Racial/Ethnic Differences in Long-COVID-Associated Symptoms among Pediatrics Population: Findings from Difference-in-differences Analyses in RECOVER Program (preprint)

Racial/ethnic differences are associated with the potential symptoms and conditions of post-acute sequelae SARS-CoV-2 infection (PASC) in adults. These differences may exist among children and warrant further exploration. We conducted a retrospective cohort study for children and adolescents under the age of 21 from the thirteen institutions in the RECOVER Initiative. The cohort is 225,723 patients with SARS-CoV-2 infection or COVID-19 diagnosis and 677,448 patients without SARS-CoV-2 infection or COVID-19 diagnosis between March 2020 and October 2022. The study compared minor racial/ethnic groups to Non-Hispanic White (NHW) individuals, stratified by severity during the acute phase of COVID-19. Within the severe group, Asian American/Pacific Islanders (AAPI) had a higher prevalence of fever/chills and respiratory symptoms, Hispanic patients showed greater hair loss prevalence in severe COVID-19 cases, while Non-Hispanic Black (NHB) patients had fewer skin symptoms in comparison to NHW patients. Within the non-severe group, AAPI patients had increased POTS/dysautonomia and respiratory symptoms, and NHB patients showed more cognitive symptoms than NHW patients. In conclusion, racial/ethnic differences related to COVID-19 exist among specific PASC symptoms and conditions in pediatrics, and these differences are associated with the severity of illness during acute COVID-19.

Real-world Effectiveness and Causal Mediation Study of BNT162b2 on Long COVID Risks in Children and Adolescents (preprint)

BackgroundThe impact of pre-infection vaccination on the risk of long COVID remains unclear in the pediatric population. Further, it is unknown if such pre-infection vaccination can mitigate the risk of long COVID beyond its established protective benefits against SARS-CoV-2 infection. ObjectiveTo assess the effectiveness of BNT162b2 on long COVID risks with various strains of the SARS-CoV-2 virus in children and adolescents, using comparative effectiveness methods. To disentangle the overall effectiveness of the vaccine on long COVID outcomes into its independent impact and indirect impact via prevention of SARS-CoV-2 infections, using causal mediation analysis. DesignReal-world vaccine effectiveness study and mediation analysis in three independent cohorts: adolescents (12 to 20 years) during the Delta phase, children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. SettingTwenty health systems in the RECOVER PCORnet electronic health record (EHR) Program. Participants112,590 adolescents (88,811 vaccinated) in the Delta period, 188,894 children (101,277 vaccinated), and 84,735 adolescents (37,724 vaccinated) in the Omicron period. ExposuresFirst dose of the BNT162b2 vaccine vs. no receipt of COVID-19 vaccine. MeasurementsOutcomes of interest include conclusive or probable diagnosis of long COVID following a documented SARS-CoV-2 infection, and body-system-specific condition clusters of post-acute sequelae of SARS-CoV-2 infection (PASC), such as cardiac, gastrointestinal, musculoskeletal, respiratory, and syndromic categories. The effectiveness was reported as (1-relative risk)*100 and mediating effects were reported as relative risks. ResultsDuring the Delta period, the estimated effectiveness of the BNT162b2 vaccine against long COVID among adolescents was 95.4% (95% CI: 90.9% to 97.7%). During the Omicron phase, the estimated effectiveness against long COVID among children was 60.2% (95% CI: 40.3% to 73.5%) and 75.1% (95% CI: 50.4% to 87.5%) among adolescents. The direct effect of vaccination, defined as the effect beyond their impact on SARS-CoV-2 infections, was found to be statistically non-significant in all three study cohorts, with estimates of 1.08 (95% CI: 0.75 to 1.55) in the Delta study among adolescents, 1.24 (95% CI: 0.92 to 1.66) among children and 0.91 (95% CI: 0.69 to 1.19) among adolescents in the Omicron studies. Meanwhile, the estimated indirect effects, which are effects through protecting SARS-CoV-2 infections, were estimated as 0.04 (95% CI: 0.03 to 0.05) among adolescents during Delta phase, 0.31 (95% CI: 0.23 to 0.42) among children and 0.21 (95% CI: 0.16 to 0.27) among adolescents during the Omicron period. LimitationsObservational study design and potentially undocumented infection. ConclusionsOur study suggests that BNT162b2 was effective in reducing risk of long COVID outcomes in children and adolescents during the Delta and Omicron periods. The mediation analysis indicates the vaccines effectiveness is primarily derived from its role in reducing the risk of SARS-CoV-2 infection. Primary Funding SourceNational Institutes of Health.

