AUTOANTIBODIES RELATED TO RHEUMATIC DISEASES AFTER COVID-19 INFECTION

BackgroundSARS-CoV-2(Severe acute respiratory syndrome coronavirus 2) has been circulating worldwide for three years. It mainly causes upper respiratory tract infection, which can manifest as pulmonary infection and even respiratory distress syndrome in severe cases. Different autoantibodies can be detected in patients infected with COVID-19.ObjectivesTo explore autoantibodies related to rheumatic diseases after COVID-19 infection.MethodsNinety-eight inpatients were tested for antinuclear antibodies (ANA), antibodies to extractable nuclear antigens(ENA), anti-neutrophil cytoplasmic antibodies（ANCA), anticardiolipin antibodies,a-β2GPI (IgG/IgM). They were from a tertiary hospital in Guangzhou during the COVID-19 epidemic. Data were described statistically.ResultsNinety-eight hospitalized patients were tested for relevant antibodies. The average age was 50.64±19.54;67 (68.4%) were male, 64 (65.3%) were COVID-19 positive, 90 (90.9%) had rheumatic diseases, and 56 of them were COVID-19 positive patients with rheumatic diseases.There were 76 patients tested for antinuclear antibodies;29 （38.16%）were negative, 18 （23.68%）had a 1/80 titre, and 29（28.16%） had a titre greater than 1:80. The 31 covid patients were positive for ANA. In the high-titer group, 19 patients with rheumatic diseases were positive for COVID-19, and 12 patients had an exacerbation of the rheumatic diseases (6 of whom had previously had pulmonary fibrosis). Of 31 covid patients, only two were non-rheumatic patients, and both were elderly, aged 85 and 100, respectively.Fifty-six patients had ENA results, and 29 for positive antibodies, 8 for ds-DNA antibodies, 2 for anti-Sm antibodies, 6 for anti-nucleosome antibodies, 12 for anti-U1RNP antibodies, 2 for anti-Scl-70 antibodies, 12 for anti-SS-A antibodies, 3 for anti-mitochondrial M2 antibodies, 2 for anti-centromere antibodies, 1 for anti-Po antibodies, and one for anti-Jo-1 antibody. All 56 patients had rheumatic diseases, and no new patients were found.There were 62 patients with ANCA data. P-ANCA was positive in 12 cases(19.35%), and MPO-ANCA was positive in 2 cases. An 85-year-old non-rheumatic COVID-19 patient was P-ANCA positive. She had a history of hypertension, colon cancer, CKD3, coronary heart disease, and atrial flutter.In the anticardiolipin antibodies group, there were 62 patients;only 6 were positive, and 2 were rheumatic patients infected with COVID-19. Antiphospholipid antibodies were detected in 33 patients, and a-β2GPI was tested in one patient, an 82-year-old COVID-19 patient with gout, diabetes, and cerebral infarction in the past. We did not find a statistical difference in the above results.ConclusionWe have not found a correlation between SARS-CoV-2 and serum autoantibodies of rheumatic immune diseases. It needs large samples and an extended follow-up to research.AcknowledgementsThis work was supported by Scientific and Technological Planning Project of Guangzhou City [202102020150], Guangdong Provincial Basic and Applied Basic Research Fund Project [2021A1515111172], National Natural Science Foundation of China Youth Fund [82201998] and Third Affiliated Hospital of Sun Yat-Sen University Cultivating Special Fund Project for National Natural Science Foundation of China [2022GZRPYQN01].Disclosure of Interestsone declared.

EFFICACY AND SAFETY OF DAZODALIBEP (VIB4920/HZN4920) IN SUBJECTS WITH SJÖGREN'S SYNDROME: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PROOF OF CONCEPT STUDY

