Analysis of pathogen detection results of upper respiratory tract specimens from fever clinic patients

Objective: To explore the pathogen composition and distribution characteristics of pathogens in respiratory samples from patients with fever of unknown origin. Methods: A total of 96 respiratory samples of patients with unknown cause fever with respiratory symptoms were collected from four hospitals above grade II in Shijiazhuang area (Hebei Provincial Hospital of Traditional Chinese Medicine, Luancheng District People's Hospital, Luquan District People's Hospital, Shenze County Hospital) from January to April 2020, and multiplex-fluorescent polymerase chain reaction(PCR)was used to detect influenza A virus, influenza B virus, enterovirus, parainfluenza virus I/II/III/IV, respiratory adenovirus, human metapneumovirus, respiratory syncytial virus, human rhinovirus, human bocavirus, COVID-19, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa, Streptococcus pneumoniae, Klebsiella pneumoniae, Group A streptococcus, Haemophilus influenzae, Staphylococcus aureus nucleic acid detection, the results were analyzed for chi-square. Results: A total of 8 pathogens were detected in the upper respiratory tract samples of 96 fever patients, including 1 kind of virus, 6 kinds of bacterias, and Mycoplasma pneumoniae. There were 12 viruses including influenza virus and parainfluenza virus, Legionella pneumophila and Chlamydia pneumoniae were not detected. The pathogen detection rates in descending order were Streptococcus pneumoniae (58/96, 60.42%), Haemophilus influenzae(38/96, 39.58%), Klebsiella pneumoniae (14/96, 14.58%), Staphylococcus aureus (10/96, 10.42%), Mycoplasma pneumoniae (8/96, 8.33%), Pseudomonas aeruginosa (6/96, 6.25%), Group A streptococcus (4/96, 4.17%) and human rhinovirus (2/96, 2.08%). The proportions of single-pathogen infection and multi-pathogen mixed infection in fever clinic patients were similar, 41.67% (40/96) and 45.83% (44/96), respectively, and 12.50% (12/96)of the cases had no pathogens detected. The infection rate of Mycoplasma pneumoniae in female patients with fever (21.43%) was higher than that in male patients with fever (2.94%) (P < 0.05). There was no statistical difference between the distribution of of other pathogens and gender and age(P > 0.05). Conclusions: The upper respiratory tract pathogens were mainly bacterial infections, and occasional human rhinovirus and Mycoplasma pneumonia infections. In clinical diagnosis and treatment, comprehensive consideration should be given to the pathogen detection.

Expressions of miR-21 TGF-beta/Smad signaling pathway in peripheral blood of bronchial asthma patients complicated with respiratory virus infection

OBJECTIVE: To investigate the expressions of peripheral blood microRNA-21(miR-21) and transforming growth factor-beta(TNF-beta)/Smad signaling transduction pathway in patients with bronchial asthma complicated with respiratory virus infection. METHODS: Totally 109 patients with asthma complicated with respiratory virus infection(study group) and 104 patients without virus infection(control group) in the Third People's Hospital of Gansu Province between Feb.2019 and Feb.2021 were selected for the cross-sectional study. The basic data of the two groups were collected, and parameters including vital signs, lung function, peripheral blood miR-21 and TGF-beta/Smad signaling pathway proteins were measured. According to the guidelines, the patients of the two groups were divided into acute exacerbation phase and stable phase. The examination results of each group were compared and the levels of peripheral blood miR-21 and TGF-beta/Smad signaling pathway proteins expression of patients with asthma complicated with respiratory virus infection were analyzed. RESULTS: In study group, the proportion of respiratory virus infection among 109 patients was 33.94% for influenza virus, 23.85% for human rhinovirus, 19.27% for respiratory syncytial virus, 10.09% for parainfluenza virus, 6.42% for adenovirus, 4.59% for human coronavirus and 1.83% for human metapneumovirus respectively. The proportion of patients with acute exacerbation phase in the study group was higher than that in the control group, and the levels of peripheral blood miR-21, TGF-beta1, Smad7, pSmad2 and pSmad3 were higher than those in control group(P<0.05). The levels of miR-21, TGF-beta1, Smad2, Smad3, Smad7, pSmad2 and pSmad3 in peripheral blood of patients with acute exacerbation phase of asthma were higher than those of patients with stable phase of asthma(P<0.05). There were no statistical differences in peripheral blood miR-21, TGF-beta1, Smad2, Smad3, Smad7, pSmad2 and pSmad3 levels in asthma patients with different virus infections. CONCLUSION: Early respiratory virus infections might lead to increased expression of peripheral blood miR-21 and increased activation of TGF-beta/Smad signaling pathway in patients with asthma, which played an important role in acute attack of asthma.

