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1.
Pharmacophore ; 13(1):48-55, 2022.
Article in English | Web of Science | ID: covidwho-1822791

ABSTRACT

At the current time, obesity itself can be a pandemic for many risk factors such as what is occurring in western countries were quickly comforted by the increase in the frequency of obesity, whose effects on health were soon manifested by a significant increase in cardiovascular disease in the general population. Inflammatory proteins can be classified according to their functions into different categories, although they are mainly involved in the response of the acute phase of inflammation, among which is the C-reactive protein (CRP). This study aimed to provide the effects of obesity according to the inflammatory analysis with CRP test on obese patients having a high-frequency inflammation which is one of several causes lead toward the infection and catching by Coronavirus COVID-19 disease because the influence of the obesity on the immunity system, according to sex, ethnicity, and age. We focused that obese patients must avoid any high-level CRP concentration to prevent them from any risk factors of contamination by COVID-19 pandemic. Copyright (C) 2013 - All Rights Reserved - Pharmacophore

2.
PeerJ ; 10, 2022.
Article in English | EMBASE | ID: covidwho-1822578

ABSTRACT

Background. It remains unclear how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection started, spread worldwide, and mutated to result in the present variants. This difficulty can be attributed to the limitations associated with the analytical methodology for presenting the differences among genomic sequences. In this study, we critically analysed the early data to explain the start and spread of the pandemic. Methods. Objective analyses of the RNA sequences of earlier variants of SARS-CoV-2 (up to September 1, 2020, available in DDBJ and GISAID) were performed using Principal Component Analysis (PCA). The results were compared with information on the collection dates and location. The PCA was also conducted for 12 variants of interest to the WHO as of September 2021, and compared with earlier data. Results. The pandemic began in Wuhan, China. This strain was suspected to be related to other reported animal viruses;however, they had a minimal similarity. The strain then spreads via three routes while accumulating mutations. Several viral subgroups were identified along the routes, each with a large number of patients reported, indicating high infectivity to humans. These routes were only confirmed by the early data analysis, because newer variants would have more mutations, and would be preferentially be examined by PCA if they were included. On the original axes found in the early variants, the newer variants revealed that they retained previously acquired mutations, which helped to reveal the viral ancestors of the newer variants. The rate of mutation was found to be comparable to that of the influenza H1N1 virus, which causes recurrent seasonal epidemics. Another threat imposed by SARS-CoV-2 is that if the pandemic cannot be contained, new variants may emerge annually, preventing herd immunity. DOI 10.7717/peerj.12681

3.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822475

ABSTRACT

Background: Longitudinal surveys to monitor the seroprevalence are required to support efforts for assessment of the levels of endemic stability in certain countries. We investigated seroprevalence of anti-SARS-CoV-2-S1 receptor-binding domain (RBD)-specific antibodies in the serum samples in 2011–2021, including a cohort study of 2019–2021, to evaluate the vaccination and anti-IgG-SARS-CoV-2–S1 RBD-positive statuses to assess the resistance and severity of COVID-19. Materials and Methods: Anti-SARS-CoV-2-S1 RBD-specific antibodies were assayed in the serum samples (N = 565) randomly selected from various cohorts previously recruited from 2011 to 2021 from the city of Moscow and Moscow Region. Among them there were the participants (N = 310) recruited in 2019–2021 with an endpoint of 30 October 2021 when these participants were interviewed over phone with relevant questionnaire. Results: Obtained data indicated a percentage of 3–6% of SARS-CoV-2-S1 RBD-specific antibodies detected in participants recruited in 2011–2019. The percentage of SARS-CoV-2-S1 RBD-specific antibodies was increased to 16.5% in 2020 and to 46% in 2021. The vaccination rate of 238 respondents of this cohort was 58% from August 2020 to October 2021. In total, 12% of respondents were hospitalized. The morbidity rate in the subgroup of anti-SARS-CoV-2-S1 RBD-positive respondents was 5.4-fold higher than that in the subgroup of vaccinated respondents. Conclusions: A small percentage of SARS-CoV-2-S1 RBD-specific antibodies detected in 2011–2019 indicated possible spreading of coronaviruses during the pre-pandemic period. Collective immunity in Moscow and the Moscow region was able to reach 69% from August 2020 to October 2021 if this rate is added to the rate of not vaccinated SARS-CoV-2-S1 RBD-positive subjects.

