BBIBP-CorV vaccination accelerates anti-viral antibody responses in heterologous Omicron infection: A retrospective observation study in Shanghai.

OBJECTIVES: To investigate how BBIBP-CorV vaccination affecting antibody responses upon heterologous Omicron infection. METHODS: 440 Omicron-infected patients were recruited in this study. Antibodies targeting SARS-CoV-2 spike protein receptor binding domain (RBD) and nucleoprotein of both wild-type (WT) and Omicron were detected by ELISA. The clinical relevance was further analyzed. RESULTS: BBIBP-CorV vaccinated patients exhibited higher anti-RBD IgG levels targeting both WT and Omicron than non-vaccinated patients at different stages. By using a 3-day moving average analysis, we found that BBIBP-CorV vaccinated patients exhibited the increases in both anti-WT and Omicron RBD IgG from the onset and reached the plateau at Day 8 whereas those in non-vaccinated patients remained low during the disease. Significant increase in anti-WT RBD IgA was observed only in vaccinated patients. anti-Omicron RBD IgA levels remained low in both vaccinated and non-vaccinated patients. Clinically, severe COVID-19 only occurred in non-vaccinated group. anti-RBD IgG and IgA targeting both WT and Omicron were negatively correlated with virus load, hospitalization days and virus elimination in vaccinated patients. CONCLUSIONS: BBIBP-CorV vaccination effectively reduces the severity of Omicron infected patients. The existence of humoral memory responses established through BBIBP-CorV vaccination facilitates to induce rapid recall antibody responses when encountering SARS-CoV-2 variant infection.

DNA Repair Mechanisms are Activated in Circulating Lymphocytes of Hospitalized Covid-19 Patients.

Purpose: Reactive oxygen species (ROS) are an important part of the inflammatory response during infection but can also promote DNA damage. Due to the sustained inflammation in severe Covid-19, we hypothesized that hospitalized Covid-19 patients would be characterized by increased levels of oxidative DNA damage and dysregulation of the DNA repair machinery. Patients and Methods: Levels of the oxidative DNA lesion 8-oxoG and levels of base excision repair (BER) proteins were measured in peripheral blood mononuclear cells (PBMC) from patients (8-oxoG, n = 22; BER, n = 17) and healthy controls (n = 10) (Cohort 1). Gene expression related to DNA repair was investigated in two independent cohorts of hospitalized Covid-19 patients (Cohort 1; 15 patents and 5 controls, Cohort 2; 15 patients and 6 controls), and by publicly available datasets. Results: Patients and healthy controls showed comparable amounts of oxidative DNA damage as assessed by 8-oxoG while levels of several BER proteins were increased in Covid-19 patients, indicating enhanced DNA repair in acute Covid-19 disease. Furthermore, gene expression analysis demonstrated regulation of genes involved in BER and double strand break repair (DSBR) in PBMC of Covid-19 patients and expression level of several DSBR genes correlated with the degree of respiratory failure. Finally, by re-analyzing publicly available data, we found that the pathway Hallmark DNA repair was significantly more regulated in circulating immune cells during Covid-19 compared to influenza virus infection, bacterial pneumonia or acute respiratory infection due to seasonal coronavirus. Conclusion: Although beneficial by protecting against DNA damage, long-term activation of the DNA repair machinery could also contribute to persistent inflammation, potentially through mechanisms such as the induction of cellular senescence. However, further studies that also include measurements of additional markers of DNA damage are required to determine the role and precise molecular mechanisms for DNA repair in SARS-CoV-2 infection.

[The Response of Tribal Cultural Care to the Physical and Emotional Needs of Older Adults During the COVID-19 Pandemic].

As Taiwan's society ages, Tribal Cultural Health Stations serve as in situ long-term care centers that are committed to building a long-term care service model for indigenous peoples based on cultural care. The cultural sensitivity, cultural ability, and tribal ability of long-term care planners and professional helpers remains insufficient, making it difficult to achieve the policy goals of "designing for the tribes and for the locals" and "creating a cultural care mechanism". However, based on a foundation of local blood and geo-relationship and through the care expertise and interpersonal network established through long-term tribal cultivation and service, a cultural care mechanism that meets local awareness, local needs, and human trust has been formed by expanding linkages among the resources of all local stakeholders. During the COVID-19 epidemic, this has helped facilitate the recovery of the emotional and physical health of older tribal adults. For example, caregivers have been able to help ease the anxieties among older adults in indigenous communities regarding vaccination, fear of infection, isolation, and interpersonal suspicions. In addition, the positive role of the tribal cultural care mechanism as a social safety valve during the pandemic has been demonstrated.

Toward a Deeper Understanding of Gut Microbiome in Depression: The Promise of Clinical Applicability.

