Disrupted seasonality and association of COVID-19 with medically attended respiratory syncytial virus infections among young children in the US: January 2010-January 2023 (preprint)

Respiratory syncytial virus (RSV) infections and hospitalizations surged sharply in 2022 among young children. To assess whether COVID-19 contributed to this surge, we leveraged a real-time nation-wide US database of electronic health records (EHRs) using time series analysis from January 1, 2010 through January 31, 2023, and propensity-score matched cohort comparisons for children aged 0-5 years with or without prior COVID-19 infection. Seasonal patterns of medically attended RSV infections were significantly disrupted during the COVID-19 pandemic. The monthly incidence rate for first-time medically attended cases, most of which were severe RSV-associated diseases, reached a historical high rate of 2,182 cases per 1,0000,000 person-days in November 2022, corresponding to a related increase of 143% compared to expected peak rate (rate ratio: 2.43, 95% CI: 2.25-2.63). Among 228,940 children aged 0-5 years, the risk for first-time medically attended RSV during 10/2022-12/2022 was 6.40% for children with prior COVID-19 infection, higher than 4.30% for the matched children without COVID-19 (risk ratio or RR: 1.40, 95% CI: 1.27-1.55); and among 99,105 children aged 0-1 year, the overall risk was 7.90% for those with prior COVID-19 infection, higher than 5.64% for matched children without (RR: 1.40, 95% CI: 1.21-1.62). These data provide evidence that COVID-19 contributed to the 2022 surge of severe pediatric RSV cases.

Distinct profiles and kinetics of soluble infammatory markers in patients with acute and chronic HCV-infections and SARS-CoV-2-infections: Implications for the long-term consequences of viral infections?

Background and Aims Viral infections occur acutely but can also progress chronically, with the immune system having a central role in immunopathoge-nesis. The question arises whether all alterations in immune responses are reversible after viral elimination (spontaneously or by therapy). Therefore, the aim of this study is to compare soluble infammatory markers (SIM) during and after infection with SARS-CoV-2 and acute and chronic HCV-infections. Patients and Method Patients with acute HCV (n = 29), chronic HCV (n = 54), SARS-CoV-2 (n = 39) and 31 healthy-controls were included. Blood samples were tested at baseline, end of treatment/infection, and follow-up ( >= 9 months after baseline). IL-12p70, IL-1b, IL-4, IL-5, IL-6, IL-8, TNF, IFN-g, IL-10, IL-22, CXCL-10, MCP-1, MIP-1b, ITAC were quantified using the HD-SP-X Imaging and Analysis SystemTM. Results SIM profiles in patients with acute HCV were substantially elevated at baseline and the decrease during follow-up was considerably less compared to the SARS-CoV-2 cohort. In chronic HCV-patients, viral elimination by therapy resulted in a decrease in SIM, although not always to those of controls. Cirrhotic HCV patients had higher SIM levels after HCV elimination than non-cirrhotic chronic HCV-patients. In the SARS-CoV-2 cohort, most SIM returned to levels of controls 3 months after baseline. Conclusions SIM profiles and kinetics after viral elimination difer between blood-borne acute and chronic HCV- and respiratory SARS-CoV-2-infections. The immunologic imprint 9 months after cured HCV-infection (both acute and chronic) appears to be more pronounced than after SARS-CoV-2-infection. Further analysis is needed to correlate the SIM profle with the clinical pheno-type (long-HepC vs. long-COVID-19).

Association of COVID-19 with New-Onset Alzheimer's Disease.

An infectious etiology of Alzheimer's disease has been postulated for decades. It remains unknown whether SARS-CoV-2 viral infection is associated with increased risk for Alzheimer's disease. In this retrospective cohort study of 6,245,282 older adults (age ≥65 years) who had medical encounters between 2/2020-5/2021, we show that people with COVID-19 were at significantly increased risk for new diagnosis of Alzheimer's disease within 360 days after the initial COVID-19 diagnosis (hazard ratio or HR:1.69, 95% CI: 1.53-1.72), especially in people age ≥85 years and in women. Our findings call for research to understand the underlying mechanisms and for continuous surveillance of long-term impacts of COVID-19 on Alzheimer's disease.

