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1.
Frontiers in Immunology ; 13:819058, 2022.
Article in English | MEDLINE | ID: covidwho-1834399

ABSTRACT

Vaccines for COVID-19 are now a crucial public health need, but the degree of protection provided by conventional vaccinations for individuals with compromised immune systems is unclear. The use of viral vectors to express neutralizing monoclonal antibodies (mAbs) in the lung is an alternative approach that does not wholly depend on individuals having intact immune systems and responses. Here, we identified an anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody, NC0321, which can efficiently neutralize a range of SARS-CoV-2 variants, including alpha, beta, delta, and eta. Both prophylactic and therapeutic NC0321 treatments effectively protected mice from SARS-CoV-2 infection. Notably, we adopted viral vector-mediated delivery of NC0321 IgG1 as an attractive approach to prevent SARS-CoV-2 infection. The NC0321 IgG1 expression in the proximal airway, expressed by a single direct in-vivo intranasal (I.N.) administration of a self-inactivating and recombinant lentiviral vector (rSIV.F/HN-NC0321), can protect young, elderly, and immunocompromised mice against mouse-adapted SARS-CoV-2 surrogate challenge. Long-term monitoring indicated that rSIV.F/HN-NC0321 mediated robust IgG expression throughout the airway of young and SCID mice, importantly, no statistical difference in the NC0321 expression between young and SCID mice was observed. A single I.N. dose of rSIV.F/HN-NC0321 30 or 180 days prior to SARS-CoV-2 challenge significantly reduced lung SARS-CoV-2 titers in an Ad5-hACE2-transduced mouse model, reconfirming that this vectored immunoprophylaxis strategy could be useful, especially for those individuals who cannot gain effective immunity from existing vaccines, and could potentially prevent clinical sequelae.

2.
Thromb J ; 20(1):27, 2022.
Article in English | PubMed | ID: covidwho-1833318

ABSTRACT

BACKGROUND: High incidence of deep vein thrombosis (DVT) has been observed in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 and those by bacterial pneumonia. However, the differences of incidence and risk factors of DVT in these two groups of ARDS had not been reported before. STUDY DESIGN AND METHODS: We performed a retrospective cohort study to investigate the difference of DVT in incidence and risk factors between the two independent cohorts of ARDS and eventually enrolled 240 patients, 105 of whom with ARDS caused by COVID-19 and 135 caused by bacterial pneumonia. Lower extremity venous compression ultrasound scanning was performed whenever possible regardless of clinical symptoms in the lower limbs. Clinical characteristics, including demographic information, clinical history, vital signs, laboratory findings, treatments, complications, and outcomes, were analyzed for patients with and without DVT in these two cohorts. RESULTS: The 28-days incidence of DVT was higher in patients with COVID-19 than in those with bacterial pneumonia (57.1% vs 41.5%, P = 0.016). Taking death as a competitive risk, the Fine-Gray test showed no significant difference in the 28-day cumulative incidence of DVT between these two groups (P = 0.220). Fine-Gray competing risk analysis also showed an association between increased CK (creatine kinase isoenzyme)-MB levels (P = 0.003), decreased PaO(2) (partial pressure of arterial oxygen)/FiO(2) (fraction of inspired oxygen) ratios (P = 0.081), increased D-dimer levels (P = 0.064) and increased incidence of DVT in COVID-19 cohort, and an association between invasive mechanical ventilation (IMV;P = 0.001) and higher incidence of DVT and an association between VTE prophylaxis (P = 0.007) and lower incidence of DVT in bacterial pneumonia cohort. The sensitivity and specificity of the corresponding receiver operating characteristic curve originating from the combination of CK-MB levels, PaO(2)/FiO(2) ratios, and D-dimer levels ≥0.5 μg/mL were higher than that of the DVT Wells score (P = 0.020) and were not inferior to that of the Padua prediction score (P = 0.363) for assessing the risk of DVT in COVID-19 cohort. CONCLUSIONS: The incidence of DVT in patients with ARDS caused by COVID-19 is higher than those caused by bacterial pneumonia. Furthermore, the risk factors for DVT are completely different between these two ARDS cohorts. It is suggested that COVID-19 is probably an additional risk factor for DVT in ARDS patients.

