IgA and FcαRI: Versatile Players in Homeostasis, Infection, and Autoimmunity.

Mucosal surfaces constitute the frontiers of the body and are the biggest barriers of our body for the outside world. Immunoglobulin A (IgA) is the most abundant antibody class present at these sites. It passively contributes to mucosal homeostasis via immune exclusion maintaining a tight balance between tolerating commensals and providing protection against pathogens. Once pathogens have succeeded in invading the epithelial barriers, IgA has an active role in host-pathogen defense by activating myeloid cells through divers receptors, including its Fc receptor, FcαRI (CD89). To evade elimination, several pathogens secrete proteins that interfere with either IgA neutralization or FcαRI-mediated immune responses, emphasizing the importance of IgA-FcαRI interactions in preventing infection. Depending on the IgA form, either anti- or pro-inflammatory responses can be induced. Moreover, the presence of excessive IgA immune complexes can result in continuous FcαRI-mediated activation of myeloid cells, potentially leading to severe tissue damage. On the one hand, enhancing pathogen-specific mucosal and systemic IgA by vaccination may increase protective immunity against infectious diseases. On the other hand, interfering with the IgA-FcαRI axis by monovalent targeting or blocking FcαRI may resolve IgA-induced inflammation and tissue damage. This review describes the multifaceted role of FcαRI as immune regulator between anti- and pro-inflammatory responses of IgA, and addresses potential novel therapeutic strategies that target FcαRI in disease.

CT findings and dynamic changes of COVID-19 in the patients younger than 18 years old infected with SARS-CoV-2 omicron variant

Objective: To investigate the chest computed tomography (CT) manifestations and dynamic changes of coronavirus disease 2019 (COVID-19) in the patients younger than 18 years old infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and to provide a basis for determining the chest CT changes and efficacy of COVID-19 caused by Omicron virus variant in patients younger than 18 years old. Methods The clinical and imaging data of 30 cases of patients younger than 18 years old infected with COVID-19 Omicron variant, who admitted to the Third People's Hospital of Shenzhen from February 11 to March 26, 2022 were collected and retrospectively analyzed. The clinical manifestations, imaging features and dynamic changes of lesions were summarized. Results A total of 41 intrapulmonary lesions in 30 patients with COVID-19 caused by SARS-CoV-2 Omicron variant. The main manifestations were patchy or nodular ground-glass opacities and/or consolidation, with focal subpleural distribution, lesions mainly occur in the right lung (70.73%, 29/41). There were 42 lesion morphologies, with 22 (52.38%) striped shadows and 16 (38.10%) nodular shadows, with small lamellar and patchy shadows predominating. There were 36 lesion density variations, with ground glass shadows being the most common, with a total of 24 ground glass shadows (66.66%) in each lobe of the lung, and also 6 consolidation lesions (16.67%) and 6 mixed ground glass opacity and consolidation lesions (16.67%). With the progression of the disease, lesions gradually enlarged, appeared on the 2nd day (312.93 mm3), peaked on the 9th day (1 837.18 mm3). The average absorption time of the lesions was (16+or-3) days, and there was no significant difference between the absorption time of patchy and nodular lesions (ground glass and/or consolidation) (t=0.853, P > 0.05). The lesions showed focal ground-glass opacity in the early stage, 77.78% lesions were absorbed after treatment in the late stage. Inflammatory nodules were absorbed slowly (9-19 days), without residual fibrotic changes. Conclusions The imaging manifestations of COVID-19 in patients younger than 18 years old infected with SARS-CoV-2 Omicron variant have certain characteristics, showed patchy or nodular ground glass opacities and/or consolidation, mainly distributed in the subpleural area, with small and few lesions and slow change, didn't remain fibrosis. Being familiar with its clinical and imaging manifestations can assist in early diagnosis, but confirming the diagnosis requires a combination of epidemiological history, clinical symptoms, SARS-CoV-2 nucleic acid and radiological manifestations.

Is the prognostic nutritional index a predictor of Covid-19 related hospitalizations and mortality?