Tobacco, Alcohol, Cannabis, and Other Drug Use in the US Before and During the Early Phase of the COVID-19 Pandemic.

Importance: Information about national substance use trends among youths and adults after mid-March 2020 is limited due to constraints on surveillance during the COVID-19 pandemic. Objective: To evaluate whether substance use prevalence in the early part of the pandemic (2020) differed from the prepandemic periods of 2018 to 2019 and 2016 to 2018. Design, Setting, and Participants: This cross-sectional study was a repeated analysis of 2016 to 2020 data from a nationally representative sample of youths and adults in the Population Assessment of Tobacco and Health (PATH) Study. Participants were representative of the US civilian noninstitutionalized population. Household residents age 13 years or older were interviewed in person from 2016 to 2019 and via telephone in 2020. Exposures: Age, calendar year. Main Outcomes and Measures: Past 30-day self-reported use of any tobacco, any alcohol, binge drinking, cannabis, and any other illegal or misused prescription drugs. Results: The overall nationally representative 2020 sample included 7129 youths (ages 13-17 years), 3628 young adults (ages 18-20 years), and 8874 adults (ages ≥21 years). Comparing 2018 to 2019 with 2020 among youths, prevalence of all substances used declined (eg, cannabis use declined in those aged 16-17 years from 14.9% to 7.6%; absolute difference, -7.3 percentage points [95% CI -8.8 to -5.8 percentage points]). Among young adults, prevalence of all substances other than any alcohol decreased significantly (eg, tobacco use declined from 37.8% to 22.8%; absolute difference, -15.1 percentage points [95% CI -16.8 to -13.3 percentage points]). In adults ages 21 to 24 years, any tobacco use declined from 39.0% to 30.9% (absolute difference, -8.2 percentage points [95% CI, -10.6 to -5.7 percentage points]), and alcohol use increased from 60.2% to 65.2% (absolute difference, 5.0 percentage points [95% CI, 2.3 to 7.7 percentage points]). Among adults aged 25 years or older, any tobacco use declined from 39.0% to 30.9% (absolute difference, -8.2 percentage points [95% CI, -10.6 to -5.7 percentage points]), cannabis use increased from 11.3% to 12.4% (absolute difference, 1.2 percentage points [95% CI, 0.3 to 2.0 percentage points]), and other substance use declined from 5.8% to 3.7% (absolute difference, -2.1 percentage points [95% CI, -2.9 to -1.4 percentage points]). Conclusions and Relevance: In this cross-sectional study, substance use decreased between 2019 and 2020 among those aged 13 to 20 years; consistent declines were not seen in older persons other than tobacco use reductions, and cannabis use increased among adults ages 25 years and older. While social changes during the COVID-19 pandemic could have affected substance use, findings should be interpreted with caution due to differences in data collection methods in 2016 to 2019 and 2020.

Trends and Characteristics of Buprenorphine-Involved Overdose Deaths Prior to and During the COVID-19 Pandemic.

