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<title>26 August, 2021</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>LRR protein RNH1 dampens the inflammasome activation and is associated with adverse clinical outcomes in COVID-19 patients</strong> -
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<div>
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Inflammasomes are cytosolic innate immune sensors of pathogen infection and cellular damage that induce caspase-1 mediated inflammation upon activation. Although inflammation is protective, uncontrolled excessive inflammation can cause inflammatory diseases and can be detrimental, such as in COVID-19. However, the underlying mechanisms that control inflammasome activation are incompletely understood. Here we report that the leucine rich repeat (LRR) protein Ribonuclease inhibitor (RNH1), which shares homology with LRRs of NLRP proteins, attenuates inflammasome activation. Deletion of RNH1 in macrophages increases IL-1b production and caspase-1 activation for inflammasome stimuli. Mechanistically, RNH1 decreases pro-IL-1b expression and induces proteasome-mediated caspase-1 degradation. Corroborating this, mouse models of monosodium urate (MSU)-induced peritonitis and LPS-induced endotoxemia, which are dependent on caspase-1, respectively show increased neutrophil infiltration and lethality in Rnh1-/- mice compared to WT mice. Furthermore, RNH1 protein levels are negatively correlated with inflammation and disease severity in hospitalized COVID-19 patients. We propose that RNH1 is a new inflammasome regulator with relevance to COVID-19 severity.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.04.12.438219v2" target="_blank">LRR protein RNH1 dampens the inflammasome activation and is associated with adverse clinical outcomes in COVID-19 patients</a>
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</div></li>
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<li><strong>Filthy Animals: Integrating the Behavioral Immune System and Disgust into A Model of Prophylactic Dehumanization</strong> -
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<div>
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The behavioral immune system (BIS) is an evolved psychological mechanism that motivates prophylactic avoidance of disease vectors by eliciting disgust. When felt toward social groups, disgust can dampen empathy and promote dehumanization. Therefore, we investigated whether the BIS facilitates the dehumanization of groups associated with disease by inspiring disgust toward them. An initial content analysis found that Nazi propaganda predominantly dehumanized Jews by portraying them as disease vectors or contaminants. This inspired three correlational studies supporting a Prophylactic Dehumanization Model in which the BIS predicted disgust toward disease-relevant outgroups, and this disgust in turn accounted for the dehumanization of these groups. In a final study, we found this process of prophylactic dehumanization had a downstream effect on increasing anti-immigrant attitudes during the COVID-19 pandemic. However, consistent with the evolutionary logic of a functionally-flexible BIS, this effect only occurred when the threat of COVID-19 was salient. The implications of these results for the study of dehumanization and evolutionary theories of xenophobia are discussed.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/egxt6/" target="_blank">Filthy Animals: Integrating the Behavioral Immune System and Disgust into A Model of Prophylactic Dehumanization</a>
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</div></li>
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<li><strong>Staying home so you can keep going out: A multiplayer self-isolation game modelling pandemic behaviour</strong> -
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<div>
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The effectiveness of a nation’s COVID-19 response in limiting transmission depends on people complying with unfamiliar restrictions. The immediate cost of abiding by these restrictions (e.g., by staying home) to the individual is relatively clear, yet other outcomes are delayed and noisy. It is difficult to infer whether others have fallen ill because of one’s own actions, or whether one has played a part in causing a ‘lockdown’. This uncertainty leads people to take cues from their dynamic environment and social norms on the right course of action. This preregistered study investigates how people cooperate, and how the social context influences their decisions using an iterated multiplayer game (akin to a public goods game), wherein they encounter various levels of compliance of others, variations in disease prevalence, and differences in the costliness of a lockdown. Participants indicate how much they would hypothetically isolate themselves for each level of average self-isolation by others in the group, they predict how much others will self-isolate, and make a decision about their own self-isolation. We show that participants tend to self-isolate more when they predict others will self-isolate more, and when there are more infected players in the group; we show that participants suffer from illusory superiority, underestimating others’ self-isolation compared to their own, and we show that higher perceived cost of lockdown leads to more compliance, but that this effect is stronger when players predict that others will be compliant too.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/mh69r/" target="_blank">Staying home so you can keep going out: A multiplayer self-isolation game modelling pandemic behaviour</a>