Introduction Prognostic nutritional index (PNI) is a novel inflammation marker that useful in predicting prognosis of certain conditions. We aimed to study PNI of the outpatient and inpatient subjects with established Covid-19 and also aimed to compare PNI of deceased and survived Covid-19 patients. Methods The patients with Covid-19 whom presented to outpatient or inpatient clinics of Abant Izzet Baysal University Hospital were enrolled to the study. PNI levels of the inpatients and outpatients, deceased and survived were compared. PNI values of deceased and survived in inpatients were also compared. Results Study population was consisted of 4419 subjects (2907 outpatients and 1512 inpatients). PNI of the inpatient (41.55 (36.42-47.1)) group was significantly lower than the PNI of the outpatient (51.95 (47.95-55.75)) subjects (p<0.001). The sensitivity and specificity of PNI (≤46.2 level) in determination of requirement inpatient treatment were 71.2% and 83.5%, respectively. PNI of the deceased patients (37(33.39-40.86)) was lower than the PNI of the survivors (50.45(45.6-54.65)), (p<0.001). The sensitivity and specificity of PNI at ≤44.55 level in determining mortality were 89.22% and 78.87%, respectively. Conclusion We suggest that PNI could serve as a reliable prognostic index in covid-19 patients. Reduced level of PNI should alert physicians since it is associated with need for hospitalization and mortality in this population. © 2023 Kamuzu University of Health Sciences.

Safety and Immunogenicity of Coronavac and Chadox1 Vaccines against Sars-Cov-2 in Patients with Rheumatoid Arthritis: Brazilian Multicentric Study

Objectives: To evaluate the safety and immunogenicity of CoronaVac and ChAdOx1 vaccines against SARS-CoV-2 in patients with Rheumatoid Arthritis (RA). Method(s): These data are from the 'SAFER (Safety and Efficacy on COVID-19 Vaccine in Rheumatic Diseases)' study, a Brazilian multicentric longitudinal phase IV study to evaluate COVID-19 vaccine in immunomediated rheumatic diseases (IMRDs). Adverse events (AEs) in patients with RA were assessed after two doses of ChAdOx1 or CoronaVac. Stratification of postvaccination AEs was performed using a diary, filled out daily. The titers of neutralizing antibodies against the receptor-biding domain of SARS-CoV-2 (anti-RBD) were measured by chemilumine scence test after each dose of immunizers. Proportions between groups were compared using the Chi-square and Fisher's exact tests for categorical variables. Clinical Disease Activity Index (CDAI) before and after vaccination was assessed using the McNemar test. Result(s): A total of 188 patients with RA were included in the study, most of them were female. CoronaVac was used in 109 patients and ChAdOx1 in 79. Only mild AEs were observed. The more common AEs after the first dose were pain at injection site (46,7%), headache (39,4%), arthralgia (39,4%) and myalgia (30,5%), and ChAdOx1 had a higher frequency of pain at the injection site (66% vs 32 %, p alpha 0.001) arthralgia (62% vs 22%, p alpha 0.001) and myalgia (45% vs 20%, p alpha 0.001) compared to CoronaVac. The more common AEs after the second dose were pain at the injection site (37%), arthralgia (31%), myalgia (23%) and headache (21%). Arthralgia (41,42 % vs 25 %, p = 0.02) and pain at injection site (51,43% vs 27%, p = 0.001) were more common with ChAdOx1. No patients had a flare after vaccination. The titers of anti-RBDafter two doses of ChAdOx1 were higher compared to two doses of CoronaVac (6,03 BAU/mL vs 4,67 BAU/mL, p alpha 0,001). Conclusion(s): The frequency of local adverse effects, particularly pain at injection site, was high. AEs were more frequent with ChAdOx1, especially after the first dose. The use of the immunizers dis not change the degree of inflammatory activity of the disease. In patients with RA, ChAdOx1 was more immunogenic than CoronaVac. .

