Early autoimmunity and outcome in virus encephalitis: a retrospective study based on tissue-based assay.

To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.

Healthcare Personnel Hand Hygiene Compliance: Are We There Yet?

Purpose of Review: Poor hand hygiene is well documented as a factor in healthcare-associated infections and excellent rates of hand hygiene remains elusive. Recent Findings: There is increased use of universal or increased gloving to minimize hand contamination, but its use does not replace hand hygiene opportunities. There is significant interest in electronic hand hygiene monitoring systems, but they are not without their unique issues. Behavioral psychology remains a significant factor in motivating hand hygiene behaviors; even in COVID-19, hand hygiene rates initially improved but trended down back to baseline while still dealing with the pandemic. Summary: More emphasis should be placed on the how to properly perform hand hygiene and why it is so important, as well as the role of gloves, is needed. Continued investment and awareness of their status as role models from both system leadership and senior healthcare providers are needed.

Pilot Study for Immunogenicity of SARS-CoV-2 Vaccine with Seasonal Influenza and Pertussis Vaccines in Pregnant Women.

Background: It is well known that the implementation of routine immunizations to prevent vaccine-preventable diseases has a significant impact on the health and well-being of infants, children, and pregnant women. We aimed to evaluate the influence of influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine on the immunogenicity of SARS-CoV-2 vaccine among pregnant women, the priority population recommended for vaccination. Methods: We conducted a prospective study among pregnant women without previous SARS-CoV-2 infection in Taiwan. Maternal and umbilical cord blood samples at delivery were analyzed for the percentage of inhibition of neutralizing antibodies (NAbs) against the original strain, Delta, and Omicron variants of SARS-CoV-2 as well as the total antibody to the SARS-CoV-2 spike protein. We examined the association between different doses of SARS-CoV-2 vaccine in combination with influenza and Tdap vaccination, and two-dose SARS-CoV-2 vaccination with or without influenza and Tdap vaccines via a two-sample t-test. Results of p < 0.05 were considered to be statistically significant. Results: 98 pregnant women were enrolled in our study, with 32 receiving two doses of SARS-CoV-2 mRNA-1273 vaccine, 60 receiving three-dose of mRNA-1273, and 6 receiving one-dose of ChAdOx1 and two-dose of mRNA-1273. Twenty-one participants were immunized with SARS-CoV-2, influenza, and Tdap vaccines. Of these 21 individuals, there were no significant NAbs levels in maternal and cord blood samples against the Omicron variant, regardless of doses or type of SARS-CoV-2 vaccine. However, antibody responses against the wild-type and Delta variant were significantly lower in all maternal sera in the two-dose SARS-CoV-2 vaccine group. Among 32 women receiving two-dose mRNA-1273, significantly lower levels of NAbs in maternal sera were observed against the Delta variant and total antibody both in maternal sera and cord blood were observed in individuals receiving SARS-CoV-2 and influenza vaccine. Conclusion: This is the pilot study to demonstrate the effects of influenza and the Tdap vaccine on the immunogenicity of the SARS-CoV-2 vaccine among pregnant women. These results suggest that combination vaccination during pregnancy may result in immunogenic interactions.

COVID-19, Family Dynamics, and Perceived Mental Health Among Families in Singapore

The COVID-19 pandemic presents a significant challenge to the well-being of families with children. Although previous studies have documented COVID-related deterioration in parents' mental health, the underlying mechanisms remain unclear. It is also unclear how much of the deterioration is due to the pandemic itself, versus mandated lockdown measures. We conducted a cross-sectional study in Singapore to examine perceived changes in parents' lives and mental health related to the pandemic and lockdown measures. In June 2020, when Singapore had just exited a nationwide lockdown, we asked families to retrospectively report on the family dynamics, daily activities, and mental health of family members during the phases before local transmission (Pre-pandemic), during local transmission but before the lockdown (Pre-lockdown), and during the lockdown (Lockdown). Results from 180 mothers and 166 fathers from 198 families showed significant changes in jobs and income, childcare arrangements, family dynamics, and parents' perceived mental health across the three timepoints. Mothers' increased time spent on housework was associated with the increase in their mental health problems from Pre-lockdown to Lockdown. Parents' increased conflict with other adults in the household was associated with the increase in their mental health problems from Pre-pandemic to Pre-lockdown, and from Pre-lockdown to Lockdown. Mental health problems increased more for young mothers, parents with a graduate or professional degree, and fathers high on authoritarian values. Findings suggest that both the pandemic and the imposed lockdown measures impact parents' lives and family dynamics, in turn leading to deterioration in parents' mental health. Highlights There were significant changes in Singaporean parents' daily activities, family dynamics, and mental health during the COVID-19 period. Rule setting and conflict with children increased among authoritarian fathers, and autonomy granting decreased among authoritarian mothers. Mothers' time spent on housework was associated with their increased mental health problems during lockdown. Parents' conflict with other adults in the household was associated with their increased mental health problems during both pandemic and lockdown. Mental health problems increased more for young mothers, parents with a graduate or professional degree, and authoritarian fathers.