Importance: Buprenorphine remains underused in treating opioid use disorder, despite its effectiveness. During the onset of the COVID-19 pandemic, the US government implemented prescribing flexibilities to support continued access. Objective: To determine whether buprenorphine-involved overdose deaths changed after implementing these policy changes and highlight characteristics and circumstances of these deaths. Design, Setting, and Participants: This cross-sectional study used data from the State Unintentional Drug Overdose Reporting System (SUDORS) to assess overdose deaths in 46 states and the District of Columbia occurring July 2019 to June 2021. Data were analyzed from March 7, 2022, to June 30, 2022. Main Outcomes and Measures: Buprenorphine-involved and other opioid-involved overdose deaths were examined. Monthly opioid-involved overdose deaths and the percentage involving buprenorphine were computed to assess trends. Proportions and exact 95% CIs of drug coinvolvement, demographics, and circumstances were calculated by group. Results: During July 2019 to June 2021, 32 jurisdictions reported 89 111 total overdose deaths and 74 474 opioid-involved overdose deaths, including 1955 buprenorphine-involved overdose deaths, accounting for 2.2% of all drug overdose deaths and 2.6% of opioid-involved overdose deaths. Median (IQR) age was similar for buprenorphine-involved overdose deaths (41 [34-55] years) and other opioid-involved overdose deaths (40 [31-52] years). A higher proportion of buprenorphine-involved overdose decedents, compared with other opioid-involved decedents, were female (36.1% [95% CI, 34.2%-38.2%] vs 29.1% [95% CI, 28.8%-29.4%]), non-Hispanic White (86.1% [95% CI, 84.6%-87.6%] vs 69.4% [95% CI, 69.1%-69.7%]), and residing in rural areas (20.8% [95% CI, 19.1%-22.5%] vs 11.4% [95% CI, 11.2%-11.7%]). Although monthly opioid-involved overdose deaths increased, the proportion involving buprenorphine fluctuated but did not increase during July 2019 to June 2021. Nearly all (92.7% [95% CI, 91.5%-93.7%]) buprenorphine-involved overdose deaths involved at least 1 other drug; higher proportions involved other prescription medications compared with other opioid-involved overdose deaths (eg, anticonvulsants: 18.6% [95% CI, 17.0%-20.3%] vs 5.4% [95% CI, 5.2%-5.5%]) and a lower proportion involved illicitly manufactured fentanyls (50.2% [95% CI, 48.1%-52.3%] vs 85.3% [95% CI, 85.1%-85.5%]). Buprenorphine decedents were more likely to be receiving mental health treatment than other opioid-involved overdose decedents (31.4% [95% CI, 29.3%-33.5%] vs 13.3% [95% CI, 13.1%-13.6%]). Conclusions and Relevance: The findings of this cross-sectional study suggest that actions to facilitate access to buprenorphine-based treatment for opioid use disorder during the COVID-19 pandemic were not associated with an increased proportion of overdose deaths involving buprenorphine. Efforts are needed to expand more equitable and culturally competent access to and provision of buprenorphine-based treatment.

Association of COVID-19 with endocarditis in patients with cocaine or opioid use disorders in the US.

The incidence of endocarditis in the US is increasing, driven in part by the rise in intravenous drug use, mostly opioids and stimulant drugs (cocaine and methamphetamine). Recent reports have documented that individuals with COVID-19 are at increased risk for cardiovascular diseases. However, it is unknown whether COVID-19 is associated with increased risk for endocarditis in patients with opioid or stimulant use disorders. This is a retrospective cohort study based on a nationwide database of electronic health records (EHRs) of 109 million patients in the US, including 736,502 patients with a diagnosis of opioid use disorder (OUD) and 379,623 patients with a diagnosis of cocaine use disorder (CocaineUD). Since Metamphetamine use disorder is not coded we could not analyze it. We show that the incidence rate of endocarditis among patients with OUD or CocaineUD significantly increased from 2011 to 2022 with acceleration during 2021-2022. COVID-19 was associated with increased risk of new diagnosis of endocarditis among patients with OUD (HR: 2.23, 95% CI: 1.92-2.60) and with CocaineUD (HR: 2.24, 95% CI: 1.79-2.80). Clinically diagnosed COVID-19 was associated with higher risk of endocarditis than lab-test confirmed COVID-19 without clinical diagnosis. Hospitalization within 2 weeks following COVID-19 infection was associated with increased risk of new diagnosis of endocarditis. The risk for endocarditis did not differ between patients with and without EHR-recorded vaccination. There were significant racial and ethnic differences in the risk for COVID-19 associated endocarditis, lower in blacks than in whites and lower in Hispanics than in non-Hispanics. Among patients with OUD or CocaineUD, the 180-day hospitalization risk following endocarditis was 67.5% in patients with COVID-19, compared to 58.7% in matched patients without COVID-19 (HR: 1.21, 95% CI: 1.07-1.35). The 180-day mortality risk following the new diagnosis of endocarditis was 9.2% in patients with COVID-19, compared to 8.0% in matched patients without COVID-19 (HR: 1.16, 95% CI: 0.83-1.61). This study shows that COVID-19 is associated with significantly increased risk for endocarditis in patients with opioid or cocaine use disorders. These results highlight the need for endocarditis screening and for linkage to infectious disease and addiction treatment in patients with opioid or cocaine use disorders who contracted COVID-19. Future studies are needed to understand how COVID-19 damages the heart and the vascular endothelium among people who misuse opioids or cocaine (presumably also methamphetamines).

