Development of Equine Polyclonal Antibodies as a Broad-Spectrum Therapy Against SARS-CoV-2 Variants

The Coronavirus disease 19 (COVID-19) pandemic has accumulated over 550 million confirmed cases and more than 6.34 million deaths worldwide. Although vaccinations has largely protected the population through the last two years, the effect of vaccination has been increasingly challenged by the emerging SARS-CoV-2 variants. Although several therapeutics including both monoclonal antibodies and small molecule drugs have been used clinically, high cost, viral escape mutations, and potential side effects have reduced their efficacy. There is an urgent need to develop a low cost treatment with wide-spectrum effect against the novel variants of SARS-CoV-2. Here we report a product of equine polyclonal antibodies that showed potential broad spectrum neutralization effect against the major variants of SARS-CoV-2. The equine polyclonal antibodies were generated by horse immunization with the receptor binding domain (RBD) of SARS-CoV-2 spike protein and purified from equine serum. A high binding affinity between the generated equine antibodies and the RBD was observed. Although designed against the RBD of the early wild type strain sequenced in 2020, the equine antibodies also showed a highly efficient neutralization capacity against the major variants of SARS-CoV-2, including the recent BA.2 Omicron variant (IC50 =1.867g/ml) in viral neutralization assay in Vero E6 cells using live virus cultured. The broad-spectrum neutralization capacity of the equine antibodies was further confirmed using pseudovirus neutralization assay covering the major SARS-CoV-2 variants including wild type, alpha, beta, delta, and omicron, showing effective neutralization against all the tested strains. Ex vivo reconstructed human respiratory organoids representing nasal, bronchial, and lung epitheliums were employed to test the treatment efficacy of the equine antibodies. Antibody treatment protected the human nasal, bronchial, and lung epithelial organoids against infection of the novel SARS-CoV-2 variants challenging public health, the Delta and Omicron BA.2 isolates, by reducing >95% of the viral load. The equine antibodies were further tested for potential side effects in a mouse model by inhalation and no significant pathological feature was observed. Equine antibodies, as a mature medical product, have been widely applied in the treatment of infectious diseases for more than a century, which limits the potential side effects and are capable of large scale production at a low cost. A cost-effective, wide-spectrum equine antibody therapy effective against the major SARS-CoV-2 variants can contribute as an affordable therapy to cover a large portion of the world population, and thus potentially reduce the transmission and mutation of SARS-CoV-2.

Spike Protein Targeting "Nano-Glue" that Captures and Promotes SARS-CoV-2 Elimination

The global emergency caused by the SARS-CoV-2 pandemics can only be solved with adequate preventive and therapeutic strategies, both currently missing. The electropositive Receptor Binding Domain (RBD) of SARS-CoV-2 spike protein with abundant {beta}-sheet structure serves as target for COVID-19 therapeutic drug design. Here, we discovered that ultrathin 2D CuInP2S6 (CIPS) nanosheets as a new agent against SARS-CoV-2 infection, which also able to promote viral host elimination. CIPS exhibits extremely high and selective binding capacity with the RBD of SARS-CoV-2 spike protein, with consequent inhibition of virus entry and infection in ACE2-bearing cells and human airway epithelial organoids. CIPS displays nano-viscous properties in selectively binding with spike protein (KD < 1 pM) with negligible toxicity in vitro and in vivo. Further, the CIPS-bound SARS-CoV-2 was quickly phagocytosed and eliminated by macrophages, suggesting CIPS could be successfully used to capture and facilitate the virus host elimination with possibility of triggering anti-viral immunization. Thus, we propose CIPS as a promising nanodrug for future safe and effective anti-SARS-CoV-2 therapy, as well as for use as disinfection agent and surface coating material to constrain the SARS-CoV-2 spreading.

