Long term neuropsychiatric consequences in COVID-19 survivors: Cognitive impairment and inflammatory underpinnings fifteen months after discharge.

BACKGROUND: Emerging evidence shows that cognitive dysfunction may occur following coronavirus disease 19 (COVID-19) infection which is one of the most common symptoms reported in researches of "Long COVID". Several inflammatory markers are known to be elevated in COVID-19 survivors and the relationship between long-term inflammation changes and cognitive function remains unknown. METHODS: We assessed cognitive function and neuropsychiatric symptoms of 66 COVID-19 survivors and 79 healthy controls (HCs) matched with sex, age, and education level using a digital, gamified cognitive function evaluation tool and questionnaires at 15 months after discharge. Venous blood samples were collected to measure cytokine levels. We performed correlation analyses and multiple linear regression analysis to identify the factors potentially related to cognitive function. RESULTS: The COVID-19 survivors performed less well on the Trails (p = 0.047) than the HCs, but most of them did not report subjective neuropsychiatric symptoms. Intensive care unit experience (ß = -2.247, p < 0.0001) and self-perceived disease severity (ß = -1.522, p = 0.007) were positively correlated, whereas years of education (ß = 0.098, p = 0.013) was negatively associated with the performance on the Trails. Moreover, the abnormally elevated TNF-α levels (r = -0.19, p = 0.040) were negatively correlated with performance on the Trails in COVID-19 group. CONCLUSION: Our findings suggest that COVID-19 survivors show long-term cognitive impairment in executive function, even at 15 months after discharge. Serum TNF-α levels may be an underlying mechanism of long-term cognitive impairment in patients recovering from COVID-19.

Trends in Research of Prenatal Stress From 2011 to 2021: A Bibliometric Study.

Background: Maternal stress during pregnancy can raise the risk of mental disorders in offspring. The continuous emergence of clinical concepts and the introduction of new technologies are great challenges. In this study, through bibliometric analysis, the research trends and hotspots on prenatal stress (PS) were explored to comprehend clinical treatments and recommend future scientific research directions. Methods: Studies on PS published on the Web of Science Core Collection (WoSCC) database between 2011 and 2021 were reviewed. Bibliometric analysis was conducted according to the number of publications, keywords, journals, citations, affiliations, and countries. With the data collected from the WoSCC, visualization of geographic distribution; clustering analysis of keywords, affiliations, and authors; and descriptive analysis and review of PS were carried out. Results: A total of 7,087 articles published in 2011-2021 were retrieved. During this period, the number of publications increased. Psychoneuroendocrinology is the leading journal on PS. The largest contributor was the United States. The University of California system was leading among institutions conducting relevant research. Wang H, King S, and Tain YL were scholars with significant contributions. Hotspots were classified into four clusters, namely, pregnancy, prenatal stress, oxidative stress, and growth. Conclusion: The number of studies on PS increased. Journals, countries, institutions, researchers with the most contributions, and most cited articles worldwide were extracted. Studies have mostly concentrated on treating diseases, the application of new technologies, and the analysis of epidemiological characteristics. Multidisciplinary integration is becoming the focus of current development. Epigenetics is increasingly used in studies on PS. Thus, it constitutes a solid foundation for future clinical medical and scientific research.

Antibiotic-Induced Primary Biles Inhibit SARS-CoV-2 Endoribonuclease Nsp15 Activity in Mouse Gut

The gut microbiome profile of COVID-19 patients was found to correlate with a viral load of SARS-CoV-2, COVID-19 severity, and dysfunctional immune responses, suggesting that gut microbiota may be involved in anti-infection. In order to investigate the role of gut microbiota in anti-infection against SARS-CoV-2, we established a high-throughput in vitro screening system for COVID-19 therapeutics by targeting the endoribonuclease (Nsp15). We also evaluated the activity inhibition of the target by substances of intestinal origin, using a mouse model in an attempt to explore the interactions between gut microbiota and SARS-CoV-2. The results unexpectedly revealed that antibiotic treatment induced the appearance of substances with Nsp15 activity inhibition in the intestine of mice. Comprehensive analysis based on functional profiling of the fecal metagenomes and endoribonuclease assay of antibiotic-enriched bacteria and metabolites demonstrated that the Nsp15 inhibitors were the primary bile acids that accumulated in the gut as a result of antibiotic-induced deficiency of bile acid metabolizing microbes. This study provides a new perspective on the development of COVID-19 therapeutics using primary bile acids.