eHealth Intervention via LINE® Social Media as an Adjunct for Postoperative Care After Bariatric-Metabolic Surgery: Single Institution Experience.

PURPOSE: Applying eHealth interventions via social media is common in modern medicine. LINE® is a popular communication app in Taiwan that can deliver messages 24 h a day. In addition to being free of charge, it also allows bariatric nurses (BNs) and patients to enjoy bidirectional communication via telecommunication services instead of direct, face-to-face contact for patients undergoing bariatric-metabolic surgery (BMS). We conducted this retrospective study to determine the frequency and reasons for early post-discharge of LINE® messages/calls and investigate the relationship between this frequency and contents of these messages and postoperative outcomes after BMS. MATERIALS AND METHODS: A retrospective review of prospectively collected data was conducted in an Asian weight management center. The study period ran from August 2016 to December 2021, and a total of 143 native patients with severe obesity were enrolled. All patients were informed of the necessity of a postoperative dietitian consultation before bariatric surgery. The patterns of LINE® communication with the BN and associated actions to resolve patients' needs within 180 days after index BMS were analyzed. RESULTS: Among the 143 enrolled patients, 100 underwent laparoscopic sleeve gastrectomy and 43 underwent laparoscopic Roux-en-Y gastric bypass. A total of 1205 messages/calls were analyzed concomitantly; most LINE® communications focused on diet problems (47.97%; n = 578), weight problems (11.54%; n = 139), and medications (9.21%; n = 111). Most problems could be resolved by LINE® communications directly, and only a small portion (5.6%) was directed to local clinics or emergency departments. During the COVID-19 pandemic, the usage of LINE® communications significantly increased (12.2 ± 10.4 vs. 6.4 ± 4.9; p < 0.01); nonetheless, a higher frequency of LINE® communications would not hinder the regular clinic visits (r = 0.359; p = 0.01). CONCLUSION: Based on our limited experience, the LINE® consultation service operated by the BN could effectively address patients' problems. Moreover, it might reduce the need for emergency department visits or unexpected clinic appointments for patients after BMS.

Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) rapidly infects humans and animals which make coronavirus disease 2019 (COVID-19) a grievous epidemic worldwide which broke out in 2020. According to data analysis of the other coronavirus family, for instance severe acute respiratory syndrome SARS coronavirus (SARS-CoV), can provide experience for the mutation of SARS-CoV-2 and the prevention and treatment of COVID-19. Toll-like receptors (TLRs) as a pattern recognition receptor (PRRs), have an indispensable function in identifying the invader even activate the innate immune system. It is possible for organism to activate different TLR pathways which leads to secretion of proinflammatory cytokines such as Interleukin 1 (IL-1), Interleukin 6 (IL-6), Tumor necrosis factor α (TNFα) and type Ⅰ interferon. As a component of non-specific immunity, TLRs pathway may participate in the SARS-CoV-2 pathogenic processes, due to previous works have proved that TLRs are involved in the invasion and infection of SARS-CoV and MERS to varying degrees. Different TLR, such as TLR2, TLR4, TLR7, TLR8 and TLR9 probably have a double-sided in COVID-19 infection. Therefore, it is of great significance for a correctly acknowledging how TLR take part in the SARS-CoV-2 pathogenic processes, which will be the development of treatment and prevention strategies.

