Serum Antibody Tests Research Articles

PS-BPR03-8: MALIGNANT HYPERTENSION WITH ACUTE KIDNEY INJURY AND THROMBOTIC MICROANGIOPATHY SUCCESSFULLY TREATED WITH ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITOR

Background: Malignant hypertension is a disease characterized by severe hypertension and multi-organ damage. Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor (ARNi), has already demonstrated the superiority of reducing blood pressure versus olmesartan in patients with hypertension. ARNi has also been shown to improve cardiac biomarkers, cardiac remodeling, and prognosis in patients with heart failure, and a new AHA/ACC/HFSA guideline (2022) redefined to recommend ARNi as first-line renin-angiotensin-system inhibitors (class 1a) in patients with HFrEF (heart failure with reduced ejection fraction). However, the evidence about the efficacy and safety of ARNi in end-stage renal disease (ESRD) patients undergoing hemodialysis has been limited. Presentation: A 23-year-old man with no prior medical history was admitted to the previous hospital with severe hypertension (blood pressure 224/159 mmHg) associated with acute kidney injury (BUN 228.5 mg/dl, serum creatinine 25.50 mg/dl) and was referred to our hospital with the initiation of hemodialysis. He was also complicated with hypertensive heart failure with a preserved ejection fraction (NT-proBNP 172113 pg/ml). Blood test results also revealed thrombocytopenia (platelet 11.9 x 103/μL), hemolytic anemia (hemoglobin 7.4 g/dl, LDH 1076 U/L, haptoglobin < 10 mg/dl), and schistocyte on the blood smear, which was suggestive of thrombotic microangiopathy. His blood cell counts and serum LDH levels improved after antihypertensive treatment. Secondary hypertension, such as primary aldosteronism, Cushing's syndrome, pheochromocytoma, and renal artery stenosis, was deniable by further examination. The elevated levels of renin (65.5 ng/ml/hr) and aldosterone (685 pg/ml) were consistent with malignant hypertension. Serum antibody tests for screening of autoimmune disease were all negative. Renal biopsy revealed findings of malignant nephrosclerosis: glomerular collapse, glomerulosclerosis, endothelial swelling, and media thickening of the arteries. Oliguria recovered during the clinical course; however, his renal function did not fully recover. An arterio-venous fistula was created, and maintenance hemodialysis two times per week was continued during hospitalization. Even though his dry weight was adjusted to normal by repeated dialysis, his blood pressure was poorly controlled to systolic blood pressure of 160–170 mmHg by calcium channel blockers, angiotensin II receptor blocker (ARB), and alpha/beta-blockers. After switching from ARB to ARNi by increasing the dose to a maximum of 400 mg, his systolic blood pressure improved to 130–140 mmHg and was stable throughout the day, assessed by ambulatory blood pressure monitoring. Conclusion: Through our experience, it is conceivable that ARNi may be helpful in the settings of resistant hypertension in ESRD patients undergoing hemodialysis.

Mimics of Pediatric Small Vessel Primary Angiitis of the Central Nervous System.

Small vessel primary angiitis of the central nervous system is a rare and often severe disease characterized by central nervous system-restricted inflammatory vasculitis on histopathology. Diagnosis requires brain biopsy for confirmation and is suggested prior to starting immunotherapy when feasible. However, emerging evidence suggests that other neuroinflammatory conditions may have a clinical and radiographic phenotype that mimics small vessel primary angiitis, at times with overlapping pathologic features as well. Such diagnoses, including myelin oligodendrocyte glycoprotein antibody-associated disease and central nervous system-restricted hemophagocytic lymphohistiocytosis, can be non-invasively diagnosed with serum antibody or genetic testing that would prompt different monitoring and treatment paradigms. To determine the ultimate diagnosis of patients who were suspected prior to biopsy to have small vessel primary angiitis, we reviewed the clinical, radiographic, and pathological features of a cohort of patients at a single center undergoing brain biopsy for non-oncologic indications. Clinical data were retrospectively extracted from the medical record. Pathology and neuroimaging review was conducted. We identified 21 patients over a 19-year time-period, of whom 14 (66.7%) were ultimately diagnosed with entities other than small vessel primary angiitis that would have obviated the need for brain biopsy. Diagnoses included anti-myelin oligodendrocyte glycoprotein antibody associated disease (n=9), central nervous system-restricted hemophagocytic lymphohistiocytosis (n=3), anti-GABAA receptor encephalitis (n=1), and Aicardi-Goutières syndrome (n=1). This study highlights the importance of pursuing now readily available non-invasive testing for mimicking diagnoses before performing a brain biopsy for suspected small vessel primary angiitis of the central nervous system. ANN NEUROL 2023;93:109-119.