3.
Jci Insight ; 05:05, 2022.
Article in English | MEDLINE | ID: covidwho-1832829

ABSTRACT

Studies have demonstrated the phenotypic heterogeneity of vascular endothelial cells (ECs) within a vascular bed;however, little is known about how distinct endothelial subpopulations in a particular organ respond to an inflammatory stimulus. We performed single cell RNA-sequencing of 35,973 lung ECs obtained during the baseline state as well as post-injury time points following inflammatory lung injury induced by lipopolysaccharide. Seurat clustering and gene expression pathway analysis identified two major subpopulations in the lung microvascular endothelium, a subpopulation enriched for expression of immune response genes such as major histocompatibility complex genes (immuneEC) and another defined by increased expression of vascular development genes such as Sox17 (devEC). The presence of immuneEC and devEC subpopulations was also observed in non-human primate lungs infected with SARS-CoV-2 and murine lungs infected with H1N1 influenza virus. Following the peak of inflammatory injury, we observed the emergence of a proliferative lung EC subpopulation. Overexpression of Sox17 prevented inflammatory activation in ECs. Thus, there appears to be a" division of labor" within the lung microvascular endothelium with some ECs showing propensity for inflammatory signaling and others for endothelial regeneration. These results provide underpinnings for the development of targeted therapies to limit inflammatory lung injury and promote regeneration.

4.
Nat Metab ; 2022.
Article in English | PubMed | ID: covidwho-1830111

ABSTRACT

The severity and mortality of COVID-19 are associated with pre-existing medical comorbidities such as diabetes mellitus. However, the underlying causes for increased susceptibility to viral infection in patients with diabetes is not fully understood. Here we identify several small-molecule metabolites from human blood with effective antiviral activity against SARS-CoV-2, one of which, 1,5-anhydro-D-glucitol (1,5-AG), is associated with diabetes mellitus. The serum 1,5-AG level is significantly lower in patients with diabetes. In vitro, the level of SARS-CoV-2 replication is higher in the presence of serum from patients with diabetes than from healthy individuals and this is counteracted by supplementation of 1,5-AG to the serum from patients. Diabetic (db/db) mice undergo SARS-CoV-2 infection accompanied by much higher viral loads and more severe respiratory tissue damage when compared to wild-type mice. Sustained supplementation of 1,5-AG in diabetic mice reduces SARS-CoV-2 loads and disease severity to similar levels in nondiabetic mice. Mechanistically, 1,5-AG directly binds the S2 subunit of the SARS-CoV-2 spike protein, thereby interrupting spike-mediated virus-host membrane fusion. Our results reveal a mechanism that contributes to COVID-19 pathogenesis in the diabetic population and suggest that 1,5-AG supplementation may be beneficial to diabetic patients against severe COVID-19.

5.
Journal of Physical Chemistry Letters ; : 4111-4118, 2022.
Article in English | MEDLINE | ID: covidwho-1829965

ABSTRACT

Inhibition of RNA-dependent RNA polymerase (RdRp) by nucleotide analogues with ribose modification provides a promising antiviral strategy for the treatment of SARS-CoV-2. Previous works have shown that remdesivir carrying 1'-substitution can act as a "delayed chain terminator", while nucleotide analogues with 2'-methyl group substitution could immediately terminate the chain extension. However, how the inhibition can be established by the 3'-ribose modification as well as other 2'-ribose modifications is not fully understood. Herein, we have evaluated the potential of several adenosine analogues with 2'- and/or 3'-modifications as obligate chain terminators by comprehensive structural analysis based on extensive molecular dynamics simulations. Our results suggest that 2'-modification couples with the protein environment to affect the structural stability, while 3'-hydrogen substitution inherently exerts "immediate termination" without compromising the structural stability in the active site. Our study provides an alternative promising modification scheme to orientate the further optimization of obligate terminators for SARS-CoV-2 RdRp.