Metagenomic assessment of gut microbial communities and risk of severe COVID-19 (preprint)

The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure. We profiled 127 hospitalized patients with COVID-19 (n=79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites. 48 species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or “long COVID”, suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with predicting whether stool was obtained from patients with severe vs. moderate COVID-19. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease. Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to validate these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention.

Whole-genome sequence analysis of four human coronavirus NL63 strains regionally prevalent in Shenzhen, 2020

In this study, the genomic RNA of HCoV-NL63 from throat swab samples obtained from cases of respiratory tract infection was sequenced. The cases were collected from clustered or sporadic epidemics in the Nanshan district of Shenzhen City in 2020. Four whole genomes of HCoV-NL63 strains were obtained and analyzed with phylogenetic tree reconstruction and other bioinformatics analyses. The sequence similarity among the four strains was 99.80%~99.98% for nucleotides and 99.64%~99.93% for amino acids. The four strains of HCoV-NL63 belonged to the B genotype, B2 subgenotype, which were on the same branch of the phylogenetic tree and were genetically closest to MK334046.1. Analysis of the amino acid variation sites of the S protein indicated that L196F was present in the strains obtained from sporadic epidemic cases, and A946S was present in the strains acquired from clustered epidemic cases. The prediction of N-glycosylation sites indicated ten N-glycosylation sites in S protein and two N-glycosylation sites in M protein. Through whole genome sequencing and feature analysis, we determined that the HCoV-NL63 obtained in this study probably originated from the Guangzhou virus strain. Our current results provide some clues as to the basis for biological traceability, and might facilitate future epidemic prevention and control.

A Meta-Analysis of Accuracy and Sensitivity of CRISPR and Chest CT in COVID‑19 Diagnosis (preprint)

Objective: To clarify the accuracy of clusters of regularly spaced short palindrome repeats (CRISPR) technology and chest CT in the diagnosis of Corona Virus Disease2019(COVID-19). Methods: The term "Corona Virus Disease " "clustered regularly spaced short palindromic repeats" "CRISPR", "chest CT", "sensitivity and specificity" as the subject words or keywords were searched in databases such as Pubmed, Embase, Cochrane Library, Wiley and Scopus and Chinese academic databases (such as CNKI, Wanfang and Chongqing VIP data) for relevant literature on the use of CRISPR technology and chest CT for the diagnosis of COVID-19. Meta-analysis was performed after literature screening, quality assessment and data extraction . Results: A total of 418 articles were retrieved, and 17 articles were finally included. The results showed that the combined sensitivity of CRISPR technology for diagnosing new coronary pneumonia infection was 0.96 [95% CI (0.93, 0.98)], and the combined specificity was 1.00 [95% CI (0.92, 1.00)], the combined positive likelihood ratio is 458.69 [95%CI (11.51, 18280.8)], the combined negative likelihood ratio is 0.04 [95% CI (0.02, 0.07)], the area under the SROC curve is 0.99 [95%CI(0.97,0.99)]. The combined sensitivity of chest CT in diagnosing new coronary pneumonia infection was 0.94 [95%CI (0.83, 0.98)], combined specificity was 0.55 [95% CI (0.22, 0.83)], combined diagnostic odds ratio was 19.90 [95% CI (7.88, 50.25)], the combined positive likelihood ratio is 2.08 [95%CI (1.00, 4.32)], the combined negative likelihood ratio is 0.10 [95% CI (0.05, 0.23)], the area under the SROC curve is 0.91 [95% CI (0.88, 0.93)]. The Deek funnel chart indicates that there is no potential publication bias among the included studies (PCRISPR = 0.03, P chest CT = 0.55). Conclusion: CRISPR technology has a better ability to detect infections in patients with COVID-19, and is better than chest CT in disease diagnosis. CRISPR technology, especially non-SHERLOCK type and multi-target gene detection, can be used to diagnose COVID-19 with higher accuracy ,and can be used for large-scale population screening.

Guillain-​Barré Syndrome Associated with COVID-19 Vaccination.

We conducted a multi-institutional study in Taiwan and a systematic review of the literature for reports of Guillain-​Barré syndrome after coronavirus disease vaccination. This condition, mostly the classic form and the acute inflammatory demyelinating polyneuropathy subtype, has been reported in 39 cases and has occurred within 2 weeks of vaccine administration.