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</div></li>
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<li><strong>Yeast-expressed Recombinant SARS-CoV-2 Receptor Binding Domain, RBD203-N1 as a COVID-19 Protein Vaccine Candidate</strong> -
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<div>
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Background: SARS-CoV-2 protein subunit vaccines are being evaluated by multiple manufacturers to fill the need for low-cost, easy to scale, safe, and effective COVID-19 vaccines for global access. Vaccine candidates relying on the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein have been the focus of our development program. In this paper, we report on the generation of the RBD203-N1 yeast expression construct, which produces a recombinant protein that when formulated with alum and the TLR-9 agonist, CpG1826 elicits a robust immune response and protection in mice. Method: The RBD203-N1 antigen was expressed in the yeast Pichia pastoris X33. After fermentation at the 5 L scale, the protein was purified by hydrophobic interaction chromatography followed by anion exchange chromatography. The purified protein was characterized biophysically and biochemically, and after its formulation, the immunogenicity and efficacy were evaluated in mice. Results, Conclusions, and Significance: The RBD203-N1 production process yielded 492.9 {+/-} 3.0 mg/L of protein in the fermentation supernatant. A two-step purification process produced a >96% pure protein with a recovery rate of 55 {+/-} 3% (total yield of purified protein: 270.5 {+/-} 13.2 mg/L fermentation supernatant). The protein was characterized as a homogeneous monomer with well-defined secondary structure, thermally stable, antigenic, and when adjuvanted on alum and CpG, it was immunogenic and induced robust levels of neutralizing antibodies against SARS-CoV-2 pseudovirus. These characteristics show that this vaccine candidate is well suited for technology transfer with feasibility of its transition into the clinic to evaluate its immunogenicity and safety in humans.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.08.24.457518v1" target="_blank">Yeast-expressed Recombinant SARS- CoV-2 Receptor Binding Domain, RBD203-N1 as a COVID-19 Protein Vaccine Candidate</a>
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</div></li>
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<li><strong>Woodsmoke particulates alter expression of antiviral host response genes in human nasal epithelial cells infected with SARS-CoV-2 in a sex-dependent manner</strong> -
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<div>
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We have previously shown that exposure to particulate air pollution, both from natural and anthropogenic sources, alters gene expression in the airways and increases susceptibility to respiratory viral infection. Additionally, we have shown that woodsmoke particulates (WSP) affect responses to influenza in a sex-dependent manner. In the present study, we used human nasal epithelial cells (hNECs) from both sexes to investigate how particulate exposure could modulate gene expression in the context of SARS-CoV-2 infection. We used diesel exhaust particulate (DEP) as well as WSP derived from eucalyptus or red oak wood. HNECs were exposed to particulates at a concentration of 22 g/cm2 for 2 h then immediately infected with SARS-CoV-2 at a MOI (multiplicity of infection) of 0.5. Exposure to particulates had no significant effects on viral load recovered from infected cells. Without particulate exposure, hNECs from both sexes displayed a robust upregulation of antiviral host response genes, though the response was greater in males. However, WSP exposure before infection dampened expression of genes related to the antiviral host response by 72 h post infection. Specifically, red oak WSP downregulated IFIT1, IFITM3, IFNB1, MX1, CCL3, CCL5, CXCL11, CXCL10, and DDX58, among others. After sex stratification of these results, we found that exposure to WSP prior to SARS-CoV-2 infection downregulated anti-viral gene expression in hNECs from females more so than males. These data indicate that WSP, specifically from red oak, alter virus-induced gene expression in a sex-dependent manner and potentially suppress antiviral host defense responses following SARS-CoV-2 infection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.08.23.457411v1" target="_blank">Woodsmoke particulates alter expression of antiviral host response genes in human nasal epithelial cells infected with SARS-CoV-2 in a sex-dependent manner</a>
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</div></li>
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<li><strong>Direct RNA sequencing reveals SARS-CoV-2 m6A sites and possible differential DRACH motif methylation among variants</strong> -
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<div>