4.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822474

ABSTRACT

In the present study, antibody and T cell-mediated immune responses elicited by BBIBP-CorV and BNT162b2 vaccines were compared 6 months after the two-dose immunization of healthy individuals. Additionally, antibody and T cell responses after the third dose of BBIBP-CorV or BNT162b2 were compared using a homologous or heterologous vaccination strat-egy. The third dose was consistently administered 6 months after the second dose. Six months following the two-dose vaccination, the cumulative IFNγ-positive T cell response was almost identical in participants immunized with either two doses of BNT162b2 or BBIBP-CorV vaccines;however, significant differences were revealed regarding humoral immunity: the two-dose BNT162b2 vaccine maintained a significantly higher antireceptor-binding domain (RBD) IgG, anti-spike (S1/S2) IgG, and IgA antibody levels. The BNT162b2 + BNT162b2 + BBIBP-CorV vaccine series elicited significantly lower anti-RBD IgG and anti-S1/S2 IgG levels than three doses of BNT162b2, while the anti-S IgA level was equally negligible in both groups. Importantly, the cumulative IFNγ-positive T cell response was highly similar in both groups. Surprisingly, the BBIBP-CorV + BBIBP-CorV + BNT162b2 vaccination series provided a much higher cumulative IFNγ-positive T cell response than that elicited by three doses of BNT162b2;moreover, the levels of anti-RBD IgG and anti-S IgA were almost identical. Only the mean anti-S1/S2 IgG levels were higher after receiving three mRNA vaccines. Based on these data, we can conclude that adminis-tering a third dose of BNT162b2 after two doses of BBIBP-CorV is an effective strategy to significantly enhance both humoral and T cell-mediated immune response, and its effectiveness is com-parable to that of three BNT162b2 vaccines.

5.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822471

ABSTRACT

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, has caused over 460 million cases of infection and over 6 million deaths world-wide. The pandemic has called for science, technology, and innovation to provide solutions and, due to an incredible scientific and financial global effort, several prophylactic and therapeutic apparatuses such as monoclonal antibodies and vaccines were developed in less than one year to address this emergency. After SARS-CoV-2 infection, serum neutralizing antibodies are produced by B cells and studies on virus-neutralizing antibodies’ kinetics are pivotal. The process of protective immunity and the duration of this kind of protection against COVID-19 remain to be clarified. We tested 136 sera from 3 groups of individuals, some of them providing multiple sequential sera (1—healthy, no previous CoV2-infected, vaccinated;2—healthy, previous CoV2 infected, vaccinated;3—healed, previous CoV2-infected, not vaccinated) to assess the kinetics of antibodies (Abs) neutralizing activity. We found that SARS-CoV-2 infection elicits moderate neutralizing antibody activity in most individuals;neither age nor gender appear to have any influence on Abs responses. The BNT162b2 vaccine, when administered in two doses, induces high antibodies titre endowed with potent neutralizing activity against bare SARS-CoV-2 in in vitro neutralizing assay. The residual neutralization capability and the kinetic of waning immunity were also evaluated over 9 months after the second dose in a reference group of subjects. Neutralization titre showed a decline in all subjects and the median level of S-protein IgG, over 270 days after the second vaccination dose, was below 10 AU/mLin 53% of serum tested.

6.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822466

ABSTRACT

The COVID-19 pandemic continues to be a worldwide health issue. Among hemodialysis (HD) patients, two-dose immunization schemes with mRNA vaccines have contributed to preventing severe COVID-19 cases;however, some have not produced a sufficient humoral response, and most have developed a rapid decline in antibody levels over the months following vaccination. This observational, prospective, multi-center study evaluated the humoral response in terms of presence and levels of IgG antibodies to the receptor-binding domain of the S1 spike antigen of SARS-CoV-2 (anti-S1-RBD IgG) to the third dose of SARS-CoV-2 mRNA vaccines, either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer), in 153 patients from three dialysis units affiliated to Hospital Clínic of Barcelona (Spain). Most hemodialysis patients responded intensely to this third vaccine dose, achieving the seroconversion in three out of four non-or weak responders to two doses. Moreover, 96.1% maintained the upper limit or generated higher titers than after the second. BNT162b2 vaccine, active cancer, and immunosuppressive treatment were related to a worse humoral response. Every hemodialysis patient should be administered a third vaccine dose six months after receiving the second one. Despite the lack of data, immunosuppressed patients and those with active cancer may benefit from more frequent vaccine boosters.

