The opportunity for massage therapy development for relieving long COVID symptoms: a literature review

The COVID-19 pandemic situation affected population health and lifestyle not only for a short period but also long period. Long COVID symptoms is a long-term illness after COVID condition. Long COVID symptoms greatly affected to quality of life of patients. Massage is a unique treatment form of alternative medicine that can promote health in various dimensions. From the previous studies, massage has affected to Long COVID mechanism via anti-inflammatory process, immune system enhancing process, and hormone level balancing that related to Long COVID symptoms as well as being able to reduce the symptoms of the long COVID symptoms. The study about the efficacy and safety of massage against Long COVID symptoms is the essential approach to increase the value of massage and develop health services in the future.

Progress in understanding the health promoting effect of egg yolk immunoglobulin

As an important immuneoactive component in eggs, yolk immunoglobulin (IgY) shows great competitiveness in research and production due to its good stability, high safety, low cost, easy availability, strong immune activity, and no drug resistance. This article highlights the significant advantages of IgY as a good antibiotic substitute in the prevention and treatment of viral and bacterial diseases. Also, IgY has great potential in the regulation of nutrient metabolism balance, intestinal microflora and immune homeostasis by affecting key rate-limiting enzymes, and relevant receptors and inflammatory factors specifically. Proper diet and targeted delivery of foodborne IgY may be a new perspective on inflammation regulation, disease control, nutritional balance or homeostasis, and oral microencapsulated IgY is expected to be a new approach against increasing public health emergencies (such as COVID-19 pandemic).

PLACEBO-CONTROLLED EFFICACY AND SAFETY OF UPADACITINIB THROUGH ONE YEAR IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

BackgroundUpadacitinib (UPA), a Janus kinase inhibitor, was effective and well tolerated in patients (pts) with non-radiographic axial spondyloarthritis (nr-axSpA) through 14 weeks (wks) of treatment.[1]ObjectivesThis analysis assessed the efficacy and safety of UPA vs placebo (PBO) through 1 year.MethodsThe SELECT-AXIS 2 nr-axSpA study included a 52-wk randomized, double-blind, PBO-controlled period. Enrolled adults had a clinical diagnosis of active nr-axSpA fulfilling the 2009 ASAS classification criteria, objective signs of inflammation based on MRI sacroiliitis and/or elevated C-reactive protein, and an inadequate response to NSAIDs. One-third of pts had an inadequate response to biologic DMARDs. Pts were randomized 1:1 to UPA 15 mg once daily or PBO. Concomitant medications, including NSAIDs, had to be kept stable through wk 52. The study protocol outlined that pts who did not achieve ASAS20 at any two consecutive study visits between wks 24 to 52 should receive rescue therapy with NSAIDs, corticosteroids, conventional synthetic/biologic DMARDs, or analgesics. Cochran-Mantel-Haenszel (CMH) test with non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle missing data and intercurrent events for binary efficacy endpoints. Mixed-effect model repeated measures (MMRM) was used to assess continuous efficacy endpoints. NRI was used for binary endpoints after rescue and as observed analysis excluding data after rescue for continuous endpoints. Treatment-emergent adverse events (TEAEs) are reported through wk 52.ResultsOf the 314 pts randomized, 259 (82%;UPA, n=130;PBO, n=129) completed wk 52 on study drug. More pts achieved an ASAS40 response with UPA vs PBO from wks 14 to 52 with a 20% treatment difference at wk 52 (63% vs 43%;nominal P <.001;Figure 1). The proportion of pts achieving ASDAS inactive disease with UPA remained higher than PBO at wk 52 (33% vs 11%;nominal P <.0001;Figure 1). Consistent improvements and maintenance of efficacy were also seen across other disease activity measures. Between wks 24 and 52, fewer pts on UPA (9%) than PBO (17%) received rescue therapy. A similar proportion of pts in each treatment group had a TEAE (Table 1). Infections were the most common TEAE;the rates of serious infections and herpes zoster were higher with UPA vs PBO, although no new serious infections were reported from wks 14 to 52. COVID-19 events were balanced between treatment groups. No opportunistic infections, malignancy excluding non-melanoma skin cancer, adjudicated major adverse cardiovascular events, inflammatory bowel disease, or deaths were reported. Two pts (1.3%) on PBO had adjudicated venous thromboembolic events.ConclusionUPA showed consistent improvement and maintenance of efficacy vs PBO through 1 year across multiple disease activity measures. No new safety risks were identified with longer-term UPA exposure. These results continue to support the benefit of UPA in pts with active nr-axSpA.Reference[1]Deodhar A, et al. Lancet. 2022;400(10349):369–379.Table 1.Safety through week 52Event, n (%)PBO (n = 157)UPA 15 mg QD (n = 156)Any AE103 (66%)107 (69%)Serious AE6 (3.8%)6 (3.8%)AE leading to D/C4 (2.5%)6 (3.8%)COVID-19-related AE22 (14%)24 (15%)Deaths00Infection60 (38%)68 (44%) Serious infection1 (0.6%)2 (1.3%) Herpes zoster1 (0.6%)5 (3.2%)Malignancy other than NMSC00NMSC1 (0.6%)0Hepatic disorder7 (4.5%)6 (3.8%)Neutropenia1 (0.6%)8 (5.1%)MACE (adjudicated)00VTE (adjudicated)2 (1.3%)a0Uveitisb3 (1.9%)2 (1.3%)Inflammatory bowel disease00aBoth patients had non-serious events of deep vein thrombosis in the lower limb with risk factors including obesity and prior deep vein thrombosis in one patient and concomitant COVID-19 infection in the other patient.bThree events of uveitis occurred in each treatment group (among n = 3 patients in the PBO group and n = 2 patients in the UPA group);two events in the PBO group and one in the UPA group occurred in patients with a history of uveitis.AcknowledgementsAbbVie funded this study and participated in the study design, res arch, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsFilip van den Bosch Speakers bureau: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, GSK, Lilly, Novartis, Pfizer, and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Consultant of: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer., Walter P Maksymowych Consultant of: AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology BV, Tae-Hwan Kim Speakers bureau: AbbVie, Celltrion, Kirin, Lilly, and Novartis., Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB., Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie and Novartis, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Peter Wung Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie.