The Effect of Health Action Process Approach on Adherence to Infection Prevention and Control Measures Among Chinese Healthcare Workers in the Post-pandemic Period of COVID-19 (preprint)

Background: Although the COVID-19 pandemic has been brought under control, strict infection and control measures are still recommended for healthcare workers to prevent the rebound of the pandemic. However, adherence to prevention measures might be decreased due to fatigue caused by the prolonged duration of the pandemic.  Objective: This study examines the effects of social-cognitive factors suggested in the health action process approach on adherence to infection prevention and control measures among Chinese healthcare workers two years after the onset of the COVID-19 pandemic. Methods: A total of 521 healthcare workers from two COVID-19 designated hospitals in Beijing participated in the survey in August 2021 and reported risk perception, outcome expectance, action self-efficacy, preventive intention, action control, and prevention behaviors during work. Results: 1) Action self-efficacy and outcome expectancy were positively associated with intention to adhere to preventive measures. 2) Action control mediated the association between intention and preventive behaviors during work. Conclusion: Social-cognitive factors such as action self-efficacy, action control, and intention should be addressed to improve healthcare workers’ adherence to infection and control measures during the COVID-19 pandemic.

Current State, Development and Future Directions of Medical Waste Valorization

Elevated medical waste has urged the improvement of sustainable medical waste treatments. A bibliometric analysis is initially conducted to investigate scientific development of medical waste management to pinpoint the publication trends, influential articles, journals and countries and study hotspots. Publications on medical waste and its management sharply increased since 2020. The most influential article was written by Klemešet al., and 'Waste Management and Research';is the most productive journal. India, China, the United Kingdom, Iran and Italy have published the most works. The research spotlights have switched from 'human';and 'sustainable development';in 2019 to 'COVID-19';and 'circular economy';in 2021. Since government acts essentially in handling medical waste and controlling disease transmission, rule implementations among the abovementioned countries are summarized to seek gaps between scientific advancement and regulatory frameworks. For accomplishing a circular economy, waste-to-energy technologies (incineration, gasification, pyrolysis, plasma-based treatments, carbonization, hydrogenation, liquefaction, biomethanation, fermentation and esterification) are comprehensively reviewed. Incineration, gasification, pyrolysis and carbonization are relatively feasible methods, their characteristics and limitations are further compared. By holistically reviewing current status of medical waste research, the focal points involved in management at the policy and technical level have been highlighted to find proper routes for medical waste valorization.

Wastewater-based epidemiology predicts COVID-19-induced hospital and ICU admission numbers in over 100 USA counties (preprint)

With the ease of coronavirus disease (COVID-19) emergency status globally, a population-wide low-cost prediction for COVID-19-induced hospitalization and intensive care unit (ICU) admission numbers is essential for healthcare systems. For the first time, we evaluated the feasibility of using wastewater-based epidemiology (WBE) to predict COVID-19-induced hospitalization and ICU admission numbers in 102 counties across 42 states in the United States of America (USA), covering a population of nearly 60 million, through random forest models using the county-level weekly wastewater surveillance data (over 15 months). WBE-based models accurately predicted the admission numbers, allowing a preparation window of 5-28 days. In real applications, periodically updated WBE-based models showed good accuracy and transferability, with mean absolute error within 20 and 2 patients/100k population for upcoming hospitalization and ICU admission numbers in 28 days, respectively. Our study demonstrated the potential of using WBE as a cost-effective method to provide early warnings for healthcare systems.

Lung Ultrasound in Pediatric Acute Respiratory Distress Syndrome Received Extracorporeal Membrane Oxygenation: A Prospective Cohort Study