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The causative agent of COVID-19 pandemic, the SARS-CoV-2 coronavirus, has a 29,903 bases positive-sense single- stranded RNA genome. RNAs exhibit about 100 modified bases that are essential for proper function. Among internal modified bases, the N6-methyladenosine, or m6A, is the most frequent, and is implicated in SARS-CoV-2 immune response evasion. Although the SARS-CoV-2 genome is RNA, almost all genomes sequenced so far are in fact, reverse transcribed complementary DNAs. This process reduces the true complexity of these viral genomes because incorporation of dNTPs hides RNA base modifications. Here, in this perspective paper, we present an initial exploration on Nanopore direct RNA sequencing to assess the m6A residues in the SARS-CoV-2 sequences of ORF3a, E, M, ORF6, ORF7a, ORF7b, ORF8, N, ORF10 and the 3’-untranslated region. We identified 15 m6A methylated positions, of which, 6 are in ORF N. Also, because m6A is associated with the DRACH motif, we compared its distribution in major SARS-CoV-2 variants. Although DRACH is highly conserved among variants we show that variants Beta and Eta have a fourth position C>T mutation in DRACH at 28,884b that could affect methylation. The Nanopore technology offers a unique opportunity for the study of viral epitranscriptomics. This technique is PCR-free and is not sequencing-by-synthesis, therefore, no PCR bias and synthesis errors are introduced. The modified bases are preserved and assessed directly with no need for chemical treatments or antibodies. This is the first report of direct RNA sequencing of a Brazilian SARS-CoV-2 sample coupled with identification of modified bases.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.08.24.457397v1" target="_blank">Direct RNA sequencing reveals SARS- CoV-2 m6A sites and possible differential DRACH motif methylation among variants</a>
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</div></li>
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<li><strong>Directing an mRNA-LNP vaccine toward lymph nodes improves humoral and cellular immunity against SARS-CoV-2</strong> -
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The exploration and identification of safe and effective vaccines for the SARS-CoV-2 pandemic has captured the worlds attention and remains an ongoing issue in order to protect against emerging variants of concern (VoCs) while generating long lasting immunity. Here, we report the synthesis of a novel messenger ribonucleic acid (mRNA) encoding the spike protein in a lipid nanoparticle formulation (LNP) (STI-7264) that generates robust humoral and cellular immunity following immunization of C57Bl6 mice. In efforts to continually improve immunity, a lymphatic drug delivery device (MuVaxx) was engineered and tested to immunize the immune cells at the injection site (epidermis and dermis) and draining lymph node (LN) for adaptive immunity. Using MuVaxx, immune responses were elicited and maintained at a 10-fold dose reduction compared to traditional intramuscular (IM) administration as measured by anti-spike antibodies, cytokine producing CD8 T cells, and neutralizing antibodies against the Washington (Wild Type, WT) and South African (beta) variants. Remarkably, a 4-fold elevated T cell response was observed in MuVaxx administered vaccination as compared to that of IM administered vaccination. Thus, these data support further investigation into STI-7264 and lymphatic mediated delivery using MuVaxx for SARS-CoV-2 and VoCs vaccines.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.08.25.457699v1" target="_blank">Directing an mRNA-LNP vaccine toward lymph nodes improves humoral and cellular immunity against SARS-CoV-2</a>
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<li><strong>Structure-based screening of drug candidates targeting the SARS-CoV-2 envelope protein</strong> -
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The COVID-19 (coronavirus disease 2019) pandemic is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). SARS-CoV-2 produces a small hydrophobic envelope (E) protein which shares high homology with SARS-CoV E protein. By patch-clamp recording, the E protein is demonstrated to be a cation-selective ion channel. Furthermore, the SARS-CoV-2 E protein can be blocked by a SARS-CoV E protein inhibitor hexamethylene amiloride. Using structural model and virtual screening, another E protein inhibitor AZD5153 is discovered. AZD5153 is a bromodomain protein 4 inhibitor against hematologic malignancies in clinical trial. The E protein amino acids Phe23 and Val29 are key determinants for AZD5153 sensitivity. This study provides two promising lead compounds and a functional assay of SARS-CoV-2 E protein for the future drug candidate discovery.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.08.25.457645v1" target="_blank">Structure-based screening of drug candidates targeting the SARS-CoV-2 envelope protein</a>
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<li><strong>How COVID-19 has Impacted American Attitudes Toward China: A Study on Twitter</strong> -
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Past research has studied social determinants of attitudes toward foreign countries. Confounded by potential endogeneity biases due to unobserved factors or reverse causality, the causal impact of these factors on public opinion is usually difficult to establish. Using social media data, we leverage the suddenness of the COVID-19 pandemic to examine whether a major global event has causally changed American views of another country. We collate a database of more than 297 million posts on the social media platform Twitter about China or COVID-19 up to June 2020, and we treat tweeting about COVID-19 as a proxy for individual awareness of COVID-19. Using regression discontinuity and difference- in-difference estimation, we find that awareness of COVID-19 causes a sharp rise in anti-China attitudes. Our work has implications for understanding how self-interest affects policy preference and how Americans view migrant communities.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/h3r5u/" target="_blank">How COVID-19 has Impacted American Attitudes Toward China: A Study on Twitter</a>
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<li><strong>Understanding experiences of changing socioeconomic and psychosocial adversities during COVID-19 for freelancers working in the UK cultural sector: A rapid approach</strong> -