COVID-19 OUTCOME IN AN ITALIAN RHEUMATOID ARTHRITIS COHORT

BackgroundIt is known that rheumatologic patients often present a course of COVID-19 similar to that of the general population. Some factors are linked to a worse COVID-19 outcome, such as moderate glucocorticoid (GC) dose, high body mass index (BMI), and comorbidities.ObjectivesTo describe the outcome of COVID-19 in patients with rheumatoid arthritis (RA) in terms of symptoms, therapy and need for hospitalization compared to a control group. Also, to evaluate the variation in disease activity before and after COVID-19.MethodsIn this monocentric prospective study, we recruited consecutive adult patients with RA classified according to ACR-EULAR 2010 criteria who received a diagnosis of COVID-19 through molecular or rapid antigen swab tests between September 2020 and December 2022. Demographic and clinical data, including age, BMI, smoking habit, comorbidities, treatment at the diagnosis of COVID-19, duration of COVID-19, symptoms related to the infection and therapy required, together with the vaccination status were collected through a self-administered questionnaire. We compared DAS28-CRP before the infection and at the first visit after the resolution. As controls (Cs), individuals with COVID-19 but with no referred diagnosis of rheumatic/autoimmune disease were recruited.ResultsWe enrolled 111 patients affected by RA (males 15%, median age 56 years, IQR 25) and 89 Cs (males 44%, median age 47 years, IQR 43), whose demographic and clinical characteristics are reported in Table 1. The median RA disease duration was 108 months (IQR 201). At the COVID-19 diagnosis, 62 patients (56%) were assuming csDMARDs, 67 (60%) bDMARDs, and 18 (16%) GC with a median prednisone equivalent dose of 4 mg/day (IQR 1). DAS28-CRP was available for 62 patients, with a median value of 1.67 (IQR 2.71);42 patients (60%) were in remission (Figure 1). Before developing COVID-19, only 35 (32%) RA patients and 42 (47%) Cs had completed the vaccinal cycle, which was performed by mRNA vaccine in all the patients and 87% of Cs. The median COVID-19 duration was 18 days (IQR 18) for RA patients and 14 days (IQR 13.5) for Cs (p>0.7). Cs reported a significantly higher frequency of constitutional symptoms (headache and asthenia) compared to RA patients (p<0.00001). When hospitalization was required, RA patients received heparin more frequently than Cs (p<0.039). Once COVID-19 was resolved, RA patients were evaluated after a median of 2 months (IQR 2). DAS28-CRP was available for 68 patients, with a median value of 1.61 (IQR 1.77);42 patients (68%) were in remission (Figure 1).No differences in terms of COVID-19 duration, clinical manifestations, and therapy emerged comparing RA patients in remission (40;58%) with patients with the active disease before COVID-19 (29;42%). Also, in vaccinated subjects, the outcome of COVID-19 was similar in RA patients and Cs, irrespective of RA activity.ConclusionCOVID-19's impact on patients with RA was not significantly different from the general population, even for patients with active RA. Patients did not suffer from reactivation of RA because of COVID-19. In our opinion, these positive results could be ascribed to the massive vaccination campaign.References[1]Conway R et al, Ir J Med Sci. 2023[2]Andersen KM et al, Lancet Rheumatol. 2022Table 1.Clinical characteristics, COVID-19 symptoms, and therapy of the two groups. Values in brackets are expressed as percentages unless specified. Musculoskeletal diseases: osteoarthritis and osteoporosis.Rheumatoid arthritis N=111Controls N=89P value*ACTIVE SMOKERS13 (12)20 (22)BMI (IQR)24 (7)23(6)COMORBIDITIES64 (58)44 (49)Cardiovascular26 (23)18 (20)Endocrine24 (22)14 (16)Musculoskeletal11 (10)6 (7)Neoplastic12 (11)3 (3)CLINICAL MANIFESTATIONS96 (86)74 (83)Fever50 (45)47 (53)Constitutional symptoms52 (47)75 (84)p <0.00001Respiratory symptoms100 (90)86 (97)Gastrointestinal symptoms12 (11)13 (15)THERAPY88 (79)74 (67)NSAIDs41 (37)31 (35)Glucocorticoids24 (22)21 (30)Antibiotics33 (30)27 (24)Oxygen6 (5)5 (6)Heparin8 (7)0 (0)p <0.039HOSPITALIZATION10 (9)6 (9)*Where not indi ated, p value >0.5Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Non-steroidal anti-inflammatory drugs amid COVID-19 pandemic: An ally or an enemy?