BackgroundSjögren's syndrome (SS) is a chronic, systemic autoimmune disease affecting exocrine glands, primarily the salivary and tear glands, with potentially severe manifestations in multiple organs. No approved disease-modifying therapies exist. Dazodalibep (DAZ) is a biologic antagonist of CD40L.ObjectivesThe objective of this study was to evaluate the efficacy and safety of DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity (NCT04129164).MethodsWe conducted a randomized, double-blind, placebo-controlled, crossover study to evaluate DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity, as defined by a EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ≥ 5. Eligible subjects were randomized 1:1 to receive intravenous DAZ 1500 mg or placebo (PBO) Q2W x 3 doses, then Q4W x 4 additional doses. Starting on Day 169, subjects initially randomized to DAZ received PBO Q4W x 5 doses and subjects randomized to PBO received DAZ Q4W x 5 doses and were then followed for 12 weeks. The primary endpoint was the change from Baseline in ESSDAI at Day 169. Safety assessments included the incidence of adverse (AEs), serious AEs (SAEs), and AEs of special interest (AESIs).ResultsThe 74 randomized subjects all received ≥1 dose of study medication (DAZ, N=36;PBO, N=38). The baseline demographics and disease characteristics were balanced between the two groups. The change from Baseline to Day 169 in ESSDAI score (LS mean ± SE), was -6.3 ± 0.6 in DAZ-treated subjects compared to -4.1 ± 0.6 in the PBO group, a difference of -2.2 (p = 0.0167). Compared to the PBO group, the DAZ group showed positive trends in the EULAR Sjögren's Syndrome Patient Reported Index score, and Functional Assessment of Chronic Illness Therapy-Fatigue score at Day 169. A post-hoc responder analysis of subjects achieving high levels (5 and 6 points) of improvement on ESSDAI favored DAZ (61.1% and 60.0%) over PBO (35.1% and 34.3%).The reported AEs were generally mild through Day 169 and similar in frequency between treatment groups. The most frequently reported AEs occurring in ≥5% of DAZ-treated subjects and >PBO were COVID-19, diarrhea, dizziness, ligament sprain, upper respiratory tract infection, contusion, device allergy, fatigue, hypertension, and oropharyngeal pain. Two SAEs were reported in a single DAZ-treated subject: this subject was a 59-year-old female who experienced a grade 3 SAE of COVID-19 infection and later died of unknown cause 46 days after last administration of DAZ (12 days after COVID-19 diagnosis). There was a single AESI of herpes zoster in a DAZ-treated subject.ConclusionDAZ is a potential new therapy for the treatment of systemic disease activity in patients with SS. SS subjects with moderate-to-high systemic disease receiving DAZ experienced a statistically significant reduction in disease activity relative to PBO as measured by the improvement in ESSDAI score. Except for a case of severe COVID-19 infection, DAZ therapy in SS subjects appeared to be well tolerated. Larger controlled trials of DAZ therapy for SS are warranted to further explore its safety profile and confirm its clinical efficacy.Table 1.Efficacy and Safety DataPBO N=38DAZ 1500 mg N=36EfficacyΔESSDAI, LS mean (SE) †-4.1 (0.6)-6.3 (0.6)*ΔESSPRI, LS mean (SE) †-1.12 (0.29)-1.80 (0.31)ΔFACIT-Fatigue, LS mean (SE) †5.8 (1.6)8.1 (1.6)AE Summary, n (%)≥1 AE23 (60.5)28 (77.8)≥1 related AE8 (21)10 (27.8)≥1 SAE01 (2.8)≥1 related SAE00≥1 AE leading to discontinuation00≥1 AESI01 (2.8)≥1 Death01 (2.8)Efficacy endpoints as of Day 169;† Analyzed using MMRM;Comparisons vs PBO;*p<0.05;AE summaries based on AEs that occurred through Day 169;AE, adverse event;AESI, adverse event of special interest;ESSDAI, EULAR Sjögren's Syndrome Disease Activity Index;ESSPRI, EULAR Sjögren's Syndrome Patient Reported Index;FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue;PBO, placebo;SAE, serious adverse eventFigure 1.AcknowledgementsFunded by Horizon herapeutics. Medical writing support provided by B Lujan, PhD, an employee of Horizon Therapeutics.Disclosure of InterestsE. William St. Clair Consultant of: Horizon Therapeutics, Bristol Myers Squibb, CSL Behring, Resolve Therapeutics, Sonoma Biotherapeutics. Royalties: UpToDate, Liangwei Wang Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Ilias Alevizos Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, William Rees Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Alan Baer Consultant of: Bristol Myers Squibb, Wan Fai Ng Consultant of: Novartis, GlaxoSmithKline, Abbvie, BMS, Sanofi, MedImmune, Janssen and UCB, Ghaith Noaiseh Consultant of: Novartis, Chiara Baldini Consultant of: GSK, and Sanofi.

EVALUATION OF TELENURSING FOLLOW-UP IN A COHORT OF STABLE/LOW DISEASE ACTIVITY PATIENTS WITH INFLAMMATORY ARTHRITIDES: A FEASIBILITY STUDY

