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During pandemics, healthcare providers struggle with balancing obligations to self, family, and patients. While HIV/AIDS seemed to settle this issue, coronavirus disease 2019 (COVID-19) rekindled debates regarding treatment refusal. We searched MEDLINE, Embase, CINAHL Complete, and Web of Science using terms including obligation, refusal, HIV/AIDS, COVID-19, and pandemics. After duplicate removal and dual, independent screening, we analyzed 156 articles for quality, ethical position, reasons, and concepts. Diseases in our sample included HIV/AIDS (72.2%), severe acute respiratory syndrome (SARS) (10.2%), COVID-19 (10.2%), Ebola (7.0%), and influenza (7.0%). Most articles (81.9%, n = 128) indicated an obligation to treat. COVID-19 had the highest number of papers indicating ethical acceptability of refusal (60%, P <.001), while HIV had the least (13.3%, P =.026). Several reason domains were significantly different during COVID-19, including unreasonable risks to self/family (26.7%, P <.001) and labor rights/workers' protection (40%, P <.001). A surge in ethics literature during COVID-19 has advocated for permissibility of treatment refusal. Balancing healthcare provision with workforce protection is crucial in effectively responding to a global pandemic. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has decreasing protection from acquiring any infection with emergence of new variants; however, vaccination continues to protect against progression to severe coronavirus disease 2019 (COVID-19). The impact of vaccination status on symptoms over time is less clear. Methods Within a randomized trial on early outpatient COVID-19 therapy testing metformin, ivermectin, and/or fluvoxamine, participants recorded symptoms daily for 14 days. Participants were given a paper symptom diary allowing them to circle the severity of 14 symptoms as none (0), mild (1), moderate (2), or severe (3). This is a secondary analysis of clinical trial data on symptom severity over time using generalized estimating equations comparing those unvaccinated, SARS-CoV-2 vaccinated with primary vaccine series only, or vaccine-boosted. Results The parent clinical trial prospectively enrolled 1323 participants, of whom 1062 (80%) prospectively recorded some daily symptom data. Of these, 480 (45%) were unvaccinated, 530 (50%) were vaccinated with primary series only, and 52 (5%) vaccine-boosted. Overall symptom severity was least for the vaccine-boosted group and most severe for unvaccinated at baseline and over the 14 days (P <.001). Individual symptoms were least severe in the vaccine-boosted group including cough, chills, fever, nausea, fatigue, myalgia, headache, and diarrhea, as well as smell and taste abnormalities. Results were consistent over Delta and Omicron variant time periods. Conclusions SARS-CoV-2 vaccine-boosted participants had the least severe symptoms during COVID-19, which abated the quickest over time. Clinical Trial Registration. NCT04510194. [ABSTRACT FROM AUTHOR]

Background Few pediatric cases of coronavirus disease 2019 (COVID-19) have been reported and we know little about the epidemiology in children, although more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes, and transmission dynamics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to inform clinical and public health measures. Methods We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in pediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched 3 databases and the COVID-19 resource centers of 11 major journals and publishers. English abstracts of Chinese-language papers were included. Data were extracted and narrative syntheses conducted. Results Twenty-four studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, although radiological abnormalities are noted. Severe cases are not reported in detail and there are few data relating to transmission. Conclusions Children appear to have a low observed case rate of COVID-19 but may have rates similar to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention and be tested and counted in observed cases of COVID-19. [ABSTRACT FROM AUTHOR]

In high-income countries that were first to roll out coronavirus disease 2019 (COVID-19) vaccines, older adults have thus far usually been prioritized for these vaccines over younger adults. Age-based priority primarily resulted from interpreting evidence available at the time, which indicated that vaccinating the elderly first would minimize COVID-19 deaths and hospitalizations. The World Health Organization counsels a similar approach for all countries. This paper argues that some low- and middle-income countries that are short of COVID-19 vaccine doses might be justified in revising this approach and instead prioritizing certain younger persons when allocating current vaccines or future variant-specific vaccines. [ABSTRACT FROM AUTHOR]

Background We aimed to review the evidence from studies relating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) culture with the results of reverse-transcription polymerase chain reaction (RT-PCR) and other variables that may influence the interpretation of the test, such as time from symptom onset. Methods We searched LitCovid, medRxiv, Google Scholar, and the World Health Organization coronavirus disease 2019 (COVID-19) database for COVID-19 up to 10 September 2020. We included studies attempting to culture or observe SARS-CoV-2 in specimens with RT-PCR positivity. Studies were dual-extracted and the data summarized narratively by specimen type. Where necessary, we contacted corresponding authors of included papers for additional information. We assessed quality using a modified Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2) risk-of-bias tool. Results We included 29 studies reporting attempts at culturing, or observing tissue infection by, SARS-CoV-2 in sputum, nasopharyngeal or oropharyngeal, urine, stool, blood, and environmental specimens. The quality of the studies was moderate with lack of standardized reporting. The data suggest a relationship between the time from onset of symptom to the timing of the specimen test, cycle threshold (Ct), and symptom severity. Twelve studies reported that Ct values were significantly lower and log copies higher in specimens producing live virus culture. Two studies reported that the odds of live virus culture were reduced by approximately 33% for every 1-unit increase in Ct. Six of 8 studies reported detectable RNA for >14 days, but infectious potential declined after day 8 even among cases with ongoing high viral loads. Four studies reported viral culture from stool specimens. Conclusions Complete live viruses are necessary for transmission, not the fragments identified by PCR. Prospective routine testing of reference and culture specimens and their relationship to symptoms, signs, and patient co-factors should be used to define the reliability of PCR for assessing infectious potential. Those with high Ct are unlikely to have infectious potential. [ABSTRACT FROM AUTHOR]

Background The bacille Calmette-Guérin (BCG) tuberculosis vaccine has immunity benefits against respiratory infections. Accordingly, it has been hypothesized to have a protective effect against coronavirus disease 2019 (COVID-19). Recent research found that countries with universal BCG childhood vaccination policies tend to be less affected by the COVID-19 pandemic. However, such ecological studies are biased by numerous confounders. Instead, this paper reports on a rare nationwide natural experiment that occurred in Sweden in 1975, where discontinuation of newborns' BCG vaccination led to a dramatic decrease in BCG coverage rate, thus allowing us to estimate BCG's effect without the biases associated with cross-country comparisons. Methods Numbers of COVID-19 cases and hospitalizations were recorded for birth cohorts born just before and just after 1975, representing 1 026 304 and 1 018 544 individuals, respectively. We used regression discontinuity to assess the effect of BCG vaccination on COVID-19–related outcomes. On such a large population, this method allows for a precision that would be hard to achieve using a randomized controlled trial. Results The odds ratios (95% CI) for COVID-19 cases and COVID-19–related hospitalizations were 1.0005 (.8130–1.1881) and 1.2046 (.7532–1.6560), allowing us to reject fairly modest effects of universal BCG vaccination. We can reject with 95% confidence that universal BCG vaccination reduces the number of cases by 19% and the number of hospitalizations by 25%. Conclusions While the effect of a recent vaccination must be evaluated, we provide strong evidence that receiving the BCG vaccine at birth does not have a protective effect against COVID-19 among middle-aged individuals. [ABSTRACT FROM AUTHOR]