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There is a dearth of qualitative research exploring how freelancers working in the cultural industries have been affected during COVID-19. In particular, there is a lack of research exploring how socioeconomic and psychosocial adversities may have changed or evolved, and how these changes have been experienced. This study builds on qualitative interviews carried out in July-November 2020 (n=20) by exploring findings from follow-up interviews conducted in May-July 2021 (n=16). It presents a diversity of experiences, showing how some freelancers experienced small changes (e.g., to the kind of work carried out), with others experiencing major changes (e.g., leaving the sector completely). The study also explores experiences of ongoing or increased mental health impact, as well as changing attitudes to cultural work. It concludes with a call for highly bespoke support in the future that can address the huge disparity of experiences during this time.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/bu4af/" target="_blank">Understanding experiences of changing socioeconomic and psychosocial adversities during COVID-19 for freelancers working in the UK cultural sector: A rapid approach</a>
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</div></li>
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<li><strong>Viral dynamics of SARS-CoV-2 variants in vaccinated and unvaccinated individuals</strong> -
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Background. The alpha and delta SARS-CoV-2 variants have been responsible for major recent waves of COVID-19 despite increasing vaccination rates. The reasons for the increased transmissibility of these variants and for the reduced transmissibility of vaccine breakthrough infections are unclear. Methods. We quantified the course of viral proliferation and clearance for 173 individuals with acute SARS-CoV-2 infections using longitudinal quantitative RT-PCR tests conducted using anterior nares/oropharyngeal samples (n = 199,941) as part of the National Basketball Association9s (NBA) occupational health program between November 28th, 2020, and August 11th, 2021. We measured the duration of viral proliferation and clearance and the peak viral concentration separately for individuals infected with alpha, delta, and non-variants of interest/variants of concern (non-VOI/VOC), and for vaccinated and unvaccinated individuals. Results. The mean viral trajectories of alpha and delta infections resembled those of non-VOI/VOC infections. Vaccine breakthrough infections exhibited similar proliferation dynamics as infections in unvaccinated individuals (mean peak Ct: 20.5, 95% credible interval [19.0, 21.0] vs. 20.7 [19.8, 20.2], and mean proliferation time 3.2 days [2.5, 4.0] vs. 3.5 days [3.0, 4.0]); however, vaccinated individuals exhibited faster clearance (mean clearance time: 5.5 days [4.6, 6.6] vs. 7.5 days [6.8, 8.2]). Conclusions. Alpha, delta, and non-VOI/VOC infections feature similar viral trajectories. Acute infections in vaccinated and unvaccinated people feature similar proliferation and peak Ct, but vaccinated individuals cleared the infection more quickly. Viral concentrations do not fully explain the differences in infectiousness between SARS-CoV-2 variants, and mitigation measures are needed to limit transmission from vaccinated individuals.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.02.16.21251535v3" target="_blank">Viral dynamics of SARS-CoV-2 variants in vaccinated and unvaccinated individuals</a>
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<li><strong>Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial (HERO-HCQ)</strong> -
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Objective: To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCW). Design: Multicenter, 1:1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial. Setting: 34 clinical centers in the United States. Participants: 1360 HCW at risk for COVID-19 infection enrolled between April and November 2020. Interventions: A loading dose of HCQ 600 mg twice on Day 1 followed by 400 mg daily for 29 days or matching placebo taken orally. Main Outcome Measure: Composite of confirmed or suspected COVID-19 clinical infection by Day 30 defined as new onset fever, cough, or dyspnea and either a positive SARS-CoV-2 PCR test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected). Results: Enrollment for the study was closed before full accrual due to difficulties recruiting additional participants. The primary composite endpoint occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No statistically significant difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6% to 0.9%, p=0.20). We identified no significant safety issues. Conclusion: Oral HCQ taken as prescribed appeared to be safe in a group of HCW. No significant clinical benefits were observed. The study was underpowered to rule out a small but potentially important reduction in COVID-19 infections.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.08.19.21262275v1" target="_blank">Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial (HERO- HCQ)</a>
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<li><strong>Prioritizing COVID-19 vaccination efforts and dose allocation within Madagascar</strong> -