BackgroundPeriodic follow-up (FU) is necessary for patients with Rheumatic Diseases (RDs). In the case of a stable clinical condition or low disease activity, FU can be carried out also by rheumatology nurses (RNs). Recent studies focusing on FUs led by RNs either in Rheumatology Clinics and with Telenursing (TN), showed promising results in terms of outcomes, cost reduction and users' satisfaction.ObjectivesTo evaluate the feasibility of a Telenursing FU in a Rheumatology Centre in Florence, Italy.MethodsIn this pilot study, patients with stable inflammatory arthritis or low disease activity were contacted, after their first visit, through TN (T0) and then assessed during the following in-person visit (V12) by RNs for treatment adherence, for pain, for mental and physical health, for workability, for perception of disease activity and satisfaction concerning the TN service.ResultsOut of 27 interviewed patients, 59.3% (n=16/27) was affected by Rheumatoid Arthritis (RA), 18.5% (n=5/27) by Spondyloarthritis (AS), 14.8% (n=4/27) by Psoriatic Arthritis (PsA) and 7.4% (n=2/27) by Juvenile Idiopathic Arthritis. The mean age was 57.5±13.1 (M± DS) years and the treatment adherence level was optimal. 11.1% (n=3/27) of patients was referred for medical consultation because of the urgent clinical situation assessed by the RNs according to the clinical multidisciplinary checklist. After specialist consultation, 1 patient was revalued in presence for a transient ischemic attack;1 patient was contacted by the rheumatologist following independent discontinuation of methotrexate therapy;1 patient was redirected to urgent dermatology consultation because of a suspected cutaneous drug reaction.During the TN period (12 months), 33.3% (n=9/27) of the patients contracted SARS-CoV-2 infection and 11.1% (n=3/27) contracted urinary or upper respiratory tract infections.RA patients showed a mean Rheumatoid Arthritis Impact of Disease-RAID score of 2.4 at T0 and 2.5 at V12 (Range 0-10);AS patients showed a mean Assessment of Spondyloarthritis International Society-ASAS score of 0.3 in both periods and PsA showed a mean Psoriatic Arthritis Impact of Disease-PSAID score of 0.7 and 0.8 at T0 and V12, respectively. Among RA, AS and PsA patients, as a pain score of 3 was recorded in both periods.In order to attend the in-person FU visit, 68.4% (n=13/19) of the patients took work leave. 37% (n=10/27) of them waited 40.9±18.6 minutes at V12 control. The average distance between the Rheumatology Centre and patients' home was 29.3±25.6 km. 15.4% (n=5/13) of the respondents did not own a car and 23.1% (n=3/13) was accompanied to visit by their caregiver.All the included patients expressed high satisfaction for the TN service, corresponding to 5 point Likert scale.ConclusionThe data show that TN FU is a valuable model for maintaining an adequate level of therapeutic adherence, reducing the travel time and working day loss, intercepting remotely clinical issues, as well as registering a high level of user acceptance and satisfaction. Further studies on larger samples are needed to confirm our findings.References[1] Bech B et al (2020) 2018 update of the EULAR recommendations for the role of the nurse in the management of chronic inflammatory arthritis. Annals of the Rheumatic Diseases;79:61-68. doi: 10.1136/annrheumdis-2019-215458.[2] Alcazar B, Ambrosio L. (2019) Tele-nursing in patients with chronic illness: a systematic review. An Sist Sanit Navar;42(2):187-197. doi: 10.23938/ASSN.0645.[3] Larsson I et al. (2013) Randomized controlled trial of a nurse-led rheumatology clinic for monitoring biological therapy. Journal of Advanced Nursing;70(1), 164–175., 2013 doi:10.1111/jan.12183Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BIMEKIZUMAB MAINTAINED IMPROVEMENTS IN EFFICACY ENDPOINTS AND HAD A CONSISTENT SAFETY PROFILE THROUGH 52 WEEKS IN PATIENTS WITH NON-RADIOGRAPHIC AND RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: RESULTS FROM TWO PARALLEL PHASE 3 STUDIES

BackgroundBimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, met all primary/secondary endpoints at Week (Wk) 16 in patients (pts) with active non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axSpA (r-axSpA;i.e., ankylosing spondylitis), in the parallel phase 3 BE MOBILE 1 and 2 studies, respectively.[1,2]ObjectivesTo assess efficacy and safety of BKZ in these pts up to Wk 52.MethodsBE MOBILE 1 (NCT03928704) and 2 (NCT03928743) both involved a 16-wk placebo (PBO)-controlled and 36-wk maintenance period.[1,2] Pts were randomised to subcutaneous BKZ 160 mg Q4W (BKZ) or to PBO then BKZ from Wk 16 (PBO/BKZ).Results220/254 (86.6%) randomised pts with nr-axSpA and 298/332 (89.8%) with r-axSpA completed Wk 52. Efficacy was sustained to Wk 52 in both studies (Table 1). ASAS40 responses in BKZ-randomised pts increased from Wk 16 (nr-axSpA: 47.7%;r-axSpA: 44.8%;non-responder imputation [NRI]) to Wk 52 (60.9%;58.4%;NRI) with high levels of efficacy across TNFi-naïve and TNFi-IR populations (Table 1). At Wk 52, ASDAS <2.1 was achieved by 61.6% and 57.1%, and ASDAS <1.3 by 25.2% and 23.4%, of BKZ-randomised pts with nr-axSpA and r-axSpA, respectively (Figure 1). Wk 16 reductions from baseline in objective signs of inflammation (MRI, hs-CRP), and improvements in function (BASFI) and ASQoL, were maintained through 52 wks. Efficacy at Wk 52 was similar in PBO/BKZ-treated and BKZ-randomised pts (Table 1).At Wk 52, 75.0% (183/244) of pts with nr-axSpA and 75.5% (249/330) of pts with r-axSpA had ≥1 treatment-emergent adverse event (TEAE) on BKZ;the most frequent (% pts) TEAEs by preferred term (MedDRA v19.0) were nasopharyngitis (nr-axSpa: 12.3%;r-axSpA 9.1%) and upper respiratory tract infection (9.4%;6.4%);few COVID-19 infections were reported (7.0%;2.1%). Incidence (pts/100 pt years) of serious TEAEs were low (4.4;7.1);no major adverse cardiovascular events, active tuberculosis cases, serious COVID-19 infections, or deaths were reported. Most incidences of fungal infection (19.6;14.9;none serious or systemic) were Candida (12.8;8.3) and mild to moderate;two pts in both studies discontinued the study due to Candida infections. Incidence of IBD (1.0;1.0) and uveitis (1.5;2.4) were low.ConclusionAcross the axSpA spectrum, BKZ resulted in sustained efficacy to Wk 52. No new safety signals were observed, consistent with the Wk 24 safety profile.[1,2]References[1]Deodhar A. Ann Rheum Dis 2022;81:772–3;2.[2]van der Heijde D. Ann Rheum Dis 2022;81:12–3.Table 1.Efficacy at Wk 52Mean (SE), unless statedBE MOBILE 1BE MOBILE 2PBO→BKZ N=126BKZ N=128PBO→BKZ N=111BKZ N=221ASAS40 [NRI] n (%)64 (50.8)78 (60.9)76 (68.5)129 (58.4)ASAS40 in TNFi-naïve [NRI] n (%)58 (53.2)a73 (61.9)b67 (71.3)c108 (58.7)dASAS40 in TNFi-IRe [NRI] n (%)6 (35.3)f5 (50.0)g9 (52.9)f21 (56.8)hASAS20 [NRI] n (%)88 (69.8)94 (73.4)89 (80.2)158 (71.5)ASAS PR [NRI] n (%)38 (30.2)38 (29.7)41 (36.9)66 (29.9)ASAS 5/6 [NRI] n (%)65 (51.6)71 (55.5)74 (66.7)124 (56.1)BASDAI CfB [MI]–3.5 (0.2)–3.9 (0.2)–4.0 (0.2)–3.6 (0.1)BASFI CfB [MI]–2.6 (0.2)–3.0 (0.2)–2.8 (0.2)–2.8 (0.1)ASDAS-MI [NRI] n (%)37 (29.4)47 (36.7)49 (44.1)71 (32.1)Nocturnal spinal pain CfB [MI]–4.1 (0.2)–4.3 (0.3)–4.6 (0.3)–4.1 (0.2)ASQoL CfB [MI]–5.3 (0.4)–5.9 (0.4)–5.6 (0.4)–5.7 (0.3)SF-36 PCS CfB [MI]11.4 (0.9)12.2 (0.9)12.3 (0.9)12.0 (0.6)BASMI CfB [MI]–0.4 (0.1)–0.6 (0.1)–0.7 (0.1)–0.7 (0.1)Total resolution of enthesitisi [NRI] n (%)41 (44.6)j51 (54.3)c31 (46.3)k67 (50.8)lASDAS-CRP CfB [MI]–1.6 (0.1)–1.8 (0.1)–1.9 (0.1)–1.7 (0.1)SPARCC MRI SIJ score CfB [OC]mMean (SD)–6.4 (10.7)n–7.6 (10.5)o–2.8 (6.1)p–4.7 (8.2)qBerlin MRI spine score CfB [OC]mMean (SD)–0.4 (2.0)k–0.7 (2.5)r–2.1 (3.4)p–2.4 (3.9)shs-CRP, mg/L [MI] Median2.21.72.02.3RS. n: a109, b118, c94, d184;eMax 1 TNFi;n: f17, g10, h37;iMASES=0 in pts with MASES >0 at BL;n: j92, k67;l132;mMRI sub-study;n: n70, o82, p48, q90, r79, s89.AcknowledgementsThis study was funded by UCB Ph rma. Medical writing support was provided by Costello Medical, funded by UCB Pharma.Disclosure of InterestsXenofon Baraliakos Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Atul Deodhar Speakers bureau: Janssen, Novartis and Pfizer, Consultant of: AbbVie, Amgen, Aurinia, BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, BMS, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer and UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Eli Lilly, Novartis, Pfizer and UCB Pharma, Employee of: Director of Imaging Rheumatology BV, Marina Magrey Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie and UCB Pharma, Walter P Maksymowych Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie and Pfizer;educational grants from AbbVie, Janssen, Novartis and Pfizer, Employee of: Chief Medical Officer for CARE ARTHRITIS, Tetsuya Tomita Speakers bureau: AbbVie, Astellas, BMS, Eisai, Eli Lilly, Janssen, Kyowa Kirin, Mitsubishi-Tanabe, Novartis and Pfizer, Consultant of: AbbVie, Eli Lilly, Gilead, Novartis and Pfizer, Huji Xu Speakers bureau: AbbVie, Janssen, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Beigene, BioMap, IASO, Pfizer and UCB Pharma, Employee of: Clinical investigator for Peking-Tsinghua Center for Life Sciences, Marga Oortgiesen Shareholder of: UCB Pharma, Employee of: UCB Pharma, Ute Massow Employee of: UCB Pharma, Carmen Fleurinck Employee of: UCB Pharma, Alicia Ellis Employee of: UCB Pharma, Thomas Vaux Employee of: UCB Pharma, julie smith Employee of: UCB Pharma, Alexander Marten Employee of: UCB Pharma, Lianne S. Gensler Consultant of: AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: Novartis and UCB Pharma paid to institution.