This is an account that should be heard of an important struggle: the struggle of a large group of experts who came together at the beginning of the COVID-19 pandemic to warn the world about the risk of airborne transmission and the consequences of ignoring it. We alerted the World Health Organization about the potential significance of the airborne transmission of SARS-CoV-2 and the urgent need to control it, but our concerns were dismissed. Here we describe how this happened and the consequences. We hope that by reporting this story we can raise awareness of the importance of interdisciplinary collaboration and the need to be open to new evidence, and to prevent it from happening again. Acknowledgement of an issue, and the emergence of new evidence related to it, is the first necessary step towards finding effective mitigation solutions. [ABSTRACT FROM AUTHOR]

The article highlights a study that distinguishes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome–related coronavirus (MERS-CoV). It discusses that the findings have pointed out how the viral load in COVID-19 is high at the very onset of the disease and then decreases over time, underlining the probability of a high load also in the presymptomatic phase.

Understanding the contribution of routes of transmission, particularly the role of fomites in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission is important in developing and implementing successful public health infection prevention and control measures. This article will look at case reports, laboratory findings, animal studies, environmental factors, the need for disinfection, and differences in settings as they relate to SARS-CoV-2 transmission. [ABSTRACT FROM AUTHOR]

Background Although much of the public health effort to combat coronavirus disease 2019 (COVID-19) has focused on disease control strategies in public settings, transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within households remains an important problem. The nature and determinants of household transmission are poorly understood. Methods To address this gap, we gathered and analyzed data from 22 published and prepublished studies from 10 countries (20 291 household contacts) that were available through 2 September 2020. Our goal was to combine estimates of the SARS-CoV-2 household secondary attack rate (SAR) and to explore variation in estimates of the household SAR. Results The overall pooled random-effects estimate of the household SAR was 17.1% (95% confidence interval [CI], 13.7–21.2%). In study-level, random-effects meta-regressions stratified by testing frequency (1 test, 2 tests, >2 tests), SAR estimates were 9.2% (95% CI, 6.7–12.3%), 17.5% (95% CI, 13.9–21.8%), and 21.3% (95% CI, 13.8–31.3%), respectively. Household SARs tended to be higher among older adult contacts and among contacts of symptomatic cases. Conclusions These findings suggest that SARs reported using a single follow-up test may be underestimated, and that testing household contacts of COVID-19 cases on multiple occasions may increase the yield for identifying secondary cases. [ABSTRACT FROM AUTHOR]

The article reports disparity and social unrest amid COVID-19 pandemic. It mentions Black, Latinx, and other non-White individuals account for 60 per cent of COVID-19 deaths; and also mentions genetic or physiologic reason that COVID-19 is a more serious infection among Black or Latinx people than White people, then race or ethnicity should be an independent predictor of mortality.

BackgroundThe bacille Calmette-Guérin (BCG) tuberculosis vaccine has immunity benefits against respiratory infections. Accordingly, it has been hypothesized to have a protective effect against coronavirus disease 2019 (COVID-19). Recent research found that countries with universal BCG childhood vaccination policies tend to be less affected by the COVID-19 pandemic. However, such ecological studies are biased by numerous confounders. Instead, this paper reports on a rare nationwide natural experiment that occurred in Sweden in 1975, where discontinuation of newborns' BCG vaccination led to a dramatic decrease in BCG coverage rate, thus allowing us to estimate BCG's effect without the biases associated with cross-country comparisons.MethodsNumbers of COVID-19 cases and hospitalizations were recorded for birth cohorts born just before and just after 1975, representing 1 026 304 and 1 018 544 individuals, respectively. We used regression discontinuity to assess the effect of BCG vaccination on COVID-19-related outcomes. On such a large population, this method allows for a precision that would be hard to achieve using a randomized controlled trial.ResultsThe odds ratios (95% CI) for COVID-19 cases and COVID-19-related hospitalizations were 1.0005 (.8130-1.1881) and 1.2046 (.7532-1.6560), allowing us to reject fairly modest effects of universal BCG vaccination. We can reject with 95% confidence that universal BCG vaccination reduces the number of cases by 19% and the number of hospitalizations by 25%.ConclusionsWhile the effect of a recent vaccination must be evaluated, we provide strong evidence that receiving the BCG vaccine at birth does not have a protective effect against COVID-19 among middle-aged individuals.

Background This phase 2b part of a randomized phase 2/3 study assessed the efficacy and safety of ensitrelvir for mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron epidemic. Methods Patients were randomized (1:1:1) to orally receive ensitrelvir fumaric acid 125 mg (375 mg on day 1) or 250 mg (750 mg on day 1) or placebo once daily for 5 days. The co-primary endpoints were the change from baseline in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer on day 4 and time-weighted average change from baseline up to 120 hours in the total score of predefined 12 COVID-19 symptoms. Safety was assessed through adverse events. Results A total of 341 patients (ensitrelvir 125-mg group: 114; ensitrelvir 250-mg group: 116; and placebo group: 111; male: 53.5–64.9%; mean age: 35.3–37.3 years) were included in the efficacy analyses. The change from baseline in SARS-CoV-2 titer on day 4 was significantly greater with both ensitrelvir doses than with placebo (differences from placebo: −0.41 log10 50% tissue-culture infectious dose/mL; P <.0001 for both). The total score of the 12 COVID-19 symptoms did not show a significant difference between the ensitrelvir groups and placebo group. The time-weighted average change from baseline up to 120 hours was significantly greater with ensitrelvir versus placebo in several subtotal scores, including acute symptoms and respiratory symptoms. Most adverse events were mild in severity. Conclusions Ensitrelvir treatment demonstrated a favorable antiviral efficacy and potential clinical benefit with an acceptable safety profile. Clinical Trials Registration Japan Registry of Clinical Trials: jRCT2031210350 (https://jrct.niph.go.jp/en-latest-detail/jRCT2031210350) [ABSTRACT FROM AUTHOR]