Assessing Immune Response to 3rd Dose of COVID-19 Vaccine Series in Patients Undergoing Cancer Treatment at University Medical Center- New Orleans

Background: COVID-19 pandemic remains a global emergencies. Vaccines against the virus SARS-CoV-2 have been shown to reduce incidence and severe complications from COVID-19 infection. Previous studies have shown that patients receiving active cancer therapies for solid or hematological malignancies demonstrated a significantly lower response after initial 2- doses of vaccines, in comparison to the general population. There is limited data on the immune response to a 3rd dose of the mRNA COVID-19 vaccine in patients receiving active treatment for malignancies and especially in minorities. This study aims to assess immune response against SARS-CoV-2 after 3rd dose of mRNA vaccination in this particular population. Study Design: Between September 2021 and January 2022, 119 patients on active cancer treatments at University Medical Center- New Orleans were enrolled on this prospective study (IRB Protocol 641). Plasma samples were collected before and approximately 3-6 weeks after the 3rd vaccine dose. 40 patients received the 3rd vaccine dose and completed the study. Serum antibody testing by ELISA was performed. IgG response was assessed by testing for antibodies against the wild type SARS-CoV-2 proteins RBD and N (natural COVID-19 infection). Results: Patient demographics consisted of 66.4% African American, 27.3% Caucasian, and 6.4% others. On the average, there was an approximately 8x fold increase in titer response after the 3rd dose of SAR-CoV-2 vaccination. Titer response was highest in patients on immunotherapy compared to those on cytotoxic chemotherapy. Higher titer response were also observed in patients with metastatic cancers compared to non-metastatic cancers, in African Americans compared to other ethnicities, and males. Patients who received the 3rd vaccine dose six months after initial 2-dose series tended to mount higher titer response compared to those who received their 3rd dose within 3 months. None of study subjects were hospitalized for COVID-19 infection during the duration of this study. Conclusion: 3rd dose mRNA vaccines against SAR-CoV-2 were effective in preventing infections and complications from COVID-19 infection in patients and ethnic minorities who are on active treatment for solid and liquid malignancies. Our study is limited by the small number of subjects. Studies are being conducted to evaluate duration of antibodies response in this patient group compared to general population.