As the current global pandemic of the novel coronavirus diseases 2019 (COVID-19) continues to rage, the scientific and medical worlds are working to establish an effective therapy against the illness. Recently questions regarding non-steroidal anti-inflammatory drugs (NSAIDs) as a potential therapeutic option for COVID-19 have surfaced. While some studies hint towards the possible benefit of NSAIDs against SARS-CoV-2 infection, the current body of evidence also sheds light on the potential risk of using NSAIDs in COVID-19 patients. Thus, the available literature does not provide conclusive evidence for or against the use of NSAIDs for treating COVID-19 patients. Given the limited data available, we suggest cautionary approaches for the public to avoid possible harm until further evidence emerges. NSAIDs should not be used as the first-line agents for COVID-19 unlessunder medical supervision. Moreover, patients with chronic inflammatory conditions should continue the NSAIDs as per their regular prescriptions.

Antiviral Effects of Fructans

Infectious diseases of viral origin have never received so much interest globally since the emergence of the COVID-19 pandemic disease. In contrast to bacterial infections, antibiotic treatments do not have any effect on viral infections, requiring alternative solutions to reduce the impact of viral spread on animal populations. More important than curing, preventing viral replication before disease development is probably the best strategy to minimalize the negative effects of viruses on a global scale. Fructans, known to stimulate the immune system (by either interacting directly or indirectly with the immune system), may be interesting candidates as part of this broader prevention strategy. This chapter discusses the potential antiviral properties of fructans in relation to their well-described immunomodulating, antioxidant and prebiotic attributes, as well as a possible role as protein binders which may disturb the proper function of viral proteins, and thus reduce the infection ability of certain viral strains. © 2023 Elsevier Inc. All rights reserved.

FREQUENCY OF VACCINE-RELATED ADVERSE EVENTS IN PATIENTS WITH RHEUMATIC DISEASE

BackgroundPatients with rheumatic diseases are at greater risk of developing serious infections due to dysregulation of the immune system and the use of immunosuppressants1. Therefore, preventing infection is crucial, with vaccination being the most important primary prevention intervention, leading to a lower rate of hospital admissions due to infections. However, vaccine hesitancy among persons with rheumatic diseases is widespread due to concerns regarding the safety of vaccines2.ObjectivesDescribe the frequency of adverse events associated with vaccination in patients with rheumatic diseases.MethodsObservational, descriptive, cross-sectional and retrospective study was carried out in patients with rheumatic diseases from the Rheumatology Department of the Hospital Regional 1° de Octubre ISSSTE, from February to May 2022;it included patients over 18 years of age with an established diagnosis of rheumatic disease who had received a vaccine;the researcher applied the vaccine-associated adverse events survey to those patients who agreed to participate by signing the informed consent. The sample size was of 95 patients. Descriptive statistics and summary measures were employed for analysis. We used the chi-square test or Fisher's exact test (when <5) for the comparative analysis of the frequencies of nominal qualitative variables. P<0.05 was considered significant.ResultsThe survey was applied to 115 patients. 85.2% were women;mean age 57.9 years;61.7% had rheumatoid arthritis (RA), followed by systemic lupus erythematosus (SLE) in 13.9%. 55.6% of the patients were treated with steroids, 52.2% received bDMARDs and 48.7% csDMARDs. Patients received various vaccines, of which the most frequent was the one for COVID-19, with 99.1% of included patients having received at least one dose, followed by influenza in 30.4%. 78% of the patients who received at least one dose of a vaccine against COVID-19 presented ≥1 adverse events. The disease in which the highest frequency of adverse events occurred was RA, without this difference being statistically significant (Table 1). The adverse events according to the type of COVID-19 vaccine were the following: Sputnik-V 80%, Pfizer 76.6% and AstraZeneca 76.1%, without statistically significant difference between vaccine types. The most frequently occurring adverse events were injection site pain (80.1%), headache (30.7%), and fatigue (30.7%);In addition, the main vaccine-associated musculoskeletal symptoms were joint pain, myalgia, and morning joint stiffness (Figure 1), which on most cases improved after a NSAID use. Joint pain was more frequent after the second dose of certain vaccine types.Table 1.Frequency of AE after COVID-19 vaccination in patients according to disease.AE (%)pRA560.790SLE140.326Spondyloarthritis40.068Osteoarthritis60.614ConclusionVaccination-associated AE occurred more frequently than reported in international studies;however, they were not more serious. Providing this information to patients is important to improve vaccine acceptance. In addition, the administration of NSAID after the application of the vaccine could be proposed to reduce the presence of side effects.References[1]Rotondo, Cinzia, et. al. Preliminary Data on Post Market Safety Profiles of COVID 19 Vaccines in Rheumatic Diseases: Assessments on Various Vaccines in Use, Different Rheumatic Disease Subtypes, and Immunosuppressive Therapies: A Two-Centers Study. Vaccines, 2021;9(7):730-440.[2]Furer, Victoria, et. al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 2020;79:39–52.AcknowledgementsTo the residents and staff at HR 1 Octubre for their help in compilating data.Disclosure of InterestsDaniel Xavier Xibille Friedmann Speakers bureau: GSK, Lilly, UCB, Paid instructor for: GSK, Lilly, UCB, Consultant of: GSK, Lilly, UCB, Vanessa Balderas Reyes: None declared, María Olvera: None declared, María Alcocer León: None declared, ALFREDO ALEXANDRI REYES SALINAS Paid instructor for: Abbvie, Janssen, ovartis, Minerva Rodríguez Falcón: None declared, Sandra Miriam Carrillo Vazquez Speakers bureau: Abbvie, Janssen, UCB, Paid instructor for: Abbvie, Janssen, UCB, Consultant of: Abbvie, Janssen, UCB.

