety measures, individual meal consumption, and enhanced infection prevention and control measures including vaccination during incarceration.

Organ dysfunction and death in patients admitted to hospital with COVID-19 in pandemic waves 1 to 3 in British Columbia, Ontario and Quebec, Canada: a cohort study.

BACKGROUND: There have been multiple waves in the COVID-19 pandemic in many countries. We sought to compare mortality and respiratory, cardiovascular and renal dysfunction between waves in 3 Canadian provinces. METHODS: We conducted a substudy of the ARBs CORONA I study, a multicentre Canadian pragmatic observational cohort study that examined the association of pre-existing use of angiotensin receptor blockers with outcomes in adults admitted to hospital with acute COVID-19 up to April 2021 from 9 community and teaching hospitals in 3 Canadian provinces (British Columbia, Ontario and Quebec). We excluded emergency department admissions without hospital admission, readmissions and admissions for another reason. We used logistic and 0-1-inflated ß regression models to compare 28-day and in-hospital mortality, and the use of invasive mechanical ventilation, vasopressors and renal replacement therapy (RRT) between the first 3 waves of the COVID-19 pandemic in these provinces. RESULTS: A total of 520, 572 and 245 patients in waves 1, 2 and 3, respectively, were included. Patients in wave 3 were on average younger and had fewer comorbidities than those in waves 1 and 2. The unadjusted 28-day mortality rate was significantly lower in wave 3 (7.8%) than in wave 1 (18.3%) (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.24-0.78) and wave 2 (16.3%) (OR 0.46, 95% CI 0.27-0.79). After adjustment for differences in baseline characteristics, the difference in 28-day mortality remained significant (adjusted OR wave 3 v. wave 1: 0.46, 95% CI 0.26-0.81; wave 3 v. wave 2: 0.52, 95% CI 0.29-0.91). In-hospital mortality findings were similar. Use of invasive mechanical ventilation or vasopressors was less common in waves 2 and 3 than in wave 1, and use of RRT was less common in wave 3 than in wave 1. INTERPRETATION: Severity of illness decreased (lower mortality and less use of organ support) across waves among patients admitted to hospital with acute COVID-19, possibly owing to changes in patient demographic characteristics and management, such as increased use of dexamethasone. Continued application of proven therapies may further improve outcomes. STUDY REGISTRATION: ClinicalTrials.gov, no. NCT04510623.

Séroprévalence du SRAS-CoV-2 chez les travailleurs de la santé de 10 hôpitaux du Québec, au Canada: étude transversale.

CONTEXTE: La pandémie de COVID-19 a affecté de manière disproportionnée les travailleurs de la santé. Nous avons voulu mesurer la séroprévalence du SRAS-CoV-2 chez les travailleurs de la santé dans les hôpitaux du Québec, au Canada, après la première vague de la pandémie, afin d'explorer les facteurs associés à la SRAS-CoV-2-séropositivité. MÉTHODES: Entre le 6 juillet et le 24 septembre 2020, nous avons recruté des travailleurs de la santé de 10 hôpitaux, dont 8 d'une région où l'incidence de la COVID-19 était élevée (région de Montréal) et 2 de régions du Québec où l'incidence était faible. Les travailleurs de la santé admissibles étaient des médecins, des infirmières, des préposées aux bénéficiaires et des préposés à l'entretien ménager travaillant dans 4 types d'unité de soins (urgences, soins intensifs, unité hospitalière COVID-19 et unité hospitalière non-COVID-19). Les participants ont répondu à un questionnaire et subi un dépistage sérologique du SRAS-CoV-2. Nous avons identifié les facteurs ayant un lien indépendant avec une séroprévalence plus élevée. RÉSULTATS: Parmi les 2056 travailleurs de la santé recrutés, 241 (11,7 %) se sont révélés SRAS-CoV-2-positifs. Parmi eux, 171 (71,0 %) avaient déjà reçu un diagnostic de COVID-19. La séroprévalence a varié d'un hôpital à l'autre, de 2,4 %­3,7 % dans les régions où l'incidence était faible, à 17,9 %­32,0 % dans les hôpitaux ayant connu des éclosions touchant 5 travailleurs de la santé ou plus. La séroprévalence plus élevée a été associée au fait de travailler dans un hôpital où des éclosions sont survenues (rapport de prévalence ajusté 4,16, intervalle de confiance [IC] à 95 % 2,63­6,57), au fait d'être infirmière ou auxiliaire (rapport de prévalence ajusté 1,34, IC à 95 % 1,03­1,74), préposée aux bénéficiaires (rapport de prévalence ajusté 1,49, IC à 95 % 1,12­1,97) et d'ethnicité noire ou hispanique (rapport de prévalence ajusté 1,41, IC à 95 % 1,13­1,76). La séroprévalence moindre a été associée au fait de travailler dans une unité de soins intensifs (rapport de prévalence ajusté 0,47, IC à 95 % 0,30­0,71) ou aux urgences (rapport de prévalence ajusté 0,61, IC à 95 % 0,39­0,98). INTERPRÉTATION: Les travailleurs de la santé des hôpitaux du Québec ont été exposés à un risque élevé d'infection par le SRAS-CoV-2, particulièrement lors des éclosions. Il faudra travailler à mieux comprendre la dynamique de la transmission du SRAS-CoV-2 dans les milieux de soins.