Emerging and Miscellaneous Viral Infections

• The infectious diseases described in this chapter are either: (1) diseases of humans or other animals generally transmitted through contact with the secretions or excretions of rodents (hantaviruses, arenaviruses, and encephalomyocarditis virus), swine (hepatitis E virus), monkeys (Ebola virus), or bats (systemic coronaviruses);(2) common diseases of humans where the role of companion animals in transmission has been investigated (enteroviruses, SARS-CoV-2);(3) diseases of significant importance to the agricultural industry (foot-and-mouth disease virus, vesicular exanthema, encephalomyocarditis virus);or (4) significant diseases of potential prey of dogs and cats (rabbit hemorrhagic disease virus). • Clinical illness has not always been confirmed in dogs and cats with these infections, but evidence of seroconversion to these viruses exists. • In some cases, concern has been raised in the possible role of dogs and cats in zoonotic transmission;this has been heightened by the COVID-19 pandemic. • In general, research suggests that dogs and cats do not play a major role in transmission of these viruses, but the potential exists should new viral variants emerge. © 2021 Elsevier Inc. All rights reserved.

PPP1R13L-Related Cardiomyopathy Stability Following IL1 Inhibition

Introduction: Variants in PPP1R13L are associated with severe childhood-onset cardiomyopathy resulting in rapid progression to death or cardiac transplantation. PPP1R13L is proposed to encode a protein that limits the transcriptional activity of the NFkappaB pathway leading to elevated IL-1, IL-6, and TNF-alpha production in murine models. Optimal medical management for PPP1R13L-related cardiomyopathy is unknown. Here we report usage of a targeted anti-IL-1 immuno-modulatory therapy resulting in cardiac stabilization in a pediatric patient with congenital cardiomyopathy secondary to PPP1R13L variants. Case Report: A 4-year-old boy presented acutely with fever in the setting of persistent abdominal pain, vomiting, fatigue, and decreased appetite for two months following a mild COVID-19 related illness. Echocardiogram revealed severely depressed biventricular systolic function with an ejection fraction of 30%. Due to acute decompensated heart failure symptoms with hemodynamic instability, he was intubated and placed on continuous inotropic infusions with aggressive diuresis. Cardiac MRI demonstrated extensive subepicardial to near transmural fibrosis by late gadolinium enhancement in right and left ventricles. An implantable cardioverter-defibrillator (ICD) was placed due to frequent runs of polymorphic non-sustained ventricular tachycardia. Testing for viral pathogens was positive for rhino/enterovirus. Initial genetic testing was non-diagnostic (82-gene cardiomyopathy panel) but given the patient's significant presentation whole genome sequencing was pursued that showed two separate PPP1R13L variants in trans (c.2167A>C,p.T723P and c.2179_2183del,p. G727Hfs*25, NM_006663.4). Patient serum cytokine testing revealed elevations in IL-10 (4.7 pg/mL) and IL-1beta (20.9 pg/mL). Given the patient's tenuous circumstances and concern for continued progression of his cardiac disease, a trial of IL-1 inhibition via anakinra dosed at 3 mg/kg or 45 mg daily was initiated following hospital discharge. With approximately 6 months of therapy, the patient's cardiac function is stable with normalization of IL-10 and IL-1beta serum levels. Notably, the ventricular arrhythmia decreased after initiation of anakinra with no ICD shocks given. Therapy overall has been well tolerated without infectious concerns. Conclusion(s): In patients with PPP1R13L-related cardiomyopathy, immuno-modulatory therapies should be considered in an attempt to slow cardiac disease progression.Copyright © 2023 Elsevier Inc.