In Vitro Potential Virucidal Effect Evaluation of Xibornol on Human Adenovirus Type 5, Human Rhinovirus Type 13, Human Coronavirus 229E, Human Parainfluenza Virus Type 1, and Human Respiratory Syncytial Virus.

The availability of virucidal compounds to reduce the impact of respiratory viruses is a relevant topic for public health, especially during the recent coronavirus disease (COVID-19) pandemic. Antimicrobial properties of Xibornol are known since the 1970s, but its activity on viruses is currently little explored. In this study, Xibornol activity at a fixed concentration of 0.03 mg/100 ml has been evaluated on five respiratory viruses (Human Adenovirus 5, Human Rhinovirus type 13, Human Coronavirus 229E, Human Parainfluenza Virus type 1, and Human Respiratory Syncytial Virus) through in vitro experiments based on adapted European standard UNI EN 14476-20019. The experiments were carried out under two different environmental conditions, one with the addition of fetal bovine serum to simulate an in vivo condition (dirty condition) and the other without the addition of any organic substances (clean condition). The viral abatement of Xibornol (expressed as Log10 reduction - LR) was statistically significant under both clean and dirty environmental conditions. Namely, in clean condition, LR ranged from 2.67 to 3.84, while in the dirty one the abatement was slightly lower (from 1.75 to 3.03). Parainfluenza Virus and Human Adenovirus were most resistant compared to the other viruses. The obtained data confirmed Xibornol activity and its use as topic substance for viral inactivation to prevent upper respiratory tract disease.

Pathogen spectrum analysis of acute respiratory infection among inpatients before and after the outbreak of COVID-19 pandemic in Huairou district of Beijing

Objective To analyze the composition and epidemiological characteristics of respiratory pathogens in hospitalized patients with respiratory tract infections in Huairou district before and after the outbreak of corona virus disease 2019（COVID-19）. Methods Respiratory specimens were collected from hospitalized patients who met the case definition in Huairou district during the period of January 2018 and December 2021. The samples were tested for influenza virus, respiratory syncytial virus, adenovirus, parainfluenza virus, metapneumovirus, coronavirus, rhinovirus, bocavirus, enterovirus, mycoplasma pneumoniae, chlamydophila pneumoniae and other respiratory pathogens by using ABI 7500 real-time fluorescent quantitative PCR assay. Results From January 2018 to December 2021, a total of 1 148 samples were tested and the overall positive rate was 24. 65%（283cases）. The positive detection rate after the outbreak of COVID-19 in 2020-2021（79/522） was significantly lower than that before the outbreak of COVID-19 in 2018-2019（204/626）（15. 13% vs 32. 59%, χ~2=46. 683, P＜0. 01）. The positive rates in children aged 0-＜2 years and 2-＜5 years after the outbreak of COVID-19were 46. 15% and 45. 45% respectively, were significantly higher than those in other age groups （χ~2=73. 053,P＜0. 01）. Mycoplasma pneumoniae（12. 75%）, enterovirus（10. 29%） and adenovirus（10. 29%） were the top three pathogens before the outbreak, while, after the outbreak, the top three pathogens were syncytial virus（21. 52%）, parainfluenza（17. 72%） and rhinovirus（17. 72%）. In Huairou district, the detection rate of respiratory pathogens peaked in winter, there was also a small peak in summer. Conclusion After the outbreak of COVID-19, children under 5 years old are still the main population for respiratory infection control. The change of pathogen spectrum before and after the outbreak of covid-19 is helpful for clinician to recognize and diagnose the disease.

Neurological diseases caused by coronavirus infection of the respiratory airways

Infections of the central nervous system (CNS) infections are critical problems for public health. They are caused by several different organisms, including the respiratory coronaviruses (CoVs). CoVs usually infect the upper respiratory tract causing the common cold. However, in infants, and in elderly and immunocompromised persons, they can also affect the lower respiratory tract causing pneumonia and various syndromes of respiratory distress. CoVs also have neuroinvasive capabilities because they can spread from the respiratory tract to the CNS. Once infection begins in the CNS cells, it can cause various CNS problems such as status epilepticus, encephalitis, and long‐term neurological disease. This neuroinvasive properties of CoVs may damage the CNS as a result of misdirected host immune response, which could be associated with autoimmunity in susceptible individuals (virus‐induced neuro‐immunopathology) or associated with viral replication directly causing damage to the CNS cells (virus‐induced neuropathology). In December 2019, a new disease named COVID‐19 emerged which is caused by CoVs. The significant clinical symptoms of COVID‐19 are related to the respiratory system, but they can also affect the CNS, causing acute cerebrovascular and intracranial infections. We describe the possible invasion routes of coronavirus in this review article, and look for the most recent findings associated with the neurological complications in the recently published literature.

Literature Highlights

Literature Highlights is a digest of notable papers recently published in the leading respiratory journals. Coverage includes a 6-month, all-oral regimen for rifampicin-resistant TB;phase 3 trials of two shorter regimen for drug-resistant TB;heterogeneity in M. tuberculosis transmission through whole-genome sequencing;vaping and pulmonary inflammation;impact of COVID-19 during pregnancy on mother and newborn;migrants and TB.

