Exploring risk factors for persistent neurocognitive sequelae after hospitalization for COVID-19.

OBJECTIVE: In this study of patients hospitalized during acute SARS-CoV2 infection with 6-months of follow-up data, we identified risk factors associated with the development of neuro-PASC. METHODS: We conducted an exploratory, observational single-center cohort study of patients hospitalized for COVID-19 from November 2020 to March 2022. Our primary outcome was persistent neurocognitive symptoms, defined as fatigue, headache, loss of taste/smell, brain fog, confusion, concentration/memory/word finding difficulty, and/or change in speech present at 1-month and persisting for 6-months following acute SARS-CoV2 infection. Secondary outcomes included persistent impairment scores on PROMIS cognitive function and abilities scales. Multivariate logistic regression analyses identified potential risk factors for neuro-PASC. RESULTS: Of 89 participants, 60% reported persistent neurocognitive symptoms at 6-months; fatigue was the most prevalent, occurring in 53% of participants, followed by brain fog in 34% of participants. Lower self-reported socioeconomic status and increased pre-COVID-19 anxiety scores on the Hospital Anxiety and Depression Scale were associated with increased odds of developing persistent neurocognitive symptoms. Being female and of Hispanic descent were associated with increased odds of persistent cognitive function and ability impairment. INTERPRETATION: Sociodemographic factors and pre-COVID-19 anxiety symptoms may be important risk factors for neuro-PASC. These findings underscore the need to assess various sociodemographic factors in research on PASC. Our study also highlights premorbid mental health symptoms as a potential predictor of persistent neurocognitive symptoms following hospitalization with SARS-CoV2 infection.

Dendrobium officinale aqueous extract influences the immune response following vaccination against SARS-CoV-2.

BACKGROUND: Vaccination is the most effective way to prevent coronavirus disease 2019 (COVID-19). However, it is often less protective and does not significantly increase antibody levels, especially in individuals with impaired immune systems. Nevertheless, the immunocompetence can be enhanced using a natural immunomodulator, such as Dendrobium officinale aqueous extract (DoAE). METHODS: To determine whether DoAE promotes antibody production, we treated healthy volunteers with DoAE during COVID-19 vaccination. Meanwhile, the control volunteers were given a placebo (cornstarch) during the vaccination. Antibody levels were measured at three-week intervals in the DoAE and control groups. RESULTS: DoAE enhanced immunity and preserved immune cell homeostasis. However, the neutralizing antibody (nAb) levels in the DoAE group were lower than those in the control group. Analysis of the gut microbiota revealed that the abundance of anti-inflammatory flora was increased, while the pro-inflammatory flora was reduced in the DoAE group. CONCLUSION: DoAE has immunomodulatory and anti-inflammatory properties. Therefore, DoAE has the potential for COVID-19 prophylaxis, treatment, and recovery from the adverse effects of COVID-19. However, its anti-inflammatory activity affects the production of nAbs. Thus, DoAE may not be recommended for consumption during COVID-19 vaccination.

Economic burden of healthcare-associated infection due to carbapenem-resistant gram-negative bacilli in a tertiary general hospital of Qinghai Province

OBJECTIVE: To explore the prevalence of carbapenem-resistant gram-negative bacilli(CRO) infection and the economic burden in a tertiary general hospital of Qinghai province. METHODS: The clinical data, length of hospital stay and costs of hospitalization were retrospectively collected from the patients with Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa hospital-acquired infection who were hospitalized in Qinghai Provincial Hospital from Jan 2017 to Dec 2017. The patients were divided into the drug-resistant group and the non drug-resistant group according to the result of drug susceptibility testing. The length of hospital stay and hospitalization cost were compared between the two groups of patients. RESULTS: A total of 521 patients were involved in the study, 120 of who had CRO infection(the drug-resistant group), and 40 had carbapenem-sensitive organisms infection(the non drug-resistant group). The median length of hospital stay of the drug-resistant group was 19 days, the median total hospitalization cost was 31 292 yuan;the median length of hospital stay of the non drug-resistant group was 15 days, the median total hospitalization cost was 22 610 yuan, and there were significant differences between the two groups(P<0.05). Stratified analysis showed that the median length of hospital stay of the patients with carbapenem-resistant K.pneumoniae infection was 17 days, the medial total hospitalization cost 25 227 yuan, the length of hospital stay of the non drug-resistant group was 14 day, the median total hospitalization cost 20 326 yuan;the median lengths of hospital stay of the patients with respiratory tract infection and the patients with bloodstream infection were respectively 19 days and 30 days in the drug-resistant group, the median total hospitalization costs were respectively 30 315 yuan and 30 050 yuan;the median lengths of hospital stay of the patients with respiratory tract infection and the patients with bloodstream infection were respectively 15 days and 13 days in the non drug-resistant group, the median total hospitalization costs were respectively 21 562 yuan and 24 853 yuan, and there were significant differences(P<0.05). CONCLUSION: The hospital-acquired CRO infection may lead to the increase of length of hospital stay and hospitalization cost of the hospitalized patients as well as the economic burden. It is necessary to take effective measures to reduce the incidence of hospital-acquired CRO infection.