Circumferential Gastric Wall Thickening With Lymphadenopathy

Question: A 78-year-old Japanese man with a history of hypertension and abdominal aortic aneurysm visited our hospital for epigastric discomfort lasting more than a week. Blood examination revealed mildly elevated white blood cell counts (9900/μL) and normal red blood cell and platelet counts. Biochemical analyses indicated no specific abnormalities except mildly elevated C-reactive protein levels (1.89 mg/dL, normal range <0.14 mg/dL). Serum tumor marker levels, including carcinoembryonic antigen and carbohydrate antigen 19-9, were within the normal ranges. Although Helicobacter pylori infection was detected via serum antibody test, he had not received eradication therapy previously. Contrast-enhanced computed tomography (CT) showed circumferential gastric wall thickening with hyperenhancement on the mucosal surface, accompanied by infrapyloric lymphadenopathies (Figure A). Minimal ascites was found around the liver and in the pelvis. On fluorodeoxyglucose (FDG) positron emission tomography–CT, the thickened gastric wall and swollen lymph nodes showed intense accumulation of FDG with a maximum standardized uptake value of 5.23 and 4.33, respectively (Figure B). Moreover, minor mucosal erosions and ulcerations on the gastric body and the antrum were observed during esophagogastroduodenoscopy (EGD) (Figure C). The distensibility of the gastric wall by CO2 insufflation was not impaired on EGD. Endoscopic mucosal biopsies were performed on the thickened gastric wall with ulcerations. What is the most likely diagnosis here, and how should these lesions be treated? Look on page 339 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Gastric linitis plastica (GLP), a distinct subtype of gastric cancer characterized by thickening and rigidity of the gastric wall,1Vivier-Chicoteau J. Lambert J. Coriat R. et al.Development and internal validation of a diagnostic score for gastric linitis plastica.Gastric Cancer. 2020; 23: 639-647Crossref PubMed Scopus (10) Google Scholar was primarily suspected from the imaging findings. Perigastric lymphadenopathies and ascites suggested lymph node metastases and peritoneal dissemination, reflecting the aggressive behavior of GLP.1Vivier-Chicoteau J. Lambert J. Coriat R. et al.Development and internal validation of a diagnostic score for gastric linitis plastica.Gastric Cancer. 2020; 23: 639-647Crossref PubMed Scopus (10) Google Scholar However, the biopsy obtained from the margins of the ulceration did not reveal any malignant cells suggestive of GLP. Hematoxylin and eosin (HE) staining showed infiltration of numerous histiocytes and noncaseating granuloma formation (Figure D). Because the superficial biopsy often results in inconclusive diagnosis of GLP, laparoscopic resection of the swollen infrapyloric lymph nodes was performed to obtain a more substantial amount of tissue. HE staining of the surgically resected lymph nodes showed the formation of multiple small-size epithelioid granulomas (Figure E). To determine the etiology of granuloma formation, various kinds of immunohistochemical studies were performed. Accumulation of H pylori was observed inside the granuloma of both gastric mucosa (Figure F) and lymph nodes (Figure G) with the use of H pylori–specific antibody (B0471; Dako, Denmark) whereas Epstein-Barr virus or tuberculosis was not detected by in situ hybridization or Ziehl-Neelsen staining. In addition, the possibility of gastric sarcoidosis was low because the serum angiotensin-converting enzyme level was not elevated and gastric granuloma was negative for immunostaining of monoclonal antibody against Propionibacterium acnes (D371-3; MBL, Japan).2Yamaguchi T. Costabel U. McDowell A. et al.Immunohistochemical detection of potential microbial antigens in granulomas in the diagnosis of sarcoidosis.J Clin Med. 2021; 10: 983Crossref PubMed Scopus (17) Google Scholar,3Inomata M. Ikushima S. Awano N. et al.Upper gastrointestinal sarcoidosis: report of three cases.Intern Med. 2012; 51: 1689-1694Crossref PubMed Scopus (16) Google Scholar Therefore, the diagnosis of granulomatous gastritis associated with H pylori infection was made. Successful H pylori eradication therapy with vonoprazan, amoxicillin, and clarithromycin improved his symptoms. Furthermore, gastric wall thickening on CT as well as gastric mucosal ulcerations on EGD disappeared entirely 6 months after the H pylori eradication (Figures H and I), which further verified the diagnosis. This case highlights that granulomatous gastritis associated with H pylori infection needs to be considered in the differential diagnosis when encountering H pylori–positive cases exhibiting circumferential gastric wall thickening with lymphadenopathy.

Changes in prevalence of Helicobacter pylori in Japan from 2008 to 2018: a repeated cross-sectional study

ObjectivesTo understand the recent prevalence and time trends of Helicobacter pylori infection rates in the Japanese population.DesignRepeated cross-sectional study.ParticipantsA total of 22 120 workers (age: 35–65 years) from one Japanese...

Identification of serum microRNAs as potential diagnostic biomarkers for detecting precancerous lesions of gastric cancer.