Discovering the positives in healthcare

There are nonetheless grounds for some optimism that advances are being made, not least in the progress made by research funders in cracking down on unpublished clinical trials (doi:10.1136/bmj.p840).7 Two new research papers also carry some good news. Denosumab use for osteoporosis in adults may simultaneously reduce the risk of type 2 diabetes (doi:10.1136/bmj-2022-073435).8 And discussion with patients, using a prognostic algorithm, and providing information could help GPs identify patients with respiratory tract infections who are at lower risk and do not need immediate antibiotic treatment (doi:10.1136/bmj-2022-072488).9 Finally, Helen Salisbury writes about not just good news but "something so positive, so joyful and life affirming”—an initiative in which medical students mentor asylum seekers and support them through the healthcare system (doi:10.1136/bmj.p919).10 A junior doctor who helped coordinate the work spoke of finding focus and purpose and "falling in love with medicine again.” BMJ 2023;381: e073435. 10.1136/bmj-2022-073435 37072150 9 Blair PS Young G Clement C. Multi-faceted intervention to improve management of antibiotics for children presenting to primary care with acute cough and respiratory tract infection (CHICO): efficient cluster randomised controlled trial.

Loculated Pneumothorax in COVID-19 Patient – A Case Report

Aim: Loculated pneumothorax and multilocular cystic lung lesions are rare complications of acute respiratory distress syndrome in patients with COVID-19 infection. In this case report we wanted to emphasize that not only mechanically ventilated patients are at increased risk of pneumothorax and cystic lung lesions. Those lesions can also be found in non-ventilated patients. Case report: We present a case report of a 52-year-old man who was hospitalized because of COVID-19 pneumonia. MSCT pulmonary angiography revealed ground glass opacities, multilocular cystic lesions and loculated pneumothorax. On follow-up computerized tomography examination in an outpatient hospital two months later, there was a significant regression of the lung parenchymal ground glass opacities, as well as the regression of the cystic lesions with residual fluid-filled lesion in the oblique interlobar fissure. Conclusion: Only few case reports have been published on this specific lung pathology in COVID-19 disease. Increased incidence of complications such as pneumothorax in COVID-19 pneumonia is common, but physicians should also be aware of the possibility of other lung pathologies such as loculated pneumothorax and multilocular cystic lesions which can present not only in mechanically ventilated patients. © 2023, Croatian Medical Association. All rights reserved.

Guillain-Barre Syndrome and COVID-19 Vaccine: A Report of Nine Patients

Introduction: Guillain-Barre Syndrome (GBS) is an autoimmune acute inflammatory demyelinating polyneuropathy usually elicited by an upper respiratory tract infection. Several studies reported GBS associated with Coronavirus Disease 2019 (COVID-19) infection. In this study, we described nine GBS patients following the COVID-19 vaccine.Methods: In this study, nine patients were introduced from six referral centers for neuromuscular disorders in Iran between April 8 and June 20, 2021. Four patients received the Sputnik V, three patients received the Sinopharm, and two cases received the AstraZeneca vaccine. All patients were diagnosed with GBS evidenced by nerve conduction studies and/or cerebrospinal fluid analysis.Results: The median age of the patients was 54.22 years (ranged 26-87 years), and seven patients were male. The patients were treated with Intravenous Immunoglobulin (IVIg) or Plasma Exchange (PLEX). All patients were discharged with some improvements.Conclusion: The link between the COVID-19 vaccine and GBS is not well understood. Given the prevalence of GBS over the population, this association may be coincidental;therefore, more studies are needed to investigate a causal relationship.

A Multicenter Study about the Population Treated in the Respiratory Triage Stations Deployed by the Red Cross during the COVID-19 Pandemic.

BACKGROUND: Care demand exceeded the availability of human and material resources during the COVID-19 pandemic, which is the reason why triage was fundamental. The objective is to know the clinical and sociodemographic factors of confirmed or suspected COVID-19 cases in triage stations from different Ecuadorian provinces. METHOD: A multicenter study with a retrospective and descriptive design. The patients included were those who accessed the Respiratory Triage stations deployed by the Ecuadorian Red Cross in eight Ecuadorian provinces during March and April 2021. Triage allows for selecting patients that need urgent treatment and favors efficacy of health resources. RESULTS: The study population consisted of a total of 21,120 patients, of which 43.1% were men and 56.9% were women, with an age range between 0 and 98 years old. Severity of COVID-19 behaved differently according to gender, with mild symptoms predominating in women and severe or critical symptoms in men. Higher incidence of critical cases was observed in patients over 65 years old. It was observed that overweight predominated in critical, severe, and moderate cases, while the body mass index of patients with mild symptoms was within the normal range. CONCLUSIONS: The Ecuadorian Red Cross units identified some suspected COVID-19 cases, facilitating their follow-up and isolation. Fever was the most significant early finding.