Background Social determinants of health (SDOH) have been associated with coronavirus disease 2019 (COVID-19) outcomes. We examined patterns in COVID-19–related mortality by SDOH and compared these patterns to those for non–COVID-19 mortality. Methods Residents of Ontario, Canada, aged ≥20 years were followed from 1 March 2020 to 2 March 2021. COVID-19–related death was defined as death within 30 days following or 7 days prior to a positive COVID-19 test. Area-level SDOH from the 2016 census included median household income; proportion with diploma or higher educational attainment; proportion essential workers, racially minoritized groups, recent immigrants, apartment buildings, and high-density housing; and average household size. We examined associations between SDOH and COVID-19–related mortality, and non-COVID-19 mortality using cause-specific hazard models. Results Of 11 810 255 individuals, we observed 3880 COVID-19–related deaths and 88 107 non–COVID-19 deaths. After accounting for demographics, baseline health, and other area-level SDOH, the following were associated with increased hazards of COVID-19–related death (hazard ratio [95% confidence interval]: lower income (1.30 [1.04–1.62]), lower educational attainment (1.27 [1.07–1.52]), higher proportions essential workers (1.28 [1.05–1.57]), racially minoritized groups (1.42 [1.08–1.87]), apartment buildings (1.25 [1.07–1.46]), and large vs medium household size (1.30 [1.12–1.50]). Areas with higher proportion racially minoritized groups were associated with a lower hazard of non–COVID-19 mortality (0.88 [0.84–0.92]). Conclusions Area-level SDOH are associated with COVID-19–related mortality after accounting for demographic and clinical factors. COVID-19 has reversed patterns of lower non–COVID-19 mortality among racially minoritized groups. Pandemic responses should include strategies to address disproportionate risks and inequitable coverage of preventive interventions associated with SDOH. [ABSTRACT FROM AUTHOR]

Background Increasing the availability of antigen rapid diagnostic tests (Ag-RDTs) in low- and middle-income countries (LMICs) is key to alleviating global SARS-CoV-2 testing inequity (median testing rate in December 2021–March 2022 when the Omicron variant was spreading in multiple countries: high-income countries = 600 tests/100 000 people/day; LMICs = 14 tests/100 000 people/day). However, target testing levels and effectiveness of asymptomatic community screening to impact SARS-CoV-2 transmission in LMICs are unclear. Methods We used Propelling Action for Testing and Treating (PATAT), an LMIC-focused agent-based model to simulate coronavirus disease 2019 (COVID-19) epidemics, varying the amount of Ag-RDTs available for symptomatic testing at healthcare facilities and asymptomatic community testing in different social settings. We assumed that testing was a function of access to healthcare facilities and availability of Ag-RDTs. We explicitly modelled symptomatic testing demand from individuals without SARS-CoV-2 and measured impact based on the number of infections averted due to test-and-isolate. Results Testing symptomatic individuals yields greater benefits than any asymptomatic community testing strategy until most symptomatic individuals who sought testing have been tested. Meeting symptomatic testing demand likely requires at least 200–400 tests/100 000 people/day, on average, as symptomatic testing demand is highly influenced by individuals without SARS-CoV-2. After symptomatic testing demand is satisfied, excess tests to proactively screen for asymptomatic infections among household members yield the largest additional infections averted. Conclusions Testing strategies aimed at reducing transmission should prioritize symptomatic testing and incentivizing test-positive individuals to adhere to isolation to maximize effectiveness. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic and associated increase in family care responsibilities resulted in unsustainable personal and professional workloads for infectious diseases (ID) faculty on the front lines. This was especially true for early-stage faculty (ESF), many of whom had caregiving responsibilities. In addition, female faculty, underrepresented in medicine and science faculty and particularly ESF, experienced marked declines in research productivity, which significantly impacts career trajectories. When combined with staffing shortages due to an aging workforce and suboptimal recruitment and retention in ID, these work-life imbalances have brought the field to an inflection point. We propose actionable recommendations and call on ID leaders to act to close the gender, racial, and ethnic gaps to improve the recruitment, retention, and advancement of ESF in ID. By investing in systemic change to make the ID workforce more equitable, we can embody the shared ideals of diversity and inclusion and prepare for the next pandemic. [ABSTRACT FROM AUTHOR]

Background We explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow immunoassay (LFIA) performance under field conditions compared to laboratory-based electrochemiluminescence immunoassay (ECLIA) and live virus neutralization. Methods In July 2021, 3758 participants performed, at home, a self-administered Fortress LFIA on finger-prick blood, reported and submitted a photograph of the result, and provided a self-collected capillary blood sample for assessment of immunoglobulin G (IgG) antibodies using the Roche Elecsys® Anti-SARS-CoV-2 ECLIA. We compared the self-reported LFIA result to the quantitative ECLIA and checked the reading of the LFIA result with an automated image analysis (ALFA). In a subsample of 250 participants, we compared the results to live virus neutralization. Results Almost all participants (3593/3758, 95.6%) had been vaccinated or reported prior infection. Overall, 2777/3758 (73.9%) were positive on self-reported LFIA, 2811/3457 (81.3%) positive by LFIA when ALFA-reported, and 3622/3758 (96.4%) positive on ECLIA (using the manufacturer reference standard threshold for positivity of 0.8 U mL–1). Live virus neutralization was detected in 169 of 250 randomly selected samples (67.6%); 133/169 were positive with self-reported LFIA (sensitivity 78.7%; 95% confidence interval [CI]: 71.8, 84.6), 142/155 (91.6%; 95% CI: 86.1, 95.5) with ALFA, and 169 (100%; 95% CI: 97.8, 100.0) with ECLIA. There were 81 samples with no detectable virus neutralization; 47/81 were negative with self-reported LFIA (specificity 58.0%; 95% CI: 46.5, 68.9), 34/75 (45.3%; 95% CI: 33.8, 57.3) with ALFA, and 0/81 (0%; 95% CI: 0, 4.5) with ECLIA. Conclusions Self-administered LFIA is less sensitive than a quantitative antibody test, but the positivity in LFIA correlates better than the quantitative ECLIA with virus neutralization. [ABSTRACT FROM AUTHOR]

Background Molnupiravir was granted emergency use authorization for the treatment of mild to moderate coronavirus disease 2019 (COVID-19). In this study, we used population-based real-world data to evaluate the effectiveness of molnupiravir. Methods The database of the largest healthcare provider in Israel was used to identify all adults with first-ever positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) performed in the community during January–February 2022, who were at high risk for severe COVID-19, and had no contraindications for molnupiravir use. Patients were included regardless of SARS-CoV-2 vaccination status. A total of 2661 patients who received molnupiravir were propensity score matched with 2661 patients who have not received molnupiravir (control group). Patients were followed through 10 March 2022 for up to 28 days for the first occurrence of the composite severe COVID-19 or COVID-19-specific mortality. Results The composite outcome occurred in 50 patients in the molnupiravir group and 60 patients in the control group. Molnupiravir was associated with a nonsignificant reduced risk of the composite outcome: hazard ratio, 0.83 (95% confidence interval,.57–1.21). However, subgroup analyses showed that molnupiravir was associated with a significant decrease in the risk of the composite outcome in older patients 0.54 (0.34–0.86), in females 0.41 (0.22–0.77), and in patients with inadequate COVID-19 vaccination 0.45 (0.25–0.82). The results were similar when each component of the composite outcome was examined separately. Conclusions This study suggests that in the era of Omicron and in real-life setting, molnupiravir might be effective in reducing the risk of severe COVID-19 and COVID-19-related mortality, particularly in specific subgroups. [ABSTRACT FROM AUTHOR]