Diagnostic Testing for Severe Acute Respiratory Syndrome-Related Coronavirus 2: A Narrative Review.

Diagnostic testing to identify persons infected with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection is central to control the global pandemic of COVID-19 that began in late 2019. In a few countries, the use of diagnostic testing on a massive scale has been a cornerstone of successful containment strategies. In contrast, the United States, hampered by limited testing capacity, has prioritized testing for specific groups of persons. Real-time reverse transcriptase polymerase chain reaction-based assays performed in a laboratory on respiratory specimens are the reference standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging. Although excellent tools exist for the diagnosis of symptomatic patients in well-equipped laboratories, important gaps remain in screening asymptomatic persons in the incubation phase, as well as in the accurate determination of live viral shedding during convalescence to inform decisions to end isolation. Many affluent countries have encountered challenges in test delivery and specimen collection that have inhibited rapid increases in testing capacity. These challenges may be even greater in low-resource settings. Urgent clinical and public health needs currently drive an unprecedented global effort to increase testing capacity for SARS-CoV-2 infection. Here, the authors review the current array of tests for SARS-CoV-2, highlight gaps in current diagnostic capacity, and propose potential solutions.

Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial.

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Longitudinal Plasma Proteomics Analysis Reveals Novel Candidate Biomarkers in Acute COVID-19.

The host response to COVID-19 pathophysiology over the first few days of infection remains largely unclear, especially the mechanisms in the blood compartment. We report on a longitudinal proteomic analysis of acute-phase COVID-19 patients, for which we used blood plasma, multiple reaction monitoring with internal standards, and data-independent acquisition. We measured samples on admission for 49 patients, of which 21 had additional samples on days 2, 4, 7, and 14 after admission. We also measured 30 externally obtained samples from healthy individuals for comparison at baseline. The 31 proteins differentiated in abundance between acute COVID-19 patients and healthy controls belonged to acute inflammatory response, complement activation, regulation of inflammatory response, and regulation of protein activation cascade. The longitudinal analysis showed distinct profiles revealing increased levels of multiple lipid-associated functions, a rapid decrease followed by recovery for complement activation, humoral immune response, and acute inflammatory response-related proteins, and level fluctuation in the regulation of smooth muscle cell proliferation, secretory mechanisms, and platelet degranulation. Three proteins were differentiated between survivors and nonsurvivors. Finally, increased levels of fructose-bisphosphate aldolase B were determined in patients with exposure to angiotensin receptor blockers versus decreased levels in those exposed to angiotensin-converting enzyme inhibitors. Data are available via ProteomeXchange PXD029437.

A randomized controlled trial of renin-angiotensin-aldosterone system inhibitor management in patients admitted in hospital with COVID-19.

BACKGROUND: Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection coronavirus disease 2019 (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes. METHODS: The RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]) and the intention-to-treat principle. RESULTS: Overall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); P = .60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 [95% CI 1.06-2.62]; P = .027); RAASi discontinuation increased brain natriuretic peptide levels (% change from baseline: +16.7% vs -27.5%; P = .024) and the incidence of acute heart failure (33% vs 4.2%, P = .016). CONCLUSION: RAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased brain natriuretic peptide levels and may increase risk of acute heart failure; where possible, RAASi should be continued.