Chad J. Achenbach

Background: This study updates the COVID-19 pandemic surveillance in East Asia and the Pacific region that we first conducted in 2020 with 2 additional years of data for the region. Objective: First, we aimed to measure whether there was an expansion or contraction of the pandemic in East Asia and the Pacific region when the World Health Organization (WHO) declared the end of the COVID-19 public health emergency of international concern on May 5, 2023. Second, we used dynamic and genomic surveillance methods to describe the dynamic history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Finally, we aimed to provide historical context for the course of the pandemic in East Asia and the Pacific region. Methods: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether the regional weekly speed was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. Results: Several countries in East Asia and the Pacific region had COVID-19 transmission rates above an outbreak threshold at the point of the WHO declaration (Brunei, New Zealand, Australia, and South Korea). However, the regional transmission rate had remained below the outbreak threshold for 4 months. In the rolling 6-month window t test for regional outbreak status, the final P value ≤.10 implies a rejection of the null hypothesis (at the α=.10 level) that the region as a whole was not in an outbreak for the period from November 5, 2022, to May 5, 2023. From January 2022 onward, nearly every sequenced SARS-CoV-2 specimen in the region was identified as the Omicron variant. Conclusions: While COVID-19 continued to circulate in East Asia and the Pacific region, transmission rates had fallen below outbreak status by the time of the WHO declaration. Compared to other global regions, East Asia and the Pacific region had the latest outbreaks driven by the Omicron variant. COVID-19 appears to be endemic in the region, no longer reaching the threshold for a pandemic definition. However, the late outbreaks raise uncertainty about whether the pandemic was truly over in the region at the time of the WHO declaration.

Background: This study provides an update on the status of the COVID-19 pandemic in Canada, building upon our initial analysis conducted in 2020 by incorporating an additional 2 years of data. Objective: This study aims to (1) summarize the status of the pandemic in Canada when the World Health Organization (WHO) declared the end of the public health emergency for the COVID-19 pandemic on May 5, 2023; (2) use dynamic and genomic surveillance methods to describe the history of the pandemic in Canada and situate the window of the WHO declaration within the broader history; and (3) provide historical context for the course of the pandemic in Canada. Methods: This longitudinal study analyzed trends in traditional surveillance data and dynamic panel estimates for COVID-19 transmissions and deaths in Canada from June 2020 to May 2023. We also used sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. For these sequences, we used Nextclade nomenclature to collect clade designations and Pangolin nomenclature for lineage designations of SARS-CoV-2. We used 1-sided t tests of dynamic panel regression coefficients to measure the persistence of COVID-19 transmissions around the WHO declaration. Finally, we conducted a 1-sided t test for whether provincial and territorial weekly speed was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. Results: Canada’s speed remained below the outbreak threshold for 8 months by the time of the WHO declaration ending the COVID-19 emergency of international concern. Acceleration and jerk were also low and stable. While the 1-day persistence coefficient remained statistically significant and positive (1.074; P<.001), the 7-day coefficient was negative and small in magnitude (–0.080; P=.02). Furthermore, shift parameters for either of the 2 most recent weeks around May 5, 2023, were negligible (0.003 and 0.018, respectively, with P values of .75 and .31), meaning the clustering effect of new COVID-19 cases had remained stable in the 2 weeks around the WHO declaration. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling 1-sided t test of speed equal to 10 became entirely insignificant from mid-October 2022 onward. Conclusions: While COVID-19 continues to circulate in Canada, the rate of transmission remained well below the threshold of an outbreak for 8 months ahead of the WHO declaration. Both standard and enhanced surveillance metrics confirm that the pandemic had largely ended in Canada by the time of the WHO declaration. These results can inform future public health interventions and strategies in Canada, as well as contribute to the global understanding of the trajectory of the COVID-19 pandemic.