SARS-CoV-2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global pandemic. The virus is rapidly evolving, characterized by the emergence of several major variants. Stable prefusion spike protein (Pre) is the immunogen in current vaccines but is limited in protecting against different variants. Here, the immune responses induced by the relatively conserved stem subunit (S2) of spike protein versus Pre are investigated. Pre generates the most robust neutralization responses against SARS-CoV-2 variants in vesicular stomatitis virus pseudovirus-based assessment but elicits less antibody-dependent cellular cytotoxicity (ADCC) activity than S2. By contrast, S2 induces the most balanced immunoglobulin G (IgG) antibodies with potent and broad ADCC activity although produces weaker neutralization. The immunogenicity of S2 and Pre improves by incorporating the two proteins into double-layered protein nanoparticles. The resulting protein nanoparticles Pre/S2 elicit higher neutralizing antibodies than Pre alone, and stronger ADCC than S2 alone. Moreover, nanoparticles produce more potent and balanced serum IgG antibodies than the corresponding soluble protein mixture, and the immune responses are sustained for at least four months after the immunization. Thus, the double-layered protein nanoparticles have the potential to be developed into broader SARS-CoV-2 vaccines with excellent safety profiles.

Prognostic Factors for COVID-19 Hospitalized Patients with Preexisting Type 2 Diabetes.

BACKGROUND: Type 2 diabetes (T2D) as a worldwide chronic disease combined with the COVID-19 pandemic prompts the need for improving the management of hospitalized COVID-19 patients with preexisting T2D to reduce complications and the risk of death. This study aimed to identify clinical factors associated with COVID-19 outcomes specifically targeted at T2D patients and build an individualized risk prediction nomogram for risk stratification and early clinical intervention to reduce mortality. METHODS: In this retrospective study, the clinical characteristics of 382 confirmed COVID-19 patients, consisting of 108 with and 274 without preexisting T2D, from January 8 to March 7, 2020, in Tianyou Hospital in Wuhan, China, were collected and analyzed. Univariate and multivariate Cox regression models were performed to identify specific clinical factors associated with mortality of COVID-19 patients with T2D. An individualized risk prediction nomogram was developed and evaluated by discrimination and calibration. RESULTS: Nearly 15% (16/108) of hospitalized COVID-19 patients with T2D died. Twelve risk factors predictive of mortality were identified. Older age (HR = 1.076, 95% CI = 1.014-1.143, p=0.016), elevated glucose level (HR = 1.153, 95% CI = 1.038-1.28, p=0.0079), increased serum amyloid A (SAA) (HR = 1.007, 95% CI = 1.001-1.014, p=0.022), diabetes treatment with only oral diabetes medication (HR = 0.152, 95%CI = 0.032-0.73, p=0.0036), and oral medication plus insulin (HR = 0.095, 95%CI = 0.019-0.462, p=0.019) were independent prognostic factors. A nomogram based on these prognostic factors was built for early prediction of 7-day, 14-day, and 21-day survival of diabetes patients. High concordance index (C-index) was achieved, and the calibration curves showed the model had good prediction ability within three weeks of COVID-19 onset. CONCLUSIONS: By incorporating specific prognostic factors, this study provided a user-friendly graphical risk prediction tool for clinicians to quickly identify high-risk T2D patients hospitalized for COVID-19.

Abnormal Liver Function Tests Were Associated With Adverse Clinical Outcomes: An Observational Cohort Study of 2,912 Patients With COVID-19.

Background and Aim: The impact of liver function test (LFTs) abnormality on adverse clinical outcomes in coronavirus disease 2019 (COVID-19) patients remains controversial. The aim of this study was to assess the impact of abnormal LFTs on clinical outcomes in a large cohort of hospitalized patients with COVID-19. Methods: We retrospectively collected data on 2,912 consecutive patients with COVID-19 who were admitted to a makeshift hospital in China between 5 February and 23 March 2020. The association between LFTs abnormalities (baseline and peak values) and clinical outcomes was measured by using Cox regression models. Results: On admission 1,414 patients (48.6%) had abnormal LFTs, with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) elevation in 662 (22.7%), 221 (7.6%), 52 (1.8%), 135 (4.6%), and 536 (18.5%) patients, respectively, and hypoalbuminemia in 737 (25.3%) patients. During a median 13 (IQR: 8-19) days of hospitalization, 61 patients (2.1%) died, 106 patients (3.6%) admitted to intensive care unit (ICU), and 75 patients (2.6%) required mechanical ventilation. After adjustment for confounders, baseline abnormal LFTs were independently associated with increased risks of mortality (adjusted HR 3.66, 95%CI 1.64-8.19, p = 0.002), ICU admission (adjusted HR 3.12 95%CI 1.86-5.23, p < 0.001), and mechanical ventilation (adjusted HR 3.00, 95%CI 1.63-5.52, p < 0.001), which was homogeneous across the severity of COVID-19 infection. Among the parameters of LTFs, the associations with the outcomes were more pronounced for AST and albumin abnormality. In contrast, ALT elevation was not significantly associated with those outcomes. Similar results were observed for peak values of LFTs during hospitalization. Conclusions: Abnormality of AST, albumin, TBIL, ALP, and GGT but not ALT were independently associated with adverse outcomes.