Gastric mucosal changes associated with chronic gastritis are known to be precancerous lesions of gastric cancer. We aimed to identify individuals with a high risk of gastric cancer by detection of microRNAs (miRNA) in the blood as biomarkers. Of 1206 individuals screened, 144 who were positive for Helicobacter pylori (H.pylori) by the serum antibody test and who underwent endoscopy were the subjects of this study. For the gross assessment of mucosal inflammation, we applied the Kimura-Takemoto classification, in which normal mucosa was defined as grade 0, and atrophy was categorized as grade 1 (C-1 and C-2), grade 2 (C-3 and O-1), and grade 3 (O-2 and O-3). Serum samples were divided into two phases and used for miRNA microarray profiling. We compared the expression of miRNAs in grade 3 mucosa and other grades. Expression in gastric cancer was confirmed with TCGA data. miR-196b-3p was significantly upregulated, and miR-92a-2-5p was downregulated (P < .05 and q < 0.2). TCGA data showed a high expression of miR-196b-3p in gastric cancer cases (P < .001). Comparing grade 3 and the others, the area under the receiver operating characteristic curve using the detected miRNAs was as high as about 0.7. Furthermore, the combination of miRNAs resulted in higher accuracy. In terms of the significance of the combinatory mRNAs, the combination of three miRNAs (miR-196b-3p, miR-92a-2-5p, and miR-6791-3p) revealed high sensitivity and specificity, with the area under the curve exceeding 0.8. The identified combinatory miRNAs may represent promising biomarkers of precancerous lesions in gastric cancer.

Epidemiological Study on Salmonella Prevalence in Sow Herds Using Direct and Indirect Detection Methods.

In piglet production, the beginning of pork production, Salmonella prevalence requires greater attention as having an impact on the subsequent production steps. The aim of this study was to investigate Salmonella prevalence in three sow herds with attached piglet rearing units. Salmonella prevalence was investigated either directly by boot swabs and feces or indirectly by serum samples taken during gilt integration, the peripartal period, and piglet rearing. Boot swabs and feces were analyzed by real-time PCR and subsequent microbiology. Results indicated that high biosecurity measures in sow husbandry do not necessarily result in a low Salmonella prevalence. Furthermore, the sow herds’ Salmonella prevalence should not be used to infer the situation in the associated piglet rearing. The proportion of positive boot swabs was 10.5, 3.6, and 21.3% for sows (gilts and peripartal) with an inverse situation in piglet rearing with 50.0, 63.3, and 5.8% positive swabs for farms A, B, and C, respectively. Boot swabs are suitable as a direct sampling method to gain an overview of Salmonella prevalence in both sows and piglets. Indirect serum antibody testing can be useful, although it should be evaluated considering age-dependent levels of antibody titres.

Case Report: Acute Retinal Necrosis after a Cervical Epidural Steroid Injection

Acute retinal necrosis is a rare, sight-threatening condition typically found in immunocompromised patients and is most commonly caused by varicella zoster virus. Due to the poor prognosis and rapid progression of the disease course, prompt antiviral management is paramount. A case report of acute retinal necrosis in a patient with herpes virus infection following a cervical epidural corticosteroid injection. Extensive laboratory work and frequent follow-ups are necessary for management. This case report outlines the clinical signs of acute retinal necrosis and discusses the appropriate referrals and treatment needed to improve prognosis. A 63-year-old man presented to our eye clinic with symptoms of pain and light sensitivity. Examination revealed anterior uveitis, vitritis, optic disc edema, macular edema, vasculitis, and retinitis of the left eye. The serum antibody test results showed abnormal ranges for varicella zoster virus and herpes simplex virus type 1, and the patient was diagnosed with acute retinal necrosis. Treatment prescribed by a retina specialist included oral valacyclovir and later oral prednisolone, for which the patient responded well before developing the common complication of retinal detachment. The progressive nature of acute retinal necrosis is usually debilitating to vision, even when managed properly. Because prognosis is often poor, it is important to make proper diagnoses combined with a complete review of the patient's medical history and immune status to prevent further vision loss.