Background: This study updates the initial COVID-19 pandemic surveillance in sub-Saharan Africa (SSA) from 2020 by providing 2 additional years of data for the region. Objective: First, we aimed to measure whether there was an expansion or contraction in the pandemic in SSA when the World Health Organization (WHO) declared an end to the public health emergency for the COVID-19 pandemic on May 5, 2023. Second, we used dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aimed to provide historical context for the course of the pandemic in SSA. Methods: In addition to updates of traditional surveillance data and dynamic panel estimates from the original study by Post et al (2021), this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and used Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t-test to assess whether regional weekly speed was greater than an outbreak threshold of 10. We ran the test iteratively with a rolling 6-month window of data across the sample period. Results: Speed for the region remained well below the outbreak threshold before and after the WHO declaration. Acceleration and jerk were also low and stable. The 7-day persistence coefficient remained somewhat large (1.11) and statistically significant. However, both shift parameters for the weeks around the WHO declaration were negative, meaning the clustering effect of new COVID-19 cases had become recently smaller. From November 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t-test of speed equal to 10 was insignificant for the entire sample period. Conclusions: While COVID-19 continues to circulate in SSA, the region never reached outbreak status, and the weekly transmission rate remained below 1 case per 100,000 population for well over 1 year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold for its classification as a pandemic. Both standard and enhanced surveillance metrics confirm that the pandemic ended in SSA by the time the WHO made its declaration.

Objective We assessed the association of early statin initiation with inpatient mortality among hospitalised COVID-19 patients. Design, setting and participants This observational study emulated a hypothetical target trial using electronic health records data from Northwestern Medicine Health System, Illinois, 2020–2022. We included patients who were ≥40 years, admitted ≥48 hours for COVID-19 from March 2020 to August 2022 and had no evidence of statin use before admission. Interventions Individuals who initiated any statins within 48 hours of admission were compared with individuals who did not initiate statins during this period. Primary outcome measures Inpatient mortality at hospital days 7, 14, 21 and 28 were determined using hospital records. Risk differences between exposure groups were calculated using augmented inverse propensity weighting (AIPW) with SuperLearner. Results A total of 8893 individuals (24.5% early statin initiators) were included. Early initiators tended to be older, male and have higher comorbidity burdens. Unadjusted day 28 mortality was higher in early initiators (6.0% vs 3.6%). Adjusted analysis showed slightly higher inpatient mortality risk at days 7 (RD: 0.5%, 95% CI: 0.2 to 0.8) and 21 (RD: 0.6%, 95% CI: 0.04 to 1.1), but not days 14 (RD: 0.4%, 95% CI: −0.03 to 0.9) and 28 (RD: 0.4%, 95% CI: −0.2 to 1.1). Sensitivity analyses using alternative modelling approaches showed no difference between groups. Conclusions Early statin initiation was not associated with lower mortality contrasting with findings of previous observational studies. Trial emulation helped in identifying and addressing sources of bias incompletely addressed by previous work. Statin use may be indicated for other conditions but not COVID-19.

Nirmatrelvir/ritonavir (NM/r) is a safe and effective oral antiviral therapeutic used for treatment of mild-to-moderate COVID-19. Case reports described a clinical rebound syndrome whereby individuals experience a relapse of symptoms shortly after completing successful treatment. There is a lack of information on frequency of COVID-19 rebound after NM/r in routine clinical care, contributing factors, and clinical outcomes. We reviewed electronic medical records to verify COVID-19 diagnosis, symptoms, and treatment with NM/r from January-June 2022. We defined COVID-19 clinical rebound as clear improvement in symptoms followed by recurrence or worsening of symptoms within 30 days of a five-day course of NM/r. We studied 268 adults with median age 57 (IQR 47, 68), 80% White race, 85% non-Hispanic ethnicity, 55% female, 80% vaccinated and boosted against SARS-CoV-2, and 68% with any co-morbidity. Sixteen (6.0%) of studied patients were determined to have COVID-19 clinical rebound. The median time from starting NM/r to rebound was 11 days (IQR 9, 13). Notable demographic and clinical factors with higher proportion (not statistically significant) among COVID-19 rebound patients were female sex (75% rebound vs. 54.5% no rebound), Black race (12.5% rebound vs. 4.9% no rebound), presence of at least one co-morbidity (81.3% rebound vs. 67.5% no rebound), and lack of prior SARS-CoV-2 infection (100% rebound vs. 92.9% no rebound). Only one patient (6.25%) was hospitalized after COVID-19 rebound. COVID-19 clinical rebound after treatment with NM/r is mild with favorable outcomes and more common than previously reported from real-world clinical care studies.