PERICARDITIS AFTER COVID-19 VACCINATION: A CASE SERIES

BackgroundCOVID-19 vaccination campaigns successfully impacted on viral spreading and in particular on clinical course of the disease. However, secondary to a highly extended vaccination program, several local and systemic adverse events associated with mRNA COVID-19 vaccines have been reported. Pericarditis and myocarditis are examples of cardiac complications related to these vaccines. In particular, cases of pericarditis have occurred after mRNA COVID-19 vaccination (mostly secondary to vaccination with Moderna than Pfizer-BioNTech), especially in male adolescents and young adults, more often after the second dose. The incidence is approximately of 1-2 cases/100.000.ObjectivesAim of our study was to study the clinical profile of pericarditis occurred within 30 days after COVID-19 vaccines in our clinic.MethodsWe present a case series of patients who developed pericarditis after COVID-19 vaccination in the Department of Internal Medicine at Fatebenefratelli Hospital in Milan, followed from December 1, 2021 to April 15, 2022.ResultsTwenty-five individuals, of which 18 (72%) were women and 7 (28%) were males, had vaccine related pericarditis. Two patients were vaccinated with AstraZeneca, 2 with Moderna, the remaining with Pfizer-BioNTech. Median age was of 42 years. Of all patients, one subject was affected by constrictive effusive pericarditis, while another required treatment of pericarditis with Anakinra, switched to Canakinumab after severe skin reactions, because of failure of therapeutic response to first-line treatments.Two patients required hospital admission, in one case for a transient constrictive pericarditis. In the remaining cases clinical symptoms associated with post-vaccines pericarditis were mild and didn't require hospitalization.Chest pain was reported in 100% of cases, whereas pericardial effusion (in one case larger than 10 mm) was evidenced in 30% of subjects. Eighty percent of patients experienced tachycardia, whereas 90% reported asthenia.An increase in indices of inflammation (CRP) was documented in 50% of patients, usually mild.With regard to therapy, 90% of patients were treated with NSAIDs, 95% with colchicine, while 50% of cases required treatment with low-dose steroids.ConclusionCOVID-19 vaccination induces a particular form of pericarditis, often insidious and very troublesome, but with good prognosis. The clinical phenotype showed less typical chest pain, often normal indices of inflammation and little or no instrumental changes, but patients often experimented tachycardia and functional limitation. With regard to therapy, we used NSAIDs at adequate dosages to control the clinical condition, or low-dose colchicine. Low doses of cortisone (e.g., prednisone 5-10 mg a day) were useful in the presence of marked asthenia or systemic symptoms. Beta-blockers or ivabradine were used in the presence of tachycardia.References[1]Barda N, Children 2021, 8(7), 607;Safety of the BNT162b2 mRNA Covid-19 in a Nationwide setting. N Engl J med 2021;385:1078-1090.[2]Diaz GA, Myocarditis and Pericarditis After Vaccination for COVID-19. JAMA 2021;326 (12): 1210-1212.[3]Bibhuti D, Myocarditis and Pericarditis Following mRNA COVID-19 Vaccination: What Do We Know So Far?. Children 2021, 8(7), 607.[4]Giacomo Maria Viani, Patrizia Pedrotti, Romano Seregni, and Brucato Antonio;Effusive–constrictive pericarditis after the second dose of BNT162b2 vaccine (Comirnaty): a case report;European Heart Journal - Case Reports (2022) 6(2), 1–6.[5]Francesco Perna, Elena Verecchia, Gaetano Pinnacchio, Laura Gerardino, Antonio Brucato, and Raffaele Manna;Rapid resolution of severe pericardial effusion using anakinra in a patient with COVID-19 vaccine-related acute pericarditis relapse:a case report;European Heart Journal - Case Reports (2022) 6, 1–6.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