Why Xi Jinping Reversed His Zero-Covid Policy in China

The rare display of public anger, with some protesters directly criticizing Mr. Xi and the Communist Party, alarmed Mr. Xi and his inner circle, the officials and advisers said. Keywords: leder;wsjworld;photo-news;Political/General News;Respiratory Tract Diseases;Global/World Issues;Health;Medical Conditions;Outbreaks/Epidemics;Politics/International Relations EN leder wsjworld photo-news Political/General News Respiratory Tract Diseases Global/World Issues Health Medical Conditions Outbreaks/Epidemics Politics/International Relations N.PAG N.PAG 1 01/11/23 20230105 NES 230105 A wave of protests coupled with urgent pleas from many corners of the government finally prodded the leader to scrap the strict lockdown system he had touted throughout the pandemic BEIJING - By the end of an otherwise triumphant Communist Party Congress for Xi Jinping in October, it was growing harder for China's leader to argue that his zero-Covid policy was working. [Extracted from the article] Copyright of Wall Street Journal (Online) is the property of Dow Jones & Company Inc and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

The effect of the COVID-19 pandemic on pediatric emergency admissions and tendency towards prescribing antibiotics

Aim: To determine the changes in the diagnoses of patients admitted to pediatric emergency department due to infection and the change in the tendency towards prescribing antibiotics during the COVID-19 pandemic.Methods: Age, gender and the diagnoses of and the antibiotics prescribed for patients under the age of 18 who admitted to the pediatric emergency department on two separate days before and during the pandemic period were compared retrospectively.Results: It was found that the admissions to the pediatric emergency department decreased by 83% during the pandemic period compared to the pre-pandemic period. Upper respiratory tract infection (URTI) was diagnosed in 61.6% of the patients during the pre-pandemic period compared to 32.6% of the patients during the pandemic periods, indicating a statistically significant difference between the groups (p<0.001). The percentage of patients diagnosed with paranasal infection in the pandemic period was also significantly lower than in the pre-pandemic period. On the other hand, the percentages of patients diagnosed with urinary infection and diagnoses other than infection in the pandemic period were significantly higher than in the pre-pandemic period. Additionally, the percentage of patients who were prescribed amoxicillin-clavulanic acid (CAM) was significantly higher, whereas the percentage of patients who were prescribed Clarithromycin was significantly lower in the pandemic period than in the pre-pandemic period. Furthermore, it was determined that Oseltamivir was not prescribed during the pandemic period.Conclusions: Quarantines imposed due to the COVID-19 pandemic and the use of masks have reduced the incidence of upper and lower respiratory tract infections. In parallel, it was determined that the percentage of patients presented to the pediatric emergency department with the diagnosis of non-infectious diagnoses has increased. This result has been attributed to the use of masks and the attention paid to the hygiene, which caused a decrease in the incidence of infectious diseases, influenza in particular.

The Effects of Propolis on Viral Respiratory Diseases.

Propolis remains an interesting source of natural chemical compounds that show, among others, antibacterial, antifungal, antiviral, antioxidative and anti-inflammatory activities. Due to the growing incidence of respiratory tract infections caused by various pathogenic viruses, complementary methods of prevention and therapy supporting pharmacotherapy are constantly being sought out. The properties of propolis may be important in the prevention and treatment of respiratory tract diseases caused by viruses such as severe acute respiratory syndrome coronavirus 2, influenza viruses, the parainfluenza virus and rhinoviruses. One of the main challenges in recent years has been severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing COVID-19. Recently, an increasing number of studies are focusing on the activity of various propolis preparations against SARS-CoV-2 as an adjuvant treatment for this infection. Propolis has shown a few key mechanisms of anti-SARS-CoV-2 action such as: the inhibition of the interaction of the S1 spike protein and ACE-2 protein; decreasing the replication of viruses by diminishing the synthesis of RNA transcripts in cells; decreasing the particles of coronaviruses. The anti-viral effect is observed not only with extracts but also with the single biologically active compounds found in propolis (e.g., apigenin, caffeic acid, chrysin, kaempferol, quercetin). Moreover, propolis is effective in the treatment of hyperglycemia, which increases the risk of SARS-CoV-2 infections. The aim of the literature review was to summarize recent studies from the PubMed database evaluating the antiviral activity of propolis extracts in terms of prevention and the therapy of respiratory tract diseases (in vitro, in vivo, clinical trials). Based upon this review, it was found that in recent years studies have focused mainly on the assessment of the effectiveness of propolis and its chemical components against COVID-19. Propolis exerts wide-spectrum antimicrobial activities; thus, propolis extracts can be an effective option in the prevention and treatment of co-infections associated with diseases of the respiratory tract.

THERAPEUTIC PROFILE OF Glycyrrhiza glabra: A RAY OF HOPE IN TREATING COVID-19

Glycyrrhiza glabra Linn (licorice) has been widely studied because of the possible ethnopharmacological benefit. It was among the essential Ayurvedic medicines studied for immunomodulatory, antiviral, antibacterial, antioxidant, hepato-protective activities. Nowadays, licorice's root parts have been evaluated to contain numerous bioactive components responsible for the treatment of respiratory tract infections and influenzalike illnesses. Most importantly, several investigations have now assessed the multiple mechanisms by which these biomolecules could attack the essential proteins and enzymes responsible for SARS-CoV-2 cellular entry and interaction. Our findings gathered that the metabolites of Glycyrrhiza glabra could interfere with COVID-19 cellular entrance and replication by blocking all five key proteins and enzymes essential for the survival and attachment of the virus. In addition to their ability to neutralise, the inflammatory cytokines storm reaction following the COVID-19 viral infection. This review was designed to digest the potential pharmacological importance of Glycyrrhiza glabra and its likeness in combating the pandemic COVID-19.

