A Case of X-Linked Moesin-Associated Immune Deficiency in a Pediatric Patient

Background: X-Linked Moesin-Associated Immune Deficiency (X-MAID) is a rare severe combined immunodeficiency (SCID) subtype that can present at any age due to its variability. Depending on severity, patients demonstrate failure to thrive, recurrent bacterial and viral infections, and increased susceptibility to varicella zoster. It has been characterized by marked lymphopenia with hypogammaglobulinemia and impaired T-cell migration and proliferation. Case Presentation: This is a report of a Cuban 7-year-old male with poor weight gain and facial dysmorphia. He had a history of recurrent bacterial gastrointestinal infections and pneumonia beginning at 4 months of age. He additionally had 4-6 upper respiratory tract and ear infections annually. While still living in Cuba, he was admitted for a profound EBV infection in the setting of significant leukopenia. A bone marrow biopsy confirmed no malignancy. After he moved to the United States, his laboratory work-up revealed marked leukopenia with low absolute neutrophil and lymphocyte count with low T and B cells, very low immunoglobulin levels IgG, IgA, and IgM, and poor vaccination responses to streptococcus pneumonia, varicella zoster, and SARS-CoV-2. Genetic testing revealed a missense pathogenic variant c.511C>T (p.Arg171Trp) in the moesin (MSN) gene associated with X-MAID. He was managed with Bactrim and acyclovir prophylaxis, and immunoglobulin replacement therapy, and considered for hematopoietic stem cell transplantation. Discussion(s): Diagnosis of X-MAID should be considered in patients with recurrent infections and profound lymphopenia. As with SCID, early diagnosis and intervention is of utmost importance to prevent morbidity and mortality. This case demonstrates the importance of genetic testing in identifying this disease as it may prompt an immunologist to consider HSCT if conservative management is suboptimal. In the current literature, HSCT appears promising, but the long-term outcomes have yet to be described.Copyright © 2023 Elsevier Inc.

Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study

Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Clinical profile of hospitalized spanish patients allergic to antibiotics

Background: Only between 1% and 10% of patients labelled of penicillin allergy are allergic. The negative events associated with this condition include risk of antimicrobial treatment failure, antimicrobial resistance, side-effects from use of a broader spectrum antibiotic, and increased healthcare costs. Our objective was to know the clinical profile of hospitalized allergic patients to estimate the future need for an allergy study. Method(s): We collected data from 15 Spanish hospitals about hospitalized patients labelled as allergic to antibiotics in February 2020 and October 2020 (one-month sample) outside the peak of the Covid-19 pandemic. Result(s): 620 patients were collected, 59% women. Mean age 70.6 years (3-103). 416 patients were labelled as allergic to beta-lactams (105 aminopenicillins, 18 cephalosporins, 4 carbapenems). 41 to aminoglycosides, 26 to macrolides, 55 to quinolones and 4 to glycopeptides. The causes of hospitalization were: Respiratory infection 221 (35.6%), abdominal infection 95 (15.3%), orthopaedic surgery 58 (9.4%), urine infections 57 (9.2%), skin infections 51 (8.2%), gynaecological/ obstetric pathology 21 (3.4%) Only 163 patients (26%) had previously received a clinical allergy work-up. 70 confirmed allergy to antibiotics, however the rest 93 (74%) were not delabelled. Patients received alone or combined alternative antibiotics: 79 glycopeptides, 49 aminoglycosides, 28 macrolides, 254 quinolones, 205 beta-lactams (102 cephalosporins, 41 carbapenems and 57 aminopenicillins). 74 patients (12%) would need an immediate allergic study in order to receive first-line antibiotic, but it was only really done in 38 (6.1%). The studied antibiotics were: 15 carbapenems, 10 ceftriaxone, and others not specified. Of the 416 patients labeled as allergic to beta-lactams, 150 (36%) received beta-lactam antibiotics despite the warning in their clinical reports. Conclusion(s): Allergy to beta-lactams remains the most frequent diagnosis of allergy to antibiotics and implies treatment with second-line antibiotics. Respiratory, trauma, digestive and urinary infections are the main causes of the use of antibiotics in hospitalized patients. The underlying diseases could be a risk factor for antibiotic requirements. Some patients received beta-Lactams despite the alert with a potential risk of an allergic reaction and legal implications. The promptly allergological study would imply an improvement in the use of more specific antibiotics with a good level of security.