Background: This study updates the COVID-19 pandemic surveillance in Central Asia we conducted during the first year of the pandemic by providing 2 additional years of data for the region. The historical context provided through additional data can inform regional preparedness and early responses to infectious outbreaks of either the SARS-CoV-2 virus or future pathogens in Central Asia. Objective: First, we aim to measure whether there was an expansion or contraction in the pandemic in Central Asia when the World Health Organization (WHO) declared the end of the public health emergency for the COVID-19 pandemic on May 5, 2023. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aim to provide historical context for the course of the pandemic in Central Asia. Methods: Traditional surveillance metrics, including counts and rates of COVID-19 transmissions and deaths, and enhanced surveillance indicators, including speed, acceleration, jerk, and persistence, were used to measure shifts in the pandemic. To identify the appearance and duration of variants of concern, we used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID). We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether regional speed was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. Results: Speed for the region had remained below the outbreak threshold for 7 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant, the coefficients were relatively small in magnitude (0.125 and 0.347, respectively). Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, were both significant and negative, meaning the clustering effect of new COVID-19 cases became even smaller in the 2 weeks around the WHO declaration. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of speed equal to 10 became entirely insignificant for the first time in March 2023. Conclusions: Although COVID-19 continues to circulate in Central Asia, the rate of transmission remained well below the threshold of an outbreak for 7 months ahead of the WHO declaration. COVID-19 appeared to be endemic in the region and no longer reached the threshold of a pandemic. Both standard and enhanced surveillance metrics suggest the pandemic had ended by the time of the WHO declaration.

Background: This study updates our findings from the COVID-19 pandemic surveillance we first conducted in South Asia in 2020 with 2 additional years of data for the region. We assess whether COVID-19 had transitioned from pandemic to endemic at the point the World Health Organization (WHO) ended the public health emergency status for COVID-19 on May 5, 2023. Objective: First, we aim to measure whether there was an expansion or contraction in the pandemic in South Asia around the WHO declaration. Second, we use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history. Third, we aim to provide historical context for the course of the pandemic in South Asia. Methods: In addition to updating the traditional surveillance data and dynamic panel estimates from our original study, this study used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Finally, we conducted a 1-sided t test to determine whether regional weekly speed or transmission rate per 100,000 population was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. Results: Speed for the region had remained below the outbreak threshold for over a year by the time of the WHO declaration. Acceleration and jerk were also low and stable. While the 1-day persistence coefficients remained statistically significant and positive (1.168), the 7-day persistence coefficient was negative (–0.185), suggesting limited cluster effects in which cases on a given day predict cases 7 days forward. Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, did not indicate any overall change in the persistence measure around the time of the WHO declaration. From December of 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling t test of speed equal to 10 was statistically insignificant across the entire pandemic. Conclusions: While COVID-19 continued to circulate in South Asia, the rate of transmission had remained below the outbreak threshold for well over a year ahead of the WHO declaration. COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. Both standard and enhanced surveillance metrics confirm that the pandemic had ended by the time of the WHO declaration. Prevention policies should be a focus ahead of future pandemics. On that point, policy should emphasize an epidemiological task force with widespread testing and a contact-tracing system.