Background Despite vaccination, many remain vulnerable to coronavirus disease 2019 (COVID-19) and its complications. Oral antivirals to prevent COVID-19 progression are vital. Based on perceived potency and clinical efficacy, favipiravir is widely used to treat COVID-19. Evidence from large randomized controlled trials (RCT) is lacking. Methods In this multicenter double-blinded placebo-controlled RCT, adults with early mild-to-moderate COVID-19 were 1:1 randomized to favipiravir or placebo. The study evaluated time to sustained clinical recovery (TT-SCR), COVID-19 progression, and cessation of viral shedding. Results Of 1187 analyzed patients across 40 centers, 83.3% were Hispanic, 89.0% unvaccinated, 70.3% severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seronegative, and 77.8% had risk factors for COVID-19 progression. The median time from symptom presentation and from positive test to randomization was 3 and 2 days, respectively. There was no difference in TT-SCR (median of 7 days for both groups; P =.80), COVID-19 progression [11 patients each (1.9% vs 1.8%); P =.96], time to undetectable virus (median = 6 days, 95% confidence interval [CI] [6–8] vs 7 days, 95% CI [6-9]), or in undetectable virus by end of therapy (73.4% vs 72.3%; P =.94). Outcomes were consistent across the analyzed sub-groups. Adverse events were observed in 13.8% and 14.8% of favipiravir-treated and placebo-treated subjects, respectively. Uric acid elevation was more frequent among favipiravir-treated subjects (19.9% vs 2.8%). Conclusions Favipiravir was well tolerated but lacked efficacy in TT-SCR, progression to severe COVID-19, or cessation of viral shedding and should not be used to treat patients with COVID-19. (Supported by Appili Therapeutics) Clinical Trials Registration NCT04600895 [ABSTRACT FROM AUTHOR]

Background Identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden. Methods This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 US integrated healthcare networks (sites 1–3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020–February 2021 and ≥1 antenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing and compare pregnancy and neonatal outcomes among persons tested. Results Among 17 858 pregnant persons, 10 863 (60.8%) had peripartum SARS-CoV-2 testing; 222/10 683 (2.0%) had positive results. Testing prevalence varied by site and was lower during March–May 2020. Factors associated with higher peripartum SARS-CoV-2 testing odds were Asian race (adjusted odds ratio [aOR]: 1.36; 95% confidence interval [CI]: 1.03–1.79; referent: White) (site 1), Hispanic or Latino ethnicity (aOR: 1.33; 95% CI: 1.08–1.64) (site 2), peripartum Medicaid coverage (aOR: 1.33; 95% CI: 1.06–1.66) (site 1), and preterm hospitalization (aOR: 1.69; 95% CI: 1.19–2.39 [site 1]; aOR: 1.39; 95% CI: 1.03–1.88 [site 2]). Conclusions Findings highlight potential disparities in SARS-CoV-2 peripartum testing by demographic and pregnancy characteristics. Testing practice variations should be considered when interpreting studies relying on convenience samples of pregnant persons testing positive for SARS-CoV-2. Efforts to address testing differences between groups could improve equitable testing practices and care for pregnant persons with SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

Background Although several coronavirus disease 2019 (COVID-19) vaccines initially showed high efficacy, there have been concerns because of waning immunity and the emergence of variants with immune escape capacity. Methods A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic severe acute respiratory syndrome coronavirus 2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period compared with unvaccinated individuals. Results The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received messenger RNA (mRNA)-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% confidence interval [CI], 82–93) 14 days to 3 months after dose 2 and 87% (95% CI, 38–97) 3 to 6 months after dose 2. During the Omicron-dominant period, VE was 56% (95% CI, 37–70) 14 days to 3 months since dose 2, 52% (95% CI, 40–62) 3 to 6 months after dose 2, 49% (95% CI, 34–61) 6+ months after dose 2, and 74% (95% CI, 62–83) 14+ days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (ie, mask wearing/high-risk behaviors) yielded similar estimates, respectively. Conclusions In Japan, where most are infection-naïve, and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level. [ABSTRACT FROM AUTHOR]

Background Work-related exposures play an important role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, yet few studies have compared SARS-CoV-2 expsoure risk across occupations and industries. Methods During September 2020 to May 2021, the Wisconsin Department of Health Services collected occupation and industry data as part of routine coronavirus disease 2019 (COVID-19) case investigations. Adults aged 18–64 years with confirmed or probable COVID-19 in Wisconsin were assigned standardized occupation and industry codes. Cumulative incidence rates were weighted for non-response and calculated using full-time equivalent (FTE) workforce denominators from the 2020 American Community Survey. Results An estimated 11.6% of workers (347 013 of 2.98 million) in Wisconsin, ages 18–64 years, had COVID-19 from September 2020 to May 2021. The highest incidence by occupation (per 100 FTE) occurred among personal care and services workers (22.1), healthcare practitioners and support staff (20.7), and protective services workers (20.7). High-risk sub-groups included nursing assistants and personal care aides (28.8), childcare workers (25.8), food and beverage service workers (25.3), personal appearance workers (24.4), and law enforcement workers (24.1). By industry, incidence was highest in healthcare (18.6); the highest risk sub-sectors were nursing care facilities (30.5) and warehousing (28.5). Conclusions This analysis represents one of the most complete examinations to date of COVID-19 incidence by occupation and industry. Our approach demonstrates the value of standardized occupational data collection by public health and may be a model for improved occupational surveillance elsewhere. Workers at higher risk of SARS-CoV-2 exposure may benefit from targeted workplace COVID-19 vaccination and mitigation efforts. [ABSTRACT FROM AUTHOR]

Background Pregnancy represents a physiological state associated with increased vulnerability to severe outcomes from infectious diseases, both for the pregnant person and developing infant. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic may have important health consequences for pregnant individuals, who may also be more reluctant than nonpregnant people to accept vaccination. Methods We sought to estimate the degree to which increased severity of SARS-CoV-2 outcomes can be attributed to pregnancy using a population-based SARS-CoV-2 case file from Ontario, Canada. Because of varying propensity to receive vaccination, and changes in dominant circulating viral strains over time, a time-matched cohort study was performed to evaluate the relative risk of severe illness in pregnant women with SARS-CoV-2 compared to other SARS-CoV-2 infected women of childbearing age (10–49 years old). Risk of severe SARS-CoV-2 outcomes was evaluated in pregnant women and time-matched nonpregnant controls using multivariable conditional logistic regression. Results Compared with the rest of the population, nonpregnant women of childbearing age had an elevated risk of infection (standardized morbidity ratio, 1.28), whereas risk of infection was reduced among pregnant women (standardized morbidity ratio, 0.43). After adjustment for confounding, pregnant women had a markedly elevated risk of hospitalization (adjusted odds ratio, 4.96; 95% confidence interval, 3.86–6.37) and intensive care unit admission (adjusted odds ratio, 6.58; 95% confidence interval, 3.29–13.18). The relative increase in hospitalization risk associated with pregnancy was greater in women without comorbidities than in those with comorbidities (P for heterogeneity,.004). Conclusions Given the safety of SARS-CoV-2 vaccines in pregnancy, risk-benefit calculus strongly favors SARS-CoV-2 vaccination in pregnant women. [ABSTRACT FROM AUTHOR]