7.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822460

ABSTRACT

The worldwide pandemic of coronavirus disease 2019 (COVID-19) has imposed a challenge on human health worldwide, and vaccination represents a vital strategy to control the pandemic. To date, multiple COVID-19 vaccines have been granted emergency use authorization, including inactivated vaccines, adenovirus-vectored vaccines, and nucleic acid vaccines. These vaccines have different technical principles, which will necessarily lead to differences in safety and efficacy. Therefore, we aim to implement a systematic review by synthesizing clinical experimental data combined with mass vaccination data and conducting a synthesis to evaluate the safety and efficacy of COVID-19 vaccines. Compared with other vaccines, adverse reactions after vaccination with inactivated vaccines are relatively low. The efficacy of inactivated vaccines is approximately 60%, adenovirus-vectored vaccines are 65%, and mRNA vaccines are 90%, which are always efficient against asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, symptomatic COVID-19, COVID-19 hospitalization, severe or critical hospitalization, and death. RNA-based vaccines have a number of advantages and are one of the most promising vaccines identified to date and are particularly important during a pandemic. However, further improvements are required. In time, all the antibody levels weaken gradually, so a booster dose is needed to maintain immunity. Compared with homologous prime-boost immunization, heterologous prime-boost immunization prompts more robust humoral and cellular immune responses.

8.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822453

ABSTRACT

Information on the effects of a heterologous booster in adult patients first vaccinated with the BBIBP-CorV vaccine is limited. This prospective cohort study evaluated the humoral response of 152 healthcare workers (HCWs) from a private laboratory in Lima (Peru) before and after receiving the BNT162b2 vaccine, with a seven-month interval since the BBIBP-CorV doses. We employed the Elecsys® anti-SARS-CoV-2 S and the cPass™ SARS-CoV-2 Neutralization Antibody (NAbs) assays to evaluate anti-S-RBD IgG and NAbs, respectively. Of the 152 HCWs, 79 (51.98%) were previously infected (PI) with SARS-CoV-2 and 73 (48.02%) were not previously infected (NPI). The proportion of HCWs with positive NAbs, seven months after the BBIBP-CorV immunization, was 49.31% in NPI and 92.40% in PI. After the booster, this ratio increased to 100% in both groups. The anti-S-RBD IgG and NAbs in the HCWs’ NPI increased by 32.7 and 3.95 times more, respectively. In HCWs’ PI, this increment was 5 and 1.42 times more, respectively. There was no statistical association between the history of previous SARS-CoV-2 infection and the titer of anti-S-RBD IgG and NAbs after the booster. The humoral immunity presented a robust increase after receiving the BNT162b2 booster and was more pronounced in NPI.

9.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822452

ABSTRACT

Emergent SARS-CoV-2 variants and waning humoral immunity in vaccinated individuals have resulted in increased infections and hospitalizations. Children are not spared from infection nor complications of COVID-19, and the recent recommendation for boosters in individuals ages 12 years or older calls for broader understanding of the adolescent immune profile after mRNA vaccination. We tested the durability and cross-reactivity of anti-SARS-CoV-2 serologic responses over a six-month time course in vaccinated adolescents against the SARS-CoV-2 D614G (“wild type”) and Omicron antigens. Serum from 77 adolescents showed that anti-Spike antibodies wane significantly over six months. After completion of a two-vaccine series, cross-reactivity against Omicron-specific receptor-binding domain (RBD) was seen. Functional humoral activation against wild type and Omicron SARS-CoV-2 also declines over time in vaccinated adolescent children. Evidence of waning mRNA-induced vaccine immunity underscores vulnerabilities in long-term pediatric protection against SARS-CoV-2 infection, while cross-reactivity highlights the additional benefits of vaccination. Characterization of adolescent immune signatures post-vaccination will inform guidance on vaccine platforms and timelines, and ultimately optimize immunoprotection of children.