6.
Science China. Life sciences ; 28:28, 2022.
Article in English | MEDLINE | ID: covidwho-1826874

ABSTRACT

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-kappaB 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-kappaB. 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.

7.
Journal of Clinical Laboratory Analysis ; : e24479, 2022.
Article in English | MEDLINE | ID: covidwho-1826009

ABSTRACT

BACKGROUND: SARS-CoV-2 has spread worldwide causing more than 400 million people with virus infections since early 2020. Currently, the existing vaccines targeting the spike glycoprotein (S protein) of SARS-CoV-2 are facing great challenge from the infection of SARS-CoV-2 virus and its multiple S protein variants. Thus, we need to develop a new generation of vaccines to prevent infection of the SARS-CoV-2 variants. Compared with the S protein, the nucleocapsid protein (N protein) of SARS-CoV-2 is more conservative and less mutations, which also plays a vital role in viral infection. Therefore, the N protein may have the great potential for developing new vaccines. METHODS: The N protein of SARS-CoV-2 was recombinantly expressed and purified in Escherichia coli. Western Blot and ELISA assays were used to demonstrate the immunoreactivity of the recombinant N protein with the serum of 22 COVID-19 patients. We investigated further the response of the specific serum antibodies and cytokine production in BALB/c mice immunized with recombinant N protein by Western Blot and ELISA. RESULTS: The N protein had good immunoreactivity and the production of IgG antibody against N protein in COVID-19 patients was tightly correlated with disease severity. Furthermore, the N protein was used to immunize BALB/c mice to have elicited strong immune responses. Not only high levels of IgG antibody, but also cytokine-IFN-gamma were produced in the N protein-immunized mice. Importantly, the N protein immunization induced a high level of IgM antibody produced in the mice. CONCLUSION: SARS-CoV-2 N protein shows a great big bundle of potentiality for developing a new generation of vaccines in fighting infection of SARS-CoV-2 and its variants.

8.
Viruses ; 14(5), 2022.
Article in English | EMBASE | ID: covidwho-1822443

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially emerging variants, poses an increased threat to global public health. The significant reduction in neutralization activity against the variants such as B.1.351 in the serum of convalescent patients and vaccinated people calls for the design of new potent vaccines targeting the emerging variant. However, since most vaccines approved and in clinical trials are based on the sequence of the original SARS-CoV-2 strain, the immunogenicity and protective efficacy of vaccines based on the B.1.351 variant remain largely unknown. In this study, we evaluated the immunogenicity, induced neutralization activity, and protective efficacy of wild-type spike protein nanoparticle (S-2P) and mutant spike protein nanoparticle (S-4M-2P) carrying characteristic mutations of B.1.351 variant in mice. Although there was no significant difference in the induction of spike-specific IgG responses in S-2P-and S-4M-2P-immunized mice, neutralizing antibodies elicited by S-4M-2P exhibited noteworthy, narrower breadth of reactivity with SARS-CoV-2 variants compared with neutralizing antibodies elicited by S-2P. Furthermore, the decrease of induced neutralizing antibody breadth at least partly resulted from the amino acid substitution at position 484. Moreover, S-4M-2P vaccination conferred insufficient protection against live SARS-CoV-2 virus infection, while S-2P vaccination gave definite protection against SARS-CoV-2 challenge in mice. Together, our study provides direct evidence that the E484K substitution in a SARS-CoV-2 subunit protein vaccine limited the cross-reactive neutralizing antibody breadth in mice and, more importantly, draws attention to the unfavorable impact of this mutation in spike protein of SARS-CoV-2 variants on the induction of potent neutralizing antibody responses.