Impact of Covid-19 Pandemic on Epidemiology of Infections in Pre- and Post-Covid-19 Pandemic a Single Centre Study

Introduction: Infections are the leading cause of death in kidney transplant recipients (KTR) at all time intervals. The non-pharmaceutical interventions (NPIs) taken during the COVID-19 pandemic have reduced almost all kinds of infections in the general population, as shown in the Chunmei Su et al. study. The aim of this study was to investigate the impact of NPIs for the COVID-19 pandemic on infections in KTR patients. Method(s): This was a single-center retrospective observational study conducted at Mumbai's Jaslok Hospital and Research Centre.Samples from symptomatic KTR patients were taken and those who had positive cultures were thought to be infected. The data were analysed and compared between the years 2021 (during the COVID-19 pandemic) and 2019 (before the COVID-19 pandemic). Result(s): A total of 224 patients were enrolled, including 117 patients in 2019 and 107 patients in 2021. In 2019 and 2021, the prevalence of nosocomial infection and community-acquired infection in KTR patients remains unchanged.In 2021, both the number of protective gloves and level 2 PPE kits used per individual, as well as the number of healthcare professionals per patient, have increased dramatically. Regarding the source of infections, no significant change in major infections was observed in respiratory tract infections (12% vs. 10.3%, p = 0.8985), gastrointestinal infections (1.8% vs. 6.5%, p = 0.0786), catheter related blood stream infections (CRBSI) (4.5% vs. 3.7%, p = 0.776), and blood stream infections (11.7% vs. 10.3%, p = 0.73), However, there were increases in urinary tract infections (23% vs. 42.1%;p = 0.0006). The microorganism analysis of respiratory infections shows declines in nocardia and tuberculosis. Gastrointestinal infections show increased Clostridium difficile cases in 2021 compared to 2019, which can be attributed to the overuse of antibiotics. Regarding urinary tract infection, a decline in mixed infection cases and an increase in Enterobacter faecalis and Enterobacter cloacae cases were observed. There were no significant variations in catheter-related nosocomial infections between 2019 and 2021. In comparison to an older study done in the general population by Chunmei Su et al, our study shows no significant change in respiratory, gastrointestinal, and catheter-related blood infections in 2021 compared to 2019 in KTR, despite restrictions being relaxed in general populations beginning in June 2020.Also, there was no significant increase in community acquired pneumonia in 2021, even after reopening public places. Conclusion(s): Our institutional NPIs for KTR patients in the pre-COVID-19 era were shown to be as effective as NPIs for the COVID-19 pandemic in reducing the prevalence of common infections like respiratory, gastrointestinal, blood stream, and catheter-related infections in KTR patients. No conflict of interestCopyright © 2023

Molecular identification and characterization of SARS-Co V-2 from the clinical stool and sewage samples to study waste water-based epidemiology and monitoring circulating virus

The Coronaviridae family's severe acute respiratory syndrome corona virus 2 (SARS-Co V-2) outbreak has infected a large number of the population during the COVID- 19 pandemic. The most prominent mode of virus transmission is considered through respiratory droplets of the infected person. Virus-mediated respiratory infection depends upon the binding between spike protein and the Angiotensinconverting enzyme 2 (ACE2) receptor expressed in lung alveolar type 2 cells. But some studies reported that gastrointestinal infection is also one of the prominent symptoms of COVID-19 because of the high expression of the ACE2 receptor in absorptive enterocytes of the small intestine. In a country like India, with high population density and due to unhygienic sanitation, it is crucial to understand the potential fecal-oral transmission route of SARS-CoV-2 during infection because of presence of ACE2 in small intestine. Therefore in our study, we aim to trace the potential fecal-oral transmission route of SARS-Co V-2 by examining human stool (collected from hospital settings) and nearby sewage water systems, followed by molecular characterization and viral load kinetics evaluation of SARSCOV- 2. qRT-PCR and NGS sequencing methods were used. The presence of SARS-COV-2 was reported in around 70% of samples (both clinical and environmental), this will help us to establish the epidemiological link between clinical and environmental samples after genomic analysis to alter the circulation of silent SARS Co V2 in the community.