10.
Vaccines ; 10(4), 2022.
Article in English | EMBASE | ID: covidwho-1822451

ABSTRACT

COVID-19 remains a deadly disease that poses a serious threat to humanity. COVID-19 vaccines protect the public and limit viral spread. However, public acceptance is significantly dependent on the efficacy and side effects (SEs) of the vaccinations being produced. Four important mechanisms have been examined for COVID-19 vaccines: DNA-based, mRNA-based, protein-based, and inactivated viruses. Vaccination safety research was formerly limited to manufacturer-sponsored studies, but numerous additional cross-sectional survey-based studies conducted globally have contributed to the generation of vaccine-related safety data reports. Twenty-seven studies and twenty-four case reports published-up till 2021 were overviewed for the presentation of SEs and their severity. Injection site pain remained the most dominant localized SE, while headache and fatigue were the most prevalent systemic SEs. Most studies reported that all vaccinations were safe, with very little or no adverse effects, but the nature of SEs was reported to be more persistent in DNA-and mRNA-based vaccines, while inactivated viral vaccines were associated with longer-duration SEs. Overall, SEs were found to be more dominant in women and youngsters. Case reports of adverse reactions have also been documented, but there is still a need to find out their pathological linkage with the COVID-19 vaccination.

11.
Viruses ; 14(5), 2022.
Article in English | EMBASE | ID: covidwho-1822447

ABSTRACT

Background: This study aimed to investigate the early and longitudinal humoral response in Healthcare Workers (HCWs) after two doses of the BNT162b2 vaccine and to assess the association between metabolic and anthropometric parameters and the humoral response after vaccination. Methods: The study included 243 fully vaccinated HCWs: 25.50% previously infected with SARS-CoV-2 (with prior history of COVID-19—PH) and 74.40%—uninfected, seronegative before the first vaccination (with no prior history of COVID-19—NPH). IgG antibodies were measured, and sera were collected: prior to the vaccination, 21 days after the first dose, and 14 days and 8 months after the second dose. Results: 21 days after the first dose, 90.95% of individuals were seropositive;14 days after the second dose, persistent immunity was observed in 99.18% HCWs, 8 months after complete vaccination—in 61.73%. Statistical analysis revealed that HCWs with PH had a greater chance of maintaining a humoral response beyond eight months after vaccination. Increased muscle mass, decreased fat mass, and younger age may positively affect long-term immunity. Smokers have a reduced chance of developing immunity compared to non-smokers. Conclusions: Fully vaccinated HCWs with PH are more likely to be seropositive than fully inoculated volunteers with NPH.

12.
Pathogens ; 11(4), 2022.
Article in English | EMBASE | ID: covidwho-1822431

ABSTRACT

Background: SARS-CoV-2 enters the body through inhalation or self-inoculation to mucosal surfaces. The kinetics of the ocular and nasal mucosal-specific-immunoglobulin A(IgA) responses remain under-studied. Methods: Conjunctival fluid (CF, n = 140) and nasal epithelial lining fluid (NELF, n = 424) obtained by paper strips and plasma (n = 153) were collected longitudinally from SARS-CoV-2 paediatric (n = 34) and adult (n = 47) patients. The SARS-CoV-2 spike protein 1(S1)-specific mucosal antibody levels in COVID-19 patients, from hospital admission to six months post-diagnosis, were assessed. Results: The mucosal antibody was IgA-predominant. In the NELF of asymptomatic paediatric patients, S1-specific IgA was induced as early as the first four days post-diagnosis. Their plasma S1-specific IgG levels were higher than in symptomatic patients in the second week after diagnosis. The IgA and IgG levels correlated positively with the surrogate neutralization readout. The detectable NELF “receptor-blocking” S1-specific IgA in the first week after diagnosis correlated with a rapid decline in viral load. Conclusions: Early and intense nasal S1-specific IgA levels link to a rapid decrease in viral load. Our results provide insights into the role of mucosal immunity in SARS-CoV-2 exposure and protection. There may be a role of NELF IgA in the screening and diagnosis of SARS-CoV-2 infection.