Immunological and Inflammatory Indicators of COVID-19 Patients With Returned-positive Nucleic Acid Tests During Hospitalization: a Retrospective Cohort Study (preprint)

Background: COVID-19 cases with suspected returned-positive SRAS-CoV-2 tests following consecutive negative tests have been reported, but evidence-based explanations for this phenomenon is still lacking. We aimed to describe the clinical and laboratory characteristics of returned-positive COVID-19 patients during treatment in comparison with other patients.Methods: From January 20 to April 10, 2020, all COVID-19 inpatient with at least three RT-PCR SARS-CoV-2 tests in Renmin Hospital in Wuhan, China were enrolled. Patients with 2 consecutively negative RT-PCR results followed by a positive result were classified as returned-positive patients, and their characteristics and repeatedly measured laboratory results were compared with the rest of the patients. Linear mixed effects models were performed.Results: A total of 789 COVID-19 patients were included and 22.8% patients returned positive in RT-PCR SARS-CoV-2 test. No significant differences were found for general characteristics between the returned-positive and the control groups. The trends of inflammatory and immune factors including the third component of complement (C3), C-reactive protein, procalcitonin (PCT), IL-4, IL-6, the counts of lymphocyte, CD3+, CD8+, white blood cell and immunoglobulin levels during hospitalization were significantly different between the two groups. During the returned-positive period, C3, PCT, serum IgM, anti-SARS-CoV-2 IgM and anti-SARS-CoV-2 IgG were significantly higher in the returned-positive patients at certain time points.Conclusions: Returned-positive COVID-19 patients appeared to be more sever at admission, and had periodically higher levels in C3, PCT, serum IgM and two specific antibodies during hospitalization. This suggests that positive return of SARS-COV-2 could not be completely explained by false-negative testing and longer observation of these patients is warranted. 

Long-term effects of appendectomy in humans: is it the optimal management of appendicitis?

INTRODUCTION: Appendectomy remains the gold standard for treating uncomplicated and complicated appendicitis. However, the vermiform appendix may play a significant role in the immune system (secondary immune function) and maintain a reservoir of the normal microbiome for the human body. The aim of this study was to summarize the long-term effects after appendectomy and discuss whether appendectomy is suitable for all appendicitis patients. AREAS COVERED: A comprehensive and unbiased literature search was performed in PubMed. The terms 'appendix,' 'appendicitis,' 'appendectomy,' and 'endoscopic retrograde appendicitis therapy' were searched in the title and/or abstract. This review summarizes the long-term effects of appendectomy on some diseases in humans and describes three methods including appendectomy, medical treatment, and an 'organ-sparing' technique, named endoscopic retrograde appendicitis therapy (ERAT) to treat appendicitis. EXPERT OPINION: Appendectomy remains the first-line therapy for appendicitis. The patient's problem is appendix, not appendicitis. If we treat appendicitis, the problem should be resolved. During COVID-19, an initial antibiotic treatment of mild appendicitis represents a promising strategy. For patients who are worried about the long-term adverse effect after appendectomy and have a strong desire to preserve the appendix and are aware of the risk of appendicitis recurrence, medical treatment, or ERAT could be proposed.

Prevalence and Influencing Factors of Anxiety and Depression Symptoms Amongst Surgical Nurses During COVID-19 Pandemic: A Large-Scale Cross-Sectional Study (preprint)