A 22-year-old woman with uncontrolled advanced human immunodeficiency virus (HIV) infection was persistently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) beta variant for 9 months, the virus accumulating >20 additional mutations. Antiretroviral therapy suppressed HIV and cleared SARS-CoV-2 within 6 to 9 weeks. Increased vigilance is warranted to benefit affected individuals and prevent the emergence of novel SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Background Little is currently known about vaccine effectiveness (VE) for either 2 doses of Oxford-AstraZeneca (ChAdOx1) viral vector vaccine or CoronaVac (Instituto Butantan) inactivated viral vaccine followed by a third dose of mRNA vaccine (Pfizer/BioNTech) among healthcare workers (HCWs). Methods We conducted a retrospective cohort study among HCWs (aged ≥18 years) working in a private healthcare system in Brazil from January to December 2021. VE was defined as 1 – incidence rate ratio (IRR), with IRR determined using Poisson models with the occurrence of laboratory-confirmed coronavirus disease 2019 (COVID-19) infection as the outcome, adjusting for age, sex, and job type. We compared those receiving viral vector or inactivated viral primary series (2 doses) with those who received an mRNA booster. Results A total of 11 427 HCWs met the inclusion criteria. COVID-19 was confirmed in 31.5% of HCWs receiving 2 doses of CoronaVac vaccine versus 0.9% of HCWs receiving 2 doses of CoronaVac vaccine with mRNA booster (P <.001) and 9.8% of HCWs receiving 2 doses of ChAdOx1 vaccine versus 1% among HCWs receiving 2 doses of ChAdOx1 vaccine with mRNA booster (P <.001). In the adjusted analyses, the estimated VE was 92.0% for 2 CoronaVac vaccines plus mRNA booster and 60.2% for 2 ChAdOx1 vaccines plus mRNA booster, when compared with those with no mRNA booster. Of 246 samples screened for mutations, 191 (77.6%) were Delta variants. Conclusions While 2 doses of ChAdOx1 or CoronaVac vaccines prevent COVID-19, the addition of a Pfizer/BioNTech booster provided significantly more protection. [ABSTRACT FROM AUTHOR]

Background The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. Methods This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection. Results In total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P =.49) and COVID-19 (26.3 vs 25.9 days; P =.35) was similar for both groups. Conclusions Administration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection. Clinical Trials Registration NCT04323800. [ABSTRACT FROM AUTHOR]

Background The short-term effectiveness of a 2-dose regimen of the BioNTech/Pfizer BNT162b2 vaccine for adolescents has been demonstrated. However, little is known about the long-term effectiveness in this age group. It is known, however, that waning of vaccine-induced immunity against infection in adult populations is evident within a few months. Methods Leveraging the database of Maccabi Healthcare Services (MHS), we conducted a matched case-control design for evaluating the association between time since vaccination and the incidence of infections, where 2 outcomes were evaluated: documented SARS-CoV-2 infection (regardless of symptoms) and symptomatic infection (COVID-19). Cases were defined as individuals aged 12–16 with a positive polymerase chain reaction (PCR) test occurring between 15 June and 8 December 2021, when the Delta variant was dominant in Israel. Controls were adolescents who had not tested positive previously. Results We estimated a peak vaccine effectiveness between 2 weeks and 3 months following receipt of the second dose, with 85% (95% confidence interval [CI]: 84–86%) and 90% (95% CI: 89–91%) effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19), respectively. However, in line with findings for adults, waning effectiveness was evident. Long-term protection was reduced to 73% (95% CI: 68–77%) against infection and 79% (95% CI: 73–83%) against COVID-19 3–5 months after the second dose and waned to 53% (95% CI: 46–60%) against infection and 66% (95% CI: 59–72%) against COVID-19 after 5 months. Conclusions Although vaccine-induced protection against both infection and COVID-19 continues over time in adolescents, the protection wanes with time since vaccination, starting 3 months after inoculation and continuing for more than 5 months. [ABSTRACT FROM AUTHOR]

The unprovoked aggression of Russian military forces on Ukraine in February 2022 has caused a high influx of refugees, including children, to neighboring countries, particularly Poland. This caused additional pressures on the healthcare system and the need to meet challenges for public health, such as those related to infectious diseases. Here, we discuss the potential epidemiological risks associated with the war-induced influx of refugees (coronavirus disease 2019, measles, pertussis, tetanus, and poliomyelitis) and highlight the need for their swift management through institutional support, educational campaigns, counteracting antiscience misinformation, and pursuing vaccinations of refugees but also improving or maintaining good levels of immunization in populations of countries welcoming them. These are necessary actions to avoid overlapping of war and infectious diseases and associated public health challenges. [ABSTRACT FROM AUTHOR]

The article explores rapid identification of infected individuals in the early stages of an outbreak in order to isolate and prevent further transmission is of utmost importance. Public health responses utilized to accomplish this goal include identification and isolation of infected individuals based on symptom presentation then monitoring of contacts for symptoms before proceeding with further isolation.

Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic began 2 years ago, the scientific community has swiftly worked to understand the transmission, pathogenesis, and immune response of this virus to implement public health policies and ultimately project an end to the pandemic. In this perspective, we present our work identifying SARS-CoV-2 epitopes to quantify T-cell responses and review how T cells may help protect against severe disease. We examine our prior studies which demonstrate durable humoral and cell-mediated memory in natural infection and vaccination. We discuss how SARS-CoV-2–specific T cells from either natural infection or vaccination can recognize emerging variants of concern, suggesting that the currently approved vaccines may be sufficient. We also discuss how pre-existing cross-reactive T cells promote rapid development of immune memory to SARS-CoV-2. We finally posit how identifying SARS-CoV-2 epitopes can help us develop a pan-coronavirus vaccine to prepare for future pandemics. [ABSTRACT FROM AUTHOR]

Vaccine clinical trials have been essential to developing effective severe acute respiratory syndrome coronavirus 2 vaccines. The challenges of supply chain disruptions, infection control, study designs, and participant factors that affect trial procedures are reviewed, with specific solutions to streamline the clinical trial process. [ABSTRACT FROM AUTHOR]