13.
Pathogens ; 11(4), 2022.
Article in English | EMBASE | ID: covidwho-1822430

ABSTRACT

It has been posited SARS-CoV-2 contains at least one unique superantigen-like motif not found in any other SARS or endemic coronaviruses. Superantigens are potent antigens that can send the immune system into overdrive. SARS-CoV-2 causes many of the biological and clinical consequences of a superantigen, and, in the context of reinfection and waning immunity, it is important to better understand the impact of a widely circulating, airborne pathogen that may be a superantigen, superantigen-like or trigger a superantigenic host response. Urgent research is needed to better understand the long-term risks being taken by governments whose policies enable widespread transmission of a potential superantigenic pathogen, and to more clearly define the vaccination and public health policies needed to protect against the consequences of repeat exposure to the pathogen.

14.
Frontiers in Pediatrics ; 10, 2022.
Article in English | EMBASE | ID: covidwho-1822389

ABSTRACT

X-linked lymphoproliferative disease (XLP1) is an inborn error of immunity (IEI) with severe immune dysregulation caused by a mutation in the SH2D1A gene resulting in the absence or dysfunction of signaling lymphocytic activation molecule (SLAM)-associated protein (SAP). The severe acute respiratory syndrome (SARS) caused by SARS-coronavirus (CoV), a highly pathogenic CoV, has been shown to only cause mild diseases in Asian children. We report on a 5-year-old Nepalese boy with agammaglobulinemia and probable SARS who died of diffuse alveolar damage 22 days after admission amid the SARS outbreak. The index patient and his younger brother were genetically confirmed to have XLP1. In the current coronavirus disease 2019 (COVID-19) pandemic, most children also had mild disease only. Children with severe COVID-19 would warrant investigations for underlying IEI, particularly along the pathways leading to immune dysregulation.

15.
Frontiers in Microbiology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-1822382

ABSTRACT

Identifying immunogenic targets of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to advance diagnostic and disease control strategies. We analyzed humoral (ELISA) and T-cell (ELISpot) immune responses to spike (S) and nucleocapsid (N) SARS-CoV-2 proteins as well as to human endemic coronavirus (eCoV) peptides in serum from convalescent coronavirus disease 2019 (COVID-19) patients from Tatarstan, Russia. We identified multiple SARS-CoV-2 peptides that were reactive with serum antibodies and T cells from convalescent COVID-19. In addition, age and gender associated differences in the reactivity to S and N protein peptides were identified. Moreover, several SARS-CoV-2 peptides tested negatively correlated with disease severity and lung damage. Cross-reactivity to eCoV peptides was analyzed and found to be lower in COVID-19 compared to controls. In this study, we demonstrate the changing pattern of immunogenic peptide reactivity in COVID-19 serum based on age, gender and previous exposure to eCoVs. These data highlight how humoral immune responses and cytotoxic T cell responses to some of these peptides could contribute to SARS-CoV-2 pathogenesis.

16.
Frontiers in Medicine ; 9, 2022.
Article in English | EMBASE | ID: covidwho-1822377

ABSTRACT

Background: The COVID-19 pandemic has major implications on kidney transplant recipients (KTRs) since they show increased mortality due to impaired immune responses to SARS-CoV-2 infection and a reduced efficacy of SARS-CoV-2 vaccination. Surprisingly, dialysis patients have shown superior seroconversion rates after vaccination compared to KTRs. Therefore, we investigated peripheral blood B cell (BC) composition before and after kidney transplantation (KT) and aimed to screen the BC compartment to explain impaired antibody generation. Methods: A total of 105 patients were recruited, and multicolor flow cytometric phenotyping of peripheral venous blood BC subpopulations was performed before and 1 year after KT. Complete follow-up was available for 71 individuals. Anti-SARS-CoV-2 antibodies were collected retrospectively and were available for 40 subjects, who had received two doses of an mRNA-based vaccine (BNT162b2 or mRNA-1273). Results: Overall, relative BC frequencies within lymphocytes decreased, and their absolute counts trended in the same direction 1 year after KT as compared to CKD G5 patients. Frequencies and absolute numbers of naïve BCs remained stable. Frequencies of double negative BCs, a heterogeneous subpopulation of antigen experienced BCs lacking CD27 expression, were increased after KT, yet their absolute counts were similar at both time points. Transitional BCs (TrBCs) and plasmablasts were significantly reduced after KT in absolute and relative terms. Memory BCs were affected differently since class-switched and IgM-only subsets decreased after KT, but unswitched and IgD-only memory BCs remained unchanged. CD86+ and CD5+ expression on BCs was downregulated after KT. Correlational analysis revealed that TrBCs were the only subset to correlate with titer levels after SARS-CoV-2 vaccination. Responders showed higher TrBCs, both absolute and relative, than non-responders. Conclusion: Together, after 1 year, KTRs showed persistent and profound compositional changes within the BC compartment. Low TrBCs, 1 year after KT, may account for the low serological response to SARS-CoV-2 vaccination in KTRs compared to dialysis patients. Our findings need confirmation in further studies as they may guide vaccination strategies.