9.
Frontiers in Cellular and Infection Microbiology ; 12, 2022.
Article in English | EMBASE | ID: covidwho-1822356

ABSTRACT

Objective: The longitudinal effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the liver are unknown. This study aimed to characterize dynamic changes in liver function test abnormalities in patients with COVID-19 at the acute phase and recovery phase. Methods: A prospective cohort study involved patients with COVID-19 who were admitted to Shenzhen Third People’s Hospital between January 11, 2020, and April 27, 2020. Patients underwent liver function tests at hospitalization and at the outpatient visit at the 1-month, 3-month, 6-month, and 12-month follow-ups. Results: Among 461 patients, 28.4% of patients had any kind of liver function tests abnormality at admission, manifested as elevated ALT (13.0%), AST (17.6%), and GGT (15.8%) levels. The trajectory analysis indicated a marked improvement in liver function after discharge, with any kind of liver function test abnormalities of 25.1% at 1 month, 13.2% at 3 months, 16.7% at 6 months, and 13.2% at 12 months after discharge. Persistent liver function abnormalities were observed in patients with pre-existing conditions during follow-up. A significantly higher prevalence of ultrasound determined fatty liver disease was found in those patients with more frequent LFT abnormalities at follow-up. Conclusion: In this study of patients with COVID-19, liver damage in COVID-19 was usually temporary and could return to normal at the end of the 12-month follow-up.

10.
Chinese Medicine (United Kingdom) ; 17(1), 2022.
Article in English | EMBASE | ID: covidwho-1822198

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) causes a global pandemic and has devastating effects around the world, however, there are no specific antiviral drugs and vaccines for the constant mutation of SARS-CoV-2. Purpose: In this study, we evaluted the antiviral and anti-inflammatory activities of Liushen Capsules (LS) on different novel coronavirus in vitro, studied its therapeutic effects on novel SARS-CoV-2 infected mice and observed the LS’s clinical efficacy and safety in COVID-19. Methods: The antiviral and aiti-inflammatory effects of LS on the 501Y.V2/B.1.35 and G/478K.V1/ B.1.617.2 strains were determined in vitro. A hACE2 mouse model of novel SARS-CoV-2 pneumonia was established. Survival rates, histological changes, inflammatory markers, lung virus titers and the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blotting and immumohistochemical staining in the lungs were measured. Subsequently, the disease duration, prognosis of disease, time of negative nucleic acid and the cytokines levels in serum were used to assess the efficacy of treatment with LS in patients. Results: The results showed that LS (2, 1, 0.5 μg/mL) could significantly inhibit the replication of the two SARS-CoV-2 variants and the expression of pro-inflammatory cytokines (IL-6, IL-8, IP-10, CCL-5, MIP-1α, IL-1α) induced by the virus in vitro. As for the survival experiment in mice, the survival rate of virus group was 20%, while LS-treatment groups (40, 80, 160 mg/kg) could increase the survival rate to 60, 100 and 100%, respectively. LS (40, 80, 160 mg/kg) could significantly decrease the lung titers in mice and it could improve the pathological changes, inhibit the excessive inflammatory mediators (IFN-α, IFN-γ, IP-10, MCP-1) and the protein expression of p-NF-κB p65 in mice. Moreover, LS could significantly decrease SARS-CoV-2-induced activation of p-NF-κB p65, p-IκBα, and p-p38 MAPK and increase the protein expression of the IκBα. In addition, the patient got complete relief of symptoms after being treated with LS for 6 days and was proven with negative PCR test after being treated for 23 days. Finally, treatment with LS could reduce the release of inflammatory cytokines (IL-6, PDGF-AA/BB, Eotaxin, MCP-1, MIP-1α, MIP-1β, GRO, CCL-5, MCP-3, IP-10, IL-1α). Conclusion: LS effectively alleviated novel SARS-CoV-2 or variants induced pneumonia in vitro and in vivo, and improved the prognosis of COVID-19. In light of the efficacy and safety profiles, LS could be considered for the treatment of COVID-19 with a broad-spectrum antiviral and anti-inflammatory agent.