Encuentro Nacional de Investigacion en enfermedades Infecciosas und 3. Encuentro Latinoamericano de Investigacion en Enfermedades Infecciosas

The proceedings contain 18 papers. The topics discussed include: multisystem inflammatory syndrome in children associated with COVID-19: a comparison study between cohorts from different geographic locations;knowledge attitudes and practices (KAP) about antibiotic use and antimicrobial resistance in hemodialysis patients and their household contacts Medellin-Colombia;use of endemic channels as part of a pediatric antimicrobial stewardship program: when to turn on the alarms? recommendations of pediatric ASP program;and outbreak of gastrointestinal infections caused by Yersinia enterocolitica in children Medellin-Colombia.

Bacterial Infections After Kidney Transplant Before and After the COVID-19 Pandemic

Purpose: Infectious complications are a major cause of mortality and morbidity after kidney transplantation. During the COVID-19 pandemia there were several changes in the management and behavior of patients after transplant. These included measures such as universal masking, social distancing and reinforcing hand hygiene. Our objective was to evaluate if these differences affected the incidence of infections after kidney transplant. Method(s): This is a retrospective cohort study of all kidney transplants performed in our institution from March 2017 to November 2020. We examined the incidence of wound infection, urinary tract infection (UTI), pneumonia, and gastrointestinal (GI) infections. Pediatric and multi-organ transplants were excluded. We used the Fisher test, Chi-squared test of independence and logistic regression models in the analysis. All tests were based on a level of significance of alpha=0.05. Result(s): A total of 185 deceased donor kidney transplant patients were reviewed, 153 before and 54 after the beginning of the COVID-19 pandemic in the United States. The incidence of wound infection, pneumonia and GI infection were similar before and after COVID (Table 1). There was a significant increase in UTI after the COVID pandemic, the main organisms isolated were Klebsiella pneumonia (50%) and E. coli (25%). Overall the presence of UTI and wound infection were significantly related (OR 4.2, p = 0.06). Other clinical variables such as age, BMI, KDPI, EPTS, and the occurrence of delayed graft function were not associated with UTI. COVID infection was present with similar incidence: 12% in patients transplanted before and 14.8% in patients transplanted after the onset of the pandemic. Induction with Thymoglobulin or Basiliximab was not significantly different before and after COVID, and the choice of induction was not associated with the rate of UTI. Conclusion(s): While multiple changes in the management of patients and patient behavior are different before and after the onset of the COVID-19 pandemic, this analysis did not find significant change in the incidence of infections except for UTI in comparative cohorts of kidney transplant recipients. This study did not identify specific factors associated with the increase of UTI in our population. However, in response certain measures were implemented, such as reducing the time to ureteral stent removal and giving 24 hrs of prophylactic antibiotics at the time of stent removal.