A baby girl with TBX1 haploinsufficiency who died after elective cardiac repair surgery due to suspected enteroviral meningitis

Introduction: TBX1 haploinsufficiency is an inborn error of immunity with the phenotype of DiGeorge Syndrome. DiGeorge Syndrome has variable immunodeficiency associated with grade of thymic hypoplasia ranging from mild with no infections to severe requiring thymus implant. Enterovirus is an example of an opportunistic infection that can be fatal in these patients. Case Presentation: A 1 year old girl with TBX1 haploinsufficiency complicated by Tetralogy of Fallot, pulmonary atresia, high arched palate, and vesicovaginal fistula presented for elective cardiac repair surgery from another country due to failure to thrive and cyanosis. She had no prior infectious history but was on sulfamethoxazole-trimethoprim for prophylaxis. She was asymptomatic with a negative COVID test but no other infectious studies performed. Immediately postoperatively, she was febrile and nasal respiratory viral panel was positive for rhinovirus/enterovirus with increased procalcitonin and leukocytosis with left shift. She decompensated with multi-organ failure and cardiac arrest on postoperative day two. She was cannulated to veno-arterial extracorporeal membrane oxygenation (ECMO). Pre-operatively, she had a normal absolute lymphocyte count. No thymus tissue was observed in surgery. She had profound CD3 lymphopenia to 130 cells/cmm when critically ill. Enteroviral meningitis was suspected as no infectious, cardiac, or other pathology could be identified causing decompensation. Enteroviral serum polymerase chain reaction (PCR) test was negative while lumbar puncture deferred due to clinical status. She was treated with immunoglobulin. Offlabel investigational drug pocapavir was considered but deferred to patient's irreversible neurological status. The patient was disconnected from ECMO and expired. Discussion(s): Though we cannot confirm that this patient had enteroviral meningitis, invasive enteroviral infections are associated with elevated transaminases, coagulopathy, and seizures all present in our patient. There has also been reported negative serum enteroviral PCR but positive CSF enteroviral PCR in an immunodeficient patient. Additionally, this case highlights the importance of immunologic evaluation in patients with DiGeorge Syndrome and questions if asymptomatic viral screening for viruses like enterovirus should be considered pre-operatively in patients with inborn errors of immunity. This case highlights potential treatment options for invasive enteroviral infections in patients with inborn errors of immunity: high dose immunoglobulin, fluoxetine, and pocapavir.Copyright © 2023 Elsevier Inc.

SEVERE MYOCARDITIS WITH CARDIOGENIC SHOCK IN ADULT-ONSET STILL'S DISEASE AFTER mRNA COVID-19 VACCINATION: A CASE OF ATYPICAL PRESENTATION

Background/Aims Adult-onset Still's disease is a systemic inflammatory disease of unknown aetiology. Post-COVID-19 vaccine adult-onset Still's disease has been reported and was associated with only mild myocarditis. Here we report the first case of adult-onset Still's disease after mRNA COVID-19 vaccination presenting with severe myocarditis with acute heart failure and cardiogenic shock. Methods We described the case history of the patient. Results A 72-year-old Chinese woman developed gradual onset of fever, shortness of breath, sore throat, generalised arthralgia, malaise and poor appetite 15 days after receiving the first dose of BNT162b2 mRNA COVID-19 vaccine. Physical examination revealed fever, bilateral ankle oedema and elevated jugular venous pressure. Significant investigation results are shown in Table 1. Extensive viral panel tests (including enterovirus, influenza and cytomegalovirus) were all negative. Echocardiography showed severely reduced left ventricular ejection fraction of 20%. The acute heart failure was complicated by cardiogenic shock requiring intensive care unit admission. Myocarditis was later diagnosed. Although the heart condition subsequently improved, there were persistent fever and arthralgia, as well as the development of generalised maculopapular skin rash. In view of that, series of investigations were performed, which revealed persistent neutrophilic leucocytosis, hyper-ferritinaemia and liver function derangement, while autoimmune panel was grossly unremarkable and septic/viral workup was negative (Table 1). Contrast PET-CT scan showed no features of malignancy. Adult-onset Still's disease was diagnosed, and the patient was treated with oral prednisolone 40mg daily. The patient's condition responded to the treatment;the fever subsided and the leucocyte count and inflammatory markers were normalised, and she was subsequently discharged. Three months after discharge, the patient was clinically well with prednisolone tapered down to 5mg daily. Reassessment echocardiogram showed full recovery with LVEF 60%. Conclusion Severe myocarditis with acute heart failure and cardiogenic shock is a possible initial presentation of adult-onset Still's disease after mRNA COVID-19 vaccination. After exclusion of more common aetiologies, it is important to consider adult-onset Still's disease as one of the differential diagnoses in the presence of compatible features following COVID-19 vaccination, such that appropriate and timely workup and treatment can be offered. (Table Presented).