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Background: While mass COVID-19 vaccination programs are underway in high-income countries, limited availability of doses has resulted in few vaccines administered in low and middle income countries (LMICs). The COVID-19 Vaccines Global Access (COVAX) is a WHO-led initiative to promote vaccine access equity to LMICs and is providing many of the doses available in these settings. However, initial doses are limited and countries, such as Madagascar, need to develop prioritization schemes to maximize the benefits of vaccination with very limited supplies. There is some consensus that dose deployment should initially target health care workers, and those who are more vulnerable including older individuals. However, questions of geographic deployment remain, in particular associated with limits around vaccine access and delivery capacity in underserved communities, for example in rural areas that may also include substantial proportions of the population. Methods: To address these questions, we developed a mathematical model of SARS-CoV-2 transmission dynamics and simulated various vaccination allocation strategies for Madagascar. Simulated strategies were based on a number of possible geographical prioritization schemes, testing sensitivity to initial susceptibility in the population, and evaluating the potential of tests for previous infection. Results: Using cumulative deaths due to COVID-19 as the main outcome of interest, our results indicate that distributing the number of vaccine doses according to the number of elderly living in the region or according to the population size results in a greater reduction of mortality compared to distributing doses based on the reported number of cases and deaths. The benefits of vaccination strategies are diminished if the burden (and thus accumulated immunity) has been greatest in the most populous regions, but the overall strategy ranking remains comparable. If rapid tests for prior immunity may be swiftly and effectively delivered, there is potential for considerable gain in mortality averted, but considering delivery limitations modulates this. Conclusion: At a subnational scale, our results support the strategy adopted by the COVAX initiative at a global scale.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.08.23.21262463v1" target="_blank">Prioritizing COVID-19 vaccination efforts and dose allocation within Madagascar</a>
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<li><strong>Discordant humoral and T cell immune responses to SARS-CoV-2 vaccination in people with multiple sclerosis on anti- CD20 therapy</strong> -
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Background: Sphingosine-1-phosphate receptor (S1P) modulators and antiCD20 therapies impair humoral responses to SARS-CoV-2 mRNA vaccines. Whether disease modifying therapies (DMTs) for multiple sclerosis (MS) also impact T cell immune response to vaccination is unknown. Methods: In 101 people with MS, we measured humoral responses via an immunoassay to measure IgG against the COVID-19 spike S1 glycoprotein in serum. We also measured T cell responses using FluoroSpot assay for interferon gamma (IFN-gamma; Mabtech,Sweden) using cryopreserved rested PBMCs and then incubated in cRPMI with 1microg/ml of pooled peptides spanning the entire spike glycoprotein (Genscript, 2 pools; 158 peptides each). Plates were read on an AID iSpot Spectrum to determine number of spot forming cells (SFC)/10 6 PBMCs. We tested for differences in immune responses across DMTs using linear models. Findings: Humoral responses were detected in 22/39 (56.4%) participants on anti-CD20 and in 59/63 (93.6%) participants on no or other DMTs. In a subset with immune cell phenotyping (n=88; 87%), T cell responses were detected in 76/88 (86%), including 32/33 (96.9%) participants on anti-CD20 therapies. AntiCD20 therapies were associated with an increase in IFN-gamma; SFC counts relative to those on no DMT or other DMTs (for antiCD20 vs. no DMT: 425.9% higher [95%CI: 109.6%, 1206.6%] higher; p<0.001; for antiCD20 vs. other DMTs: 289.6% [95%CI: 85.9%, 716.6%] higher; p<0.001). Interpretation: We identified a robust T cell response in individuals on anti-CD20 therapies despite a reduced humoral response to SARS-CoV-2 vaccination. Follow up studies are needed to determine if this translates to protection against COVID-19 infection.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.08.23.21262472v1" target="_blank">Discordant humoral and T cell immune responses to SARS-CoV-2 vaccination in people with multiple sclerosis on anti-CD20 therapy</a>
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<li><strong>Reduction in initiations of HIV treatment in South Africa during the COVID pandemic</strong> -
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Background: In response to the global pandemic of COVID-19, countries around the world began imposing stay-at- home orders, restrictions on transport, and closures of businesses in early 2020. South Africa implemented a strict lockdown in March 2020 before its first COVID-19 wave started, gradually lifted restrictions between May and September 2020, and then re-imposed restrictions in December 2020 in response to its second wave. There is concern that COVID-19-related morbidity and mortality, fear of transmission, and government responses may have led to a reduction in antiretroviral treatment (ART) initiations for HIV-infected individuals in countries like South Africa. Methods: We analyzed national, public sector, facility-level data from the South Africa District Health Information System (DHIS) from January 2019 to March 2021 to quantify changes in ART initiation rates stratified by province, setting, facility size and type and compared the timing of these changes to COVID-19 case numbers and government lockdown levels. We excluded facilities with missing data, mobile clinics, and correctional facilities. We estimated the total