DIFFUSE ALVEOLAR HEMORRHAGE SECONDARY TO IMMUNE THROMBOCYTOPENIA FOLLOWING SARS-COV-2 VACCINATION: A CASE REPORT

SESSION TITLE: COVID-Related Critical Care Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: We present a case of diffuse alveolar hemorrhage (DAH) secondary to Immune Thrombocytopenia (ITP) temporally related to SARS-CoV-2 (CoV) vaccine. CASE PRESENTATION: An 80-year-old female presented with dyspnea, hemoptysis, diffuse petechiae, and ecchymosis;no focal neurological deficits or hepatosplenomegaly. She had no history of bleeding or autoimmune disorders;no recent respiratory or gastrointestinal infections;but received Moderna CoV vaccine 4 weeks prior to presentation. Chest X-ray (CXR) and CTA of chest demonstrated multifocal bilateral patchy airspace opacities. Initial platelet was 1 x 109/L with normal morphology of platelet and WBC, and no schistocytes. Coagulation panel, LDH, haptoglobin, and bilirubin were all normal. CoV NAAT was negative. Dexamethasone and IVIG for high suspicion of ITP was initiated. Supportive care including platelet transfusion and oxygen via nasal cannula was maintained. Platelets were severely consumed in spite of treatment with platelets undetectable at nadir and rapid decrease of hemoglobin, approximately 6 g/dL, within 24 hours of admission. IgM and IgG plasma platelet autoantibodies returned positive, confirming ITP diagnosis. Additional workup was unremarkable for infections, rheumatologic disorders, and malignancy. Respiratory state rapidly declined with worsening hemoptysis and significant increase of bilateral airspace opacities on repeat CXR, indicative of DAH. Lung protective mechanical ventilation protocol was initiated on day 2 with medically induced deep sedation and paralysis to minimize hemorrhage exacerbation. Rituximab, romiplostim, and nebulized tranexamic acid were added for severe and refractory ITP, which eventually slowed platelet consumption, reduced pulmonary hemorrhage, and stabilized hemoglobin. Platelets recovered above 30 x 109/L on day 9, and subsequent bronchoscopy showed persistent blood on bronchoalveolar lavage. She was successfully extubated after prolonged 14-day intubation. Platelet normalized before discharge. DISCUSSION: Incidence of ITP related to CoV vaccine is approximately 0.8-0.9 case per million vaccinated. Most cases present with superficial bleeding and respond to first-line agents with rapid recovery. GI bleeding and intracranial hemorrhage, but not DAH, have been reported in several cases, requiring third-line agents to promote platelets recovery and achieve hemostasis. We report a case of DAH secondary to ITP following CoV vaccine. Temporal relationship and severe presentation are consistent with other reports of ITP with life-threatening internal bleeding probably secondary to CoV vaccine. CONCLUSIONS: When DAH is suspected, rapid escalation of treatment to include third-line agents is desired. If intubated, lung protective ventilation with paralysis is preferred to minimize further lung injury due to DAH. Reference #1: Lee EJ, Cines DB, Gernsheimer T, et al. Thrombocytopenia following Pfizer and Moderna SARS-CoV-2 vaccination. Am J Hematol. 2021;96(5):534-537. doi:10.1002/ajh.26132 doi:10.1016/J.VACCINE.2021.04.054 Reference #2: Welsh KJ, Baumblatt J, Chege W, Goud R, Nair N. Thrombocytopenia including immune thrombocytopenia after receipt of mRNA COVID-19 vaccines reported to the Vaccine Adverse Event Reporting System (VAERS). Vaccine. 2021;39(25):3329-3332. Reference #3: Tarawneh O, Tarawneh H. Immune thrombocytopenia in a 22-year-old post Covid-19 vaccine. Am J Hematol. 2021;96(5):E133-E134. doi:10.1002/ajh.26106 DISCLOSURES: No relevant relationships by Timothy Barreiro No relevant relationships by Tiewei Cheng No relevant relationships by Zeina El Amil No relevant relationships by Jin Huang No relevant relationships by Sanaullah Khalid

Case report: post-Covid-19 arthritis and peri arthritis

We present the case of a 63 years old male patient known for type 2 diabetes and sleep apnoea. He was admitted as inpatient for a nontraumatic severe and disabling left hip pain. The pain started progressively one month ago. The medical history was otherwise irrelevant, with no general symptoms nor other symptoms suggestive of an inflammatory disease. To mention a history of an asymptomatic SARS-COV2 infection, diagnosed by a naso-pharyngial PCR, approximately 10 days before the onset of the pain. On physical examination, the patient was afebrile. The palpation of the inguinal region was tender on palpation with marked limitation of the hip range of motion. The spine and other peripheral joints were painless without inflammatory sign. Moreover, there was no skin lesion nor inguinal lymph nods enlargement. Due to the importance of pain with marked functional limitation, the patient is hospitalized for investigations and pain-management. On blood sample there was a mild increase of inflammatory markers (CRP 25mg/l, VS 20mm/h) with normal cell count. Standard X-rays of the pelvis and hip were normal. The MRI of the hip showed a mild coxo-femoral arthritis with marked inflammation of the surrounding musculature. An arthrocentesis was performed and 2ml of serous fluid was aspirated. There were no crystals. The cellularity could not be tested due to small amounts of fluid. The synovial culture showed a polymicrobious growth compatible with contamination. In summary, we were facing a patient with an acute and very painful hip monoarthritis. There was no history of gastrointestinal or urinary tract infection, the search for C. trachomatis and N. gonorrhoea in urines was negative. An extensive serologic testing (HIV, HBV, HCV, HBV, HCV, HIV, Lyme, Syphilis, Coxiella, Bartonella, Brucella & Quantiferon) and the search for T. whipplei were negative as well. There was no HLA-B27 and rheumatoid factor, ACPA, ANA, ANCA and specific antibodies related to polymyositis were negative. The chest-abdomen-pelvis scan showed no sign of neoplasia. To rule out a vasculitis we proceeded to a PET-CT, which showed no sign of vasculitis or myositis. Considering the timing of the onset of the symptoms and the absence of any other diagnosis, the patient was diagnosed with reactive arthritis caused by SARS-COV2. The patient was treated with Diclofenac 150 mg/day and opioids. The clinical evaluation one month after discharge showed a spontaneous significant improvement.