BackgroundThe outbreak of novel 2019 coronavirus disease (COVID-19) has imposed an enormous physical and psychological pressure on people across the world. This study focused on evaluating the prevalence and influencing factors of anxiety and depression symptoms in surgical nurses during the epidemic in China. MethodA cross-sectional, multicenter quantitative study was conducted in Anhui province (China) from March 3, 2020 to March 19, 2020, with a questionnaire package which consisted of general information questionnaire，Zung's self-rating anxiety scale (SAS), Zung's self-rating Depression Scale (SDS) and social support rating scale (SSRS). A total of 3600 surgical nurses participated in the survey by Wechat and QQ. Data were analysed using multiple linear regression models. ResultsA total of 3492 surgical nurses from 12tertiary hospitals and 12 secondary hospitals in one province of mainland China completed the survey. The prevalence rates of anxiety symptoms and depressive symptoms were 24.83% and 22.39%, respectively. The average level of anxiety and depression of surgical nurses were higher than that of the Chinese norm (P< 0.05).Levels of social support for surgical nurses were significantly negatively associated with the degree of anxiety (r = -0.630, P < 0.001) and depression (r = -0.578, P < 0.001). Fertility status (β = 1.469, P = 0.003), hospital (β = -0.611, P < 0.001), participation in care for COVID-19 patients (β = 2.229, P < 0.001), likelihood of being infected with COVID-19 (β = 1.146, P < 0.001), social support (β = -0.623, P < 0.001) were significantly influencing surgical nurses’ anxiety degree. Similarly, these characteristics were significantly associated with the odds of experiencing depression symptoms in surgical nurses. Divorce and widowed surgical nurses (β = -2.654, P < 0.001) were significantly more likely to experience depressive symptoms than single nurses. ConclusionIn this survey, we found that the surgical nurses had high anxiety and depression symptoms during the COVID-19 outbreak in China. The findings suggest that targeted psychological interventions to promote the mental health of surgical nurses with psychological problems need to be immediately implemented. 

Features of alpha-HBDH in COVID-19 patients with different ages,outcomes and clinical types: a cohort study (preprint)

Background: Coronavirus disease-2019 (COVID-19) has spread all over the world and brought extremely huge losses. At present, there is no study to systematically analyse the features of hydroxybutyrate dehydrogenase (alpha-HBDH) in COVID-19 patients with different ages, clinical types and outcomes. Methods: Electronic medical records including demographics, clinical manifestation, alpha-HBDH test results and outcomes of 131 hospitalized COVID-19 patients, with confirmed result of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection, were extracted and analyzed. Results: The alpha-HBDH value in greater than or equal to 61 years old group, severe group and critical group, death group all increased at first and then decreased, while no obvious changes were observed in other groups. And there were significant differences of the alpha-HBDH value among different age groups, clinical type groups and outcome groups. The optimal scale regression model showed that alpha-HBDH value and age were related to clinical type. Conclusions: alpha-HBDH value increases in some COVID-19 patients, obviously in greater than or equal to 61 years old, death and critical group, indicating that patients in these three groups suffer from more serious tissues and organs damage, higher alpha-HBDH value and risk of death. The obvious difference between death and survival group in early stage may provide a approach to judge the prognosis. The accuracy of the model to distinguish severe/critical type and other types is 85.84%, suggesting that alpha-HBDH could judge the clinical type of COVID-19 patients accurately. In brief, alpha-HBDH is an important indicator to judge the severity and prognosis of COVID-19.

Rapid development of SARS-CoV-2 receptor binding domain-conjugated nanoparticle vaccine candidate (preprint)

The ongoing of coronavirus disease 2019 (COVID-19) pandemic caused by novel SARS-CoV-2 coronavirus, resulting in economic losses and seriously threating the human health in worldwide, highlighting the urgent need of a stabilized, easily produced and effective preventive vaccine. The SARS-COV-2 spike protein receptor binding region (RBD) plays an important role in the process of viral binding receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion, making it an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticles vaccine candidates, RBD-Ferritin (24-mer), RBD-mi3 (60-mer) and RBD-I53-50 (120-mer), with the application of covalent bond linking by SpyTag-SpyCatcher system. It was demonstrated that the neutralizing capability of sera from mice immunized with three RBD-conjugated nanoparticles adjuvanted with AddaVax or Sigma Systerm Adjuvant (SAS) after each immunization was ~8- to 120-fold greater than monomeric RBD group in SARS-CoV-2 pseudovirus and authentic virus neutralization assay. Most importantly, sera from RBD-conjugated NPs groups more efficiently blocked the binding of RBD to ACE2 or neutralizing antibody in vitro, a further proof of promising immunization effect. Besides, high physical stability and flexibility in assembly consolidated the benefit for rapid scale-up production of vaccine. These results supported that our designed SARS-CoV-2 RBD-conjugated nanoparticle was competitive vaccine candidate and the carrier nanoparticles could be adopted as universal platform for future vaccine development.