The emergence of the coronavirus disease 2019 pandemic has dramatically increased the global prevalence of depression. Unfortunately, antidepressant drugs benefit only a small minority of patients. Thus, there is an urgent need to develop new interventions. Accumulating evidence supports a causal relationship between gut microbiota dysbiosis and depression. To advance microbiota-based diagnostics and therapeutics of depression, a comprehensive overview of microbial alterations in depression is presented to identify effector microbial biomarkers. This procedure generated 215 bacterial taxa from humans and 312 from animal models. Compared to controls, depression shows significant differences in ß-diversity, but no changes in microbial richness and diversity. Additionally, species-specific microbial changes are identified like increased Eggerthella in humans and decreased Acetatifactor in rodent models. Moreover, a disrupted microbiome balance and functional changes, characterized by an enrichment of pro-inflammatory bacteria (e.g., Desulfovibrio and Escherichia/Shigella) and depletion of anti-inflammatory butyrate-producing bacteria (e.g., Bifidobacterium and Faecalibacterium) are consistently shared across species. Confounding effects of geographical region, depression type, and intestinal segments are also investigated. Ultimately, a total of 178 species and subspecies probiotics are identified to alleviate the depressive phenotypes. Current findings provide a foundation for developing microbiota-based diagnostics and therapeutics and advancing microbiota-oriented precision medicine for depression.

Combating the SARS-CoV-2 Omicron (BA.1) and BA.2 with potent bispecific antibodies engineered from non-Omicron neutralizing antibodies.

The highly mutated and transmissible Omicron (BA.1) and its more contagious lineage BA.2 have provoked serious concerns over their decreased sensitivity to the current COVID-19 vaccines and evasion from most anti-SARS-CoV-2 neutralizing antibodies (NAbs). In this study, we explored the possibility of combating the Omicron and BA.2 by constructing bispecific antibodies based on non-Omicron NAbs. We engineered 10 IgG-like bispecific antibodies with non-Omicron NAbs named GW01, 16L9, 4L12, and REGN10987 by fusing the single-chain variable fragments (scFvs) of two antibodies through a linker and then connecting them to the Fc region of IgG1. Surprisingly, 8 out of 10 bispecific antibodies showed high binding affinities to the Omicron receptor-binding domain (RBD) and exhibited extreme breadth and potency against pseudotyped SARS-CoV-2 variants of concern (VOCs) including Omicron and BA.2, with geometric mean of 50% inhibitory concentration (GM IC50) values ranging from 4.5 ng/mL to 103.94 ng/mL, as well as the authentic BA.1.1. Six bispecific antibodies containing the cross-NAb GW01 not only neutralized Omicron and BA.2, but also neutralized the sarbecoviruses including SARS-CoV and SARS-related coronaviruses (SARSr-CoVs) RS3367 and WIV1, with GM IC50 ranging from 11.6 ng/mL to 103.9 ng/mL. Mapping analyses of 42 spike (S) variant single mutants of Omicron and BA.2 elucidated that these bispecific antibodies accommodated the S371L/F mutations, which were resistant to most of the non-Omicron NAbs. A cryo-electron microscopy (cryo-EM) structure study of the representative bispecific antibody GW01-16L9 (FD01) in its native full-length IgG form in complex with the Omicron S trimer revealed 5 distinct trimers and one novel trimer dimer conformation. 16L9 scFv binds the receptor-binding motif (RBM), while GW01 scFv binds a epitope outside the RBM. Two scFvs of the bispecific antibody synergistically induced the RBD-down conformation into 3 RBD-up conformation, improved the affinity between IgG and the Omicron RBD, induced the formation of trimer dimer, and inhibited RBD binding to ACE2. The trimer dimer conformation might induce the aggregation of virions and contribute to the neutralization ability of FD01. These novel bispecific antibodies are strong candidates for the treatment and prevention of infection with the Omicron, BA.2, VOCs, and other sarbecoviruses. Engineering bispecific antibodies based on non-Omicron NAbs could turn the majority of NAbs into a powerful arsenal to aid the battle against the pandemic.

Comparable antigen-specific T cell responses in vaccinees with diverse humoral immune responses after the primary and booster BBIBP-CorV vaccination.

BBIBP-CorV exerts efficient protection against SARS-CoV-2 infection. However, waning vaccine-induced humoral immune responses after two-dose vaccination have significantly undermined durable immuno-protection. In this study, we have demonstrated that although anti-spike (S) antibody responses in BBIBP-CorV vaccinees exhibited three serotypes after 6 months, including de novo sero-negative, sero-positive, and sero-decay features, S-specific interferon-γ release as well as Th1 cytokine production in CD4+ and CD8+ T cells were comparable, especially in vaccinees without detectable neutralizing antibodies. Notably, regardless of dramatic increases in humoral immunity after booster vaccination, T cell responses targeting S protein from either wild type or Omicron remained stable before and after booster vaccination in all three serotype vaccinees. No severe cases were observed even in the sero-decay group during the Omicron epidemic in Shanghai. Our results thus illustrate that unlike fluctuating humoral responses, viral-specific T cell responses are extremely stable after booster vaccination. Sustained T cell responses might be dedicated to the rapid restoration of antibody responses after booster vaccination.