Herpes Gastritis: A Rare Cause of Gastric Outlet Obstruction

Introduction: Gastrointestinal tract involvement from herpes simplex virus is commonly associated with esophagitis. However, herpes simplex infection of the stomach is very rare with only a handful of cases being reported in immunocompromised patients. We present a case of herpes gastritis causing gastric outlet obstruction in an otherwise healthy, immunocompetent individual. Case Description/Methods: A 37-year-old male with a recent past medical history of COVID-19 infection, presented to the hospital with intractable nausea, vomiting, bloating, and early satiety for two days. Upon evaluation, CBC and CMP were remarkable for a WBC of 12.5 k/mm3 and ALT and AST of 124 U/L and 129 U/L, respectively. Lipase was 373 U/L. A CT abdomen/pelvis w/contrast showed circumferential wall thickening with edematous changes in the antrum consistent with localized inflammatory response. There was suspicion for gastric lymphoma and patient was admitted for further workup. An EGD was performed which showed exudative esophagitis and antral wall edema with luminal narrowing of gastric antrum. Endoscopic ultrasound (EUS) showed a 2.5 x 3 cm antral wall lesion worrisome for linitis plastica. Esophageal biopsies showed focal cytologic changes consistent with herpes esophagitis. The FNA of the gastric antral wall showed multinucleation of the basal cell layer with classic ground glass nuclei, consistent with herpes infection. No dysplasia or malignancy was seen. Both HSV1 and HSV2 IgG were elevated. HSV IgM was normal. A HSV PCR was ordered but never resulted. Patient was started on Valacyclovir 1 g PO BID for 10 days. He underwent a follow-up EGD 3 months later which showed complete resolution of the gastric antral changes (Figure). Discussion(s): Herpes gastritis is extremely rare. Literature review has revealed only 3 case reports of herpes gastritis;and all involved immunocompromised patients. To the best of our knowledge, this is the first case of herpes gastritis in an immunocompetent patient. Our patient presented with symptoms of gastric outlet obstruction which was caused by local inflammation from herpes simplex. It is unclear if having a COVID 19 infection altered patient's immunity and lead to herpes gastritis. This may need further investigation. No established guideline exists for treatment duration. Our patient received 10-day course of Valacyclovir, and his symptoms improved. Furthermore, patient had complete resolution of the herpes infection on follow-up EGD, indicating adequate treatment response.

Treatment of coronavirus disease 2019: Timing determines prognosis

The global epidemic of coronavirus disease 2019 (COVID-19) is still growing. The response to this emerging disease should be considered with the context of its clinical characteristics and pathophysiological mechanisms. Although available therapeutic options are still very limited, current experience has suggested that the choice of clinical strategies should be based upon the disease stage and immune functions of the patients. The present article reviews the clinical characteristics of COVID-19 and current evidence of various treatment approaches. Combined with first-line experience, we summarize the current clinical strategies for COVID-19 management based on disease progress and staging.Copyright © 2021, Peking Union Medical College Hospital. All rights reserved.

Clinical Features, Laboratory Findings Outcomes in Multisystem Inflammatory Syndrome (Mis-C) Following Covid-19 Infection - a Multicenter, Observational, Ambidirectional Cohort Study in Rio De Janeiro State, Brazil

Objectives: As of March 5th, 2022, around 1.585 cases of MIS-C and 98 deaths (6,4%) were reported in Brazil. The state of Rio de Janeiro State (RJ) having 94 cases (5,9%) and 4 deaths (4,2%)1.Our aim was to evaluate clinical and laboratory features, and management of MIS-C in seven pediatric hospitals in RJ, Brazil. Method(s): Multicenter, observational, ambidirectional cohort study in seven tertiary hospitals in RJ(Brazil), assessing medical charts of pediatric inpatients (0-18 years) diagnosed with MIS-C according to WHO/CDC criteria, from August, 2020 to February, 2022. Descriptive statistics were used to analyze distributions of continuous variables, frequencies, and proportions. Result(s): A total of 112 cases of MIS-C were enrolled. The mean age was 4.2 years and thre was male predominance (59,8%). All cases had a SARS-CoV-2 contact (29.5% close contact;31.3%:positive PCR;serology:43.8%).Only 12.5% had comorbidities. Length of stay (LOS) was 7 days.Median duration of fever was 8 days. Most common symptoms were: rash(67%);gastrointestinal (67%);conjunctivitis (42%);neurological(39.6%);cardiovascular(37.5%);cervical lymphadenopathy (36.6%), and shock/hypotension(28.6%).Co-infection occurred in 3 patients. Forty-four patients fulfilled criteria for Kawasaki disease. Most patients were admitted to PICU(12;62,5%) for amedian of 2 days. Respiratory distress was seen in 18,7%;hypotension:28,6%, and shock in 23,2%. Main laboratory findings were: high C-reactive protein in 95%;D-dimer:77%, anemia:77%, thrombocytosis:63%;transaminitis:43.8%, lymphopenia:38%;hypoalbuminemia:34%;thrombocytopenia: 29%;hypertriglyceridemia:28%, and high pro-BNP in 27%. Echocardiogram was performed in 91/112 patients;abnormal in 70,3%;exhibiting myocardial dysfunction( 25%);pericardial effusion(21%);coronary dilation/aneurysms(11%) and, valvulitis (14.5%). IVIG+corticosteroids (CTC) were administered in 59.8%(67/ 112);18.6%(18/112) IVIG only;10.7%(12/112) CTC only;3.4%(4/112)biologics, and 15(13.3%) received no treatment. ASA low dose in 77.7% (87/112) and moderate/high dose in 34.8%. Oxygen support was needed in 27,7%;vasoactive amines:18,7%;dialysis:5,3%, and transfusion:18,7%.One patient died from a cytokine storm syndrome. Conclusion(s): Our study reports a higher number of MIS-C cases in RJ than the number reported to Brazilian authorities, highlighting underreporting. Our patients were younger, had fewer comorbidities, cardiovascular/gastrointestinal/renal involvement, shortest LOS in ICU, and a higher frequency of myopericarditis.