Increased Expression of miR-146a in Children With Allergic Rhinitis After Allergen-Specific Immunotherapy

PURPOSE: MicroRNAs (miRs) were recently recognized to be important for immune cell differentiation and immune regulation. However, whether miRs were involved in allergen-specific immunotherapy (SIT) remains largely unknown. This study sought to examine changes in miR-146a and T regulatory cells in children with persistent allergic rhinitis (AR) after 3 months of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). METHODS: Twenty-four HDM-sensitized children with persistent AR were enrolled and treated with SCIT (n=13) or SLIT (n=11) for 3 months. Relative miR-146a and Foxp3 mRNA expression, the TRAF6 protein level, and the ratio of post-treatment to baseline IL-10+CD4+ T cells between the SCIT and SLIT groups were examined in the peripheral blood mononuclear cells (PBMCs) of AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry, and Western blot analysis, respectively. Serum levels of IL-5 and IL-10 were determined using ELISA. RESULTS: After 3 months of SIT, both the TNSS and INSS scores were significantly decreased compared to the baseline value (P<0.01). The relative expression of miR-146a and Foxp3 mRNA was significantly increased after both SCIT and SLIT (P<0.01). The ratio of post-treatment to baseline IL-10+CD4+ T cells and the serum IL-10 level were significantly increased in both the SCIT and SLIT groups (P<0.01), whereas the TRAF6 protein level and serum IL-5 level were significantly decreased (P<0.01). No significant differences in these biomarkers were observed between the SCIT and SLIT groups. CONCLUSIONS: Our findings suggest that miR-146a and its related biomarkers may be comparably modulated after both SCIT and SLIT, highlighting miR-146a as a potential therapeutic target for the improved management of AR.

Leukotriene receptor antagonist as add-on therapy to intranasal corticosteroids in the treatment of allergic rhinitis: a systematic review / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To systematically evaluate the efficacy and safety of leukotriene receptor antagonist (LTRA) combined intranasal corticosteroids in the treatment of allergic rhinitis (AR).@*METHOD@#The randomized controlled trials (RCT) about the combined therapy of LTRA and nasal corticosteroids from January 1985 to May 2014 were searched in OVID, PubMed, EMBASE, CNKI, WanFang Data, and Cochrane Library. Two reviewers independently screened the literatures, extracted the data, and evaluated the methodological quality. Then meta-ana- lyses were conducted by using RevMan 5.1 software.@*RESULT@#A total of 5 RCTs were included upon literature search. The results of meta-analyses showed that the efficacy of nasal corticosteroids plus LTRA was superior to nasal corticosteroids alone in total nasal symptom scores and individual nasal symptom scores (rhinorrhea, sneezing) [WMD = -4.49, 95% CI (-4.95(-)-4.03)-, P 0.05; WMD = 0.01, 95% CI(-) 0.06-0.08), P > 0. 05; WMD = -0.15,95% CI (-0.43(-)-0.13), P > 0.05].@*CONCLUSION@#Based on limited evidence, we preliminary concluded the combined therapy of nasal corticosteroids and LTRA was more effective than nasal corticosteroids alone in the management of AR. Further large-scale, well-designed RCTs were still required to validate the add-on efficacy of LTRA for AR patients.

Efficacy of intranasal antihistamine in the treatment of allergic rhinitis: a meta-analysis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To systematically evaluate the efficacy of intranasal antihistamine in the treatment of allergic rhinitis.</p><p><b>METHODS</b>The randomized controlled trials (RCT) about intranasal antihistamines for the treatment of allergic rhinitis between January 1985 and January 2014 were searched in OVID, PubMed, EMBASE, CNKI, WanFang Data and Cochrane Library. Two reviewers independently screened the literatures, extracted the data, and evaluated the methodological quality, then meta-analysis was performed by using RevMan 5.1 software.</p><p><b>RESULTS</b>A total of thirteen RCTs were included. The results of meta-analysis showed that the efficacy of intranasal antihistamine group was superior to the placebo group in total nasal symptom scores (TNSS), the difference was significant[WMD = -1.96, 95%CI (-2.06;-1.85), P < 0.01], and individual nasal symptom scores (blocked nose, rhinorrhea, and sneezing) [WMD = -0.18, 95%CI (-0.28;-0.08); WMD = -0.45, 95%CI (-0.52;-0.38); WMD = -0.41, 95%CI (-0.58;-0.24), all P < 0.01], with significant differences. There was no significant difference between the intranasal antihistamine group and the corticosteroid group in TNSS [WMD = -1.51, 95%CI (-3.51;0.49), P = 0.14], but the intranasal antihistamines group was superior to the corticosteroid group in individual nasal symptom scores (blocked nose, rhinorrhea, and sneezing) [WMD = -0.23, 95%CI (-0.40;-0.06); WMD = -0.35, 95%CI (-0.65;-0.05); WMD = -0.25, 95%CI (-0.42;-0.08), all P < 0.05], with significant differences. The intranasal antihistamine group was superior to the oral antihistamines group in TNSS [WMD = -0.88, 95%CI (-1.51;-0.25), P < 0.01].</p><p><b>CONCLUSION</b>Intranasal antihistamine is effective in the control of nasal symptoms in AR patients.</p>