2022 EAN/PNS GBS Guideline

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. This is the first systematic clinical guideline, developed by an international task force using formal GRADE methodology. The diagnostic criteria remain primarily clinical, based on history and examination findings of acute progressive limb weakness and areflexia. Variants of GBS may include motor GBS, Miller Fisher Syndrome, and regional variants with weakness predominantly in lower limbs, face, or pharynx/neck/ arms. The differential diagnosis is wide. When uncertain, diagnosis may be assisted by nerve conduction tests, raised cerebrospinal fluid protein, and less often by MRI spine with contrast, or serum antibodies to gangliosides (especially for variants) or nodalparanodal antibodies (especially if not improving). Axonal versus demyelinating subtyping does not affect clinical management. A history of recent gastrointestinal or respiratory infection or of surgery may support the diagnosis. The risk of GBS is only very slightly increased after Covid-19 infection and after the adenovirus-vector vaccines to SARS-CoV2 (AstraZeneca or Johnson & Johnson) but not mRNA vaccines. Immune treatment is recommended with intravenous immunoglobulin or plasma exchange, for most patients except those mildly affected or after four weeks from onset. A repeat course is reasonable after a treatment-related fluctuation. Corticosteroids are not recommended. There is no evidence of benefi t from any other disease-modifying treatment. Respiratory function should be monitored by forced vital capacity and single breath count to assess the risk of needing mechanical ventilation, guided by the mEGRIS scale. Pain is very common. It may be musculoskeletal or neuropathic, and treated with gabapentin, tricyclic antidepressants or carbamazepine. Patients who fail to improve should be reassessed for the correct diagnosis and for axonal degeneration. Around 5% of patients with GBS may later develop CIDP but no test can reliably indicate this within the first eight weeks. Nodal-paranodal antibodies should be tested if CIDP is suspected or if the patient is not recovering well. The long-term outcome is less good in patients of older age, with preceding diarrhoea, or more severe weakness, as quantified by the mEGOS scale, and also in patients with smaller motor potential amplitudes or raised serum neurofilament light chain level.