Inflammasome pathways

Inflammasomes are cytosolic multiprotein complexes. They are an important component of the innate immune system, and their activation is a process for inflammation. Their pathologies cause for many autoinflammatory diseases such as familial Mediterranean fever (FMF), cryopyrin associated periodic fever syndrome (CAPS), and autoimmune disorders. The NLRP3 inflammasome is the most famous one. Inflammasome activation pathways are canonical, non-canonical, and alternative. There is a two-step model in which signal 1 is for priming and signal 2 is for activation. Inflammasome formation is triggered by sensors of danger or damage associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs). In response to these stimuli, the caspase-1 enzyme is activated. And it converts the proactive form of interleukin (IL)-1 beta to active IL-1beta and the same procedure for IL-18 which are pro-inflammatory cytokines. According to recent studies, COVID-19 infection also has the potential to activate inflammasomes to induce hyperinflammation which may be related to disease severity. © 2023 Nova Science Publishers, Inc. All rights reserved.

Ndegree39 - Fulminant life-threatening myopathy of the genetic origin

Objectives: Acute myopathy are seen in critically ill patients, in severe SARS-CoV2 pneumonia requiring mechanical ventilation, and other infection illness, toxin and drug-induced complications, or systemic inflammation. Periodic paralysis or carnitine disorders are known genetic causes of acute muscular weakness, besides genetically determined muscle diseases rarely have an acute clinical course. Content: Case presentation: 61-years old, healthy woman, after a one-time vaccination against Covid-19 about 2 weeks earlier, was admitted to the Neurological Department due to symptoms lasting for 2 days. On the first day of the disease she complained of vertigo and double vision, on the following day dysarthia and dysphagia appeared, she stopped walking. On the second day of hospitalization, the patient required mechanical ventilation. The initial diagnosis of Guillaine-Barre syndrome was not confirmed in the electrophysiological and laboratory (CSF) studies. Myopathic pattern with polyphasic potentials of short duration and low amplitude was observed in EMG, without spontaneous activity. In the electron microscope numerous fat drops between bundles of myofibrils in most muscle fibers were seen. She received intravenous immunoglobulins, and steroid therapy, together with high doses of vitamin B2 with very good motor improvement. Multiple acyl-CoA dehydrogenase deficiency (MADD) was suspected, and the Whole Exome Sequencing (WES) was performed. Conclusion(s): The authors note the possibility of acute, life-threatening myopathy, which may be caused by a genetic defect. MADD is a very rare genetic entity which can manifest for the first time very suddenly, especially in the presence of triggers, including but not limited to after vaccinations. Keywords: Acute myopathy;Multiple acyl-CoA dehydrogenase deficiency;Vitamin B2.Copyright © 2023