number of ART initiations per study month for each stratum and compared monthly totals, by year. Results: At the 2471 facilities in the final data set (59% of all ART sites in the DHIS), 28% fewer initiations occurred in 2020 than in 2019. Numbers of ART initiations declined sharply in all provinces in April-June 2020, compared to the same months in 2019, and remained low for the rest of 2020, with some recovery between COVID-19 waves in October 2020 and possible improvement beginning in March 2021. Percentage reductions were largest in district hospitals, larger facilities, and urban areas. After the initial decline in April-June 2020, most provinces experienced a clear inverse relationship between COVID-19 cases and ART initiations but little relationship between ART initiations and lockdown level. Conclusions: The COVID-19 pandemic and responses to it resulted in substantial declines in the number of HIV-infected individuals starting treatment in South Africa, with no recovery of numbers during 2020. These delays may lead to worse treatment outcomes for those with HIV and potentially higher HIV transmission. Exceptional effort will be needed to sustain gains in combating HIV.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.08.18.21262046v1" target="_blank">Reduction in initiations of HIV treatment in South Africa during the COVID pandemic</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pulmonary Rehabilitation Post-COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Exercise program (virtual/remote)<br/><b>Sponsors</b>: University of Manitoba; Health Sciences Centre Foundation, Manitoba; Health Sciences Centre, Winnipeg, Manitoba<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase III Study to Evaluate the Efficacy and Safety of Proxalutamide (GT0918) in Hospitalized Subjects With COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: GT0918; Drug: Standard of care; Drug: Matching placebo<br/><b>Sponsor</b>: Suzhou Kintor Pharmaceutical Inc,<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of PF-07321332/Ritonavir in Non-hospitalized Low-Risk Adult Participants With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: PF-07321332; Drug: Ritonavir; Drug: Placebo<br/><b>Sponsor</b>: Pfizer<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Targeting de Novo Pyrimidine Biosynthesis by Leflunomide for the Treatment of COVID-19 Virus Disease</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: leflunomide<br/><b>Sponsor</b>: <br/>
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Ashford and St. Peter’s Hospitals NHS Trust<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Andrographis Paniculata vs Boesenbergia Rotunda vs Control in Asymptomatic COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Andrographis Paniculata; Drug: Boesenbergia; Other: Standard supportive treatment<br/><b>Sponsors</b>: Mahidol University; Ministry of Health, Thailand<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of PJS-539 for Adult Patients With COVID-19.</strong> - <b>Conditions</b>: Covid19; COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: PJS-539 Dose 1; Drug: PJS-539 Dose 2; Drug: Placebo<br/><b>Sponsors</b>: Hospital do Coracao; Covicept<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Enhancing COVID Rehabilitation With Technology</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Behavioral: NexJ Connected Wellness; Other: Usual Care<br/><b>Sponsors</b>: University of Ottawa; Canadian Institutes of Health Research (CIHR); Ottawa Hospital Research Institute<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase I/II Clinical Trial of Recombinant COVID-19 Vaccine (Sf9 Cells) in Children and Adolescents</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Recombinant COVID-19 vaccine (Sf9 cells); Other: Placebo control<br/><b>Sponsors</b>: WestVac Biopharma Co., Ltd.; West China Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Methylene Blue Antiviral Treatment</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Methylene Blue; Drug: Saline nasal spray<br/><b>Sponsors</b>: Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences; Irkutsk State Medical University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Treatment of Covid-19 With a Herbal Compound, Xagrotin</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Combination Product: Xagrotin<br/><b>Sponsors</b>: <br/>
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Biomad AS; Directorate of health of Sulaimani, Iraq -KRG<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Trial of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector, Ad5-nCoV) in Adults Living With HIV</strong> - <b>Condition</b>: Covid19<br/><b>Intervention</b>: Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (Ad5-nCoV)<br/><b>Sponsors</b>: Fundación Huésped; Canadian Center for Vaccinology; CanSino Biologics Inc.; Hospital Fernandez<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Philippine Trial to Determine Efficacy and Safety of Favipiravir for COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Combination Product: Favipiravir + Standard of Care; Procedure: Standard of Care<br/><b>Sponsors</b>: University of the Philippines; Department of Health, Philippines<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of the Effects of Bradykinin Antagonists on Pulmonary Manifestations of COVID-19 Infections (AntagoBrad- Cov Study).