The role of SARC-F scale in predicting progression risk of COVID-19 in elderly patients: a prospective cohort study in Wuhan.

BACKGROUND: Since the outbreak of COVID-19, it has been documented that old age and underlying illnesses are associated with poor prognosis among COVID-19 patients. However, it is unknown whether sarcopenia, a common geriatric syndrome, is associated with poor prognosis among older COVID-19 patients. The aim of our prospective cohort study is to investigate the association between sarcopenia risk and severe disease among COVID-19 patients aged ≥60 years. METHOD: A prospective cohort study of 114 hospitalized older patients (≥60 years) with confirmed COVID-19 pneumonia between 7 February, 2020 and 6 April, 2020. Epidemiological, socio-demographic, clinical and laboratory data on admission and outcome data were extracted from electronic medical records. All patients were assessed for sarcopenia on admission using the SARC-F scale and the outcome was the development of the severe disease within 60 days. We used the Cox proportional hazards model to identify the association between sarcopenia and progression of disease defined as severe cases in a total of 2908 person-days. RESULT: Of 114 patients (mean age 69.52 ± 7.25 years, 50% woman), 38 (33%) had a high risk of sarcopenia while 76 (67%) did not. We found that 43 (38%) patients progressed to severe cases. COVID-19 patients with higher risk sarcopenia were more likely to develop severe disease than those without (68% versus 22%, p < 0.001). After adjustment for demographic and clinical factors, higher risk sarcopenia was associated with a higher hazard of severe condition [hazard ratio = 2.87 (95% CI, 1.33-6.16)]. CONCLUSION: We found that COVID-19 patients with higher sarcopenia risk were more likely to develop severe condition. A clinician-friendly assessment of sarcopenia could help in early warning of older patients at high-risk with severe COVID-19 pneumonia.

Risk Factors Associated With Clinical Outcomes in 323 Coronavirus Disease 2019 (COVID-19) Hospitalized Patients in Wuhan, China.

BACKGROUND: With evidence of sustained transmission in more than 190 countries, coronavirus disease 2019 (COVID-19) has been declared a global pandemic. Data are urgently needed about risk factors associated with clinical outcomes. METHODS: A retrospective review of 323 hospitalized patients with COVID-19 in Wuhan was conducted. Patients were classified into 3 disease severity groups (nonsevere, severe, and critical), based on initial clinical presentation. Clinical outcomes were designated as favorable and unfavorable, based on disease progression and response to treatments. Logistic regression models were performed to identify risk factors associated with clinical outcomes, and log-rank test was conducted for the association with clinical progression. RESULTS: Current standard treatments did not show significant improvement in patient outcomes. By univariate logistic regression analysis, 27 risk factors were significantly associated with clinical outcomes. Multivariate regression indicated age >65 years (P < .001), smoking (P = .001), critical disease status (P = .002), diabetes (P = .025), high hypersensitive troponin I (>0.04 pg/mL, P = .02), leukocytosis (>10 × 109/L, P < .001), and neutrophilia (>75 × 109/L, P < .001) predicted unfavorable clinical outcomes. In contrast, the administration of hypnotics was significantly associated with favorable outcomes (P < .001), which was confirmed by survival analysis. CONCLUSIONS: Hypnotics may be an effective ancillary treatment for COVID-19. We also found novel risk factors, such as higher hypersensitive troponin I, predicted poor clinical outcomes. Overall, our study provides useful data to guide early clinical decision making to reduce mortality and improve clinical outcomes of COVID-19.

The Prognostic Nutritional Index is associated with mortality of COVID-19 patients in Wuhan, China.

