Acute hepatitis of unknown origin in children: A combination of factors.

On 5 April 2022, the World Health Organization was notified of 10 cases of severe acute hepatitis of unknown etiology in children under 10 years of age in the United Kingdom. Although the exact cause of a proportion of pediatric acute hepatitis and acute liver failure cases was unclear, the above event has caused widespread concern worldwide. As of 14 September 2022, approximately 1,296 probable cases of acute hepatitis of unknown etiology have been reported from 37 countries/regions, of which approximately 55 required or received liver transplantation and 29 died. Although the etiology of acute hepatitis of unknown origin in children remains unclear, many hypotheses have been proposed about the disease. Instead of individual factors such as "adenovirus infection," "SARS-CoV-2 related," and "Adeno-associated virus 2 with helper virus coinfection," it is more likely due to a combination of factors. Accordingly, there is an urgent need for more data and research to clarify the disease etiology. This review aims to provide a historical perspective of acute hepatitis of unknown etiology in children in the past decades and summarize the current hypothesis and evidence on this emerging disease.

Identification of serum metabolites enhancing inflammatory responses in COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a strong production of inflammatory cytokines such as TNF and IL-6, which underlie the severity of the disease. However, the molecular mechanisms responsible for such a strong immune response remains unclear. Here, utilizing targeted tandem mass spectrometry to analyze serum metabolome and lipidome in COVID-19 patients at different temporal stages, we identified that 611 metabolites (of 1,039) were significantly altered in COVID-19 patients. Among them, two metabolites, agmatine and putrescine, were prominently elevated in the serum of patients; and 2-quinolinecarboxylate was changed in a biphasic manner, elevated during early COVID-19 infection but levelled off. When tested in mouse embryonic fibroblasts (MEFs) and macrophages, these 3 metabolites were found to activate the NF-κB pathway that plays a pivotal role in governing cytokine production. Importantly, these metabolites were each able to cause strong increase of TNF and IL-6 levels when administered to wildtype mice, but not in the mice lacking NF-κB. Intriguingly, these metabolites have little effects on the activation of interferon regulatory factors (IRFs) for the production of type I interferons (IFNs) for antiviral defenses. These data suggest that circulating metabolites resulting from COVID-19 infection may act as effectors to elicit the peculiar systemic inflammatory responses, exhibiting severely strong proinflammatory cytokine production with limited induction of the interferons. Our study may provide a rationale for development of drugs to alleviate inflammation in COVID-19 patients.

Association of menopausal status with COVID-19 outcomes: a propensity score matching analysis.

BACKGROUND: Despite the growing number of studies on the coronavirus disease-19 (COVID-19), little is known about the association of menopausal status with COVID-19 outcomes. MATERIALS AND METHODS: In this retrospective study, we included 336 COVID-19 inpatients between February 15, 2020 and April 30, 2020 at the Taikang Tongji Hospital (Wuhan), China. Electronic medical records including patient demographics, laboratory results, and chest computed tomography (CT) images were reviewed. RESULTS: In total, 300 patients with complete clinical outcomes were included for analysis. The mean age was 65.3 years, and most patients were women (n = 167, 55.7%). Over 50% of patients presented with comorbidities, with hypertension (63.5%) being the most common comorbidity. After propensity score matching, results showed that men had significantly higher odds than premenopausal women for developing severe disease type (23.7% vs. 0%, OR 17.12, 95% CI 1.00-293.60; p = 0.003) and bilateral lung infiltration (86.1% vs. 64.7%, OR 3.39, 95% CI 1.08-10.64; p = 0.04), but not for mortality (2.0% vs. 0%, OR 0.88, 95% CI 0.04-19.12, p = 1.00). However, non-significant difference was observed among men and postmenopausal women in the percentage of severe disease type (32.7% vs. 41.7%, OR 0.68, 95% CI 0.37-1.24, p = 0.21), bilateral lung infiltration (86.1% vs. 91.7%, OR 0.56, 95% CI 0.22-1.47, p = 0.24), and mortality (2.0% vs. 6.0%, OR 0.32, 95% CI 0.06-1.69, p = 0.25). CONCLUSIONS: Men had higher disease severity than premenopausal women, while the differences disappeared between postmenopausal women and men. These findings support aggressive treatment for the poor prognosis of postmenopausal women in clinical practice.