Antiviral Immunoglobulins of Chicken Egg Yolk for Potential Prevention of SARS-CoV-2 Infection.

Background: Some viruses cause outbreaks, which require immediate attention. Neutralizing antibodies could be developed for viral outbreak management. However, the development of monoclonal antibodies is often long, laborious, and unprofitable. Here, we report the development of chicken polyclonal neutralizing antibodies against SARS-CoV-2 infection. Methods: Layers were immunized twice with 14-day intervals using the purified receptor-binding domain (RBD) of the S protein of SARS-CoV-2/Wuhan or SARS-CoV-2/Omicron. Eggs were harvested 14 days after the second immunization. Polyclonal IgY antibodies were extracted. Binding of anti-RBD IgYs was analyzed by immunoblot and indirect ELISA. Furthermore, the neutralization capacity of anti-RBD IgYs was measured in Vero-E6 cells infected with SARS-CoV-2-mCherry/Wuhan and SARS-CoV-2/Omicron using fluorescence and/or cell viability assays. In addition, the effect of IgYs on the expression of SARS-CoV-2 and host cytokine genes in the lungs of Syrian Golden hamsters was examined using qRT-PCR. Results: Anti-RBD IgYs efficiently bound viral RBDs in situ, neutralized the virus variants in vitro, and lowered viral RNA amplification, with minimal alteration of virus-mediated immune gene expression in vivo. Conclusions: Altogether, our results indicate that chicken polyclonal IgYs can be attractive targets for further pre-clinical and clinical development for the rapid management of outbreaks of emerging and re-emerging viruses.

Reliability and Validity of General Health Questionnaire-12 in Chinese Dental Healthcare Workers During the COVID-19 Pandemic.

BACKGROUND: The General Health Questionnaire-12 (GHQ-12) is a widely used instrument to assess mental health status. However, little is known about its applicability in Chinese healthcare workers. This study aimed to evaluate the reliability and validity of the GHQ-12 in Chinese dental healthcare workers. METHODS: Dental healthcare workers participated in the first occupational survey in China conducted by the Chongqing Stomatological Association from February 2021 to March 2021 by filling out GHQ-12. The reliability and validity of GHQ-12 were then tested. RESULTS: A total of 3,020 valid electronic questionnaires were acquired. The positive detection rate of self-reported mental health status was 23.80% (719/3,020). The Cronbach's α coefficient of the GHQ-12 was 0.892, and the Cronbach's α coefficient was 0.877-0.888 after the deletion of individual items, and the split-half reliability was 0.843. The correlation coefficient between the item-total score ranged from 0.465 to 0.762 (P<0.05). The exploratory factor analysis found 2 common factors with a factor load of 0.564-0.818. The confirmatory factor analysis showed that the factor load on the specified items was 0.480-0.790. CONCLUSIONS: The two-factor model of GHQ-12 featured good reliability and validity, which could be used to assess the mental health status of Chinese dental healthcare workers.

[Variation Characteristics of Ambient Volatile Organic Compounds (VOCs) Volume Fraction During Hangzhou COVID-19 Period].

A continuous observation campaign was carried out with the Syntech Spectras GC955 volatile organics online monitoring system from December 1, 2019 to March 31, 2020 during the COVID-19 period in Hangzhou. Composition characteristics, diurnal variation, and atmospheric chemical reactivity of VOCs were analyzed. The results showed that φ(total VOCs) were the highest before the COVID-19 pandemic in different sites and the lowest during the first response period. The φ(total VOCs) at night was higher than that during the day. The daily variation in Wolongqiao φ(total VOCs) was less than that in Xiasha. The daily variation in φ(total VOCs) during the first level response period was less than that during the other three periods. The diurnal variation in the φ (total VOCs) in Xiasha showed a "V" shape, and that in Wolongqiao showed a typical bimodal structure. The OFP in Xiasha was higher than that in Wolongqiao. The OFP were the highest at the two sites before the COVID-19 pandemic. The OFP was the lowest during the first response period in Xiasha and the lowest during the second response period in Wolongqiao. The OFP of aromatics and olefins was higher, and the OFP of alkynes was the lowest in Xiasha. The OFP of olefin in Wolongqiao was much higher than that of the other three components, followed by alkane and alkyne.

A severe case of human coronavirus 229E pneumonia in an elderly man with diabetes mellitus: a case report.