Background Older age is associated with increased severity and death from respiratory infections, including coronavirus disease 2019 (COVID-19). The tuberculosis BCG vaccine may provide heterologous protection against nontuberculous infections and has been proposed as a potential preventive strategy against COVID-19. Methods In this multicenter, placebo-controlled trial, we randomly assigned older adults (aged ≥60 years; n = 2014) to intracutaneous vaccination with BCG vaccine (n = 1008) or placebo (n = 1006). The primary end point was the cumulative incidence of respiratory tract infections (RTIs) that required medical intervention, during 12 months of follow-up. Secondary end points included the incidence of COVID-19, and the effect of BCG vaccination on the cellular and humoral immune responses. Results The cumulative incidence of RTIs requiring medical intervention was 0.029 in the BCG-vaccinated group and 0.024 in the control group (subdistribution hazard ratio, 1.26 [98.2% confidence interval,.65–2.44]). In the BCG vaccine and placebo groups, 51 and 48 individuals, respectively tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with polymerase chain reaction (subdistribution hazard ratio, 1.053 [95% confidence interval,.71–1.56]). No difference was observed in the frequency of adverse events. BCG vaccination was associated with enhanced cytokine responses after influenza, and also partially associated after SARS-CoV-2 stimulation. In patients diagnosed with COVID-19, antibody responses after infection were significantly stronger if the volunteers had previously received BCG vaccine. Conclusions BCG vaccination had no effect on the incidence of RTIs, including SARS-CoV-2 infection, in older adult volunteers. However, it improved cytokine responses stimulated by influenza and SARS-CoV-2 and induced stronger antibody titers after COVID-19 infection. Clinical trials registration EU Clinical Trials Register 2020-001591-15 ClinicalTrials.gov NCT04417335. [ABSTRACT FROM AUTHOR]

Background After coronavirus disease 2019 (COVID-19) shelter-in-place (SIP) orders, viral suppression (VS) rates initially decreased within a safety-net human immunodeficiency virus (HIV) clinic in San Francisco, particularly among people living with HIV (PLWH) who are experiencing homelessness. We sought to determine if proactive outreach to provide social services, scaling up of in-person visits, and expansion of housing programs could reverse this decline. Methods We assessed VS 24 months before and 13 months after SIP using mixed-effects logistic regression followed by interrupted time series (ITS) analysis to examine changes in the rate of VS per month. Loss to follow-up (LTFU) was assessed via active clinic tracing. Results Data from 1816 patients were included; the median age was 51 years, 12% were female, and 14% were experiencing unstable housing/homelessness. The adjusted odds of VS increased 1.34 fold following institution of the multicomponent strategies (95% confidence interval [CI], 1.21–1.46). In the ITS analysis, the odds of VS continuously increased 1.05 fold per month over the post-intervention period (95% CI, 1.01–1.08). Among PLWH who previously experienced homelessness and successfully received housing support, the odds of VS were 1.94-fold higher (95% CI, 1.05–3.59). The 1-year LTFU rate was 2.8 per 100 person-years (95% CI, 2.2–3.5). Conclusions The VS rate increased following institution of the multicomponent strategies, with a lower LFTU rate compared with prior years. Maintaining in-person care for underserved patients, with flexible telemedicine options, along with provision of social services and permanent expansion of housing programs, will be needed to support VS among underserved populations during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background We aimed to quantify the unknown losses in health-related quality of life of coronavirus disease 2019 (COVID-19) cases using quality-adjusted lifedays (QALDs) and the recommended EQ-5D instrument in England. Methods Prospective cohort study of nonhospitalized, polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2–positive (SARS-CoV-2–positive) cases aged 12–85 years and followed up for 6 months from 1 December 2020, with cross-sectional comparison to SARS-CoV-2–negative controls. Main outcomes were QALD losses; physical symptoms; and COVID-19-related private expenditures. We analyzed results using multivariable regressions with post hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. Results Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on nonprescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 13.7 (95% confidence interval [CI]: 9.7, 17.7) QALDs, whereas those reporting symptoms at month 6 lost 32.9 (95% CI: 24.5, 37.6) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 18% of the total COVID-19-related disease burden in the England. Conclusions One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms. [ABSTRACT FROM AUTHOR]

Background There is limited evidence to date about changes to sexual and reproductive health (SRH) during the initial wave of coronavirus disease 2019 (COVID-19). To address this gap, our team organized a multicountry, cross-sectional online survey as part of a global consortium. Methods Consortium research teams conducted online surveys in 30 countries. Sampling methods included convenience, online panels, and population-representative. Primary outcomes included sexual behaviors, partner violence, and SRH service use, and we compared 3 months prior to and during policy measures to mitigate COVID-19. We conducted meta-analyses for primary outcomes and graded the certainty of the evidence. Results Among 4546 respondents with casual partners, condom use stayed the same for 3374 (74.4%), and 640 (14.1%) reported a decline. Fewer respondents reported physical or sexual partner violence during COVID-19 measures (1063 of 15 144, 7.0%) compared to before COVID-19 measures (1469 of 15 887, 9.3%). COVID-19 measures impeded access to condoms (933 of 10 790, 8.7%), contraceptives (610 of 8175, 7.5%), and human immunodeficiency virus/sexually transmitted infection (HIV/STI) testing (750 of 1965, 30.7%). Pooled estimates from meta-analysis indicate that during COVID-19 measures, 32.3% (95% confidence interval [CI], 23.9%–42.1%) of people needing HIV/STI testing had hindered access, 4.4% (95% CI, 3.4%–5.4%) experienced partner violence, and 5.8% (95% CI, 5.4%–8.2%) decreased casual partner condom use (moderate certainty of evidence for each outcome). Meta-analysis findings were robust in sensitivity analyses that examined country income level, sample size, and sampling strategy. Conclusions Open science methods are feasible to organize research studies as part of emergency responses. The initial COVID-19 wave impacted SRH behaviors and access to services across diverse global settings. [ABSTRACT FROM AUTHOR]

Background Uptake of HIV pre-exposure prophylaxis (PrEP) has been increasing in the United States since its FDA approval in 2012; however, the COVID-19 pandemic may have affected this trend. Our objective was to assess the impact of COVID-19 on PrEP prescriptions in the United States. Methods We analyzed data from a national pharmacy database from January 2017 through March 2021 to fit an interrupted time-series model that predicted PrEP prescriptions and new PrEP users had the pandemic not occurred. Observed PrEP prescriptions and new users were compared with those predicted by the model. Main outcomes were weekly numbers of PrEP prescriptions and new PrEP users based on a previously developed algorithm. The impact of the COVID-19 pandemic was quantified by computing rate ratios and percentage decreases between the observed and predicted counts during 15/3/2020–31/3/2021. Results In the absence of the pandemic, our model predicted that there would have been 1 058 162 PrEP prescriptions during 15/3/2020–31/3/2021. We observed 825 239 PrEP prescriptions, a 22.0% reduction (95% CI: 19.1–24.8%) after the emergency declaration. The model predicted 167 720 new PrEP users during the same period; we observed 125 793 new PrEP users, a 25.0% reduction (95% CI: 20.9–28.9%). The COVID-19 impact was greater among younger persons and those with commercial insurance. The impact of the pandemic varied markedly across states. Conclusions The COVID-19 pandemic disrupted an increasing trend in PrEP prescriptions in the United States, highlighting the need for innovative interventions to maintain access to HIV-prevention services during similar emergencies. [ABSTRACT FROM AUTHOR]