EXCELLENT PROGNOSIS of RHEUMATIC MANIFESTATIONS FOLLOWING COVID-19 VACCINATION: 7 MONTHS FOLLOW-UP DATA

Background: It is well established that severe forms of SARS-CoV2 infection can induce a massive cytokine storm, which may disrupt the immune system stability and conceivably stimulate the development of reactive manifestations through a molecular mimicry process. Likewise, anti-COVID-19 vaccines, which have so far proved an excellent tolerability and safety profile, are able boost the immune response via different biologic technologies and adjuvant combinations possibly facilitating, in predisposed subjects, the onset of infammatory or even autoimmune manifestations. Objectives: We report a case series of suspected rheumatic adverse events following immunization (AEFI) associated with anti-COVID-19 vaccine. We focused our attention on the prognosis of these patients by analysing their available follow-up data. Methods: We included patients evaluated at frst-aid rheumatologic consultancy and at rheumatologic outpatient and inpatient clinic at Padua University Hospital between May and September 2021 presenting with new-onset rheumatic manifestation or a fare of an underlying rheumatic disease within 30 days after receiving an anti-COVID-19 vaccine dose. Inclusion and exclusion criteria were in accordance with the World Health Organization guidelines for AEFI surveillance. All patients were re-evaluated in January 2022: telemedicine or face-to-face visit. Response to therapy was classifed as complete, good or absent according to the clinician's judgment based on clinical examination, patient's reporting and analysis of laboratory data. Results: We identifed 30 cases of suspected rheumatic AEFI reported in Table 1. Comprehensively the most common manifestations were infammatory arthritis (40.0%), rheumatic polymyalgia (26.7%) and adult-onset Still disease (13.3%). Among patients with an underlying rheumatic disease we recorded an AOSD fare, a rheumatoid arthritis fare with involvement of hands proximal inter-phalangeal joints, one case of wrist arthritis in a patient with psoriatic arthritis, one of aortitis in a patient with large vessels vasculitis, one case of polyarthritis in undifferentiated connective tissue disease and a nephritis fare in a patient with systemic lupus erythematosus. Treatment for the suspected AEFI was based on systemic glucocorticoids (GC) alone (63.3%), systemic GC plus IL-1R antagonists (13.3%), non-steroidal autoinfammatory drugs (13.3%), intra-articular GC (6.6%), colchicine (3.3%) and non-steroidal anti-infammatory drugs (13.3%). At last follow-up contact (7.8±1.5 months) 26 patients (89.6%) were classified as complete responders. Eleven of them (42.3%) withdrew therapy without experiencing recurrence of disease manifestation. One patient with lupus nephritis had a proteinuric flare after the first BNT162b dose;he showed an initial good response to increased glucocorticoid therapy but had a new 24h proteinuria increase at second follow-up visit three months later requiring implementation of immunosuppressive therapy. Another patient with AOSD was in remission at last FU visit in December 2021 but required hospitalization in January 2022 for disease relapse due to a suspected gastrointestinal infection. Finally, one patient hospitalized for a seronegative polyarthritis after the first BNT162b dose achieved complete remission at last available contact (one month after hospital discharge) but was then lost in follow-up. Conclusion: After a mean follow-up of 7.8±1.5 months nearly all of patients showed a complete/good response to standard therapy and about half of them withdrew the treatment without losing the remission status.

Viral infections in hospitalized children in Germany during the COVID-19 pandemic: Association with non-pharmaceutical interventions.

Background: Non-pharmaceutical interventions (NPI) during the COVID-19 pandemic aimed at prevention of SARS-CoV-2 transmission also influenced transmission of viruses other than SARS-CoV-2. The aim of this study was to describe and compare the burden of common viral respiratory and gastrointestinal infections in children admitted to Berlin University Children's Hospital (BCH) before and during the COVID-19 pandemic at different levels of public NPI measures. Methods: In this retrospective study, we analyzed the frequency of detection of common human respiratory and gastrointestinal viruses from January 2016 through January 2022 in all patients admitted to BCH. We compared virus detection before and during the COVID-19 pandemic at different levels of public NPI measures. Results: The frequency of detection of seasonal enveloped and non-enveloped viruses [Boca-, Corona-, Influenza-, Metapneumo-, Parainfluenza-, Rota-, and Respiratory Syncytial Viruses (RSV)] was diminished during the COVID-19 pandemic, whereas detection rates of non-seasonal viruses (Rhino-/Entero-, and Adenoviruses) were stable during the pandemic. After withdrawal of major NPI measures, we observed an out of season surge of the detection rates of Boca-, Corona-, Parainfluenzaviruses, and RSV. In contrast, no increased detection frequency was observed for Influenza-, Metapneumo-, and Rotaviruses as of January 2022. Conclusion: Corona-, Boca-, Parainfluenzaviruses, and RSV returned as frequently detected pathogens after withdrawal of major NPI measures. The out of season rise might be attributed to an "immune-debt" due to missing contact to viral antigens resulting in waning of population immunity during the COVID-19 pandemic.

COVID-19 Gastrointestinal Tract Affection: An Updated Review

Although it was initially believed that the coronavirus disease 2019 (COVID-19) only attacked the respiratory system, reports over time demonstrated that this disease could attack the gastrointestinal tract (GIT) as well. The predominant presenting symptoms in patients infected with COVID-19 were gastrointestinal (GI), resulting in GI pathological changes. While clinicians' concerns are mostly related to respiratory system manifestations, GI symptoms should be monitored and managed appropriately. This review summarizes the essential information about COVID-19 GIT infection in terms of pathogenesis, major pathological changes, microbiological bases of infection, the possibility of feco-oral transmission, the severity of associated symptoms, the major radiological findings, the impact on GI surgery, the role of therapeutic agents in induction or magnification of GI symptoms, and a pitfall on the nutritional supplementation in COVID-19 patients.