Systemic Viral Infections and the Eye

Ocular manifestations of systemic viral infections are common. Because viral infection syndromes may be nonspecific, diagnosis of a particular viral infection often requires understanding of the risk factors and transmission modes of viral pathogens. Careful review of both history of the disease and the ocular exam findings can be helpful in narrowing down the differential diagnosis for the systemic condition and vice versa. A history of exposures, including animal exposures, sexual exposures, and travel, as well as the vaccination history and general medical history helps guide the workup and treatment of viral infections. Diagnostic testing for viral infections may include blood testing for serologic studies and viral detection, samples from involved extraocular organs, as well as ocular samples that can confirm a diagnosis and facilitate initiation of optimal therapy while minimizing side effects from exposure to unnecessary antiviral agents. Importantly, patients with HIV or other immunocompromising conditions may simultaneously have more than one active infection and also may manifest with syndromes that are atypical and have serologic testing that is less accurate. Careful and aggressive diagnostic evaluation of ocular symptoms is especially important in these patients, as are efforts to improve immune function while monitoring for the possible impact of immune reconstitution on the clinical course. © Springer Nature Switzerland AG 2022.

Single center retrospective study on the distribution of pathogens in elderly patients with acute exacerbation of chronic obstructive pulmonary disease

Objective: To explore the distribution and correlation of pathogens in the elderly patients with AECOPD, so as to guide the rational use of antibiotics and hormones in clinic. Methods: A total of 111 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to Nanjing First Hospital from January 2019 to January 2020 were retrospectively analyzed. The basic data such as eosinophil, neutrophil and lymphocyte count, the levels of C-reactive protein(CRP) and erythrocyte sedimentation rate (ESR)in blood routine examination were collected. Further, the pathogens were qualified by sputum fluorescence quantitative polymerase chain reaction, and the pathogens distribution was analyzed. Results: The level of ESR and the ratio of cardiovascular diseases showed significant differences between the pathogen-positive group and pathogen-negative group. In this study, the top five pathogens in AECOPD patients were EB virus (21.6%), Haemophilus influenzae (19.8%), Streptococcus pneumoniae (17.1%), herpes simplex virus(14.4%), influenza A virus(14.4%). The detection rate of influenza A virus was correlated with influenza B virus and Aspergillus (P < 0.05);The detection rate of respiratory syncytial virus was correlated with Candida, Moraxella catarrholis, Streptococcus pneumoniae and Haemophilus influenzae (P < 0.05);The detection rate of Escherichia coli was correlated with rhinovirus, adenovirus, Klebsiella pneumoniae and Acinetobacter baumannii (P < 0.05);The detection rate of Candida was correlated with that of Moraxella catarrholis and Pseudomonas aeruginosa(P<0.05);The detection rate of human coronavirus was correlated with Haemophilus influenzae, herpes simplex virus and Streptococcus pneumoniae(P < 0.05). Conclusions: AECOPD are mostly induced by different pathogens, especially mixed infection of bacteria and virus. It is helpful to guide the rational use of antibiotics by analyzing the etiological characteristics in the elderly patients with AECOPD.

Circulation of genetically diverse non-polio enteroviruses in respiratory samples during COVID-19 pandemic period (2021-22)

Enteroviruses, beyond poliovirus, are important pathogens. Several non-polio enteroviruses (NPEVs) are causing epidemics all around the world. Limited data is available on the prevalence and diversity of these viruses from India. Objective(s): Detection and characterization of NPEVs in respiratory samples during the COVID-19 pandemic period. Material(s) and Method(s): COVID-19 negative samples from acute respiratory infections (ARI) [n = 105] and severe-acute respiratory infections (SARI) [n = 148] during the period 2021-22 were screened for NPEVs. Detection was carried out using the one step RT-PCR method targeting the 5'UTR region followed by molecular analysis. Results and Conclusion(s): Total positivity of NPEVs was noted in 35.23% and 31.08% of the ARI and SARI cases, respectively. Comparison within the two groups studied, showed significant difference in the age-wise distribution for cases>18 years of age. Year round seasonality for ARI cases while autumn seasonality for SARI cases was observed. Sequencing of representative samples of ARI cases showed prevalence of Rhinovirus A (RVA), Rhinovirus B (RVB), Rhinovirus C (RVC) and Echovirus, while predominance of RVC followed by RVA was observed for the SARI cases. Phylogenetic analysis of all the strains showed clustering of RVC strains in different clusters. Divergence was also noted in RVA and RVB strains studied. Circulation of a rare Echovirus-29 strain was noted in the ARI cases. The study highlighted significant divergence in the Rhinovirus strains studied. It warrants the need for surveillance of NPEVs, whole-genome sequencing of the circulating strains for better understanding of biodiversity among the NPEVs and the potential health burden.