17.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-1822363

ABSTRACT

Acute inflammation is a localized and self-limited innate host-defense mechanism against invading pathogens and tissue injury. Neutrophils, the most abundant immune cells in humans, play pivotal roles in host defense by eradicating invading pathogens and debris. Ideally, elimination of the offending insult prompts repair and return to homeostasis. However, the neutrophils` powerful weaponry to combat microbes can also cause tissue damage and neutrophil-driven inflammation is a unifying mechanism for many diseases. For timely resolution of inflammation, in addition to stopping neutrophil recruitment, emigrated neutrophils need to be disarmed and removed from the affected site. Accumulating evidence documents the phenotypic and functional versatility of neutrophils far beyond their antimicrobial functions. Hence, understanding the receptors that integrate opposing cues and checkpoints that determine the fate of neutrophils in inflamed tissues provides insight into the mechanisms that distinguish protective and dysregulated, excessive inflammation and govern resolution. This review aims to provide a brief overview and update with key points from recent advances on neutrophil heterogeneity, functional versatility and signaling, and discusses challenges and emerging therapeutic approaches that target neutrophils to enhance the resolution of inflammation.

18.
Frontiers in Cellular and Infection Microbiology ; 12:11, 2022.
Article in English | Web of Science | ID: covidwho-1822357

ABSTRACT

Nephropathogenic infectious bronchitis virus (NIBV) is one of the most important viral pathogens in the world poultry industry. Here, we used RT-qPCR, WB and immunofluorescence to explore the interaction between NIBV and the host innate immune system of the kidney. Multiple virions were found in the kidney tissues of the disease group under electron microscopy, and pathological changes such as structural damage of renal tubules and bleeding were observed by HE staining. In addition, we found that the mRNA levels of TLR7, TRAF6, and IKK beta were upregulated after NIBV infection. IRF7 mRNA levels decreased significantly at 5 dpi and increased significantly at 11 to 18 dpi. The NF-kappa B P65 mRNA level increased significantly at 5 to 18 dpi and decreased at 28 dpi. However, NIBV infection-induced NF-kappa B P65 protein levels were downregulated at multiple time points. Moreover, we demonstrated that the cytokine (IFN-gamma, IL-8, and IL-6) mRNA and protein expression levels were increased significantly at multiple time points after NIBV infection. Furthermore, immunofluorescence analysis showed that NF-kappa B P65 and IFN-gamma were mainly located in the nuclear or perinuclear region. The positive signal intensity of NF-kappa B P65 was significantly lower than that of the normal group at 1 to 5 dpi, and there was no significant change in the subsequent time period. The positive signal intensity of IFN-gamma decreased significantly at 5 dpi, and increased significantly at 11 to 28 dpi. In conclusion, we found that NIBV promoted cytokine release through the TLR7/NF-kappa B signaling axis, thus causing kidney injury.