Anti-dipeptidyl-peptidase-like protein 6 encephalitis with pure cerebellar ataxia: a case report

BackgroundAnti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare autoimmune encephalitis. The clinical symptoms of anti-DPPX encephalitis are often severe, manifested as diarrhea/weight loss, central nervous system hyperexcitability and cognitive dysfunction.Case presentationAn 18-year-old boy was admitted for 1-week-long cerebellar symptoms including dizziness, unsteady gait and frequent vomiting. Magnetic resonance imaging (MRI) displayed no abnormal findings. However, autoimmune encephalitis panel revealed anti-DPPX antibody was positive in the serum. This patient completely recovered after immunoglobulin and corticoids therapy. In addition, repeat serum antibody test for DPPX was negative within one month.ConclusionIn addition to the classic triad, anti-DPPX encephalitis may manifest as mild and rare symptoms due to lower antibody titers. Fast identification of rare symptoms can help to quickly diagnosis and effective treatment.

Antibody-Positive Neuromyelitis Optica Spectrum Disorder After Second COVID-19 Vaccination: a Case Report

In the era of the COVID-19 pandemic declared in March 2020, widespread vaccination protocols were initiated to mitigate the severity and spread of COVID-19. Although COVID-19 vaccines have been generally considered safe, adverse events post-vaccination have been reported, including the development of demyelinating disease. We report a rare case of de novo aquaporin-4-positive neuromyelitis optica spectrum disorder (NMOSD) in an 80-year-old man following BNT162b SARS-CoV-2 vaccination to raise the awareness of this possible severe adverse event in an older adult. An 80-year-old South Asian man presented 2 days following his second dose of the Pfizer-BioNTech COVID-19 mRNA BNT162b2 vaccine with progressive left-sided leg weakness and numbness resulting in falls. MRI of the spine revealed a longitudinally extensive transverse myelitis from T3–T4 to T9–T10. Serum antibody testing revealed positive aquaporin-4 (AQP4) antibodies. He was diagnosed with AQP4-positive NMOSD and was treated with high-dose intravenous methylprednisolone and plasma exchange with some improvement. He was subsequently treated with mycophenolate mofetil and a slow steroid wean. This case report adds to the existing literature and suggests that COVID-19 vaccinations may trigger de novo NMOSD or NMOSD relapses in some individuals. Although rare, our patient presented with new-onset NMOSD in his 80 s following COVID-19 vaccination. As such, it is relevant to consider AQP4 testing in those presenting with a post-vaccination myelitis, regardless of age. Ongoing vaccine surveillance and research are needed to understand the risk of NMOSD post-COVID-19 vaccinations further.

Safety and immunogenicity of a live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine in adults: randomised, double-blind, placebo-controlled, phase 1 and 2 trials