12.
Veterinary Sciences ; 9(4):13, 2022.
Article in English | Web of Science | ID: covidwho-1818234

ABSTRACT

Swine viruses like porcine sapovirus (SaV), porcine encephalomyocarditis virus (EMCV), porcine rotavirus A (RVA) and porcine astroviruses (AstV) are potentially zoonotic viruses or suspected of potential zoonosis. These viruses have been detected in pigs with or without clinical signs and often occur as coinfections. Despite the potential public health risks, no assay for detecting them all at once has been developed. Hence, in this study, a multiplex RT-PCR (mRT-PCR) assay was developed for the simultaneous detection of SaV, EMCV, RVA and AstV from swine fecal samples. The PCR parameters were optimized using specific primers for each target virus. The assay's sensitivity, specificity, reproducibility, and application to field samples have been evaluated. Using a pool of plasmids containing the respective viral target fragments as a template, the developed mRT-PCR successfully detected 2.5 x 10(3) copies of each target virus. The assay's specificity was tested using six other swine viruses as a template and did not show any cross-reactivity. A total of 280 field samples were tested with the developed mRT-PCR assay. Positive rates for SaV, EMCV, RVA, and AstV were found to be 24.6% (69/280), 5% (14/280), 4.3% (12/280), and 17.5% (49/280), respectively. Compared to performing separate assays for each virus, this mRT-PCR assay is a simple, rapid, and cost-effective method for detecting mixed or single infections of SaV, EMCV, RVA, and AstV.

13.
Cancers ; 14(9), 2022.
Article in English | EMBASE | ID: covidwho-1818053

ABSTRACT

Observational studies have shown increased COVID-19 risk among cancer patients, but the causality has not been proven yet. Mendelian randomization analysis can use the genetic variants, independently of confounders, to obtain causal estimates which are considerably less confounded. We aimed to investigate the causal associations of cancers with COVID-19 outcomes using the MR analysis. The inverse-variance weighted (IVW) method was employed as the primary analysis. Sensitivity analyses and multivariable MR analyses were conducted. Notably, IVW analysis of univariable MR revealed that overall cancer and twelve site-specific cancers had no causal association with COVID-19 severity, hospitalization or susceptibility. The corresponding p-values for the casual associations were all statistically insignificant: overall cancer (p = 0.34;p = 0.42;p = 0.69), lung cancer (p = 0.60;p = 0.37;p = 0.96), breast cancer (p = 0.43;p = 0.74;p = 0.43), endometrial cancer (p = 0.79;p = 0.24;p = 0.83), prostate cancer (p = 0.54;p = 0.17;p = 0.58), thyroid cancer (p = 0.70;p = 0.80;p = 0.28), ovarian cancer (p = 0.62;p = 0.96;p = 0.93), melanoma (p = 0.79;p = 0.45;p = 0.82), small bowel cancer (p = 0.09;p = 0.08;p = 0.19), colorectal cancer (p = 0.85;p = 0.79;p = 0.30), oropharyngeal cancer (p = 0.31;not applicable, NA;p = 0.80), lymphoma (p = 0.51;NA;p = 0.37) and cervical cancer (p = 0.25;p = 0.32;p = 0.68). Sensitivity analyses and multivariable MR analyses yielded similar results. In conclusion, cancers might have no causal effect on increasing COVID-19 risk. Further large-scale population studies are needed to validate our findings.