COVID-19 rebound after Paxlovid treatment during Omicron BA.5 vs BA.2.12.1 subvariant predominance period (preprint)

Paxlovid was authorized by FDA to treat mild-to-moderate COVID-19. In May 2022, the Centers for Disease Control and Prevention (CDC) issued a Health Alert Network Health Advisory on potential COVID-19 rebound after Paxlovid treatment. Since June 2022, Omicron BA.5 has become the dominant subvariant in the US, which is more resistant to neutralizing antibodies than the previous subvariant BA.2.12.1. Questions remain as to how COVID-19 rebound after Paxlovid treatment differs between the BA.5 and BA.2.12.1 subvariants. This is a retrospective cohort study of 15,913 patients who contracted COVID-19 between 5/8/2022-7/18/2022 and were prescribed Paxlovid within 5 days of their COVID-19 infection. The study population was divided into 2 cohorts: (1) BA.5 cohort (n=5,161) that comprised patients who contracted COVID-19 during 6/19/22-7/18/22 when BA.5 was the predominant subvariant2. (2) BA.2.12.1 cohort (n=10,752) that comprised patients who contracted COVID-19 during 5/8/22-6/18/22 when the BA.2.12.1 was the predominant subvariant. The risks of both COVID-19 rebound infections and symptoms 2-8 days after Paxlovid treatment were higher in the BA.5 cohort than in the propensity-score matched BA.2.12.1 cohort: rebound infections (Hazard Ratio or HR: 1.32, 95% CI: 1.06-1.66), rebound symptoms (HR: 1.32, 95% CI: 1.04-1.68). As SARS-CoV-2 evolves with successive subvariants more evasive to antibodies, continuous vigilant monitoring is necessary for COVID-19 rebounds after Paxlovid treatment and longer time duration of Paxlovid treatment warrants evaluation.

COVID infection rates, clinical outcomes, and racial/ethnic and gender disparities before and after Omicron emerged in the US (preprint)