STUDY OF ADVERSE REACTIONS TO COVID-19 VACCINATION IN PATIENTS WITH RHEUMATIC DISEASES

BackgroundVaccination has been recommended in the midst of the COVID-19 pandemic, but some patients are not vaccinated due to concerns about adverse reactions.ObjectivesThe purpose of this study is to investigate the adverse reactions in rheumatic diseases and to guide the decision-making of patients and physicians.MethodsA questionnaire was sent to patients with rheumatic diseases, and patients who could be counted as of September 2021, when they consented to this study, were surveyed.ResultsThe subjects were 123 (male:female=10:113), 84 with rheumatoid arthritis and 39 with other immune diseases. The therapeutic agents used were PSL 31(25.2%), MTX 65(52.8%), NSAID/COX inhibitors 28(22.8%), bDMARDs 42(34.1%). adverse reactions after the first and second vaccination were fever 17(13.8%)/50(40.7%), joint symptoms 7(5.7%)/22(17.9%), local injection reactions (pain/irritation) 22(17.9%), local injection reactions (pain/erythema) 93(75.6)/98(79.7), systemic skin symptoms 0(0%)/2(1.6%), other symptoms (malaise, myalgia, etc.) 59(48.0%)/85(69.1%), and treatment intensification 5(4.1%)/12(9.7%). These responses differed in occurrence only for fever with and without PSL medication (22.5%: 47.3% (p=0.02)).The odds ratio for disease worsening after the first dose of vaccine and again after the second dose was 33.5 (p<0.01).ConclusionNo specific adverse reactions other than the commonly known ones were observed, but some patients experienced worsening of symptoms after vaccination, requiring intensified treatment. Based on the results of this study, we believe that adverse reactions to vaccination are acceptable. We plan to accumulate more cases and analyze them in the future.The exacerbation of disease after the first vaccination would predict the exacerbation after the second vaccination.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Repurposing Anti-inflammatory Agents in the Potential Treatment of SARS-COV-2 Infection

SARS-Cov-2 is the novel coronavirus with predominantly inflammatory pathogenesis. The inflammation can be initiated and finally aggravated through a number of interconnected inflammatory pathways such as NF-κB, JAK-STAT, MAPK TLRs, iNOS, COX, etc. In the current chapter, these signaling pathways which instigate inflammation in SARS-Cov-2 are discussed. Moreover, drugs inhibiting these pathways in other inflammatory conditions or diseases are either in clinical use as COVID-19 therapy, or have been proposed as potential future therapeutic interventions in this chapter. These repurposing strategies can halt the COVID-19 symptoms as well as disease progression. This was demonstrated by establishing a link between the regulatory actions of these molecules or drugs in the inflammatory pathway like cytokine release against the COVID-19-related inflammatory havoc. Hence, the chapter will provide profound insights in the inflammatory control pertaining to COVID-19 severity and complications. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.

Biomarker-Concordant Steroid Administration in Severe Coronavirus Disease-2019.

BACKGROUND: Although corticosteroids have become the standard of care for patients with coronavirus disease-2019 (COVID-19) on supplemental oxygen, there is growing evidence of differential treatment response. This study aimed to evaluate if there was an association between biomarker-concordant corticosteroid treatment and COVID-19 outcomes. METHODS: This registry-based cohort study included adult COVID-19 hospitalized patients between January 2020 and December 2021 from 109 institutions. Patients with available C-reactive protein (CRP) levels within 48 h of admission were evaluated. Those on steroids before admission, stayed in the hospital for <48 h, or were not on oxygen support were excluded. Corticosteroid treatment was biomarker-concordant if given with high baseline CRP ≥150 mg/L or withheld with low CRP (<150 mg/L) and vice-versa was considered discordant (low CRP with steroids, high CRP without steroids). Hospital mortality was the primary outcome. Sensitivity analyses were conducted using varying CRP level thresholds. The model interaction was tested to determine steroid effectiveness with increasing CRP levels. RESULTS: Corticosteroid treatment was biomarker-concordant in 1778 (49%) patients and discordant in 1835 (51%). The concordant group consisted of higher-risk patients than the discordant group. After adjusting for covariates, the odds of in-hospital mortality were significantly lower in the concordant group than the discordant (odds ratio [95% confidence interval (C.I.)] = 0.71 [0.51, 0.98]). Similarly, adjusted mortality difference was significant at the CRP thresholds of 100 and 200 mg/L (odds ratio [95% C.I.] = 0.70 [0.52, 0.95] and 0.57 [0.38, 0.85], respectively), and concordant steroid use was associated with lower need for invasive ventilation for 200 mg/L threshold (odds ratio [95% C.I.] = 0.52 [0.30, 0.91]). In contrast, no outcome benefit was observed at CRP threshold of 50. When the model interaction was tested, steroids were more effective at reducing mortality as CRP levels increased. CONCLUSION: Biomarker-concordant corticosteroid treatment was associated with lower odds of in-hospital mortality in severe COVID-19.