Association of Menopausal Status with COVID-19 outcomes: a Propensity Score-Matching Analysis (preprint)

Background: Despite the growing number of studies on the Coronavirus Disease-19 (COVID-19), little is known about the association of menopausal status with COVID-19 outcomes. Materials: and methods: In this retrospective study, we included 336 COVID-19 in-patients between February 15, 2020 and April 30, 2020 at the Taikang Tongji Hospital (Wuhan), China. Electronic medical records, including patient demographics, laboratory results, and chest computed tomography (CT) images were reviewed. Results: : In total, 300 patients with complete clinical outcomes were included for analysis. The mean age was 65.3 years and most patients were women (n=167, 55.7%). Over 50% of patients presented with comorbidities, with hypertension (63.5%) being the most common comorbidity. After propensity-score matching, results showed that men had significantly higher odds than premenopausal women for developing severe disease type (23.7% vs. 0%, OR 17.12, 95% CI 1.00–293.60; p =0.003) and bilateral lung infiltration (86.1% vs. 64.7%, OR 3.39, 95% CI 1.08–10.64; p = 0.04), but not for mortality (2.0% vs. 0%, OR 0.88, 95% CI 0.04–19.12, p =1.00). However, non-significant difference was observed among men and post-menopause women in the percentage of severe disease type (32.7% vs. 41.7%, OR 0.68, 95% CI 0.37–1.24, p =0.21) and bilateral lung infiltration (86.1% vs. 91.7%, OR 0.56, 95% CI 0.22–1.47, p =0.24), mortality (2.0% vs. 6.0%, OR 0.32, 95% CI 0.06–1.69, p =0.25). Conclusions: : Men had higher disease severity than premenopausal women, while the differences disappeared between postmenopausal women and men. These findings support aggressive treatment for the poor-prognosis of postmenopausal women in clinical practice.

Internet Hospitals Help Prevent and Control the Epidemic of COVID-19 in China: Multicenter User Profiling Study.

BACKGROUND: During the spread of the novel coronavirus disease (COVID-19), internet hospitals in China were engaged with epidemic prevention and control, offering epidemic-related online services and medical support to the public. OBJECTIVE: The aim of this study is to explore the role of internet hospitals during the prevention and control of the COVID-19 outbreak in China. METHODS: Online epidemic-related consultations from multicenter internet hospitals in China during the COVID-19 epidemic were collected. The counselees were described and classified into seven type groups. Symptoms were recorded and compared with reported patients with COVID-19. Hypochondriacal suspicion and offline visit motivation were detected within each counselees' group to evaluate the social panic of the epidemic along with the consequent medical-seeking behaviors. The counselees' motivation and the doctors' recommendation for an offline visit were compared. Risk factors affecting the counselees' tendency of hypochondriacal suspicion and offline visit motivation were explored by logistic regression models. The epidemic prevention and control measures based on internet hospitals were listed, and the corresponding effects were discussed. RESULTS: A total of 4913 consultations were enrolled for analysis with the median age of the counselees at 28 years (IQR 22-33 years). There were 104 (2.12%) healthy counselees, 147 (2.99%) hypochondriacal counselees, 34 (0.69%) exposed counselees, 853 (17.36%) mildly suspicious counselees, 42 (0.85%) moderately suspicious counselees, 3550 (72.26%) highly suspicious counselees, and 183 (3.72%) severely suspicious counselees. A total of 94.20% (n=4628) of counselees had epidemic-related symptoms with a distribution similar to those of COVID-19. The hypochondriacal suspicion (n=2167, 44.11%) was common. The counselees' motivation and the doctors' recommendation for offline visits were inconsistent (P<.001) with a Cohen kappa score of 0.039, indicating improper medical-seeking behaviors. Adult counselees (odds ratio [OR]=1.816, P<.001) with epidemiological exposure (OR 7.568, P<.001), shortness of breath (OR 1.440, P=.001), diarrhea (OR 1.272, P=.04), and unrelated symptoms (OR 1.509, P<.001) were more likely to have hypochondriacal suspicion. Counselees with severe illnesses (OR 2.303, P<.001), fever (OR 1.660, P<.001), epidemiological exposure history (OR 1.440, P=.01), and hypochondriacal suspicion (OR 4.826, P<.001) were more likely to attempt an offline visit. Reattending counselees (OR 0.545, P=.002) were less motivated to go to the offline clinic. CONCLUSIONS: Internet hospitals can serve different types of epidemic counselees, offer essential medical supports to the public during the COVID-19 outbreak, reduce the social panic, promote social distancing, enhance the public's ability of self-protection, correct improper medical-seeking behaviors, reduce the chance of nosocomial cross-infection, and facilitate epidemiological screening, thus, playing an important role on preventing and controlling COVID-19.