BackgroundSARS-CoV-2 infections and hospitalizations are rising in the US and other countries after the emergence of the Omicron variant. Currently, data on infection rates, severity and racial/ethnic and gender disparities from Omicron in the US is limited. MethodWe performed a retrospective cohort study of a large, geographically diverse database of patient electronic health records (EHRs) in the US. The study population comprised 881,473 patients who contracted SARS-CoV-2 infection for the first time between 9/1/2021-1/16/2022, including 147,964 patients infected when Omicron predominated (Omicron cohort), 633,581 when Delta predominated (Delta cohort) and another 99,928 infected when the Delta predominated but just before the Omicron variant was detected in the US (Delta-2 cohort). We examined monthly incidence rates of COVID-19 infections stratified by age groups, gender, race and ethnicity, compared severe clinical outcomes including emergency department (ED) visits, hospitalizations, intensive care unit (ICU) admissions, and mechanical ventilation use between propensity-score matched Omicron and Delta cohorts stratified by age groups (0-4, 5-17, 18-64 and [≥] 65 years), and examined racial/ethnic and gender differences in severe clinical outcomes. FindingsAmong 147,964 infected patients in the Omicron cohort (average age: 39.1 years), 56.7% were female, 2.4% Asian, 21.1% Black, 6.2% Hispanic, and 51.8% White. The monthly incidence rate of COVID infections (new cases per 1000 persons per day) was 0.5-0.7 when Delta predominated, and rapidly increased to 3.8-5.2 when Omicron predominated. In January 2022, the infection rate was highest in children under 5 years (11.0) among all age groups, higher in Black than in White patients (14.0 vs. 3.8), and higher in Hispanic than in non-Hispanic patients (8.9 vs. 3.1). After propensity-score matching for demographics, socio-economic determinants of health, comorbidities and medications, risks for severe clinical outcomes in the Omicron cohort were significantly lower than in the Delta cohort: ED visits: 10.2% vs. 14.6% (risk ratio or RR: 0.70 [0.68-0.71]); hospitalizations: 2.6% vs. 4.4% (RR: 0.58 [0.55-0.60]); ICU admissions: 0.47% vs. 1.00% (RR: 0.47 [0.43-0.51]); mechanical ventilation: 0.08% vs. 0.3% (RR: 0.25 [0.20-0.31]). Similar reduction in disease severity was observed for all age groups. There were significant racial/ethnic and gender disparities in severe clinical outcomes in the Omicron cohort, with Black, Hispanic patients having more ED visits and ICU admissions than White and non-Hispanic patients, respectively and women had fewer hospitalization and ICU admission than men. InterpretationThe incidence rate of COVID infection during the omicron predominant period (prevalence >92%) was 6-8 times higher than during the Delta predominant period that preceded it consistent with greater infectivity. The incidence rate was highest among those less than 5 years of age, and in Black and Hispanic patients. COVID infections occurring when the Omicron predominated were associated with significantly less frequent severe outcomes than in matched patients when the Delta variant predominated. There were significant racial, ethnic and gender disparities in severe clinical outcomes, with Black and Hispanic patients and men disproportionally impacted.

COVID infection severity in children under 5 years old before and after Omicron emergence in the US (preprint)

Abstract Importance Pediatric SARS-CoV-2 infections and hospitalizations are rising in the US and other countries after the emergence of Omicron variant. However data on disease severity from Omicron compared with Delta in children under 5 in the US is lacking. Objectives To compare severity of clinic outcomes in children under 5 who contracted COVID infection for the first time before and after the emergence of Omicron in the US. Design, Setting, and Participants This is a retrospective cohort study of electronic health record (EHR) data of 79,592 children under 5 who contracted SARS-CoV-2 infection for the first time, including 7,201 infected when the Omicron predominated (Omicron cohort), 63,203 infected when the Omicron predominated (Delta cohort), and another 9,188 infected when the Omicron predominated but immediately before the Omicron variant was detected in the US (Delta-2 cohort). Exposures First time infection of SARS-CoV-2. Main Outcomes and Measures After propensity-score matching, severity of COVID infections including emergency department (ED) visits, hospitalizations, intensive care unit (ICU) admissions, and mechanical ventilation use in the 3-day time-window following SARS-CoV-2 infection were compared between Omicron and Delta cohorts, and between Delta-2 and Delta cohorts. Risk ratios, and 95% confidence intervals (CI) were calculated. Results Among 7,201 infected children in the Omicron cohort (average age of 1.49 years), 47.4% were female, 2.4% Asian, 26.1% Black, 13.7% Hispanic, and 44.0% White. Before propensity score matching, the Omicron cohort were younger than the Delta cohort (average age 1.49 vs 1.73 years), comprised of more Black children, and had fewer comorbidities. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities and medications, risks for severe clinical outcomes in the Omicron cohort were significantly lower than those in the Delta cohort: ED visits: 18.83% vs. 26.67% (risk ratio or RR: 0.71 [0.66-0.75]); hospitalizations: 1.04% vs. 3.14% (RR: 0.33 [0.26-0.43]); ICU admissions: 0.14% vs. 0.43% (RR: 0.32 [0.16-0.66]); mechanical ventilation: 0.33% vs. 1.15% (RR: 0.29 [0.18-0.46]). Control studies comparing Delta-2 to Delta cohorts show no difference. Conclusions and Relevance For children under age 5, first time SARS-CoV-2 infections occurring when the Omicron predominated (prevalence >92%) was associated with significantly less severe outcomes than first-time infections in similar children when the Delta variant predominated.