BACKGROUND: Declared as pandemic by WHO, the coronavirus disease 2019 (COVID-19) pneumonia has brought great damage to human health. The uncontrollable spread and poor progression of COVID-19 have attracted much attention from all over the world. We designed this study to develop a prognostic nomogram incorporating Prognostic nutritional index (PNI) in COVID-19 patients. METHODS: Patients confirmed with COVID-19 and treated in Renmin Hospital of Wuhan University from January to February 2020 were included in this study. We used logistic regression analysis to find risk factors of mortality in these patients. A prognostic nomogram was constructed and receiver operating characteristics (ROC) curve was drawn to evaluate the predictive value of PNI and this prognostic model. RESULTS: Comparison of baseline characteristics showed non-survivors had higher age (P < .001), male ratio (P = .038), neutrophil-to-lymphocyte ratio (NLR) (P < .001), platelet-to-lymphocyte ratio (PLR) (P < .001), and PNI (P < .001) than survivors. In the multivariate logistic regression analysis, independent risk factors of mortality in COVID-19 patients included white blood cell (WBC) (OR 1.285, P = .039), PNI (OR 0.790, P = .029), LDH (OR 1.011, P < .015). These three factors were combined to build the prognostic model. Area under the ROC curve (AUC) of only PNI and the prognostic model was 0.849 (95%Cl 0.811-0.888) and 0.950 (95%Cl 0.922-0.978), respectively. And calibration plot showed good stability of the prognostic model. CONCLUSION: This research indicates PNI is independently associated with the mortality of COVID-19 patients. Prognostic model incorporating PNI is beneficial for clinicians to evaluate progression and strengthen monitoring for COVID-19 patients.

The association between frailty and severe disease among COVID-19 patients aged over 60 years in China: a prospective cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been a pandemic worldwide. Old age and underlying illnesses are associated with poor prognosis among COVID-19 patients. However, whether frailty, a common geriatric syndrome of reduced reserve to stressors, is associated with poor prognosis among older COVID-19 patients is unknown. The aim of our study is to investigate the association between frailty and severe disease among COVID-19 patients aged ≥ 60 years. METHODS: A prospective cohort study of 114 hospitalized older patients (≥ 60 years) with confirmed COVID-19 pneumonia was conducted between 7 February 2020 and 6 April 2020. Epidemiological, demographic, clinical, laboratory, and outcome data on admission were extracted from electronic medical records. All patients were assessed for frailty on admission using the FRAIL scale, in which five components are included: fatigue, resistance, ambulation, illnesses, and loss of weight. The outcome was the development of the severe disease within 60 days. We used the Cox proportional hazards models to identify the unadjusted and adjusted associations between frailty and severe illness. The significant variables in univariable analysis were included in the adjusted model. RESULTS: Of 114 patients, (median age, 67 years; interquartile range = 64-75 years; 57 [50%] men), 39 (34.2%), 39 (34.2%), and 36 (31.6%) were non-frail, pre-frail, and frail, respectively. During the 60 days of follow-up, 43 severe diseases occurred including eight deaths. Four of 39 (10.3%) non-frail patients, 15 of 39 (38.5%) pre-frail patients, and 24 of 36 (66.7%) frail patients progressed to severe disease. After adjustment of age, sex, body mass index, haemoglobin, white blood count, lymphocyte count, albumin, CD8+ count, D-dimer, and C-reactive protein, frailty (HR = 7.47, 95% CI 1.73-32.34, P = 0.007) and pre-frailty (HR = 5.01, 95% CI 1.16-21.61, P = 0.03) were associated with a higher hazard of severe disease than the non-frail. CONCLUSIONS: Frailty, assessed by the FRAIL scale, was associated with a higher risk of developing severe disease among older COVID-19 patients. Our findings suggested that the use of a clinician friendly assessment of frailty could help in early warning of older patients at high-risk with severe COVID-19 pneumonia.

[Clinical features of children with SARS-CoV-2 infection: an analysis of 115 cases]

OBJECTIVE: To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: A retrospective analysis was performed for the clinical data of 115 children who were diagnosed with SARS-CoV-2 infection in the Wuhan Children's Hospital, including general information, history of close contact with individuals of SARS-CoV-2 infection, early clinical symptoms, laboratory examination results, and lung CT results. RESULTS: Among the 115 children, there were 73 boys (63.5%) and 42 girls (36.5%), with a male/female ratio of 1:0.58. Of the 115 children, 105 (91.3%) had a definite history of close contact with individuals of SARS-CoV-2-infection. An increase in alanine aminotransferase was observed in 11 children (9.6%) and an increase in CK-MB was found in 34 children (29.6%). As for clinical symptoms, 29 children (25.2%) had fever, 47 (40.9%) had respiratory symptoms (including cough, rhinorrhea, and nasal congestion), and 61 (53.0%) were asymptomatic. Lung CT findings showed ground glass opacity, fiber opacities, patchy changes, and pulmonary consolidation in 49 children (42.6%), among whom 2 children had "white lung";39 children (33.9%) only had lung texture enhancement and 27 children (23.5%) had no pulmonary imaging changes. Among the 115 children, 3 were critically ill, among whom 1 had been cured and the other 2 were under continuous treatment. CONCLUSIONS: Most of the children with SARS-CoV-2 infection have a close contact history. Critical cases are rare and there is a high proportion of asymptomatic infection.