Hepatotoxicity From Marijuana Gummies

Introduction: We report a case of drug-induced liver injury (DILI) induced by cannabis gummies containing Corydalis Rhizome. Case Description/Methods: A 37-year-old female presented to her primary care clinic with recurrent fevers, night sweats, and myalgias for 7 weeks accompanied by eye redness, brain fog, headache, nausea, and abdominal pain. She denied rashes, tick-bites, cough, dyspnea, chest pain, joint swelling, or genitourinary symptoms. Past medical history was notable for IBS, migraines, and anxiety. She reported edible marijuana use four times a week, rare alcohol use, and denied tobacco use. She denied a family history of liver disease. Physical exam was notable for tachycardia to 110 and scleral injection with the remainder of vitals and exam unremarkable. Initial labs were notable for AST 61, ALT 44 and CRP of 12. CBC, BMP, urinalysis, ESR, blood cultures, blood smear for parasite screen, tests for Lyme disease, Babesia, Tularemia, Anaplasma, Ehrlichia, Rickettsia, EBV, HIV, RPR, ANA, CMV, parvovirus B19, and chest x-ray were all negative. The patient was referred to infectious disease with further testing for West Nile, Leptospira, lymphocytic choriomeningitis virus, and COVID-19 returning negative. Repeat LFTs showed worsening transaminitis with ALT 979 and AST 712, alkaline phosphatase 88, total bilirubin 0.7, and albumin 4.9. Hepatitis workup including hepatitis A, B, and C, HSV, EBV, VZV serologies, AMA, ASMA, antiLKM Ab, acetaminophen level, INR, iron panel, CPK, TSH, and abdominal ultrasound were all normal. It was later discovered that her marijuana gummies contained Corydalis rhizome extract known to be hepatotoxic. Cessation of this drug was strongly advised. She was discharged with hepatology follow-up and underwent a liver biopsy showing patchy periportal and lobular inflammation with extension across the limiting plate, hepatocyte injury and apoptosis, and increased lipofuscin for age compatible with mild to moderate hepatitis. She had complete recovery after cessation of Corydalis-containing gummies. (Figure) Discussion: Our patient consumed '1906 Midnight', an American cannabis brand containing Corydalis rhizopus 100 mg, advertised to improve sleep, pain, and have a liver protective effect. A Korean systematic review on herbal-induced liver injury reported that Corydalis was the 3rd most frequent causative herb, with 36 cases. Although there are several personal accounts on social networking sites and other websites, there are no American-based publications reported on DILI from Corydalis. (Table Presented).

Metabolic risks and prognosis of COVID-19: are dietary patterns important?

PurposeThis study aims to identify the dietary patterns of two groups of subjects (with and without COVID-19), and to assess the relationship of findings with the prognosis of COVID-19 and metabolic risk parameters.Design/methodology/approachThis study included 100 individuals in the age range of 19–65 years. The medical history, and data on biochemical, hematological and inflammatory indicators were retrieved from the files. A questionnaire for the 24-h food record and the food intake frequency was administered in face-to-face interviews, and dietary patterns of subjects were assessed.FindingsIn individuals with COVID-19, the hip circumference, the waist-hip ratio and the body fat percentage were significantly higher (p < 0.05), and the muscle mass percentage was significantly lower (p < 0.05). Mediterranean diet adherence screener (MEDAS), dietary approaches to stop hypertension (DASH) and healthy eating ındex-2015 (HEI-2015) scores were low in the two groups. A linear correlation of DASH scores was found with the muscle mass percentage (p = 0.046) and a significant inverse correlation of with the body fat percentage (p = 0.006). HEI-2015 scores were significantly and negatively correlated with body weight, body mass index, waist circumference, hip circumference and neck circumference (p < 0.05). Every one-unit increase in MEDAS, DASH and HEI-2015 scores caused reductions in C-reactive protein levels at different magnitudes. Troponin-I was significantly and negatively correlated with fruit intake (p = 0.044), a component of a Mediterranean diet and with HEI-2015 total scores (p = 0.032).Research limitations/implicationsThe limitation of this study includes the small sample size and the lack of dietary interventions. Another limitation is the use of the food recall method for the assessment of dietary patterns. This way assessments were performed based on participants' memory and statements.Practical implicationsFollowing a healthy diet pattern can help reduce the metabolic risks of COVÍD-19 disease.Originality/valueDespite these limitations, this study is valuable because, to the best of the authors' knowledge, it is the first study demonstrating the association of dietary patterns with disease prognosis and metabolic risks concerning COVID-19. This study suggests that dietary patterns during the COVID-19 process may be associated with several metabolic risks and inflammatory biomarkers.

2022 CAS Virtual Annual Meeting

The proceedings contain 63 papers. The topics discussed include: a retrospective study to optimize post-anesthetic recovery time after ambulatory lower limb orthopedic procedures at a tertiary care hospital in Canada;a virtual airway evaluation as good as the real thing?;airway management during in hospital cardiac arrest by a consultant led airway management team during the COVID-19 pandemic: a prospective and retrospective quality assurance project;prevention of cautery induced airway fire using saline filled endotracheal tube cuffs: a study in a trachea airway fire model;smart phone assisted retrograde illumination versus conventional laryngoscope illumination for orotracheal intubation: a prospective comparative trial;time to single lung isolation in massive pulmonary hemorrhage simulation using a novel bronchial blocker and traditional techniques;cannabinoid type 2 receptor activation ameliorates acute lung injury induced systemic inflammation;bleeding in patients with end-stage liver disease undergoing liver transplantation and fibrinogen level: a cohort study;endovascular Vena Cavae occlusion in right anterior mini-thoracoscopic approach for tricuspid valve in patients with previous cardiac surgery;and mesenchymal stem cell extracellular vesicles as a novel, regenerative nanotherapeutic for myocardial infarction: a preclinical systematic review.