Background: SARS-CoV-2 vaccines are safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. This study was performed to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and findings: A retrospective clinical cohort study was performed utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. The primary outcome was the incidence and time to the first positive SARS-CoV-2 molecular test in the Omicron predominant era. Multivariable Cox modeling analyses to determine the hazard of SARS-CoV-2 infection were stratified by calendar time (Period 1: January 1 –June 30, 2022; Period 2: July 1 –December 31, 2022) due to violations in the proportional hazards assumption. In total, 133,191 patients were analyzed. During Period 1, having 3+ comorbidities was associated with increased hazard for breakthrough (HR = 1.16 CI 1.08–1.26). During Period 2 of the study, having 2 comorbidities (HR = 1.45 95% CI 1.26–1.67) and having 3+ comorbidities (HR 1.73, 95% CI 1.51–1.97) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in Period 1 of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age plays an important role in breakthrough infection with the highest incidence among young adults, which may be due to age-related behavioral factors. These findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

Background: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and Findings: We performed a retrospective clinical cohort study utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. Our primary outcome was incidence and time to first positive SARS-CoV-2 molecular test in the Omicron predominant era. We performed multivariable analyses stratified by calendar time using Cox modeling to determine hazard of SARS-CoV-2. In total, 133,191 patients were analyzed. Having 3+ comorbidities was associated with increased hazard for breakthrough (HR=1.2 CI 1.2-1.6). During the second half of the study, having 2 comorbidities (HR= 1.1 95% CI 1.02-1.2) and having 3+ comorbidities (HR 1.7, 95% CI 1.5-1.9) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in the first 6 months of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age related behavioral factors play an important role in breakthrough infection with the highest incidence among young adults. Our findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

BACKGROUND This study provides an update on the status of the COVID-19 pandemic in Canada, building upon our initial analysis conducted in 2020 by incorporating an additional 2 years of data. OBJECTIVE This study aims to (1) summarize the status of the pandemic in Canada when the World Health Organization (WHO) declared the end of the public health emergency for the COVID-19 pandemic on May 5, 2023; (2) use dynamic and genomic surveillance methods to describe the history of the pandemic in Canada and situate the window of the WHO declaration within the broader history; and (3) provide historical context for the course of the pandemic in Canada. METHODS This longitudinal study analyzed trends in traditional surveillance data and dynamic panel estimates for COVID-19 transmissions and deaths in Canada from June 2020 to May 2023. We also used sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern. For these sequences, we used Nextclade nomenclature to collect clade designations and Pangolin nomenclature for lineage designations of SARS-CoV-2. We used 1-sided t tests of dynamic panel regression coefficients to measure the persistence of COVID-19 transmissions around the WHO declaration. Finally, we conducted a 1-sided t test for whether provincial and territorial weekly speed was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the sample period. RESULTS Canada’s speed remained below the outbreak threshold for 8 months by the time of the WHO declaration ending the COVID-19 emergency of international concern. Acceleration and jerk were also low and stable. While the 1-day persistence coefficient remained statistically significant and positive (1.074; P<.001), the 7-day coefficient was negative and small in magnitude (–0.080; P=.02). Furthermore, shift parameters for either of the 2 most recent weeks around May 5, 2023, were negligible (0.003 and 0.018, respectively, with P values of .75 and .31), meaning the clustering effect of new COVID-19 cases had remained stable in the 2 weeks around the WHO declaration. From December 2021 onward, Omicron was the predominant variant of concern in sequenced viral samples. The rolling 1-sided t test of speed equal to 10 became entirely insignificant from mid-October 2022 onward. CONCLUSIONS While COVID-19 continues to circulate in Canada, the rate of transmission remained well below the threshold of an outbreak for 8 months ahead of the WHO declaration. Both standard and enhanced surveillance metrics confirm that the pandemic had largely ended in Canada by the time of the WHO declaration. These results can inform future public health interventions and strategies in Canada, as well as contribute to the global understanding of the trajectory of the COVID-19 pandemic.