14.
mBio ; : e0018122, 2022.
Article in English | PubMed | ID: covidwho-1816698

ABSTRACT

Understanding immune memory to COVID-19 vaccines is critical for the design and optimal vaccination schedule for curbing the COVID-19 pandemic. Here, we assessed the status of humoral and cellular immune responses at 1, 3, 6, and 12 months after two-dose CoronaVac vaccination. A total of 150 participants were enrolled, and 136 of them completed the study through the 12-month endpoint. Our results show that, at 1 month after vaccination, both binding and neutralizing antibodies could be detected;the seropositive rate of binding antibodies and seroconversion rate of neutralizing antibodies were 99% and 50%, respectively. From 3 to 12 months, the binding and neutralizing antibodies declined over time. At 12 months, the binding and neutralizing antibodies were still detectable and significantly higher than the baseline. Gamma interferon (IFN-γ) and interleukin 2 (IL-2) secretion specifically induced by the receptor-binding domain (RBD) persisted at high levels until 6 months and could be observed at 12 months, while the levels of IL-5 and granzyme B (GzmB) were hardly detected, demonstrating a Th1-biased response. In addition, specific CD4(+) T central memory (T(CM)), CD4(+) effector memory (T(EM)), CD8(+) T(EM), and CD8(+) terminal effector (T(E)) cells were all detectable and functional up to 12 months after the second dose, as the cells produced IFN-γ, IL-2, and GzmB in response to stimulation of SARS-CoV-2 RBD. Our work provides evidence that CoronaVac induced not only detectable binding and neutralizing antibody responses, but also functional SARS-CoV-2-specific CD4(+) and CD8(+) memory T cells for up to 12 months. IMPORTANCE CoronaVac is an inactivated vaccine containing whole-virion SARS-CoV-2, which has been approved in 43 countries for emergency use as of 26 November 2021. However, the long-term immune persistence of the CoronaVac vaccine is still unknown. Here, we reported the status of the persistence of antibodies and cellular responses within 12 months after two doses of CoronaVac. Such data are crucial to inform ongoing and future vaccination strategies to combat COVID-19.

15.
British Journal of Social Work ; : 16, 2022.
Article in English | Web of Science | ID: covidwho-1816006

ABSTRACT

In their response to the initial outbreak of COVID-19 in China, Chinese social workers were able to take their place on the international stage and share their experiences and knowledge with the rest of the world. Thus, we aim to examine the experiences of social workers during the initial outbreak of COVID-19 in China to promote public health. Based on a quasi-scoping review of articles on social work practice during the initial outbreak of COVID-19 in China, this reflective article elucidates how social workers contributed in different roles and focuses over three stages. Three suggestions are also made in terms of confronting the challenges arising in each stage: increase the independence and visibility of social work in the system, prioritise practice and flexibility over rigid procedures and increase professional collaborations and do away with disputes around the provision of community and public health social work services. Social workers contributed significantly to the promotion of public and community health during the initial outbreak of COVID-19 in China. Based on a quasi-scoping review of articles on social work practice during that outbreak, this reflective article elucidates how social workers contributed in three chronological stages. In the early stage (late January and February 2020), social workers provided community services offered as part of the governmental structure (moderate information and resource provision);in the middle stage (March 2020), social workers provided services to vulnerable groups alongside supporting the quarantine strategy;and in the late stage (April 2020 onwards), their services were focused on recuperation and recovery after the national lockdown was lifted. In the meanwhile, several issues for public and community health social work as a profession in terms of how it was able to support anti-COVID-19 practices became clear, including a lack of independence and stability, the need for better flexibility and greater ability to act pragmatically and lack of professional agreement. This article aims to enlighten the development of a (re)emerging field-public health and community health social work in China in the wake of the COVID-19 pandemic.