Comparison of outcomes from COVID infection in pediatric and adult patients before and after the emergence of Omicron (preprint)

Abstract Background The Omicron SARS-CoV-2 variant is rapidly spreading in the US since December 2021 and is more contagious than earlier variants. Currently, data on the severity of the disease caused by the Omicron variant compared with the Delta variant is limited. Here we compared 3-day risks of emergency department (ED) visit, hospitalization, intensive care unit (ICU) admission, and mechanical ventilation in patients who were first infected during a time period when the Omicron variant was emerging to those in patients who were first infected when the Delta variant was predominant. Method This is a retrospective cohort study of electronic health record (EHR) data of 577,938 first-time SARS-CoV-2 infected patients from a multicenter, nationwide database in the US during 9/1/2021-12/24/2021, including 14,054 who had their first infection during the 12/15/2021-12/24/2021 period when the Omicron variant emerged (Emergent Omicron cohort) and 563,884 who had their first infection during the 9/1/2021-12/15/2021 period when the Delta variant was predominant (Delta cohort). After propensity-score matching the cohorts, the 3-day risks of four outcomes (ED visit, hospitalization, ICU admission, and mechanical ventilation) were compared. Risk ratios, and 95% confidence intervals (CI) were calculated. Results Of 14,054 patients in the Emergent Omicron cohort (average age, 36.4), 27.7% were pediatric patients (<18 years old), 55.4% female, 1.8% Asian, 17.1% Black, 4.8% Hispanic, and 57.3% White. The Emergent Omicron cohort differed significantly from the Delta cohort in demographics, comorbidities, and socio-economic determinants of health. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities, medications and vaccination status, the 3-day risks in the Emergent Omicron cohort outcomes were consistently less than half those in the Delta cohort: ED visit: 4.55% vs. 15.22% (risk ratio or RR: 0.30, 95% CI: 0.28-0.33); hospitalization: 1.75% vs. 3.95% (RR: 0.44, 95% CI: 0.38-0.52]); ICU admission: 0.26% vs. 0.78% (RR: 0.33, 95% CI:0.23-0.48); mechanical ventilation: 0.07% vs. 0.43% (RR: 0.16, 95% CI: 0.08-0.32). In children under 5 years old, the overall risks of ED visits and hospitalization in the Emergent Omicron cohort were 3.89% and 0.96% respectively, significantly lower than 21.01% and 2.65% in the matched Delta cohort (RR for ED visit: 0.19, 95% CI: 0.14-0.25; RR for hospitalization: 0.36, 95% CI: 0.19-0.68). Similar trends were observed for other pediatric age groups (5-11, 12-17 years), adults (18-64 years) and older adults (>= 65 years). Conclusions First time SARS-CoV-2 infections occurring at a time when the Omicron variant was rapidly spreading were associated with significantly less severe outcomes than first-time infections when the Delta variant predominated.

Septic shock 3.0 in severe COVID19 patients: Are we missing something clinically important?