</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: C1 Inhibitor Human; Drug: Icatibant Injection; Other: Placebo<br/><b>Sponsor</b>: GCS Ramsay Santé pour l’Enseignement et la Recherche<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Combination of Dietary Supplements Curcumin, Quercetin and Vitamin D for Early Symptoms of COVID-19</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Standard of care; Dietary Supplement: combination of curcumin, quercetin and Vitamin D<br/><b>Sponsor</b>: Ayub Teaching Hospital<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Safety and Efficacy of Artemisinin- a Herbal Supplement on COVID-19 Subjects</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Dietary Supplement: Artemisinin; Drug: Dexamethasone<br/><b>Sponsors</b>: Mateon Therapeutics; Windlas Biotech Private Limited<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Investigation of Interaction between the Spike Protein of SARS-CoV-2 and ACE2-Expressing Cells Using an In Vitro Cell Capturing System</strong> - CONCLUSIONS: This study provides a new in vitro system for investigating the interaction between SARS-CoV-2 and host cells and purifying ACE2-expressing cells.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of multiple SARS-CoV-2 proteins by an antiviral biomolecule, seselin from Aegle marmelos deciphered using molecular docking analysis</strong> - Our earlier experimental and computational report produced evidence on the antiviral nature of the compound seselin purified from the leaf extracts of Aegle marmelos against Bombyx mori Nuclear Polyhedrosis Virus (BmNPV). In the pandemic situation of COVID-19 caused by the SARS-COV-2 virus, an in silico effort to evaluate the potentiality of the seselin was made to test its efficacy against multiple targets of SARS-COV-2 such as spike protein S2, COVID-19 main protease and free enzyme of the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Concise Update on Genomics of COVID-19: Approach to Its latest Mutations, Escalated Contagiousness, and Vaccine Resistance</strong> - The novel coronavirus disease 2019 (COVID-19) that started to invade the world from the Chinese fish market, causes an acute respiratory distress syndrome. COVID-19 is a dreadful infectious disease that surfaced only less than 8 months ago and caused the deadly COVID-19 pandemic. In this new species with a positive, single-strand RNA genome and a huge size, from the proteomics point view, there are no changes in sequences of amino acids in NSP7, 13, matrix, or envelope or other proteins…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Profile of humoral and cellular immune responses to single doses of BNT162b2 or ChAdOx1 nCoV-19 vaccines in residents and staff within residential care homes (VIVALDI): an observational study</strong> - BACKGROUND: Residents of long-term care facilities (LTCFs) have been prioritised for COVID-19 vaccination because of the high COVID-19 mortality in this population. Several countries have implemented an extended interval of up to 12 weeks between the first and second vaccine doses to increase population coverage of single-dose vaccination. We aimed to assess the magnitude and quality of adaptive immune responses following a single dose of COVID-19 vaccine in LTCF residents and staff.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cancer Informatics for Cancer Centers: Scientific Drivers for Informatics, Data Science, and Care in Pediatric, Adolescent, and Young Adult Cancer</strong> - Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute-funded cancer centers. This consortium has regularly held topic-focused biannual face-to-face symposiums. These meetings are a place to review cancer informatics and data science…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibitors of anti-apoptotic Bcl-2 family proteins exhibit potent and broad-spectrum anti-mammarenavirus activity via cell cycle arrest at G0/G1 phase</strong> - Targeting host factors is a promising strategy to develop broad-spectrum antiviral drugs. Drugs targeting anti-apoptotic Bcl-2 family proteins that were originally developed as tumor suppressors have been reported to inhibit multiplication of different types of viruses. However, the mechanisms whereby Bcl-2 inhibitors exert their antiviral activity remain poorly understood. In this study, we have investigated the mechanisms by which obatoclax (OLX) and ABT-737 Bcl-2 inhibitors exhibited a potent…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Impact of the Declaration of the State of Emergency on the Spread of COVID-19: A Modeling Analysis</strong> - When encountering the outbreak and early spreading of COVID-19, the Government of Japan imposed gradually upgraded restriction policies and declared the state of emergency in April 2020 for the first time. To evaluate the efficacy of the countering strategies in different periods, we constructed a SEIADR (susceptible-exposed-infected-asymptomatic- documented-recovered) model to simulate the cases and determined corresponding spreading coefficients. The effective reproduction number R (t) was…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structure-Based Virtual Screening and Molecular Dynamics Simulation to Identify Potential SARS-CoV-2 Spike Receptor Inhibitors from Natural Compound Database</strong> - The outbreak of respiratory disease, COVID-19 caused by SARS-CoV-2 has now been spread globally and the number of new infections is rising every moment. There are no specific medications that are currently available to combat the disease. The spike receptor of SARS-CoV-2 facilitates the viral entry into a host cell and initiation of infection. Targeting the viral entry at the initial stage has a better advantage than inhibiting it in later stages of the viral life cycle. This study deals with…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>DNA-encoded chemistry technology yields expedient access to SARS-CoV-2 