A Literature Review on the Antiviral Mechanism of Luteolin

Background: Viral infections pose some of the most serious human health concerns worldwide. The infections caused by several viruses, including coronavirus, hepatitis virus, and human immunodeficiency virus, are difficult to treat. Method(s): This review details the findings of a literature search performed on the antiviral properties of luteolin. The keywords engaged in the search are "virus" along with "luteolin." Results: Luteolin possesses antiviral properties, which is the basis for the current review. It is an important natural flavonoid with numerous important biological properties, including anti-inflammatory, immune regulatory, and antitumor effects, and is found in vegetables, fruits, and several medicinal plants. Recent studies have revealed that many traditional Chinese medicines that contain luteolin inhibit the replication of coronaviruses. Conclusion(s): Luteolin effectively inhibits the replication of coronavirus, influenza virus, enterovirus, rotavirus, herpes virus, and respiratory syncytial virus, among others. In particular, it prevents viral infection by improving the body's nonspecific immunity and antioxidation capacity and inhibiting many pathways related to virus infection and replication, such as MAPK, PI3K-AKT, TLR4/8, NF-kappaB, Nrf-2/hemeoxygenase-1, and others. It also regulates the expression of some receptors and factors, including hepatocyte nuclear factor 4alpha, p53, NLRP3, TNF-alpha, and interleukins, thereby interfering with the replication of viruses in cells. Luteolin also promotes the repair of damaged cells induced by proinflammatory factors by regulating the expression of inflammatory molecules. The overall effect of these processes is the reduction in viral replication and, consequently, the viral load. This review summarizes the antiviral effect of luteolin and the mechanism underlying this property.Copyright © The Author(s) 2023.

Accelerating antiviral discovery by combining machine learning with structural biology

COVID Moonshot is an international open science consortium aiming to discover oral antiviral against SARS-CoV-2, targeting the main protease. Launched in Feb 2020, Moonshot went from fragment hits to development candidates which are now under preclinical evaluation. In my talk, I will discuss Moonshot's journey, specifically how the combination of machine learning and structural biology has accelerated our design-make-test cycle. I will also discuss our vision for pandemic preparedness, and early results from AI-driven Structure Enabled Antiviral Platform (ASAP). ASAP is a NIH-funded antiviral drug discovery center which builds on COVID Moonshot's approach to target flaviviruses, enteroviruses, and coronaviruses. We are applying machine learning to generate potent chemical matter from crystallographic fragment hits, and leveraging high throughput library synthesis guided by models to rapidly expand on promising hits. Aiming to achieve pandemic preparedness, I will also discuss our approaches to preempting resistance, and how these strategic considerations impact drug-hunting.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Bacterial and viral upper and lower airways infection in people with cystic fibrosis in stable condition