BACKGROUND: With pandemic of coronavirus disease 2019 (COVID-19), human coronaviruses (HCoVs) have recently attached worldwide attention as essential pathogens in respiratory infection. HCoV-229E has been described as a rare cause of lower respiratory infection in immunocompetent adults. CASE PRESENTATION: We reported a 72-year-old man infected by HCoV-229E with rapid progression to acute respiratory distress syndrome, in conjunction with new onset atrial fibrillation, intensive care unit acquired weakness, and recurrent hospital acquired pneumonia. Clinical and radiological data were continuously collected. The absolute number of peripheral T cells and the level of complement components diminished initially and recovered after 2 months. The patient was successfully treated under intensive support care and discharged from the hospital after 3 months and followed. CONCLUSION: HCoV-229E might an essential causative agent of pulmonary inflammation and extensive lung damage. Supportive treatment was essential to HCoVs infection on account of a long duration of immunological recovery in critical HCoV-229E infection.

Traditional Chinese medicine syndrome differentiation of coronavirus disease 2019 patients

Objective To explore the rule of traditional Chinese medicine (TCM) syndrome differentiation of coronavirus disease 2019 (COVID-19) patients. Methods The symptoms of 756 cases with COVID-19 in Guanggu Branch of Maternity and Child Healthcare Hospital of Hubei Province were collected by cross sectional survey. The incidence rates of the symptoms were recorded by frequency method at different courses of the disease: prodromal stage (onset), middle stage (7-30 days), and later stage (>30 days). The common symptoms (incidence rate>5.0%) were analyzed by systematic clustering. With expert experience, the rule of TCM syndrome differentiation of COVID-19 patients was summarized. Results Fever (52.25%, 395 cases), cough (43.25%, 327 cases), asthenia (27.25%, 206 cases), chest distress (26.72%, 202 cases), asthma (17.59%, 133 cases) and expectoration (5.03%, 38 cases) were the most common symptoms in the prodromal stage (756 cases) of the disease, which were clustered into one category except expectoration, indicating the pathogenesis of both lung and body surface suppressed by dampness. In the middle stage (383 cases), the 19 common symptoms including greasy fur (64.49%, 247 cases), yellow fur (43.86%, 168 cases), thick fur (40.21%, 154 cases), cough (34.73%, 133 cases), red tongue (32.38%, 124 cases), poor stool (25.85%, 99 cases), asthma (25.33%, 97 cases), asthenia (25.07%, 96 cases), poor appetite (23.76%, 91 cases), bitterness of mouth (14.36%, 55 cases), dry fur (12.01%, 46 cases), purple tongue (12.01%, 46 cases), perspiration (11.49%, 44 cases), constipation (10.18%, 39 cases), white phlegm (8.62%, 33 cases), insomnia (7.31%, 28 cases), nausea (7.05%, 27 cases), diarrhea (6.79%, 26 cases) and yellow phlegm (6.27%, 24 cases), were clustered into three groups, indicating the pathogenesis of damp-heat accumulation, obstruction of lung and spleen by dampness, and dryness due to dampness-heat. In the later stage (373 cases), the 13 common symptoms including greasy fur (50.94%, 190 cases), asthenia (39.41%, 147 cases), cough (37.80%, 141 cases), red tongue (33.78%, 126 cases), asthma (32.17%, 120 cases), perspiration (23.86%, 89 cases), dry mouth (22.79%, 85 cases), poor appetite (20.11%, 75 cases), poor stool (19.30%, 72 cases), bitterness of mouth (15.01%, 56 cases), white phlegm (10.72%, 40 cases), palpitation (8.31%, 31 cases) and little fur (8.04%, 30 cases), were clustered into two groups, indicating the pathogenesis of deficiency of Qi and Yin with residual dampness, and deficiency of lung Qi and spleen Qi with residual dampness. Conclusion The TCM syndromes of COVID-19 patients in different stages have its own typical characteristics, with a regular change from exterior to interior, from dampness to dampness-heat and from excess to deficiency..

Immunomodulatory Therapeutic Proteins in COVID-19: Current Clinical Development and Clinical Pharmacology Considerations.

The coronavirus disease 2019 (COVID-19) pandemic caused by infection with SARS-CoV-2 has led to more than 600 000 deaths worldwide. Patients with severe disease often experience acute respiratory distress characterized by upregulation of multiple cytokines. Immunomodulatory biological therapies are being evaluated in clinical trials for the management of the systemic inflammatory response and pulmonary complications in patients with advanced stages of COVID-19. In this review, we summarize the clinical pharmacology considerations in the development of immunomodulatory therapeutic proteins for mitigating the heightened inflammatory response identified in COVID-19.

A Comprehensive Updated Review on SARS-CoV-2 and COVID-19.

This literature review aims to provide a comprehensive current summary of the pathogenesis, clinical features, disease course, host immune responses, and current investigational antiviral and immunomodulatory pharmacotherapies to facilitate the development of future therapies and measures for prevention and control.