A cohort investigation of the allergen and pathogenesis in the patients with allergic rhinitis from three hospital of Guangdong Province / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the pathogenesis of the patients with allergic rhinitis diagnosed by Skin Prick Test (SPT), especially about the epidemiologic data of the involved allergens.@*METHOD@#The data was collected from 958 patients referred to the listed three allergy center and subsequently diagnosed as allergic rhinitis by SPT.@*RESULT@#The intermittent mild type was more prevalent in male patients (40.5%); comparably the intermittent moderate type in female patients (70.0%); in the infant patients the moderate-severe type dominated (73.7%). The positive results of SPT comprised mainly of Dermatophagoides pteronyssinus (Der. p, 98.3%), Dermatophagoides farinae(Der. f, 96.8%), and Blomia tropicalis (Blot, 73.8%). Only 1.7% of the patients was allergic to single allergen, in contrary ,the majority of patients were allergic to multiple allergens. The positive rate to Der. p and Der. f was reversely increasing with age of the patients; and contrarily the number of positive allergens was increasing along with the age of the patients. The allergy to outdoor allergen was less common, and the positive rate in skin prick test was lower than the previously reported rate in North China ,such as timothy (3.9%), birch (2.7%), ragweed (2.0%), and mugwort (1.2%).@*CONCLUSION@#Dust Mite is the predominant allergen for patients with allergic rhinitis in Guangdong province; and the positive rate to outdoor allergen is lower than that in North China.

Septoplasty and decongestant improve distribution of nasal spray / 华中科技大学学报（医学）（英德文版）

This study prospectively examined the intranasal distribution of nasal spray after nasal septal correction and decongestant administration. A cohort of 20 patients was assessed for the distribution of nasal spray before and after nasal septum surgery. Sprays were dyed and administered one puff per nostril when patients hold their head up in an upright position. Before and after decongestant administration, the intranasal distribution was semi-quantitatively determined by nasal endoscopy. The results showed that the dyed drug was preferentially sprayed onto the nasal vestibule, the head of the inferior turbinate, the anterior part of septum and nasal floor. As far as the anterior-inferior segment of the nasal cavity was concerned, the distribution was found to be influenced neither by the decongestant nor by the surgery (P>0.05). However, both the decongestant and surgery expanded the distribution to the anatomical structures in the superior and posterior nasal cavity such as olfactory fissure, middle turbinate head and middle nasal meatus. No distribution was observed in the sphenoethmoidal recess, posterior septum, tail of inferior turbinate and nasopharynx. It was concluded that nasal septum surgery and decongestant administration significantly improves nasal spray distribution in the nasal cavity.

The application, observation and discussion of indications about no packing after ESS / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the safety and feasibility after functional Endoscopic surgery(FESS), without no nasal packing in 74 patients,compare these patients with 20 packing patients, and discuss the possibility and indication of avoiding packing.@*METHOD@#No nasal packing after FESS in 74 patients, the measures had been taken to reduce postoperative bleeding including appropriate case-chosen, medical administration before and after operation, alleviation of trauma in operation, and meticulous sinus clearance to prevent synechia.@*RESULT@#The postoperative blood loss were less than 50 ml. No bleeding complication happened out of the 74 no-packing patients, the blood exudation ceased timely after FESS.@*CONCLUSION@#The nasal packing could be avoided in the majority of FESS through proper management. This choice will reduce the discomfort and the cost of the patients who have to receive FESS procedure, and increase their compliance.