M(pro) inhibitors</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration-approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CuCl(2)-catalyzed inexpensive, faster and ligand/additive free synthesis of isoquinolin-1(2H)-one derivatives via the coupling-cyclization strategy: Evaluation of a new class of compounds as potential PDE4 inhibitors</strong> - In spite of possessing a wide range of pharmacological properties the anti-inflammatory activities of isoquinolin-1(2H)-ones were rarely known or explored earlier. PDE4 inhibitors on the other hand in addition to their usefulness in treating inflammatory diseases have been suggested to attenuate the cytokine storm in COVID-19 especially TNF-α. In our effort, a new class of isoquinolin-1(2H)-ones derivatives containing an aminosulfonyl moiety were designed and explored as potential inhibitors of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Coronavirus disease-2019: A review on the disease exacerbation via cytokine storm and concurrent management</strong> - Setting up treatment strategies is the highest concern today to reduce the fatality of COVID-19. Due to a very new kind of virus attack, no specific treatment has been discovered to date. The most crucial way to dominate the disease severity is now the repurposing of drugs. In this review, we focused on the current treatment approaches targeting the crucial causative factors for the disease burden through cytokine storm or cytokine release syndrome. Several vaccines have been developed and have…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin</strong> - CONCLUSIONS: Clotting pathologies in both acute COVID-19 infection and in Long COVID/PASC might benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Paradoxical effects of cigarette smoke and COPD on SARS-CoV-2 infection and disease</strong> - CONCLUSIONS: ACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Brief report: Tempol, a novel antioxidant, inhibits both activated T cell and antigen presenting cell derived cytokines in-vitro from COVID-19 patients</strong> - COVID-19 is characterized by a dysregulation of inflammatory cytokines ultimately resulting a cytokine storm that can result in significant morbidity and mortality. We developed an in-vitro assay using activated peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS) or CD3 + CD28 to examine secretion of cytokines from antigen presenting cells (APCs) and T cells, respectively, in donor patients with a history of COVID-19 (convalescent) and uninfected negative…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The early interferon catches the SARS-CoV-2</strong> - Interferons establish innate antiviral immunity. Two recent papers in JEM by Lopez et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20211211) and Cheemarla et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210583) show that an appropriate supply of antiviral interferon enables epithelial cells of the nasopharyngeal mucosa to inhibit SARS-CoV-2 growth and that interferon-induced mucosal genes serve as biomarkers of infection.</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<ul>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Anti-Sars-Cov-2 Neutralizing Antibodies</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857732">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Expression Vector for Anti-Sars-Cov-2 Neutralizing Antibodies</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857737">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>DEVELOPMENT OF CNN SCHEME FOR COVID-19 DISEASE DETECTION USING CHEST RADIOGRAPH</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857177">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-COV-2 BINDING PROTEINS</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333402004">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A PROCESS FOR PREPARING MONTELUKAST SODIUM FOR TREATING COVID 19 PATIENTS</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857132">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>IDENTIFICATION OF ANTI-COVID 19 AGENT SOMNIFERINE AS INHIBITOR OF MPRO & ACE2-RBD INTERACTION</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857079">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Deep Learning Based System For Detection of Covid-19 Disease of Patient At Infection Risk.</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333857030">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>자외선살균등</strong> - 본 발명은 사람의 의복이나 사용한 마스크 등에 부착하여 있다 호흡기로 유입되어 감염을 유발할 수 있는 COVID-19와 같은 유해균류를 간편하게 살균하기 위한 휴대용 자와선살균등에 관한 것이다. 반감기가 길고 인체에 유해한 오존을 발생하지 않으면서 탁월한 살균능력이 있는 250~265nm(최적은 253.7nm) 파장의 자외선을 발광하는 자외선램프를 본 발명의 막대형의 자외선살균등 광원으로 사용하고 비광원부를 손으로 잡고 의복이나 사용한 마스크 등 유해균류가 부착되었을 것으로 의심되는 곳에 자외선을 조사하여 간편하게 유해균류를 살균하므로써 감염을 예방하기 위한 휴대용 자외선살균등에 관함 것이다. - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=KR332958765">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Protein chip and kit for detecting the SARS-CoV-2 S antigen</strong> - - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=AU333400883">link</a></p></li>
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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>一种新冠病毒疫苗的表达载体及其构建方法、应用和疫苗</strong> - 本发明适用于生物技术领域，提供了一种新冠病毒疫苗的表达载体及其构建方法、应用和疫苗，该表达载体的构建方法包括以下步骤：将表达新冠病毒S蛋白与NP蛋白的核苷酸序列使用2A肽进行连接，合成融合基因；在融合基因的两端分别包含两个酶切位点，并装载到质粒，得到重组质粒；对重组质粒进行双酶切，切胶回收目的基因片段；对原始的质粒进行双酶切，切胶回收载体片段；将目的基因片段和载体片段进行连接，得到所述表达载体。本发明实施例通过同时表达冠状病毒S蛋白受体结合区与NP蛋白，使该表达载体感染的细胞不但可以诱导抗体反应还能诱导T细胞反应，从而有效诱导体液免疫和细胞免疫，为受试者提供更强的免疫保护。 - <a href="https://patentscope.wipo.int/search/en/detail.jsf?docId=CN333442015">link</a></p></li>
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</ul>
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