Introduction/Purpose: COVID19 can be associated with life-threatening organ dysfunction due to septic shock, frequently requiring ICU admission, respiratory and vasopressor support. Therefore, clear clinical criteria are pivotal to early recognition of patients more likely to have poor outcomes, needing prompt organ support. Although most patients with severe COVID19 meet the Sepsis-3.0 criteria for septic shock, it has been increasingly recognized that, in this population, hyperlactatemia is frequently absent, possibly leading to an underestimation of illness severity and mortality risk. Purpose: This study aimed to identify the proportion of patients with COVID19 with hypotension despite adequate volume resuscitation, needing vasopressors to have a MAP>65mmHg, with and without hyperlactatemia, in ICU, and describe its clinical outcomes and mortality rate. Methods: We performed a single-center retrospective cohort study. All adult patients admitted to ICU with COVID19 were eligible and were further divided in 3 groups according to hyperlactatemia (lactate >2mmol/L) and persistent hypotension with vasopressor therapy requirement: (1) sepsis group (without both criteria), (2) vasoplegic shock (with persistent hypotension with vasopressor therapy requirement without hyperlactatemia) and (3) septic shock 3.0 (with both criteria). COVID19 was diagnosed using clinical and radiologic criteria with a SARS-CoV-2 positive RT-PCR test. Qui-square test was used for categorical variables and Kruskal-Wallis and logistic regression were used on continuous variables for statistical assessment of outcomes between groups. Kaplan-Meier survival curve and logrank test were also obtained. Results: 103 patients (mean age 62 years, 71% males) were included in the analysis (N=45 sepsis, N=25 vasoplegic shock;N=33 septic shock 3.0). SOFA score at ICU admission and ICU length of stay were different between groups (p<0.001). Ventilator-free days and vasopressor-free days were also different between sepsis vs vasoplegic shock and septic shock 3.0 groups (both p<0.001 and p<0.001, respectively), and similar in vasoplegic vs septic shock 3.0 groups (p=0.387 and p=0.193, respectively). Mortality was significantly higher in vasoplegic shock and septic shock 3.0 when compared with sepsis group (p<0.001) without difference between the former two groups (p=0.595). Log rank test of Kaplan-Meier survival curves were also different (p=0.07). Logistic regression identified the maximum dose of vasopressor therapy used (OR 1.065;CI 95%: 1.023-1.108, p=0.02) and serum lactate level (OR 1.543;CI 95%: 1.069-2.23, p=0.02) as the major explanatory variables of mortality rates. Conclusions: In severe COVID19 patients, the Sepsis 3 criteria of septic shock may exclude patients with a similarly high risk of poor outcomes and mortality rate, that should be equally approached. (Table Presented).

Increased risk for COVID-19 breakthrough infection in fully vaccinated patients with substance use disorders in the United States between December 2020 and August 2021.

Individuals with substance use disorders (SUDs) are at increased risk for COVID-19 infection and for adverse outcomes of the infection. Though vaccines are highly effective against COVID-19, their effectiveness in individuals with SUDs might be curtailed by compromised immune status and a greater likelihood of exposures, added to the waning vaccine immunity and the new SARS-CoV-2 variants. In a population-based cohort study, we assessed the risk, time trends, outcomes and disparities of COVID-19 breakthrough infection in fully vaccinated SUD patients starting 14 days after completion of vaccination. The study included 579,372 individuals (30,183 with a diagnosis of SUD and 549,189 without such a diagnosis) who were fully vaccinated between December 2020 and August 2021, and had not contracted COVID-19 infection prior to vaccination. We used the TriNetX Analytics network platform to access de-identified electronic health records from 63 health care organizations in the US. Among SUD patients, the risk for breakthrough infection ranged from 6.8% for tobacco use disorder to 7.8% for cannabis use disorder, all significantly higher than the 3.6% in non-SUD population (p<0.001). Breakthrough infection risk remained significantly higher after controlling for demographics (age, gender, ethnicity) and vaccine types for all SUD subtypes, except for tobacco use disorder, and was highest for cocaine and cannabis use disorders (hazard ratio, HR=2.06, 95% CI: 1.30-3.25 for cocaine; HR=1.92, 95% CI: 1.39-2.66 for cannabis). When we matched SUD and non-SUD individuals for lifetime comorbidities and adverse socioeconomic determinants of health, the risk for breakthrough infection no longer differed between these populations, except for patients with cannabis use disorder, who remained at increased risk (HR=1.55, 95% CI: 1.22-1.99). The risk for breakthrough infection was higher in SUD patients who received the Pfizer than the Moderna vaccine (HR=1.49, 95% CI: 1.31-1.69). In the vaccinated SUD population, the risk for hospitalization was 22.5% for the breakthrough cohort and 1.6% for the non-breakthrough cohort (risk ratio, RR=14.4, 95% CI: 10.19-20.42), while the risk for death was 1.7% and 0.5% respectively (RR=3.5, 95% CI: 1.74-7.05). No significant age, gender and ethnic disparities for breakthrough infection were observed in vaccinated SUD patients. These data suggest that fully vaccinated SUD individuals are at higher risk for breakthrough COVID-19 infection, and this is largely due to their higher prevalence of comorbidities and adverse socioeconomic determinants of health compared with non-SUD individuals. The high frequency of comorbidities in SUD patients is also likely to contribute to their high rates of hospitalization and death following breakthrough infection.