Monitoring of absenteeism due to respiratory symptoms and diseases among preschoolers in Guangzhou

Objective To analyse monitoring absenteeism due to respiratory symptoms/diseases among preschoolers in Guang-zhou, and to provide reference for risk prevention and control of respiratory infectious diseases in kindergartens. Methods Data of absenteeism due to symptoms and diseases in kindergartens were collected from "Guangzhou Student Health Monitoring System", and was analyzed by using R 4.1.3 software. Results During 2018-2020 academic year, there were 1 965, 2 019, 2 236 kinder-gartens being monitored respectively. The absenteeism rate of kindergarten's children due to respiratory symptoms and diseases in Guangzhou were 3.08 ‰ and 2.02 ‰. The absenteeism rates due to respiratory symptoms were 3.75 ‰, 4.17 ‰, 2.97 ‰ and 2.09 ‰ in baby class, junior class, middle class and senior class, respectively. The absenteeism rates due to respiratory diseases were 2.34 ‰, 2.60 ‰, 1.94 ‰ and 1.50 ‰, respectively. The absenteeism rate in higher grade was lower than that in lower grade (X2 = 65 197.95, 27 929.44, P<0.01). The absenteeism rates of boys (3.11 ‰, 2.05 ‰ ) due to respiratory symptoms/diseases were signif-icantly higher than those of girls (3.06 ‰, 1.97 ‰ ) (X2 =57.71, 229.45, P<0.01). The absenteeism of preschoolers due to respiratory symptoms/diseases showed two peaks in December of the this year and May of the following year. At the beginning of the second se-mester of 2019 academic year (after the outbreak of Coronavirus disease 2019), the absenteeism rate due to respiratory symptoms/diseases were lower than those of the same period in previous years. Conclusions The absences due to respiratory symptoms or dis-eases not only accounted for half of the total absences due to illness, but also had seasonal characteristics. Children in the younger-age group and most boys are treated as a focus group for absence due to respiratory symptoms/illnesses. It's necessary to give full use of timely warning function of health monitoring system. © 2022 by the Author(s).

Development and evaluation of an e-learning course in oxygen therapy.

BACKGROUND: Respiratory problems are among the most challenging situations in emergency care services. Different oxygen therapy methods are usually used to deal with these problems. In recent years, oxygen therapy has been recognized as one of the most widely used therapeutic processes in emergency departments (ED) mainly due to the Covid-19 pandemic. The aim of this study was to develop and evaluate an e-learning course in oxygen therapy for the ED clinicians. METHODS: This was a pre-post study conducted in three phases in 2021. Initially, the educational requirements of clinicians (n = 181) were investigated using a questionnaire, and in the second phase, an interactive e-learning course was developed. In the third phase, the course was assessed in terms of maintaining the principles of developing an e-learning course, affecting participants' knowledge, and supporting usability requirements. RESULTS: The findings revealed that training in oxygen therapy was essential for the ED clinicians. Therefore, an e-learning course was developed. The content production experts and the participants evaluated the content and usability of the online course at a good level. In addition, there was a statistically significant difference between the nurses' (p < 0.001) and general practitioners' (p < 0.002) pre- and post-test scores suggesting that the course improved their knowledge. CONCLUSION: It seems that the e-learning course developed in the current study can improve health care professionals' knowledge and quality of care. However, more evaluation studies are needed to investigate the effectiveness of the course for other clinicians, such as nurses who work in intensive care units.

New Insights into Avian Infectious Bronchitis Virus in Colombia from Whole-Genome Analysis.

Infectious Bronchitis (IB) is a respiratory disease caused by a highly variable Gammacoronavirus, which generates a negative impact on poultry health worldwide. GI-11 and GI-16 lineages have been identified in South America based on Infectious Bronchitis virus (IBV) partial S1 sequences. However, full genome sequence information is limited. In this study we report, for the first time, the whole-genome sequence of IBV from Colombia. Seven IBV isolates obtained during 2012 and 2013 from farms with respiratory disease compatible with IB were selected and the complete genome sequence was obtained by NGS. According to S1 sequence phylogenetic analysis, six isolates belong to lineage GI-1 and one to lineage GVI-1. When whole genome was analyzed, five isolates were related to the vaccine strain Ma5 2016 and two showed mosaic genomes. Results from complete S1 sequence analysis provides further support for the hypothesis that GVI-1, considered a geographically confined lineage in Asia, could have originated in Colombia. Complete genome information reported in this research allow a deeper understanding of the phylogenetic evolution of variants and the recombination events between strains that are circulating worldwide, contributing to the knowledge of coronavirus in Latin America and the world.