Low-dose radiation therapy suppresses viral pneumonia by enhancing broad-spectrum anti-inflammatory responses via transforming growth factor-ß production.

Low-dose radiation therapy (LDRT) can suppress intractable inflammation, such as that in rheumatoid arthritis, and is used for treating more than 10,000 rheumatoid arthritis patients annually in Europe. Several recent clinical trials have reported that LDRT can effectively reduce the severity of coronavirus disease (COVID-19) and other cases of viral pneumonia. However, the therapeutic mechanism of LDRT remains unelucidated. Therefore, in the current study, we aimed to investigate the molecular mechanism underlying immunological alterations in influenza pneumonia after LDRT. Mice were irradiated to the whole lung 1 day post-infection. The changes in levels of inflammatory mediators (cytokines and chemokines) and immune cell populations in the bronchoalveolar lavage (BALF), lungs, and serum were examined. LDRT-treated mice displayed markedly increased survival rates and reduced lung edema and airway and vascular inflammation in the lung; however, the viral titers in the lungs were unaffected. Levels of primary inflammatory cytokines were reduced after LDRT, and transforming growth factor-ß (TGF-ß) levels increased significantly on day 1 following LDRT. Levels of chemokines increased from day 3 following LDRT. Additionally, M2 macrophage polarization or recruitment was increased following LDRT. We found that LDRT-induced TGF-ß reduced the levels of cytokines and polarized M2 cells and blocked immune cell infiltration, including neutrophils, in BALF. LDRT-induced early TGF-ß production was shown to be a key regulator involved in broad-spectrum anti-inflammatory activity in virus-infected lungs. Therefore, LDRT or TGF-ß may be an alternative therapy for viral pneumonia.

Cannabinoids receptors in Covid-19: Perpetrators and victims.

COVID-19 is caused by SARS-CoV-2 and leads to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and extrapulmonary manifestations in severely affected cases. However, most of the affected cases are mild or asymptomatic. Cannabinoids (CBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD), which act on G-protein-coupled receptors called CB1 and CB2, have anti-inflammatory effects. Many published studies show that CBs are effective in various inflammatory disorders, viral infections, and attenuation of ALI and ARDS. Therefore, the aim of the present narrative review was to summarize the possible immunological role of CBs in COVID-19. The effects of CBs are controversial, although they have beneficial effects via CB2 receptors and adverse effects via CB1 receptors against ALI, ARDS, and hyperinflammation, which are hallmarks of COVID-19. The present narrative review has shown that CBs effectively manage ALI and ARDS by suppressing pro-inflammatory cytokines, which are common in COVID-19. Therefore, CBs may be used to manage COVID-19 because of their potent anti-inflammatory effects with suppression of pro-inflammatory cytokines and inhibition of inflammatory signaling pathways.

Effect of colchicine and aspirin given together in patients with moderate COVID-19.

Background: The objective of the study was to evaluate the effect of Colchicine 0.5 mg and Aspirin 75 mg oral tablets given together on management of moderate COVID-19. Methods: The study was carried out in 122 moderate COVID-19 patients between ages 40-80 years in hospital, instructed to take either 1 tablet of Colchicine 0.5 mg and Aspirin 75 mg each (treatment group), or 1 tablet of Aspirin 75 mg (Control group), twice a day along with standard of care. Result: At the end of treatment, reduction was seen in the treatment group in score of 8-point ordinal scale, troponin, D-Dimer, Hs-CRP from baseline. There was a fall of 51.1% among control arm and 53.4% among treatment arm in 8-point ordinal score. The reduction in mean D-Dimer was 37% in control group and 38.1% in treatment group. The mean reduction in CT severity score in control group was 3.65 and in treatment group was 4.82, and the difference between the two groups was statistically significant (P value = 0.018). Conclusion: It was evident from CT scan scores that the treatment group has shown significant improvement in the reduction of inflammation and other COVID-19 symptoms as compared to the control group. The fall in Ferritin, Hs-CRP and D-Dimer level after treatment were indicative of improvement in internal inflammatory response of body in COVID-19 disease. As increased troponin levels indicate some degree of heart damage, the fall in troponin levels indicated that test treatment improved heart health in COVID-19 patients.

Antimicrobial and anti-viral effects of selenium nanoparticles and selenoprotein based strategies: COVID-19 and beyond.