COVID-19 risk haplogroups differ between populations, deviate from Neanderthal haplotypes and compromise risk assessment in non-Europeans (preprint)

Recent genome wide association studies (GWAS) have identified genetic risk factors for developing severe COVID-19 symptoms. The studies reported a 1bp insertion rs11385942 on chromosome 3 and furthermore two single nucleotide variants (SNVs) rs35044562 and rs67959919, all three correlated with each other. Zeberg and Paabo subsequently traced them back to Neanderthal origin. They found that a 49.4 kb genomic region including the risk allele of rs35044562 is inherited from Neanderthals of Vindija in Croatia. Here we add a differently focused evaluation of this major genetic risk factor to these recent analyses. We show that (i) COVID-19-related genetic factors of Neanderthals deviate from those of modern humans and that (ii) they differ among world-wide human populations, which compromises risk prediction in non-Europeans. Currently, caution is thus advised in the genetic risk assessment of non-Europeans during this world-wide COVID-19 pandemic.

Computational prediction of SARS-CoV-2 encoded miRNAs and their putative host targets (preprint)

Background: Over the past two decades, there has been a continued research on the role of small non-coding RNAs including microRNAs (miRNAs) in various diseases. Studies have shown that viruses modulate the host cellular machinery and hijack its metabolic and immune signaling pathways by miRNA mediated gene silencing. Given the immensity of coronavirus disease 19 (COVID-19) pandemic and the strong association of viral encoded miRNAs with their pathogenesis, it is important to study Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) miRNAs. Results: To address this unexplored area, we identified 8 putative novel miRNAs from SARS-CoV-2 genome and explored their possible human gene targets. A significant proportion of these targets populated key immune and metabolic pathways such as MAPK signaling pathway, maturity-onset diabetes of the young, Insulin signaling pathway, endocytosis, RNA transport, TGF-{beta} signaling pathway, to name a few. The data from this work is backed up by recently reported high-throughput transcriptomics datasets obtains from SARS-CoV-2 infected samples. Analysis of these datasets reveal that a significant proportion of the target human genes were down-regulated upon SARS-CoV-2 infection. Conclusions: The current study brings to light probable host metabolic and immune pathways susceptible to viral miRNA mediated silencing in a SARS-CoV-2 infection, and discusses its effects on the host pathophysiology.

Antiviral activity of plant juices and green tea against SARS-CoV-2 and influenza virus in vitro (preprint)

Respiratory viruses initially infect the naso- and oropharyngeal regions, where they amplify, cause symptoms and may also be transmitted to new hosts. Preventing initial infection or reducing viral loads upon infection might soothe symptoms, prevent dissemination into the lower airways, or transmission to the next individual. We here analyzed the potential of plant derived products to inactivate SARS-CoV-2 and influenza virus. We found that black chokeberry (Aronia melanocarpa) juice, pomegranate (Punica granatum) juice, and green tea (Camellia sinensis) have virucidal activity against both viruses, suggesting that oral rinsing may reduce viral loads in the oral cavity thereby lowering virus transmission.

Potential Opportunity Of Antisense Therapy Of COVID-19 on an in vitro model (preprint)

Data on potential effectiveness and prospects of treatment of new coronavirus infection of COVID-19 caused by virus SARS-CoV-2 with the help of antisense oligonucleotides acting against RNA of virus on an in vitro model are given. The ability of antisense oligonucleotides to suppress viral replication in diseases caused by coronaviruses using the example of SARS and MERS is shown. The identity of the initial regulatory section of RNA of various coronaviruses was found within 50 - 100 nucleotides from the 5'-end, which allows using antisense suppression of this RNA fragment. A new RNA fragment of the virus present in all samples of coronovirus SARS-CoV-2 has been identified, the suppression of which with the help of an antisense oligonucleotide can be effective in the treatment of COVID-19. The study of the synthesized antisense oligonucleotide 5`-AGCCGAGTGACAGCC ACACAG, complementary to the selected virus RNA sequence, was carried out. The low toxicity of the preparations of this group in the cell culture study and the ability to reduce viral load at high doses according to real time-PCR data are shown. The cytopathogenic dose exceeds 2 mg/ml. At a dosage of 1 mg/ml, viral replication is reduced by 5 - 13 times. Conclusions are made about the prospects of this direction and the feasibility of using the inhalation way of drug administration into the body.