Objective The aim of this study was to assess the prognostic value of the lung ultrasound (LUS) score in patients with pediatric acute respiratory distress syndrome (pARDS) who received extracorporeal membrane oxygenation (ECMO). Methods A prospective cohort study was conducted in a pediatric intensive care unit (PICU) of a tertiary hospital from January 2016 to June 2021. The severe pARDS patients who received ECMO were enrolled in this study. LUS score was measured at initiation of ECMO (LUS-0 h), then at 24 h (LUS-24 h), 48 h (LUS-48 h), and 72 h (LUS-72 h) during ECMO, and when weaned from ECMO (LUS-wean). The value of LUS scores at the first 3 days of ECMO as a prognostic predictor was analyzed. Results Twenty-nine children with severe pARDS who received ECMO were enrolled with a median age of 26 (IQR 9, 79) months. The median duration of ECMO support was 162 (IQR 86, 273) h and the PICU mortality was 31.0% (9/29). The values of LUS-72 h and LUS-wean were significantly lower in survivors than that in non-survivors (both P < 0.001). Daily fluid balance volume during the first 3 days of ECMO support were strongly correlated with LUS score [1st day: r = 0.460, P = 0.014;2nd day: r = 0.540, P = 0.003;3rd day: r = 0.589, P = 0.001]. The AUC of LUS-72 h for predicting PICU mortality in these patients was 1.000, and the cutoff value of LUS-72 h was 24 with a sensitivity of 100.0% and a specificity of 100.0%. Furthermore, patients were stratified in two groups of LUS-72 h ≥ 24 and LUS-72 h < 24. Consistently, PICU mortality, length of PICU stay, ratio of shock, vasoactive index score value, and the need for continuous renal replacement therapy were significantly higher in the group of LUS-72 h ≥ 24 than in the group of LUS-72 h < 24 (all P < 0.05). Conclusion Lung ultrasound score is a promising tool for predicting the prognosis in patients with ARDS under ECMO support. Moreover, LUS-72 h ≥ 24 is associated with high risk of PICU mortality in patients with pARDS who received ECMO.

Trajectories of Neurological Recovery 12 Months after Hospitalization for COVID-19: A Prospective Longitudinal Study (preprint)

ABSTRACT Background/Objectives Little is known about trajectories of recovery 12-months after hospitalization for severe COVID. Methods We conducted a prospective, longitudinal cohort study of patients with and without neurological complications during index hospitalization for COVID-19 from March 10, 2020-May 20, 2020. Phone follow-up batteries were performed at 6- and 12-months post-COVID symptom onset. The primary 12-month outcome was the modified Rankin Scale (mRS) comparing patients with or without neurological complications using multivariable ordinal analysis. Secondary outcomes included: activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA) and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. Changes in outcome scores from 6 to 12-months were compared using non-parametric paired-samples sign test. Results Twelve-month follow-up was completed in N=242 patients (median age 65, 64% male, 34% intubated during hospitalization) and N=174 completed both 6- and 12-month follow-up. At 12-months 197/227 (87%) had ≥1 abnormal metric: mRS>0 (75%), Barthel<100 (64%), t-MoCA≤18 (50%), high anxiety (7%), depression (4%), fatigue (9%) and poor sleep (10%). 12-month mRS scores did not differ significantly among those with (N=113) or without (N=129) neurological complications during hospitalization after adjusting for age, sex, race, pre-COVID mRS and intubation status (adjusted OR 1.4, 95% CI0.8-2.5), though those with neurological complications had higher fatigue scores (T-score 47 vs 44, P=0.037). Significant improvements in outcome trajectories from 6- to 12-months were observed in t-MoCA scores (56% improved, median difference 1 point, P=0.002), and Neuro-QoL anxiety scores (45% improved, P=0.003). Non-significant improvements occurred in fatigue, sleep and depression scores in 48%, 48% and 38% of patients, respectively. Barthel and mRS scores remained unchanged between 6 and 12-months in >50% of patients. Discussion At 12-months post-hospitalization for severe COVID, 87% of patients had ongoing abnormalities in functional, cognitive or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a prior history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurological complications during index hospitalization. However, significant improvements in cognitive (t-MoCA) and anxiety (Neuro-QoL) scores occurred in 56% and 45% of patients, respectively, between 6- to 12-months. These results may not be generalizable to those with mild/moderate COVID.

Engineering Extracellular Vesicles Enriched with Palmitoylated ACE2 as COVID-19 Therapy (Adv. Mater. 49/2021)

COVID-19 Therapy In their work reported in article number 2103471, Long Zhang, Fangfang Zhou, and co-workers fuse the S-palmitoylation-dependent plasma membrane (PM) targeting sequence with angiotensin converting enzyme 2 (ACE2) and engineer extracellular vesicles (EVs) on their surface enriched with palmitoylated ACE2 (PM-ACE2-EVs). The PM-ACE2-EVs can bind to the SARS-CoV-2 S-RBD with high affinity and block its interaction with cell-surface ACE2, thereby preventing SARS-CoV-2 from entering the host cell. This study provides a novel EV-based candidate for prophylactic and therapeutic treatment against COVID-19.