Background Several studies indicate that coronavirus disease 2019 (COVID-19) is primarily transmitted within indoor spaces. Therefore, environmental characterization of severe acute respiratory syndrome coronavirus 2 viral load with respect to human activity, building parameters, and environmental mitigation strategies is critical to combat disease transmission. Methods We recruited 11 participants diagnosed with COVID-19 to individually occupy a controlled chamber and conduct specified physical activities under a range of environmental conditions; we collected human and environmental samples over a period of 3 days for each participant. Results Here we show that increased viral load, measured by lower RNA cycle threshold (CT) values, in nasal samples is associated with higher viral loads in environmental aerosols and on surfaces captured in both the near field (1.2 m) and far field (3.5 m). We also found that aerosol viral load in far field is correlated with the number of particles within the range of 1–2.5 µm. Furthermore, we found that increased ventilation and filtration significantly reduced aerosol and surface viral loads, while higher relative humidity resulted in lower aerosol and higher surface viral load, consistent with an increased rate of particle deposition at higher relative humidity. Data from near field aerosol trials with high expiratory activities suggest that respiratory particles of smaller sizes (0.3–1 µm) best characterize the variance of near field aerosol viral load. Conclusions Our findings indicate that building operation practices such as ventilation, filtration, and humidification substantially reduce the environmental aerosol viral load and therefore inhalation dose, and should be prioritized to improve building health and safety. [ABSTRACT FROM AUTHOR]

Background Most children recover quickly after coronavirus disease 2019 (COVID-19), but some may have ongoing symptoms. Follow-up studies have been limited by small sample sizes and lack of appropriate controls. Methods We used national testing data to identify children aged 2–16 years with a SARS-CoV-2 PCR test during 1–7 January 2021 and randomly selected 1500 PCR-positive cases and 1500 matched PCR-negative controls. Parents were asked to complete a questionnaire about the acute illness and prespecified neurological, dermatological, sensory, respiratory, cardiovascular, gastrointestinal, mental health (including emotional and behavioral well-being), and other symptoms experienced ≥5 times at 1 month after the PCR test. Results Overall, 35.0% (859/2456) completed the questionnaire, including 38.0% (472/1242) of cases and 32% (387/1214) of controls, of whom 68% (320/472) and 40% (154/387) were symptomatic, respectively. The most prevalent acute symptoms were cough (249/859, 29.0%), fever (236/859, 27.5%), headache (236/859, 27.4%), and fatigue (231/859, 26.9%). One month later, 21/320 (6.7%) of symptomatic cases and 6/154 (4.2%) of symptomatic controls (P  = .24) experienced ongoing symptoms. Of the 65 ongoing symptoms solicited, 3 clusters were significantly (P  < .05) more common, albeit at low prevalence, among symptomatic cases (3–7%) than symptomatic controls (0–3%): neurological, sensory, and emotional and behavioral well-being. Mental health symptoms were reported by all groups but more frequently among symptomatic cases than symptomatic controls or asymptomatic children. Conclusions Children with symptomatic COVID-19 had a slightly higher prevalence of ongoing symptoms than symptomatic controls, and not as high as previously reported. Healthcare resources should be prioritized to support the mental health of children. [ABSTRACT FROM AUTHOR]

Background Following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination there is significant variability between individuals in protective antibody levels against SARS-CoV-2, and within individuals against different virus variants. However, host demographic or clinical characteristics that predict variability in cross-reactive antibody levels are not well-described. These data could inform clinicians, researchers, and policymakers on the populations most likely to require vaccine booster shots. Methods In an institutional review board–approved prospective observational cohort study of staff at St. Jude Children's Research Hospital, we identified participants with plasma samples collected after SARS-CoV-2 infection, after mRNA vaccination, and after vaccination following infection, and quantitated immunoglobulin G (IgG) levels by enzyme-linked immunosorbent assay to the spike receptor binding domain (RBD) from 5 important SARS-CoV-2 variants (Wuhan Hu-1, B.1.1.7, B.1.351, P.1, and B.1.617.2). We used regression models to identify factors that contributed to cross-reactive IgG against 1 or multiple viral variants. Results Following infection, a minority of the cohort generated cross-reactive antibodies, IgG antibodies that bound all tested variants. Those who did had increased disease severity, poor metabolic health, and were of a particular ancestry. Vaccination increased the levels of cross-reactive IgG levels in all populations, including immunocompromised, elderly, and persons with poor metabolic health. Younger people with a healthy weight mounted the highest responses. Conclusions Our findings provide important new information on individual antibody responses to infection/vaccination that could inform clinicians on populations that may require follow-on immunization. [ABSTRACT FROM AUTHOR]

Background Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious virus isolation in outpatients with coronavirus disease 2019 (COVID-19) has been associated with viral RNA levels and symptom duration, little is known about the host, disease, and viral determinants of infectious virus detection. Methods COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay. Results Among 204 participants with mild-to-moderate symptomatic COVID-19, the median nasopharyngeal viral RNA was 6.5 (interquartile range [IQR] 4.7–7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (immunoglobulin (Ig)A, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (prevalence ratio [PR] = 0.12, 95% confidence interval [CI]:.04,.36; P  = .00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; P  < .0001) and fewer days since symptom onset (PR = 0.79, 95% CI:.71,.88 per day; P  < .0001). Conclusions The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion. Clinical Trials Registration NCT04405570. [ABSTRACT FROM AUTHOR]

Background To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARIs). Methods Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for 8 viral pathogens (influenza virus [IFV], respiratory syncytial virus [RSV], human parainfluenza virus [HPIV], human adenovirus [HAdV], human metapneumovirus [HMPV], human coronavirus [HCoV], human bocavirus [HBoV], and human rhinovirus [HRV]) between 2012 and 2021, were analyzed to assess the changes in respiratory infections in China during the first COVID-19 pandemic year compared with pre-pandemic years. Results Test-positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012–2019, with changes ranging from −17.2% for RSV to −87.6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year-round, RSV, HPIV, HCoV, HRV, and HBoV resurged and went beyond historical levels during September 2020–January 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children <18 years and in northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus. Conclusions Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children. [ABSTRACT FROM AUTHOR]

The optimal dosing interval for severe acute respiratory syndrome coronavirus 2 vaccines remains controversial. In this prospective study, we compared serology results of paramedics vaccinated with mRNA vaccines at the recommended short (17–28 days) vs long (42–49 days) interval. We found that a long dosing interval resulted in higher spike, receptor binding domain, and spike N terminal domain antibody concentrations. [ABSTRACT FROM AUTHOR]