Distribution and Drug Resistance of Bacterial Pathogens Associated with Lower Respiratory Tract Infection in Children and the Effect of COVID-19 on the Distribution of Pathogens.

By studying the distribution and drug resistance of bacterial pathogens associated with lower respiratory tract infection (LRTI) in children in Chengdu and the effect of the COVID-19 on the distribution of pathogens and by analyzing the epidemic trend and drug resistance changes of the main pathogens of LRTI, this research is supposed to provide a useful basis for the prevention of LRTI in children and the rational use of drugs in clinical practice. Hospitalized children clinically diagnosed with LRTI in Chengdu Women and Children's Central Hospital from 2011 to 2020 were selected as the study subjects. The pathogens of LRTI in children and the distribution of pathogens in different ages, genders, seasons, years, and departments and before and after the pandemic situation of COVID-19 were counted. The drug resistance distribution of the top six pathogens with the highest infection rate in the past three years and the trend of drug resistance in the past decade were analyzed. A total of 26,469 pathogens were isolated. Among them, 6240 strains (23.6%) were Gram-positive bacteria, 20152 strains (76.1%) were Gram-negative bacteria, and 73 strains (0.3%) were fungi. Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, and Staphylococcus aureus were highly isolated in the group of infants aged 0-1 (P < 0.01), Moraxella catarrhalis and Streptococcus pneumoniae were highly isolated in children aged 1-6 (P < 0.01), and Haemophilus influenzae was highly isolated in children over 1 (P < 0.01). The isolation rates of Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Staphylococcus aureus, and Candida albicans in the lower respiratory tract of 0-1 year-old male infants were higher than those of female infants (p < 0.05). Haemophilus influenzae was highly isolated in spring and summer, and Moraxella catarrhalis was highly isolated in autumn and winter, while the infection of Streptococcus pneumoniae was mainly concentrated in winter. This difference was statistically significant (P < 0.01). Affected by the COVID-19 pandemic, the isolation rates of Haemophilus influenzae and Streptococcus pneumoniae were significantly lower than those before the pandemic, and the isolation rate of Moraxella catarrhalis was significantly higher. The difference was statistically significant (P < 0.01). The proportion of isolated negative bacteria in NICU and PICU was higher than that in positive bacteria, and the infection rates of Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, and Acinetobacter baumannii were higher than those in other departments. The differences were statistically significant (P < 0.01). The results of drug sensitivity test showed that the drug resistance of Haemophilus influenzae and Moraxella catarrhalis was mainly concentrated in Ampicillin, First- and Second-generation cephalosporins, and Cotrimoxazole, with stable sensitivity to Third-generation cephalosporins, while the drug resistance of Streptococcus pneumoniae was concentrated in Macrolides, Sulfonamides, and Tetracyclines, with stable sensitivity to Penicillin. Staphylococcus aureus is highly resistant to penicillins and macrolides and susceptible to vancomycin. Enterobacteriaceae resistance is concentrated in cephalosporins, with a low rate of carbapenem resistance. From 2018 to 2020, 1557 strains of Staphylococcus aureus were isolated, of which 416 strains were MRSA, accounting for 27% of the isolates; 1064 strains of Escherichia coli were isolated, of which 423 strains were ESBL and 23 strains were CRE, accounting for 40% and 2% of the isolates, respectively; and 1400 strains of Klebsiella pneumoniae were isolated, of which 385 strains were ESBL and 402 strains were CRE, accounting for 28% and 29% of the isolates, respectively. Since 2011, the resistance of Escherichia coli and Klebsiella pneumoniae to Third-generation cephalosporins has increased, peaking in 2017, and has decreased after 2018, years after which carbapenem resistance has increased significantly, corresponding to an increase in the detection rate of Carbapenem-resistant Enterobacteriaceae CRE. Findings from this study revealed that there are significant differences in community-associated infectious pathogens before and after the COVID-19 pandemic, and there are significant age differences, seasonal epidemic trends, and high departmental correlation of pathogens related to lower respiratory tract disease infection in children. There was a significant gender difference in the isolation rate of pathogens associated with LRTI in infants under one year. Vaccination, implementation of isolation measures and social distance, strengthening of personal protective measures, aseptic operation of invasive medical treatment, hand hygiene, and environmental disinfection are beneficial to reducing community-associated pathogen infection, opportunistic pathogen infection, and an increase in resistant bacteria. The strengthening of bacterial culture of lower respiratory tract samples by pediatricians is conducive to the diagnosis of respiratory tract infections caused by different pathogens, contributing to the selection of effective drugs for treatment according to drug susceptibility results, which is important for the rational use of antibiotics and curbing bacterial resistance.