Correlation between C-reactive protein (Crp) level and clinicoradiological profile in COVID-19 patients admitted in a tertiary care hospital in eastern India

Background: Coronavirus disease 2019, first reported in December 2019 mainly presented with the symptoms of Cough, Fever, Shortness of breath, Myalgia, Weakness and anosmia. C-reactive Protein (CRP) is an acute-phase reactant protein which is synthesized by the liver in response to raised levels of interleukin-6 (IL-6) which is a biomarker of inflammation. Methods: This was a prospective observational study, done on 110 COVID-19 patients after applying inclusion and exclusion criteria. Detailed history, vaccination status, presence of comorbidities and thorough clinical examination was performed. Serum CRP levels was assessed and Computed Tomographic scan (CT scan) of Thorax was done. CORADS scoring and CT severity grading as per CT scan was done. All the above parameters were recorded in the preformed proforma and data was entered in excel spreadsheet and was analysed using SPSS v26 software. Results: Majority were males (56.3%) and majority were from 61-80 years of age. Majority (57.3%) patients were non-smokers. Hypertension was the most common associated comorbidity (86.4%) (r=0.743, p=0.000). There is a strong positive correlation between CRP levels and CTSS in COVID 19 patients and a strong negative correlation between the CRP levels and outcome of COVID-19 patients (r=-0.449, p=0.000). Conclusion: Elevated serum CRP value is associated with disease progression and poorer outcome.

Prognostic role of inflammatory indices in risk classification of patients with COVID-19

Objective: The Covid-19 pandemic has revealed the importance of an evidence-based efficient triage system in the early identification of high risk patients and the rational use of limited medical resources for reducing mortality. The aim of this study was to evaluate the role of various inflammatory indices that can be easily calculated using readily accessible, inexpensive routine test parameters in risk stratification and prediction of prognosis in patients with Covid-19. Material and Methods: The study was carried out retrospectively with the data of 8036 patients with Covid-19, who were grouped according to their prognosis in outpatient and inpatient follow-ups, and inpatients as survivors and death. Using the complete blood count and C-reactive protein baseline results of the patients at admission, neutrophillymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocytelymphocyte ratio (MLR), MVP-platelet ratio (MPR), platelet mass index (PMI), systemic immune-inflammatory index (SII), systemic inflammatory response index (SIRI), and multi-inflammatory indices (MII) were calculated. Results: Our results demonstrate that almost all of the inflammatory indices were significantly different in severe patients and in patients with high mortality risk, but not all of them had a predictive value. It has been seen that the most effective factors in determining the disease severity at the onset of Covid-19 are SIRI and age, and SII, MII-1 and MII-3 may also contribute to this prediction. Our results have also revealed that NLR is the most effective independent factor to predict mortality both at disease onset and for inpatients. Conclusion: Inflammatory indices, especially SIRI, NLR, SII, MII-1 and MII-3 can substantially contribute to clinical decisions in the early identification of high-risk patients and predicting mortality beginning from the onset of Covid-19.

Usual food consumption and variations in lockdown during the first wave of COVID-19 in Argentina and Paraguay

The objective was to analyze food intake and its variations during lockdown in the first wave of COVID-19 in Argentina (AR) and Paraguay (PY), year 2020 and the impact of self-perception of anxiety regarding consumption. An online survey was implemented inquiring about socio-demographic characteristics, usual food intake, self-perception of changes in consumption and anxiety during lockdown. A logistics regression model was developed to analyze the association among variables. There were 2621 participants from AR and 2164 from PY. Only 46% from AR and 36% from PY usually fulfilled the recommendation of 2 servings of vegetables a day, and 11% in total complied with the recommended 3 fruits a day. Only 1 out of 4 participants drinks enough water and optional consumption products (processed products and with high sugar level, saturated fat and sodium) were usually present in an important proportion. Fifty-six percent from AR and 72% from PY showed anxiety because of pandemic and lockdown, affecting their eating habits. In AR, anxiety perception raised significantly the OR of modifying usual consumption of vegetables (OR=1.4), fruit (OR=1.7), meat (OR=1.6), dairy products (OR=1.09), sugary products (OR=2.1) and sugary drinks (OR=1.6). The same was observed in PY for intake of vegetables (OR=1.6), fruit (OR=1.8), meat (OR=2.8), dairy products (OR=2.8), sugary products (OR=3.9) and sugary drinks (OR=2.3). In conclusion, lockdown changed eating habits and there may be an impact on immunological state and general health.