Background: Bacterial and viral airway infections are adverse factors for prognosis in people with cystic fibrosis (CF). The role of viral infections is unclear. Proper microbiological follow-up is essential, and the correlation between upper (UAW) and lower airway (LAW) microbiology may be important for lung disease management. We aim to evaluate airway microbiology in patients in stable clinical condition. Method(s): Between September 2021 and March 2022 in the Florence CF center, 144 nasal lavage-throat swab paired samples were collected from 72 clinically stable people with CF not chronically colonized by Pseudomonas aeruginosa. The study enrolled 59 children (median age 9, range 2-16) and 13 adults (median age 28, range 18-59). LAW specimens (72)were sampled as throat swab and UAWspecimens (72)were randomly collected by nasal lavage with two methods-Mainz (44) or Ryno-set (28). We performed conventional microbiological analyses on all samples. To screen for respiratory viruses, multiplex polymerase chain reaction (BioFire FilmArray RP 2.1 Plus) was performed. Respiratory symptoms and forced expiratory volume in 1 second (FEV1) valueswere evaluated for all patients. Result(s): Twenty-one (29%) patients tested positive for at least one virus in UAW and LAW specimens. The most frequently identified viruses were human rhinovirus or enterovirus (22%) and respiratory syncytial virus (6%). Two (3%) patients tested positive for SARS-CoV-2. Concordance between sampling methods for viral detection in UAW and LAW specimens was observed in 59 paired samples (82%), including 40 patients with no viral infections and 19 virus positive for both samples. Discordance was described in 13 subjects;10 of 13 did not show viral infection in nasal lavage. Twenty-one percent of positive nasal lavage was performed using Ryno-set and 36% using the Mainz approach. The prevalent bacteriumwas Staphylococcu aureus in UAW (53%) and LAW (69%) cultures, followed by Enterobacteriaceae (UAW 8%, LAW 6%), methicillin-resistant S. aureus (UAW 7%, LAW 6%), P. aeruginosa (UAW 4%, LAW 6%), and other clinically relevant gram-negative bacteria such as Achromobacter xylosoxidans, Stenotrophomonas maltophilia, and Ochrobactrum anthropi (UAW 7%, LAW 13%). Nasal lavage performed with Ryno-set tested positive in 72% of patients, and 64% of Mainz lavage were positive. Mainz nasal lavage showed different S. aureus and P. aeruginosa isolations (48% and 5%, respectively) than the samples collected with Ryno-set technique (61% and 4%, respectively). Concordance between sampling methods for bacterial detection in UAW and LAW was the same with the two methods (53%). Bacterial and viral infections were found in UAWand LAWof stable people with CF, but no clinical correlation was observed. Conclusion(s): The two methods of UAW lavage had slight differences in performance. Virus infection appeared to be less prevalent than bacterial infection in UAWand LAW.We did not find correlations between presence of viruses and respiratory symptoms, but further investigation is needed for a better understanding of the clinical role of viral infection in people with CF.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

PRIOR SARS-CoV-2 INFECTION PROTECTS AGAINST SYMPTOMATIC COMMON COLD CORONAVIRUSES

Background: Current COVID-19 vaccines provide substantial protection against severe COVID-19, but they do not completely eliminate subsequent SARS-CoV-2 infections. We examined incidence of and immune differences against related but different common cold coronaviruses (ccCoV) as a proxy for response against a future emerging CoV among those with SARS-CoV-2 infection, COVID-19 vaccination, or neither exposure. Method(s): We assessed incidence of ccCoV (229E, HKU1, NL63, OC43) and rhinovirus/enterovirus infections among those with documented prior SARSCoV- 2 infection (n=493), prior COVID-19 vaccine, but no SARS-CoV-2 infection (n=1,568), or no prior SARS-CoV-2 infection or vaccination (n=2,874). We conducted a retrospective review of all individuals at Boston Medical Center that underwent a comprehensive respiratory panel polymerase chain reaction (CRP-PCR) test from November 30, 2020 to October 8, 2021 to estimate infection incidence. A subset within each group was assessed for coronavirus specific humoral and cellular immune responses, via pseudovirus neutralization and peptide stimulation T cell assays. Comparisons among the three groups were done using Chi-square and multi-variate Cox-proportional hazards models. Result(s): Incidence of symptomatic ccCoV was lower in those individuals with documented prior SARS-CoV-2 infection (1.0%) compared to those with COVID-19 vaccination (2.9%) or no prior SARS-CoV-2 exposure (1.8%, p = 0.01). Rhinovirus/enterovirus incidence was similar in all three groups (range 6.2 - 8.7%). Individuals with prior SARS-CoV-2 infection and those with previous COVID-19 vaccination had similar plasma neutralization against SARS-CoV-2, OC43, and 229E spike bearing pseudoviruses. SARS-CoV-2 (p = 0.01) and OC43 nucleocapsid (p = 0.02), but not spike specific peptides, yielded higher T cell responses in individuals with a prior SARS-CoV-2 infection as compared to those with COVID-19 vaccination or no prior SARS-CoV-2 exposure. Conclusion(s): Prior SARS-CoV-2 infection, but not COVID-19 vaccination, protects against subsequent related but different ccCoV symptomatic infection. This protection against symptomatic ccCoVs may be mediated by cellular responses to non-spike proteins. Future pan-coronavirus vaccines could be improved by including both spike and non-spike antigens.