Beta (B.1.351)–variant coronavirus disease 2019 (COVID-19) disease was investigated in Qatar. Compared with the Alpha (B.1.1.7) variant, odds (95% confidence interval) of progressing to severe disease, critical disease, and COVID-19–related death were 1.24-fold (1.11–1.39), 1.49-fold (1.13–1.97), and 1.57-fold (1.03–2.43) higher, respectively, for the Beta variant. [ABSTRACT FROM AUTHOR]

Background We assessed the safety and immunogenicity of a recombinant adenovirus type-5 (Ad5)–vectored coronavirus disease 2019 (COVID-19) vaccine with homologous prime-boost regimens in healthy participants aged ≥6 years. Methods In this randomized, double-blind, placebo-controlled trial, participants received vaccine or placebo 56 days apart. Enzyme-linked immunosorbent assay (ELISA) antibodies to the receptor binding domain (RBD) and pseudovirus neutralizing antibodies were detected. Adverse events were monitored for 28 days following each vaccination. Results A total of 430 participants were enrolled in the study, with 30 participants aged 18–55 years (MID cohort), 250 aged ≥56 years (OLD cohort), and 150 aged 6–17 years (MIN cohort). Ad5-vectored COVID-19 vaccine induced significant RBD-specific ELISA antibodies that decreased with increasing age, with geometric mean titers (GMTs) of 1037.5 in the MIN cohort, 647.2 in the MID cohort, and 338.0 in the OLD cohort receiving 5 × 1010 viral particles on day 28 following boost vaccination. Pseudovirus neutralizing antibodies showed a similar pattern, with GMTs of 168.0 in the MIN cohort, 76.8 in the MID cohort, and 79.7 in the OLD cohort. A single dose in children and adolescents induced higher antibody responses than that elicited by 2 doses in adults, with GMTs of 1091.6 and 96.6 for ELISA antibody and neutralizing antibody, respectively. Homologous prime-boost vaccination was safe and tolerable. Conclusions Ad5-vectored COVID-19 vaccine with a single dose was safe and induced robust immune responses in children and adolescents aged 6–17 years. A prime-boost regimen needs further exploration for Ad5-vectored COVID-19 vaccine. Ad5-vectored COVID-19 vaccine with a single dose was safe and tolerated, and induced robust immune responses in children and adolescents aged 6-17 years. The boosting effect on immune responses of the homologous prime-boost regime given 56 days apart was limited. Clinical Trials Registration NCT04566770. [ABSTRACT FROM AUTHOR]

Background Few robust longitudinal data on long-term coronavirus disease 2019 (COVID-19) symptoms are available. We evaluated symptom onset, severity and recovery across the full spectrum of disease severity, up to one year after illness onset. Methods The RECoVERED Study is a prospective cohort study based in Amsterdam, the Netherlands. Participants aged ≥18 years were enrolled following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis via the local public health service and from hospitals. Standardized symptom questionnaires were completed at enrollment, 1 week and month later, and monthly thereafter. Clinical severity was defined according to World Health Organization (WHO) criteria. Kaplan-Meier methods were used to compare time from illness onset to symptom recovery, by clinical severity. We examined determinants of time to recovery using multivariable Cox proportional hazards models. Results Between 11 May 2020 and 1 May 2021, 342 COVID-19 patients (192 [56%] male) were enrolled, of whom 99/342 (29%) had mild, 145/342 (42%) moderate, 56/342 (16%) severe, and 42/342 (12%) critical disease. The proportion of participants who reported at least 1 persistent symptom at 12 weeks after illness onset was greater in those with severe/critical disease (86.7% [95% confidence interval {CI} = 76.5–92.7%]) compared to those with mild or moderate disease (30.7% [95% CI = 21.1–40.9%] and 63.8% [95% CI = 54.8–71.5%], respectively). At 12 months after illness onset, two-fifths of participants (40.7% [95% CI = 34.2–7.1]) continued to report ≥1 symptom. Recovery was slower in female compared to male participants (adjusted hazard ratio [aHR] 0.65 [95% CI = .47–.92]) and those with a body mass index [BMI]  ≥30kg/m2 compared to BMI <25kg/m2 (hazard ratio [HR] 0.62 [95% CI = .39–.97]). Conclusions COVID-19 symptoms persisted for one year after illness onset, even in some individuals with mild disease. Female sex and obesity were the most important determinants of speed of recovery from symptoms. [ABSTRACT FROM AUTHOR]

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (B.1.1.7) is associated with higher transmissibility than wild-type virus, becoming the dominant variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death. Methods With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and Office for National Statistics all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases with wild-type diagnosed from 16 November 2020 to 11 January 2021. Results Using data from 185 234 people who tested positive for SARS-CoV-2 in the community (alpha = 93 153; wild-type = 92 081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (adjusted hazard ratio [aHR]: 1.73; 95% confidence interval [CI]: 1.41–2.13; P  < .0001) and 62% higher hazards of hospital admission (1.62; 1.48–1.78; P  < .0001) compared with wild-type virus. Among patients already admitted to the intensive care unit, the association between alpha and increased all-cause mortality was smaller and the CI included the null (aHR: 1.20; 95% CI:.74–1.95; P  = .45). Conclusions The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalization and mortality than wild-type virus. [ABSTRACT FROM AUTHOR]

Background The incidence of invasive pneumococcal disease (IPD) declined during the COVID-19 pandemic. Previous studies hypothesized that this was due to reduced pneumococcal transmission resulting from nonpharmaceutical interventions. We used multiple ongoing cohort surveillance projects in children <5 years to test this hypothesis. Methods The first SARS-CoV-2 cases were detected in February 2020, resulting in a full lockdown, followed by several partial restrictions. Data from ongoing surveillance projects captured the incidence dynamics of community-acquired alveolar pneumonia (CAAP), nonalveolar lower respiratory infections necessitating chest X-rays (NA-LRIs), nasopharyngeal pneumococcal carriage in nonrespiratory visits, nasopharyngeal respiratory virus detection (by polymerase chain reaction), and nationwide IPD. Monthly rates (January 2020 through February 2021 vs mean monthly rates 2016–2019 [expected rates]) adjusted for age and ethnicity were compared. Results CAAP and bacteremic pneumococcal pneumonia were strongly reduced (incidence rate ratios [IRRs]:.07 and.19, respectively); NA-LRIs and nonpneumonia IPD were also reduced by a lesser magnitude (IRRs:.46 and.42, respectively). In contrast, pneumococcal carriage prevalence was only slightly reduced, and density of colonization and pneumococcal serotype distributions were similar to previous years. The decline in pneumococcus-associated disease was temporally associated with a full suppression of respiratory syncytial virus, influenza viruses, and human metapneumovirus, often implicated as co-pathogens with pneumococcus. In contrast, adenovirus, rhinovirus, and parainfluenza activities were within or above expected levels. Conclusions Reductions in pneumococcal and pneumococcus-associated diseases occurring during the COVID-19 pandemic in Israel were not predominantly related to reduced pneumococcal carriage and density but were strongly associated with the disappearance of specific respiratory viruses. [ABSTRACT FROM AUTHOR]