Deficiency of selenium (Se) has been described in a significant number of COVID-19 patients having a higher incidence of mortality, which makes it a pertinent issue to be addressed clinically for effective management of the COVID-19 pandemic. Se nanoparticles (SeNPs) provide a unique option for managing the havoc caused by the COVID-19 pandemic. SeNPs possess promising anti-inflammatory and anti-fibrotic effects by virtue of their nuclear factor kappa-light-chain-stimulator of activated B cells (NFκB), mitogen-activated protein kinase (MAPKs), and transforming growth factor-beta (TGF-ß) modulatory activity. In addition, SeNPs possess remarkable immunomodulatory effects, making them a suitable option for supplementation with a much lower risk of toxicity compared to their elemental counterpart. Further, SeNPs have been shown to curtail viral and microbial infections, thus, making it a novel means to halt viral growth. In addition, it can be administered in the form of aerosol spray, direct injection, or infused thin-film transdermal patches to reduce the spread of this highly contagious viral infection. Moreover, a considerable decrease in the expression of selenoprotein along with enhanced expression of IL-6 in COVID-19 suggests a potential association among selenoprotein expression and COVID-19. In this review, we highlight the unique antimicrobial and antiviral properties of SeNPs and the immunomodulatory potential of selenoproteins. We provide the rationale behind their potentially interesting properties and further exploration in the context of microbial and viral infections. Further, the importance of selenoproteins and their role in maintaining a successful immune response along with their association to Se status is summarized.

Ginkgo Biloba and Long COVID: In Vivo and In Vitro Models for the Evaluation of Nanotherapeutic Efficacy.

Coronavirus infections are neuroinvasive and can provoke injury to the central nervous system (CNS) and long-term illness consequences. They may be associated with inflammatory processes due to cellular oxidative stress and an imbalanced antioxidant system. The ability of phytochemicals with antioxidant and anti-inflammatory activities, such as Ginkgo biloba, to alleviate neurological complications and brain tissue damage has attracted strong ongoing interest in the neurotherapeutic management of long COVID. Ginkgo biloba leaf extract (EGb) contains several bioactive ingredients, e.g., bilobalide, quercetin, ginkgolides A-C, kaempferol, isorhamnetin, and luteolin. They have various pharmacological and medicinal effects, including memory and cognitive improvement. Ginkgo biloba, through its anti-apoptotic, antioxidant, and anti-inflammatory activities, impacts cognitive function and other illness conditions like those in long COVID. While preclinical research on the antioxidant therapies for neuroprotection has shown promising results, clinical translation remains slow due to several challenges (e.g., low drug bioavailability, limited half-life, instability, restricted delivery to target tissues, and poor antioxidant capacity). This review emphasizes the advantages of nanotherapies using nanoparticle drug delivery approaches to overcome these challenges. Various experimental techniques shed light on the molecular mechanisms underlying the oxidative stress response in the nervous system and help comprehend the pathophysiology of the neurological sequelae of SARS-CoV-2 infection. To develop novel therapeutic agents and drug delivery systems, several methods for mimicking oxidative stress conditions have been used (e.g., lipid peroxidation products, mitochondrial respiratory chain inhibitors, and models of ischemic brain damage). We hypothesize the beneficial effects of EGb in the neurotherapeutic management of long-term COVID-19 symptoms, evaluated using either in vitro cellular or in vivo animal models of oxidative stress.

Ganoderma Lucidum- A Potential Medicinal Mushroom Against MDR Isolates from The Secondary Infections of Covid-19

The severe acute respiratory syndrome produced by COVID-19 is a highly infectious and pathogenic viral infection. Many COVID-19 patients have secondary bacterial infections, which enhance disease and increase death, particularly when requiring invasive mechanical ventilation. One of the most important medicinal mushrooms, Ganoderma lucidum, has been used for food, feed, and medication since the dawn of humanity. The present investigation aims to discover the potential of the medicinal mushroom Ganoderma lucidum inhibited multidrug-resistant isolates from secondary infection of Covid-19 patients. Isolation and identification of urine samples from secondary infection of post-Covid-19 patients and evaluate the antibiotic sensitivity assay, as identification of bioactive compounds, anti-inflammatory and antioxidant activity from Ganoderma lucidum. Totally 6 clinical urine samples were collected from the age group 45 to 60;3 were male, and 3 were female. In total, nine bacteria and 10 fungi were isolated and identified. As antibiotic sensitivity assays of ceftriaxone, fluoroquinolones, azithromycin and amphotericin, nystatin and fluconazole were performed by the disc diffusion method against bacteria and fungi, the zone of inhibition was maximal in Klebsiella pneumoniae and Fusarium oxysporum. The aqueous and ethanolic extracts of Ganoderma lucidum were analyzed for the bioactive compounds, viz., steroids, flavonoids, alkaloids and phenolic compounds. The effect of the anti-inflammatory activity of the aqueous extract was excellent. The activity of the DPPH assay was maximum in aqueous and ethanolic extracts of all concentrations (100 to 500 ml). Antibiotic resistance could probably rise due to the frequent prescription of broad-spectrum empiric antimicrobials to COVID-19 patients. Hence, Ganoderma lucidum can be exploited to prevent secondary infection in COVID-19 patients.