Abstracts of the papers presented in the International Conference of Indian Virological Society, VIROCON 2022 on "Emerging and Re-emerging Viral Infections Impacting Humans, Animals, Plants, Fish and Environment"

The proceedings contain 206 papers. The topics discussed include: influenza: experiences from Kashmir;outbreaks of different viral etiologies amidst COVID-19 pandemic;development of a colorimetric isothermal (LAMP) assay for rapid detection of monkeypox virus;circulation of genetically diverse non-polio enteroviruses in respiratory samples during COVID-19 pandemic period (2021-22);evolutionary analysis of all eleven genes of species C rotaviruses circulating in humans and domestic animals;molecular characterization of dengue viruses circulating in Pune district, Maharashtra from 2009-2022;isolation and genomic characterization of cell fusing agent virus from aedes aegypti mosquitoes from Assam, India;structure-based identification and evaluation of antiviral activity of potent small molecule inhibitors targeting alphavirus RNA-dependent RNA polymerase;integration of HBV receptor NTCP into hepatoma cell using grnome editing;and hepatitis B virus genome targeting using CRISPR/Cas9based gene editing tool.

Recent Discovery of Peptidomimetics for the Treatment of Coronavirus (COVID-19), Human coronavirus, and Enteroviruses.

This patent describes the synthesis of compounds, methods, and compositions for preventing, treating, and/or curing Covid-19, human coronavirus, and enterovirus infections. Some peptidomimetic compounds are very potent and could be a game changer in new treatment therapy for COVID-19.

[A cross-sectional study of enterovirus nucleic acid test with throat swabs for term late neonates during coronavirus disease 2019]. / æ–°åž‹å† çŠ¶ç— æ¯’æ„ŸæŸ“æœŸé—´è¶³æœˆçš„æ™šæœŸæ–°ç”Ÿå„¿å’½æ‹­å­è‚ é“ç— æ¯’æ ¸é ¸æ£€æµ‹æ¨ªæ–­é¢ç ”ç©¶.

OBJECTIVES: To investigate the positive rate of enterovirus (EV) nucleic acid in throat swabs of term late neonates hospitalized during the coronavirus disease 2019 (COVID-19) epidemic and the clinical characteristics of the neonates. METHODS: A single-center cross-sectional study was performed on 611 term late infants who were hospitalized in the neonatal center from October 2020 to September 2021. Throat swabs were collected on admission for coxsackie A16 virus/EV71/EV universal nucleic acid testing. According to the results of EV nucleic acid test, the infants were divided into a positive EV nucleic acid group (8 infants) and a negative EV nucleic acid group (603 infants). Clinical features were compared between the two groups. RESULTS: Among the 611 neonates, 8 tested positive for EV nucleic acid, with a positive rate of 13.1‰, among whom 7 were admitted from May to October. There was a significant difference in the proportion of infants contacting family members with respiratory infection symptoms before disease onset between the positive and negative EV nucleic acid groups (75.0% vs 10.9%, P<0.001). There were no significant differences between the two groups in demographic data, clinical symptoms, and laboratory test results (P>0.05). CONCLUSIONS: There is a certain proportion of term late infants testing positive for EV nucleic acid in throat swabs during the COVID-19 epidemic, but the proportion is low. The clinical manifestations and laboratory test results of these infants are non-specific. Transmission among family members might be an important cause of neonatal EV infection.

Scientific Evaluation of the Remedies Used in Turkish Folk Medicine to Treat Possible Viral Infections

Background: Plants, with their rich phytochemical treasury, are one of the main sources of drug development. However, a randomized search on plant sources for the discovery of phyto-chemicals with specified pharmacological activity is expensive and tedious. Therefore, it is logical to constrain the sources to increase success. In the recent four decades, the importance of traditional information has been recognized by the scientific community. Consequently, interest in field sur-veys for the documentation of traditional worldwide medicines has significantly increased. Method(s): Infectious diseases induced by pathogenic bacteria, fungi, or viruses have been one of the most common health problems for the public, for which traditional remedies have been practiced. Since laypeople could not distinguish the microbial origin of the infection, the remedies used for treatment could not be delineated. The aim of this study was first to search the plants used in Turkish folk medicine for such infectious diseases. The second step was to find scientific evidence in the online databases for the frequently quoted plants whether they may have potential activity against virus replication. Result(s): A reference survey on the most frequently quoted plants revealed that 16 out of 17 were shown to possess virucide or inhibitory effects on the replication of various viruses. Conclusion(s): Since each virus type may have a different viral replication pattern, further detailed in-vestigations should be carried out to reveal their exact antiviral potentials.Copyright © 2023 Bentham Science Publishers.