Changes in serum virus-specific IgM/IgG antibody in asymptomatic and discharged patients with reoccurring positive COVID-19 nucleic acid test (RPNAT).

BACKGROUND: Studies have demonstrated the diagnostic efficiency of antibody testing in COVID-19 infection. There is limited data on the IgM/IgG changes in asymptomatic and discharged patients with reoccurring positive nucleic acid test (RPNAT). This study aims to investigate these IgM/IgG changes. METHODS: There were 111 patients with positive nucleic acid test (NAT) and 40 suspected patients enrolled in the study. The serum SARS-CoV-2 specific IgM/IgG antibody levels were retrospectively analysed with the disease progress in asymptomatic and RPNAT patients. RESULTS: The best overall performance was found by combining the IgM, IgG, and CT; 95.1% sensitivity and 75% specificity. This was tested in 111 RT-PCR positive cases. The median IgM and IgG levels were lower in the asymptomatic group compared to the symptomatic group (p < .01). Among 15 RPNAT cases, the IgM levels of the RPNAT group at the time of discharge (IgM2.79, IQR: 0.95-5.37) and retest (IgM 2.35, IQR: 0.88-8.65) were significantly higher than those of the non-reoccurring positive nucleic acid test group (Non-RPNAT) (IgM on discharge: 0.59, IQR: 0.33-1.22, IgG on retest: 0.92, IQR: 0.51-1.58). CONCLUSION: Serum SARS-CoV-2 specific IgM/IgG antibody levels remained at a low level during hospitalisation for asymptomatic patients. Elevated IgM levels may have implications in the identification of RPNAT patients before discharge. Key messages This study determined the IgM/IgG changes in asymptomatic and RPNAT patients. The rate of serum SARS-CoV-2 specific IgM/IgG antibody levels increase in the asymptomatic group was lower than in the symptomatic group during hospitalisation. The IgM level did not decrease significantly at discharge in the RPNAT patients, and was higher than that of the Non-RPNAT group on discharge. These results highlight the importance of timely monitoring of IgM levels to identify RPNAT patients before discharge.

COVID-19-Associated Acute Brain Dysfunction Related to Sepsis.

In global term, as of November 30, 2020, over 30 million people has been infected by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than 10,000,000 of them died of acute organ failure. Our reviews have shown that coronavirus disease 2019 (COVID-19) patients with pneumonia and acute respiratory distress syndrome (ARDS) have life-threatening acute brain dysfunction (ABD), ranging from altered mental status/delirium to stupor/coma. Altered mental status/delirium was the most common manifestation of ABD caused by severe COVID-19. The prevalence of altered mental status and/or delirium was up to 66-79.5%, and prevalence of coma was 10%. The most common clinical type of COVID-19-associated ABD was COVID-19-associated acute stroke including ischemic and hemorrhagic stroke (n > 350 cases), followed by COVID-19-associated encephalopathy (n > 200 cases), and COVID-19-associated central nervous system (CNS) infection (n > 70 cases). According to the Sepsis-3 criteria, we confess that severe COVID-19-associated ABD with ARDS and altered mental status is related to sepsis. Moreover, we also review the diagnosis and treatment of COVID-19-associated ABD with sepsis. In view of the fact that COVID-19 is at the peak of epidemic worldwide, we hope that this review will provide evidence of COVID-19 sepsis threating to the brain dysunction. Thus, recognizing the COVID-19-associated ABD related to sepsis is very important for early empirical combination therapy to survive severe COVID-19.

Analyzing the potential therapeutic mechanism of Huashi Baidu Decoction on severe COVID-19 through integrating network pharmacological methods.