A Prospective Study of Long-Term Outcomes Among Hospitalized COVID-19 Patients with and without Neurological Complications (preprint)

BackgroundLittle is known regarding long-term outcomes of patients hospitalized with COVID-19. MethodsWe conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. ResultsOf 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N=196 neurological patients and N=186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on [≥]1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 2.03, 95%CI 1.22-3.40, P=0.01), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P=0.01) and were less likely to return to work than controls (41% versus 64%, P=0.04). Cognitive and Neuro-QOL metrics were similar between groups. ConclusionsAbnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.

Air quality characteristics in Wuhan (China) during the 2020 COVID-19 pandemic.

Understanding the relationship between air quality, pollution emission control measures, and meteorological conditions is important for developing effective air quality improvement policies. In this study, we used pollution monitoring and meteorological data from January to May 2020 to analyze the air quality characteristics during the COVID-19 lockdown in Wuhan, which lasted from January 23 to April 8, 2020. Compared with the same period in 2019, the air quality in 2020 was significantly better. The total excellent and good air quality rates increased by 17.58%-90.08% in 2020; concentrations of NO2, particulate matter with a diameter <10 µm (PM10) and <2.5 µm (PM2.5), and total volatile organic compounds (TVOCs) also decreased by 38.23%, 30.25%, 32.92%, and 39.80%, respectively. Moreover, the number of days with NO2, PM10, and PM2.5 as the primary pollutants decreased by approximately 10%, 9%, and 15%, respectively. We compared the wind direction, wind speed, temperature, and relative humidity in January-April 2020, 2019, 2018, and 2017 and found no obvious correlation between meteorological factors and improved air quality during the 2020 lockdown. The implementation of strict lockdown measures, such as home quarantining, traffic restrictions, and non-essential enterprise shutdowns, was the dominant cause for the substantial air quality improvement during the 2020 COVID-19 lockdown in Wuhan.

Diverse Functional Autoantibodies in Patients with COVID-19 (preprint)

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1-8. While pathological innate immune activation is well documented in severe disease1, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the "exoproteome"). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.

Etiologic Subtypes of Ischemic Stroke in SARS-COV-2 Virus patients (preprint)

ObjectiveTo describe the ischemic stroke subtypes related to COVID-19 in a cohort of NYC hospitals and explore their etiopathogenesis. BackgroundExtra-pulmonary involvement of COVID-19 has been reported in the hepatic, renal and hematological systems. Most neurological manifestations are non-focal, but few have reported the characteristics of ischemic strokes or investigated its pathophysiology. MethodsData were collected prospectively from March 15 to April 15, 2020 from four centers in New York City to review possible ischemic stroke types seen in COVID-19 positive patients. Patient presentation, demographics, other related vascular risk factors, associated laboratory and coagulation markers, as well as imaging and outcomes for consecutive stroke patients positive for SARS-COV2 infection over the period studied were collected. ResultsIn our study, the age range of patients was 25-75 with no significant male preponderance. The median age of LVO patients was 48. Stroke was the presenting and hospitalizing event in 70%. One fifth of patients did not have common risk factors for ischemic stroke and none had atrial fibrillation, coronary or cerebrovascular disease, or were smokers. Half had a poor outcome with 40% ending in mortality (60% in LVO group) and one in a critical condition due ARDS. All had high neutrophil/lymphocyte ratio except one who demonstrated some neurological recovery. D-dimer levels showed mild to severe elevation when collected. None of the LVO cases had known cardiac risk factors but two out of five were found to have cardiac abnormalities during their hospitalization. All LVOs had hypercoagulable lab markers especially elevated D-dimer and/or fibrinogen. The LVO patients were younger and sicker with a median age of 46 and mean NIHSS of 24 as opposed to non-LVOs with a median age of 62 and mean NIHSS of 6 respectively. ConclusionCOVID-19 related ischemic events can be small vessel, branch emboli or large vessel occlusions. The latter is often associated with either a hypercoagulable state or cardio-embolism. Patient outcomes were worse when multi-organ or pulmonary system failure prevailed.