Traditional herbal medicine in the treatment of patients infected with new coronavirus

The purposes of this review was in the direction of epidemiology, causative agents, symptoms, vaccine research probabilities and COVID-19 infection novel Corona viruses that was investigated in China. The COVID-19 has surrounded viruses along with a practical sensation one stranded RNA genome and a nucleocapsid of helical uniformity. The COVID-19 is an enormous family of viruses that are prevalent in a public and large number of species of animals including hens, camels, bats, cat, and cattle. Human corona viruses can cause gentle disorder identical to a common cough, cold, while others reason more acute disease MERS (Middle East Respiratory Syndrome) and SARS (Severe Acute Respiratory Syndrome). Thus spreading the COVID-19 should be closely investigated to recognize the growth of particularly virulent strains in society at an early stage and to simplify the evolution of enough preventive and therapeutic measurements.Copyright © 2021, Health Biotechnology and Biopharma. All rights reserved.

Symptomatic Myocarditis After Pfizer Covid-19 Vaccination

Widely considered safe, effective, and essential for pathogenic immunity, vaccines have proven to be one of the most important discoveries to date in medicine. Adverse reactions to vaccines are typically trivial but there have been extremely rare reports of vaccine induced myocarditis, particularly with the Tdap vaccine. This is thought to be due to a hypersensitivity reaction. In efforts to combat the SARS-CoV-2, prompt response from Pfizer-BioNTech and Moderna lead to vaccine development with a novel method, synthesized from modified messenger RNA. Despite minimal side effects on initial trials, reports of vaccine induced myocarditis have resulted. A majority of these cases occurred following subsequent doses for those previously inoculated. A descriptive study published in JAMA in January 2022 reviewed the Vaccine Adverse Event Reporting System (VAERS) in collaboration with the CDC described only 1626 cases of myocarditis, of which the majority occurred within days of the second dose. This review was limited by reviewing a passive reporting syndrome with variable quality data and without follow up data post diagnosis of myocarditis. Here we present a case of myocarditis occurring less than 24 hours after the second dose of Pfizer-BioNTech vaccine with 3 month follow up. A 23 year old man received his second dose of the COVID-19 vaccine in the morning. Within a few hours he experienced chest pain, chills, weakness, and fatigue. These dissipated by 7pm. He is a member of the National Guard and during drills the next day experienced stabbing substernal chest pain for which he sought evaluation. The pain radiated into his left jaw, worse with deep inspiration and worse in the left lateral decubitus position. He is a 1 PPD smoker with no personal or family history or cardiac disease. A friction rub was heard on physical exam. His troponin I peaked at 2.6ng/mL. His EKG showed normal sinus rhythm, a TTE showed a normal EF with no pericardial effusion. He was given aspirin 81 mg and started on a heparin drip for possible NSTEMI. The next day his pain decreased and a cardiac MRI demonstrated no inflammation. His serum coxsackie and parvovirus titers were negative. He was instructed to continue the aspirin, limit exercise for 8 weeks, and stop smoking. Upon follow up 3 months later the patient denied any recurrent chest pain and was advised to continue the aspirin. But the original bout of myocarditis limited his participation in the National Guard. Our case illustrates that exposure to an immunological trigger, the COVID-19 vaccine, leading to myocarditis was extremely short compared to typical cases of viral induced or vaccine hypersensitivity reaction. A proposed mechanism is molecular mimicry between the spike protein and myocardial contraction proteins. It also demonstrates that the vaccine can cause morbidity in patients, especially younger males. It also exemplifies that this may be a short lived phenomenon, long term follow up is still needed. With the rate of vaccination increasing, there needs to be a low threshold to consider myocarditis in young adults who have new chest pain after receiving an mRNA based vaccine.Copyright © 2022