BACKGROUND AND AIM: Huashi Baidu Decoction (HSBD) is a novel complex prescription which has positive effects on severe COVID-19. This study was aimed to discover key Chinese materia medica, main active compounds, hub therapeutic target proteins and core signal pathways in the potential therapeutic mechanism of HSBD on severe COVID-19 through integrating network pharmacological methods. EXPERIMENTAL PROCEDURE: TCMSP, TCMID and STITCH databases were used to screen out active compounds and target proteins of HSBD. GeneCards database was used to screen out disease genes of severe COVID-19. The potential therapeutic targets of HSBD on severe COVID-19 were used to construct protein-protein interaction network through STRING database and the hub target proteins were discovered. Next, GO and KEGG enrichment analysis were carried out to discover core signal pathways. Finally, the network diagram of "Chinese materia medica-active compounds-therapeutic target proteins" was built, then key Chinese materia medica and main active compounds were selected. RESULTS AND CONCLUSION: HSBD might treat severe COVID-19 through 45 potential target genes, among them, there were 13 hub target genes: RELA, TNF, IL6, IL1B, MAPK14, TP53, CXCL8, MAPK3, MAPK1, IL4, MAPK8, CASP8, STAT1. Meanswhile, GO_BiologicalProcess and KEGG signaling pathways analysis results showed that the core signal pathways were inflammation and immune regulation pathways. Finally, 4 key Chinese materia medica and 11 main active compounds were discovered in the HSBD. In conclusion, the therapeutic mechanism of HSBD on severe COVID-19 might involve its pharmacological effects of anti-inflammation and immune regulation via acting on 45 disease-related proteins of severe COVID-19. TAXONOMY CLASSIFICATION BY EVISE: Viral Pneumonia, COVID-19, Acute Respiratory Distress Syndrome, Septic Shock, Chinese Herbal Medicine.

Analysis of respiratory virus infection in 114 suspected COVID-19 patients

To explore the value of simultaneous detection of multiple viruses in epidemic prevention and control of COVID-19. To analyze respiratory virus infection of 114 suspected COVID-19 patients, real-time RT-PCR was used to detect SARS-CoV-2 nucleic acid. At the same time, the thermostatic amplification was used to detect other 18 respiratory virus. As results, the nucleic acid of 114 suspected COVID-19 patients was negative, and 21 of them were infected with non-other respiratory viruses, with an infection rate of 18.42%. A total of 10 respiratory viruses were detected in 21 cases, including coronavirus NL63/229E, respiratory syncytial virus, human coxsackie virus A16, influenza B virus, human parainfluenza virus type 1, human parainfluenza virus type 3, human metapneumovirus, influenza A virus, seasonal influenza a virus subtype H3, and enterovirus/rhinovirus. There were 6 cases of influenza B virus infection and 5 cases of respiratory syncytial virus. Three patients were co-infected with two viruses: respiratory syncytial virus mixed with coxsackie virus A16, coronavirus NL63/229E mixed with human parainfluenza virus 1, and influenza A virus mixed with influenza A virus seasonal H3 subtype. In conclusion, in response to the SARS-CoV-2 epidemic, attention should be paid to the identification of SARS-CoV-2 and other respiratory viruses in suspected COVID-19 patients, so as to effectively exclude suspected cases.

Expression and immunoreactivity of a recombinant multi-epitope antigen designed based on four major structural proteins of avian infectious bronchitis virus.

The development of rapid, simple, and sensitive diagnostic methods for identification of avian infectious bronchitis virus (IBV) is crucial for the effective control of avian infectious bronchitis. In the present study, a tandemly arranged multiepitope peptide (named SEMN) was designed with four antigenic regions derived from four major structural proteins of IBV. Then, we performed codon optimization of SEMN gene by changing the codon-adaptation index from 0.45 to 0.94 and expressed the optimized gene in codon bias-adjusted Escherichia coli Rosetta (DE3), followed by determination of the immunoreactivity of the purified protein. Bioinformatics analysis of SEMN showed a high antigenicity, surface probability and hydrophilicity. The recombinant protein rSEMN was expressed both in soluble forms and as inclusion bodies, and the molecular weight of rSEMN was about 39 kDa. The preliminary diagnostic performance of rSEMN was confirmed by Western blotting analysis using chicken anti-IBV polyclonal antibodies. Further studies are needed to evaluate the immunogenicity in animal models and to give a final assessment of the diagnostic utility of this recombinant multi-epitope antigen.

Gastrointestinal involvement of COVID-19 and potential faecal transmission of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was found initially in Wuhan, China in early December 2019. The pandemic has spread to 216 countries and regions, infecting more than 23310 000 people and causing over 800 000 deaths globally by Aug. 24, 2020, according to World Health Organization (https://www.who.int/emergencies/diseases/ novel-coronavirus-2019). Fever, cough, and dyspnea are the three common symptoms of the condition, whereas the conventional transmission route for SARS-CoV-2 is through droplets entering the respiratory tract. To date, infection control measures for COVID-19 have been focusing on the involvement of the respiratory system. However, ignoring potential faecal transmission and the gastrointestinal involvement of SARS-CoV-2 may result in mistakes in attempts to control the pandemic.