16.
Signal Transduct Target Ther ; 7(1):141, 2022.
Article in English | PubMed | ID: covidwho-1815516

ABSTRACT

Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, there have been a few variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), one of which is the Omicron variant (B.1.1.529). The Omicron variant is the most mutated SARS-CoV-2 variant, and its high transmissibility and immune evasion ability have raised global concerns. Owing to its enhanced transmissibility, Omicron has rapidly replaced Delta as the dominant variant in several regions. However, recent studies have shown that the Omicron variant exhibits reduced pathogenicity due to altered cell tropism. In addition, Omicron exhibits significant resistance to the neutralizing activity of vaccines, convalescent serum, and most antibody therapies. In the present review, recent advances in the molecular and clinical characteristics of the infectivity, pathogenicity, and immune evasion of Omicron variant was summarized, and potential therapeutic applications in response to Omicron infection were discussed. Furthermore, we highlighted potential response to future waves and strategies to end the pandemic.

17.
International Journal of Infectious Diseases ; 119:87-94, 2022.
Article in English | MEDLINE | ID: covidwho-1814521

ABSTRACT

OBJECTIVES: To evaluate the cost-effectiveness of a booster strategy in the United States. METHODS: We developed a decision-analytic Markov model of COVID-19 to evaluate the cost-effectiveness of a booster strategy of the Pfizer-BioNTech BNT162b2 (administered 6 months after the second dose) among older adults from a healthcare system perspective. RESULTS: Compared with 2 doses of BNT162b2 without a booster, the booster strategy in a 100,000 cohort of older adults would incur an additional cost of $3.4 million in vaccination cost but save $6.7 million in direct medical cost and gain 3.7 quality-adjusted life-years in 180 days. This corresponds to a benefit-cost ratio of 1.95 and a net monetary benefit of $3.4 million. Probabilistic sensitivity analysis indicates that a booster strategy has a high chance (67%) of being cost-effective. Notably, the cost-effectiveness of the booster strategy is highly sensitive to the population incidence of COVID-19, with a cost-effectiveness threshold of 8.1/100,000 person-day. If vaccine efficacies reduce by 10%, 30%, and 50%, this threshold will increase to 9.7/100,000, 13.9/100,000, and 21.9/100,000 person-day, respectively. CONCLUSION: Offering the BNT162b2 booster to older adults aged >=65 years in the United States is likely to be cost-effective. Less efficacious vaccines and boosters may still be cost-effective in settings of high SARS-CoV-2 transmission.

18.
Frontiers in Public Health ; 10:10, 2022.
Article in English | Web of Science | ID: covidwho-1809619

ABSTRACT

Background: Mental health issue among college students is routinely a major public health concern, and coronavirus disease 2019 (COVID-19) pandemic may have exacerbated the students' mental health issues which include psychological distress, panic disorder, insomnia, and posttraumatic stress symptoms. However, few studies reached a consensus on the impact of COVID-19 fear on mental health among college students. Therefore, we aimed to conduct a systematic review and meta-analysis that quantitatively synthesized the fear among college students during the COVID-19 pandemic.& nbsp;Methods: PubMed, EMBASE, CINAHL, and PsycINFO electronic databases were systematically searched to identify cross-sectional study reporting the state of COVID-19 fear examined by the Fear of COVID-19 Scale (FCV-19S) published up until November 20, 2021. Methodological quality was complied with the evaluation criteria of the Agency for Healthcare Research and Quality. The random effects model was employed to estimate the pooled mean of FCV-19S score. Subgroup analysis and meta-regression analysis were also conducted. Publication bias was assessed by Begg's test and funnel plot.& nbsp;Results: A total of 16 studies with a sample size of 11,872 were included. A pooled mean of FCV-19S score was 17.60 [95% confidence interval (CI): 16.41-18.78]. The mean of COVID-19 fear in women (17.11, 95% CI: 16.59-17.64) was higher than that in men (15.21, 95% CI: 14.33-16.08). The highest and lowest pooled means of FCV-19S score were observed in the studies conducted in multiple countries that include Israel, Russian, and Belarus (21.55, 95% CI: 20.77-22.33) and in Europe (16.52, 95% CI: 15.26-17.77), respectively. No significant publication bias was detected by Begg's test.& nbsp;Conclusions: College students experienced a moderate level of fear caused by COVID-19 pandemic. It is necessary to design and implement prevention programs that target the mental health of college students.