19.
Natural Product Communications ; 17(4), 2022.
Article in English | EMBASE | ID: covidwho-1822124

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) has posed a serious threat to human health and there is an urgent need for drug development. In this study, we explored the potential mechanisms underlying the efficacy of polydatin against COVID-19. Methods: A combined approach of network pharmacology, molecular docking, and experimental verification were employed in this study. Potential targets of polydatin for treating COVID-19 were obtained from multiple drug and disease databases. Protein–protein interaction and enrichment analyses were performed to predict the potential mechanism of action of polydatin against COVID-19. The binding potential of polydatin and key targets was evaluated through molecular docking. Furthermore, experimental methods including flow cytometry and luciferase assay were used to validate the results of computational analyses. Results: The main diseases identified as polydatin targets included metabolic diseases, lung diseases, inflammation, infectious diseases, and tumors. Polydatin may be used to treat COVID-19 through interventions that alter the immune and inflammatory responses, including IL-17 signaling pathway, T-cell activation, cytokines and inflammatory response, lipopolysaccharide-mediated signaling pathway, as well as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) innate immunity evasion and cell-specific immune response. Polydatin can potentially bind to the target proteins related to COVID-19, such as SARS-CoV-2 Mpro, RdRp, and human angiotensin-converting enzyme 2 (ACE2), while directly exerting its regulatory or therapeutic functions. The experimental results showed that polydatin decreased the infectivity of the SARS-CoV-2 spike pseudovirus in HEK293T-ACE2 cells. Accordingly, polydatin may retard the entry of SARS-CoV-2 into cells by competitively binding to human ACE2. Conclusion: The potential targets and signaling pathways of polydatin against COVID-19 were preliminarily identified. The findings may benefit the development and application of polydatin as a treatment for COVID-19.

20.
FASEB Journal ; 35(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1821960

ABSTRACT

Introduction and Objectives Novel SARS-CoV-2 virus has been implicated in prompting a bold immune response that leads to severe Coronavirus disease 2019 (COVID-19). Recent studies have shown that SARSCoV-2-infected monocytes and macrophages are stimulated to produce an overabundance of pro-inflammatory cytokines and chemokines to generate a cytokine storm. Cytokines in excess can contribute to local tissue inflammation and the pathogenesis of COVID-19. However, the mechanism by which SARS-CoV-2 signal macrophage-derived inflammatory response remains unclear. In the present study, we used RAW 264.7 cells, a wellcharacterized macrophage model, to study the in vitro effects of SARS-CoV-2 on reactive oxygen species (ROS) production and its potential role in the signal transduction of cytokine production. Methods The effect of SARS-CoV-2 on ROS and cytokine generation in macrophages was assessed by treating RAW 264.7 cells with SARS-CoV-2 heat inactivated virus (0-20 million viral particles) or recombinant proteins for 24 hours. 2',7'-Dichlorodihydrofluorescein (2',7'-DCF) fluorescence analysis was utilized to quantify ROS generation within the RAW 264.7 macrophage cell line. Cell culture medium was sampled to quantify the levels of tumor necrosis factor (TNF) using enzyme-linked immunosorbent assay (ELISA). To assess the effects of SARS-CoV-2 on mitochondrial function, cells were treated with SARS-CoV-2 heat inactivated virus (0-20 million viral particles) for 24 hrs. Mitochondria-derived superoxide was measured using the MitoSOX™ red mitochondrial superoxide indicator. Results Treatment of RAW 264.7 cells with inactivated SARS-CoV-2 viral particles or recombinant proteins stimulated ROS production. Mitochondria-derived superoxide and hydrogen peroxide production were increased in response to inactivated SARS-CoV-2 viral particles and recombinant protein exposure. The increased ROS generation is linked to macrophage activation induced by SARS-CoV-2 exposures. Along with the ROS generation, increased TNF production was observed. Conclusions The results of this study suggest that both SARS-CoV-2 viral proteins and heat-inactivated viral particle exposures cause significant generation of ROS and cytokines by RAW 264.7 cells. ROS generation and the subsequent cytokine release apparently play a significant role in the pathogenesis associated with the SARS-CoV-2 viral infection. The imbalanced cellular defense system against oxidative stress commonly associated with aging could explain the increased occurrence of more severe SARS-CoV-2 illness in seniors and in patients with underlying health conditions. Based on the results from this study, we propose that antioxidants such as N-acetyl-L-cysteine, resveratrol, or Vitamin E in combination with antiinflammatory drug could be used to control excess ROS and cytokines in patients with severe COVID-19.

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