PROTECTIVE EFFICACY of A GASTROINTESTINAL SARS-CoV-2 VACCINE

Background: SARS-CoV-2 remains a global threat, despite the rapid deployment but limited coverage of multiple vaccines. Alternative vaccine strategies that have favorable manufacturing timelines, greater ease of distribution and improved coverage may offer significant public health benefits, especially in resource-limited settings. Live oral vaccines have the potential to address some of these limitations;however no studies have yet been conducted to assess the immunogenicity and protective efficacy of a live oral vaccine against SARS-CoV-2. Thus far, we assessed whether oral administration of live SARS-CoV-2 in non-human primates might offer prophylactic benefits. Methods: In this study, we assessed the immunogenicity of gastrointestinal (GI) delivery of SARS-CoV-2 and the protective efficacy against intranasal and intratracheal SARS-CoV-2 challenge in rhesus macaques. Esophagogastroduodenoscopy (EGD) administration of 106 50% Tissue Culture Infectious Dose (TCID50) of SARS-CoV-2 elicited low levels of serum neutralizing antibodies (NAb), which correlated with modestly diminished viral loads in nasal swabs (NS) and Bronchoalveolar Lavage (BAL) post-challenge. In addition, mucosal NAb titers from the rectal swabs (RS), NS, and BAL and Spike-specific T-cell responses appear to be below the limit of detection post-vaccination. Replicating virus was only observed in 44% of macaques and on limited number of dates post vaccination, suggesting limited, if any, productive infection in the GI tract. Results: We demonstrate that GI delivery of live 1x106 TCID50 SARS-CoV-2 elicited modest immune responses and provided partial protection against intranasal and intratracheal challenge with SARS-CoV-2. Moreover, serum neutralizing antibody titers correlated with protective efficacy. Conclusion: These data provide proof-of-concept that an orally administered vaccine can protect against respiratory SARS-CoV-2 challenge, but the limited immunogenicity and protective efficacy observed here suggests that the oral vaccine approach will require optimization.

The impact of the coronavirus disease 2019 pandemic on pediatric hospitalization in Kitami, Japan.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has drastically changed the recommended activities and environment for patients worldwide. Our aim was to assess the impact of COVID-19 on pediatric hospitalizations in Kitami, Japan. METHODS: A retrospective, single-center study was conducted on hospitalized patients aged 0-14 years at the Japanese Red Cross Kitami Hospital. We compared the incidence of pediatric patients hospitalized in 2020 with those in 2017-2019. RESULTS: The number of pediatric hospitalized patients dropped significantly in 2020 compared to that in 2017-2019 (median 43.0 vs 78.5 per month, P < 0.001). The patients were significantly older in 2020 (4.3 vs 3.4 years, P < 0.001). Hospitalization from respiratory (8.5 vs 30.5, P < 0.001) and gastrointestinal infections (3.0 vs 6.0, P = 0.004) significantly decreased. Admission due to respiratory syncytial virus (0.0 vs 4.0, P < 0.001), human metapneumovirus (0.0 vs 1.0, P = 0.005), influenza (0.0 vs 0.0, P = 0.009), adenovirus (0.0 vs 1.0, P = 0.003), and rotavirus infection (0.0 vs 0.0, P = 0.025) also decreased significantly. The <1-5 age groups significantly decreased (<1 year old, 6.5 vs 12.5, P < 0.001; 1-3 years old, 13.0 vs 29.5, P < 0.001; 4-5 years old, 5.5 vs 11.5, P < 0.001). Hospitalization due to foreign body ingestions increased significantly in 2020 (1.0 vs 0.0, P = 0.010). CONCLUSIONS: The COVID-19 control measures inadvertently reduced the number of hospitalized pediatric patients, especially younger children with respiratory and gastrointestinal infections.

Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection.