Rehabilitation Research During and after the COVID-19 Pandemic: Emergent Strategies From a Trainee-Faculty Workshop...American Congress of Rehabilitation Medicine (ACRM) Annual Conference (Virtual), September 24-29, 2021

1) To identify challenges for conducting ongoing and future rehabilitation research during and after the COVID-19 pandemic, and 2) to develop strategies that can support ongoing and future rehabilitation research. A two-hour facilitated online workshop with guided discussion. Online workshop synchronously recorded via Zoom. Trainees (14 doctoral;2 MSc students;1 post-doctoral fellow) and research faculty (5 physiotherapy;3 occupational therapy), School of Rehabilitation Science, McMaster University, Canada. Not applicable. Workshop transcript and field notes were cross-compared by 4 workshop facilitators from which 3 main categories emerged: 1) pandemic protocol adjustment, 2) participant accessibility, and 3) knowledge dissemination. 1) Pandemic protocol adjustment: Workshop participants identified concerns with transitioning pre- to post-pandemic research, such as variations in intervention protocols and psychometric properties of virtually guided outcome assessments. Strategies identified: Delivering toolkits containing equipment needed for virtually guided assessments, and their comprehensive psychometric evaluation prior to use. 2) Participant accessibility: Virtually guided rehabilitation research may present barriers to participation for some populations due to a lack of internet access and proficiency. Strategies identified: Including community stakeholders in the decision-making process to help guide the development of safe and feasible study protocols, and simplifying protocols to maintain participants' adherence. 3) Knowledge dissemination: Virtually delivered conferences have required additional preparation time due to requirements of pre-recorded presentations, and hinder important conversations between conference attendees. Strategies identified: Researchers should account for delays in knowledge translation plans for funding applications, and conference organizers should consider hosting networking events for attendees. This workshop served as a catalyst for creative solutions to complex methodological challenges that can be integrated within existing and future rehabilitation-focused studies during the COVID-19 pandemic and beyond. None.

Research on substance use disorders during the COVID-19 pandemic.

The COVID-19 pandemic has triggered changes in the substance use disorder (SUD) treatment delivery system, in the availability of legal and illicit drugs, and in other social and economic factors. As such, these changes necessitate that the field re-evaluate research approaches to SUDs, including in epidemiology, clinical trials, health services, implementation and policy research, as well as basic and translational neuroscience. COVID-19 has reduced researchers' access to target populations and made it difficult for them to obtain timely data to monitor changes in patterns of drug use and overdoses. These changes have increased researchers' interest in virtual technologies to expand and accelerate access to populations; increased modifications in the design, conduct, and analysis of clinical trials; and increased emphasis on implementation. Similarly, as researchers better understand the biology of COVID-19, they will better understand potential effects of COVID-19 on neurotransmitter receptors and signaling pathways, mechanisms underlying COVID-19 associated neurological and psychiatric sequelae, and interactions between COVID-19 treatments and psychoactive substances. The pandemic has also revealed the need for research that addresses health disparities. Overall, the COVID-19 pandemic has challenged several aspects of current research on SUD. Responding to these challenges provides opportunities to develop robust research approaches that align with the goals of improving patient outcomes and public health and are resilient to the challenges of future crises.