NSAID-induced gastropathies associated with the treatment of SARS-CoV-2 infection: how to improve therapy safety? Focus on esomeprazole

Objective — Using mFSSG questionnaire, to define the presences of gastrointestinal disturbances, associated with the intake of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with moderate course of SARS-CoV-2 infection and to investigate ability of esomeprazole (Ezonexa, Farmak) to preventing the development of dyspeptic and reflux symptoms in these patients. Materials and methods. All patients with the established diagnosis of coronaviral disease (n = 85), hospitalized for treatment in the Centre of Therapy of Clinical Emergency Hospital in Lviv, who signed the informed consent, became the participants of an open controlled trial of Ezonexa efficacy at this pathology. The medication was administered in a dose of 20 mg/day in the morning, 30 mins before meals, used to prevent NSAID-induces gas-tropathies for 28 days. Simple blinded method was used to randomize patients into two groups. Subjects of the first group (n = 45) took esomeprazole, second group included controls (n = 40) without active prophylaxis of NSAID-induces gastropathies. The mean patients' age was 69.4 ± 2.6 years. The men age of male subjects was 66.4 ± 2.4 years, of females 72.3 ± 2.7 years. The follow up period lasted 4 weeks. All patients underwent standard examinations and survey to assess the dynamics of clinical manifestations of the disease against the background of the treatment of coronaviral infection. Besides, patients used mFSSG questionnaire to evaluate the intensity of dyspeptic and reflux symptoms. Examinations and survey were performed on the 1st, 10 — 14th and 28th days of follow up. The quality of life indices were assessed with the use of SF-36 questionnaire in all patients at baseline and 4 weeks after the study start. Results. No significant difference in mFSSG scores was reveled in the patients of both groups on the 1st day in terms of clinical manifestations of dyspepsia and reflux. At the second testing on 10 — 14th days, the assessment of dyspeptic and reflux symptoms didn't change in patients of the 1st group, whereas in 49.6 % subjects of the control group presence of the signs of NSAID-induced gastropathy with a pronounced dyspeptic and moderate reflux syndrome was registered. At 28th day, symptoms of both dyspepsia and reflux developed in 11.3 % of patients in the first group, and 78.6 % in the second group. No differences in age and gender ratio were reveled after comparative analysis. However, comorbid pathology, for which patients constantly took low doses of ace-tylsalicylic acid, was an additional aggravating risk factor of the development of NSAID-induced gastropathy. Analysis of the baseline indices of quality of life in both groups showed the significant (р < 0.05) decrease in the majority of scores, except for the scales of physical functions and pain. Positive dynamics against the background of esomeprazole treatment was defined in all indices of the quality of life, in the most extent in the scores of pain, vitality, social and role emotional functions. Conclusions. Esomeprazole in a dose of 20 mg demonstrated excellent protective effects in regard to the gastrointestinal mucosa in elderly patients from the high-risk group, who are particularly sensitive to the gastroduo-denal NSAID-induced toxicity even at short therapeutic course for coronaviral infection. Ezonexa may be considered as a drug of choice to treat NSAID-induced gastropathy;due to its prolonged and stable acid-inhibiting ability, Ezonexa promotes prompt symptoms' relief. Owing to the phenomenon of stereoselectivity, the drug has pharmacokinetic properties that ensure its high clinical efficacy in acid-dependent diseases. © 2021, Publishing Company VIT-A-POL. All rights reserved.

Curtailing virus-induced inflammation in respiratory infections: emerging strategies for therapeutic interventions.

Acute respiratory viral infections (ARVI) are the most common illnesses worldwide. In some instances, mild cases of ARVI progress to hyperinflammatory responses, which are damaging to pulmonary tissue and requiring intensive care. Here we summarize available information on preclinical and clinical effects of XC221GI (1-[2-(1-methyl imidazole-4-yl)-ethyl]perhydroazin-2,6-dione), an oral drug with a favorable safety profile that has been tested in animal models of influenza, respiratory syncytial virus, highly pathogenic coronavirus strains and other acute viral upper respiratory infections. XC221GI is capable of controlling IFN-gamma-driven inflammation as it is evident from the suppression of the production of soluble cytokines and chemokines, including IL-6, IL-8, CXCL10, CXCL9 and CXCL11 as well as a decrease in migration of neutrophils into the pulmonary tissue. An excellent safety profile of XC221GI, which is not metabolized by the liver, and its significant anti-inflammatory effects indicate utility of this compound in abating conversion of ambulatory cases of respiratory infections into the cases with aggravated presentation that require hospitalization. This drug is especially useful when rapid molecular assays determining viral species are impractical, or when direct antiviral drugs are not available. Moreover, XC221GI may be combined with direct antiviral drugs to enhance their therapeutic effects.