19.
Front Microbiol ; 13:792532, 2022.
Article in English | PubMed | ID: covidwho-1809433

ABSTRACT

A recent study showed that patients with coronavirus disease 2019 (COVID-19) have gastrointestinal symptoms and intestinal flora dysbiosis. Yeast probiotics shape the gut microbiome and improve immune homeostasis. In this study, an oral candidate of yeast-derived spike protein receptor-binding domain (RBD) and fusion peptide displayed on the surface of the yeast cell wall was generated. The toxicity and immune efficacy of oral administration were further performed in Institute of Cancer Research (ICR) mice. No significant difference in body weights, viscera index, and other side effects were detected in the oral-treated group. The detectable RBD-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and more complex microbiota were detected from oral administration mice compared with those of the control group. Interestingly, the recombinant yeast was identified in female fetal of the high-dose group. These results revealed that the displaying yeast could fulfill the agent-driven immunoregulation and gut microbiome reconstitution. The findings will shed light on new dimensions against SARS-CoV-2 infection with the synergistic oral agents as promising non-invasive immunization and restoring gut flora.

20.
mBio ; : e0046322, 2022.
Article in English | PubMed | ID: covidwho-1807326

ABSTRACT

Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and SARS-CoV-2, the causative agents of SARS, which broke out in 2003, and coronavirus disease 2019 (COVID-2019), which broke out in 2019, probably originated in Rhinolophus sinicus and R. affinis, respectively. Rhinolophus bats are important hosts for coronaviruses. Many SARS-related coronaviruses (SARSr-CoVs) have been detected in bats from different areas of China;however, the diversity of bat SARSr-CoVs is increasing, and their transmission mechanisms have attracted much attention. Here, we report the findings of SARSr-CoVs in R. sinicus and R. affinis from South China from 2008 to 2021. The full-length genome sequences of the two novel SARSr-CoVs obtained from Guangdong shared 83 to 88% and 71 to 72% nucleotide identities with human SARS-CoV and SARS-CoV-2, respectively, while sharing high similarity with human SARS-CoV in hypervariable open reading frame 8 (ORF8). Significant recombination occurred between the two novel SARSr-CoVs. Phylogenetic analysis showed that the two novel bat SARSr-CoVs from Guangdong were more distant than the bat SARSr-CoVs from Yunnan to human SARS-CoV. We found that transmission in bats contributes more to virus diversity than time. Although our results of the sequence analysis of the receptor-binding motif (RBM) and the expression pattern of angiotensin-converting enzyme 2 (ACE2) inferred that these viruses could not directly infect humans, risks still exist after some unpredictable mutations. Thus, this study increased our understanding of the genetic diversity and transmission of SARSr-CoVs carried by bats in the field. IMPORTANCE Severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 probably originated from the SARS-related coronaviruses (SARSr-CoVs) carried by Rhinolophus bats from Yunnan, China. Systematic investigations of the reservoir hosts carrying SARSr-CoVs in Guangdong and the reservoir distribution and transmission are urgently needed to prevent future outbreaks. Here, we detected SARSr-CoV in Rhinolophus bat samples from Guangdong in 2009 and 2021 and found that the transmission of SARSr-CoV from different host populations contributes more to increased virus diversity than time. Bat SARSr-CoVs in Guangdong had genetic diversity, and Guangdong was also the hot spot for SARSr-CoVs. We once again prove that R. sinicus plays an important role in the maintenance of the SARS-CoVs. Besides, the SARSr-CoVs are mainly transmitted through the intestines in bats, and these SARSr-CoVs found in Guangdong could not use human ACE2 (hACE2), but whether they can pass through intermediate hosts or directly infect humans requires further research. Our findings demonstrate the ability of SARSr-CoVs to spread across species.

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