Background: COVID-19 manifests with respiratory, systemic, and gastrointestinal (GI) symptoms.1, SARS-CoV-2 RNA is detected in respiratory and fecal samples, and recent reports demonstrate viral replication in both the lung and intestinal tissue.2, 3, 4 Although much is known about early fecal RNA shedding, little is known about long-term shedding, especially in those with mild COVID-19. Furthermore, most reports of fecal RNA shedding do not correlate these findings with GI symptoms.5. Methods: We analyzed the dynamics of fecal RNA shedding up to 10 months after COVID-19 diagnosis in 113 individuals with mild to moderate disease. We also correlated shedding with disease symptoms. Findings: Fecal SARS-CoV-2 RNA is detected in 49.2% [95% confidence interval, 38.2%-60.3%] of participants within the first week after diagnosis. Whereas there was no ongoing oropharyngeal SARS-CoV-2 RNA shedding in subjects at 4 months, 12.7% [8.5%-18.4%] of participants continued to shed SARS-CoV-2 RNA in the feces at 4 months after diagnosis and 3.8% [2.0%-7.3%] shed at 7 months. Finally, we found that GI symptoms (abdominal pain, nausea, vomiting) are associated with fecal shedding of SARS-CoV-2 RNA. Conclusions: The extended presence of viral RNA in feces, but not in respiratory samples, along with the association of fecal viral RNA shedding with GI symptoms suggest that SARS-CoV-2 infects the GI tract and that this infection can be prolonged in a subset of individuals with COVID-19. Funding: This research was supported by a Stanford ChemH-IMA grant; fellowships from the AACR and NSF; and NIH R01-AI148623, R01-AI143757, and UL1TR003142.

Effect of the COVID-19 Outbreak on the Incidence of Other Respiratory and Gastrointestinal Infections in Children in Thai Binh, Vietnam in 2020.

INTRODUCTION: To evaluate the impact of COVID-19 mitigation measures on the total number of consultations for respiratory and gastrointestinal infections among children under 16 years in Thai Binh Pediatric Hospital, Vietnam during the year 2020. METHODS: A retrospective study was carried out to review consecutive consultations occurring in children admitted from January 01, 2016 to December 31, 2020. All medical records were collected from the central numeric database of the hospital. Diagnoses were documented according to the International Classification of Diseases 10 criteria. RESULTS: 436,276 children consulted at the outpatient department during the period of study. A gradual increase in the total number of outpatients was observed from 2016 to 2019, including those consulting for respiratory and gastrointestinal infections. However, the total number of outpatients and the numbers of those consulting for respiratory and gastrointestinal infections dramatically decreased in 2020. A significant decrease of respiratory infections relative proportion was observed in 2020 when compared to 2016-2019 (p < 0.0001). By contrast, the relative proportion of gastrointestinal infections did not significantly vary (p = 0.91). The proportion of outpatients aged under 5 years was significantly lower in 2020 compared to previous years (p < 0.0001). The proportion of male patients was significantly higher in 2020 than from 2016 to 2019 (p = 0.001). CONCLUSION: Public health measures against the COVID-19 pandemic likely decreased the prevalence of other respiratory tract infections. Further studies are needed to validate the effectiveness of each type of measure. Microbiological studies are also recommended, to better understand the effect of preventive measures.

A Series of COVID-19 Cases With Findings in the Gastrointestinal and Hepatobiliary System.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide. Most of the infected patients present with respiratory symptoms and acute lung damage. Here, we present three cases of patients with COVID-19 disease whose main clinical manifestations are gastrointestinal symptoms. In our first case, we present a COVID-19 patient with histologic findings associated with ischemic necrosis of the small bowel. In the second and third cases, we demonstrate acute cholecystitis and histology showing microvascular thrombosis. These three cases highlight the ischemic and thrombotic changes seen in the setting of COVID-19 infection without classic respiratory symptoms, with resulting severe gastrointestinal and hepatobiliary disease requiring surgical management. Although the bile or stool viral load was not tested in these patients, the small intestine and gallbladder were infected with SARS-CoV-2, most likely via the epithelial angiotensin-converting enzyme 2 (ACE2) receptor.

Linking pathogens, people and places: Using geo-ethnography to understand place-based, socio-economic inequalities in gastrointestinal infections in the UK.

This ethnographic study in two socio-economically contrasting areas employed geo-ethnography, underpinned by a relational approach, to understand inequalities in gastrointestinal infections in families with young children. In our 'relatively disadvantaged' area, gastrointestinal infections spread to multiple households within a small radius, whereas in our 'relatively advantaged' area, illness was confined to one household or dispersed long distances. These differences were shaped by historical, social and economic contrasts in: housing; social networks and childcare arrangements; employment and household income. Our findings show how linking places, pathogens and people helps us understand inequalities in gastrointestinal infections and may be pertinent to other infectious diseases such as COVID-19.