COVID-19: a perspective focus on IL-17/Th17 / COVID-19: perspectivas terapéuticas en IL-17/Th17

RESUMEN Las células T helper-17 (Th17) y la interleuquina (IL) IL-17 desempeñan funciones biológicas relacionadas con la protección contra infecciones por bacterias extracelulares y hongos. En algunas enfermedades inflamatorias y autoinmunes hay una secreción persistente y estas participan en su patogénesis. Recientemente, se ha postulado la participación de las respuestas IL-17/Th17 en la patogénesis de la enfermedad por coronavirus 2019 (COVID-19). El objetivo de esta revisión es resumir la evidencia del papel de la IL-17/Th17 en la inmunopatogénesis del COVID-19, como sustento de la possible utilización de los inhibidores de IL-17 en el manejo terapéutico de esta infección.

SUMMARY Interleukin 17 (IL-17)-producing helper T cells (Th17) and IL-17 play an important role in the defense against extracellular bacteria and fungi; however, persistent secretion of IL-17 is also an important component in the pathogenesis of many inflammatory and autoimmune diseases. Recent evidence suggests that Th17 cells and IL-17 are also involved in the immunopathogenesis of COVID-19. This review summarizes the evidence related with the role of Th17/IL-17 in severe COVID-19, which support the possible use of IL-17/IL-17R inhibitors in the treatment of this infection.

Research highlights on kidney transplantation in 2021: Voices from China

Over the past 70 years, kidney transplantation has become not only the most mature but also the highest-success-rate surgery among all organ transplantation surgeries. However, the long-term survival of kidney transplant recipients is still challenged by such key factors as ischemia-reperfusion injury related to kidney transplantation, rejection, chronic renal allograft dysfunction, renal allograft fibrosis, immunosuppressive therapy, infections and others. Relevant fundamental and clinical studies have emerged endlessly. At the same time, the research related to kidney transplantation also becomes a new hot spot accordingly in the context of the normalization of novel coronavirus pneumonia. This article reviewed the cutting-edge hot spots in relation to the fundamental and clinical aspects of kidney transplantation together with relevant new techniques and new visions. The studies included in this article focused on the reports published by Chinese teams that are more applicable to the current situation of kidney transplantation in China, for the purpose of providing new thoughts and strategies for the diagnosis and treatment of kidney transplantation related issues in China.Copyright © 2022 Organ Transplantation. All rights reserved.

Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation

Currently, human health due to corona virus disease 2019 (COVID-19) pandemic has been seriously threatened. The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19. However, the efficacy is compromised by the SARS-CoV-2 evolvement and mutation. Here we report the SARS-CoV-2 S protein receptor-binding domain (RBD) inhibitor licorice-saponin A3 (A3) could widely inhibit RBD of SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, XBB and BQ1.1. Furthermore, A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells, with EC50 of 1.016 μM. The mechanism was related with binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis combined with quantum mechanics/molecular mechanics (QM/MM) simulations. Interestingly, phosphoproteomics analysis and multi fluorescent immunohistochemistry (mIHC) respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 MAPK pathways and rebalancing the corresponding immune dysregulation. This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

The Association Between Stool Shedding of SARS-Cov-2 Microbiome Diversity and Intestinal Inflammation

Introduction: The transmission of the etiologic virus of COVID-19 (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) is thought to occur mainly via respiratory droplets even though limited evidence has shown the virus can be found in feces and involve the gastrointestinal (GI) tract. The aim of this study was to assess if patients with COVID-19 present with fecal shedding of SARS-CoV-2, intestinal inflammation or changes in their microbiota. Method(s): This was a prospective cohort study that included outpatients that presented with symptoms of COVID-19 and were tested using a nasopharyngeal PCR test (NPT). Two cohorts were selected: one with a (1) NPT and a control group with a (-) NPT. Stool and a clinical data were collected at baseline and then, days 14, 28 and 42. SARS-CoV-2 viral loads were measured in stool using PCR and stool microbiome was analyzed using 16S rRNA gene sequencing (V3/V4 region). Fecal calprotectin levels were also measured on each sample and used as a surrogate marker of intestinal inflammation. Result(s): 101 patients were recruited (410 total samples). Of those, 55 had a (1) COVID-19 NPT. Most patients with a (1) COVID-19 NPT PCR had a detectable fecal viral load (71%). Among these patients, 23 (55%) had detectable viral stool loads only at baseline, 12 through day 14, 6 through day 28 and 1 through day 42. One patient had a (-) NPT but detectable SARS-CoV-2 in the baseline stool sample. Subjects with (1) NPT presented more commonly with myalgias (p=0.02), dysgeusia (p=0.019) and anosmia (p=0.03) when compared to those with (-) NPT but there were no differences in any other symptoms including GI manifestations.Within the group with a (1) NPT, those patient with detectable SARS-CoV-2 in the stool were younger but no differences were seen in demographic, symptoms, or fecal calprotectin levels (Table). There was no correlation between fecal SARS-CoV-2 loads and fecal calprotectin levels (rho: 0.007 [p=0.95]). Patients with a (1) NPT PCR had higher evenness when compared to those that tested (-) for a NPT PCR. However, no differences were seen in other alpha or beta diversity (Figures 1A and 1B, respectively). Conclusion(s): Even though intestinal viral shedding of SARS-CoV-2 in patients with COVID-19 is common, these patients do not present with evidence of inflammation of the GI tract, a significantly disrupted gut microbiome or a higher incidence of GI symptoms when compared to patients with respiratory symptoms and no COVID-19.

Scientific debrief: cirrhosis

Globally, hepatitis C (26%), alcohol (24%), and hepatitis B (23%) contribute almost equally to the global burden of cirrhosis. The contribution from nonalcoholic fatty liver disease (8%) is small but increasing. Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acuteon-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure, Cardiovascular alterations including portal hypertension trigger the formation of portocaval shunts and varices. Systemic under filling and arterial hypotension is compensated by vasoconstriction but might decline into a state of aggravated portal hypertension and cirrhotic cardiomyopathy, leading to a hyperdynamic state, microvascular dysfunction and reduced organ perfusion culminating in decompensation. The immune system is dysfunctional showing a contrary co-existence of immune paralysis and immune overstimulation leading to secondary infections and inflammatory response syndrome aggravating cardiovascular alterations but also initiating tissue injury and metabolic alteration. This transition from compensated to decompensated cirrhosis is characterised by the occurrence of ascites, variceal bleeding and/or hepatic encephalopathy or organ failures (in the case of ACLF. Precipitating events for ACLF vary between Western countries (bacterial infection, alcohol intake) and Eastern countries (flare of HBV, superimposed HAV or HEV). In the majority of patients, systemic inflammation is a major driver of progression from compensated to decompensated cirrhosis. Once the first episode of AD develops, systemic inflammation follows a chronic course, with transient periods of aggravation due to proinflammatory precipitants or bursts of bacterial translocation resulting in repeated episodes of AD. The multistate model describing the clinical outcomes of decompensated cirrhosis has been well validated. State 3 is defined by the occurrence of variceal bleeding alone, state 4 by any single non-bleeding event, state 5 by any 2 or more events and the late decompensate state by any event with organ failures either with or without ACLF. 5-year mortality across states from 3 to 5 is in the order of, respectively: 20%, 30%, 88%. With late decompensation mortality ranges between 60 and 80% at 1 year. Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes. Aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, management of hepatic encephalopathy (HE), ascites, hepatorenal syndrome, non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue, and reduce the risk of hepatocellular carcinoma. New disease-modifying agents are expected to be identified in the next few years by systematic drug repurposing and the development of novel molecules currently undergoing pre-clinical or early clinical testing. COVID-19 continues to pose a significant healthcare challenge throughout the world. Comorbidities including diabetes and hypertension are associated with a significantly higher mortality risk. Cirrhosis is associated with an increased risk of all-cause mortality in COVID-19 infection compared to non-cirrhotic patients. Patients with cirrhosis should be considered for targeted public health interventions to prevent COVID-19 infection, such as shielding and prioritisation of vaccination.