BackgroundAll currently available SARS-CoV-2 vaccines are administered by intramuscular injection. We aimed to evaluate the safety and immunogenicity of a live-attenuated influenza virus vector-based SARS-CoV-2 vaccine (dNS1-RBD) administered by intranasal spray in healthy adults.MethodsWe did double-blind, randomised, placebo-controlled phase 1 and 2 trials, followed by a phase 2 extension trial, at a single centre in Jiangsu, China. Healthy adults (≥18 years) who had negative serum or fingertip blood total antibody tests for SARS-CoV-2 (in phases 1 and 2), with no prevalent SARS-CoV-2 infection or history of infection and no SARS-CoV-2 vaccination history (in all three trials reported here), were enrolled. Participants were randomly allocated (4:1 in phase 1, 2:1 in phase 2, and 1:1 in the extension trial) to receive two intranasal doses of the dNS1-RBD vaccine or placebo on days 0 and 14 or, for half of the participants in phase 2, on days 0 and 21. To avoid cross-contamination during administration, vaccine and placebo recipients were vaccinated in separate rooms in the extension trial. The phase 1 primary outcome was safety (adverse events recorded on days 0–44; serious adverse events recorded from day 0 until 12 months after the second dose). In the phase 2 and extension trials, the primary immunogenicity outcomes were SARS-CoV-2-specific T-cell response in peripheral blood (measured by IFN-γ ELISpot), proportion of participants with positive conversion for SARS-CoV-2 receptor-binding domain (RBD)-specific IgG and secretory IgA (s-IgA) antibodies, and concentration of SARS-CoV-2 RBD IgG in serum and SARS-CoV-2 RBD s-IgA in the nasopharynx (measured by ELISA) at 1 month after the second dose in the per-protocol set for immunogenicity. χ2 test and Fisher's exact test were used to analyse categorical data, and t test and Wilcoxon rank sum test to compare the measurement data between groups. These trials were registered with the Chinese Clinical Trial Registry (ChiCTR2000037782, ChiCTR2000039715, and ChiCTR2100048316).FindingsBetween Sept 1, 2020, and July 4, 2021, 63, 724, and 297 participants without a history of SARS-CoV-2 vaccination were enrolled in the phase 1, phase 2, and extension trials, respectively. At least one adverse reaction after vaccination was reported in 133 (19%) of 684 participants in the vaccine groups. Most adverse reactions were mild. No vaccine-related serious adverse event was noted. Specific T-cell immune responses were observed in 211 (46% [95% CI 42–51]) of 455 vaccine recipients in the phase 2 trial, and in 48 (40% [31–49]) of 120 vaccine recipients compared with one (1% [0–5]) of 111 placebo recipients (p<0·0001) in the extension trial. Seroconversion for RBD-specific IgG was observed in 48 (10% [95% CI 8–13]) of 466 vaccine recipients in the phase 2 trial (geometric mean titre [GMT] 3·8 [95% CI 3·4–4·3] in responders), and in 31 (22% [15–29]) of 143 vaccine recipients (GMT 4·4 [3·3–5·8]) and zero (0% [0–2]) of 147 placebo recipients (p<0·0001) in the extension trial. 57 (12% [95% CI 9–16]) of 466 vaccine recipients had positive conversion for RBD-specific s-IgA (GMT 3·8 [95% CI 3·5–4·1] in responders) in the phase 2 trial, as did 18 (13% [8–19]) of 143 vaccine recipients (GMT 5·2 [4·0–6·8]) and zero (0% [0–2]) of 147 placebo recipients (p<0·0001) in the extension trial.InterpretationdNS1-RBD was well tolerated in adults. Weak T-cell immunity in peripheral blood, as well as weak humoral and mucosal immune responses against SARS-CoV-2, were detected in vaccine recipients. Further studies are warranted to verify the safety and efficacy of intranasal vaccines as a potential supplement to current intramuscular SARS-CoV-2 vaccine pools. Steps should be taken in future studies to reduce the potential for cross-contamination caused by the vaccine strain aerosol during administration.FundingNational Key Research and Development Program of China, National Science, Fujian Provincial Science, CAMS Innovation Fund for Medical Sciences, and Beijing Wantai Biological Pharmacy Enterprise.

Use of machine-learning algorithms to aid in the early detection of leptospirosis in dogs.

Leptospirosis is a life-threatening, zoonotic disease with various clinical presentations, including renal injury, hepatic injury, pancreatitis, and pulmonary hemorrhage. With prompt recognition of the disease and treatment, 90% of infected dogs have a positive outcome. Therefore, rapid, early diagnosis of leptospirosis is crucial. Testing for Leptospira-specific serum antibodies using the microscopic agglutination test (MAT) lacks sensitivity early in the disease process, and diagnosis can take >2 wk because of the need to demonstrate a rise in titer. We applied machine-learning algorithms to clinical variables from the first day of hospitalization to create machine-learning prediction models (MLMs). The models incorporated patient signalment, clinicopathologic data (CBC, serum chemistry profile, and urinalysis = blood work [BW] model), with or without a MAT titer obtained at patient intake (=BW + MAT model). The models were trained with data from 91 dogs with confirmed leptospirosis and 322 dogs without leptospirosis. Once trained, the models were tested with a cohort of dogs not included in the model training (9 leptospirosis-positive and 44 leptospirosis-negative dogs), and performance was assessed. Both models predicted leptospirosis in the test set with 100% sensitivity (95% CI: 70.1–100%). Specificity was 90.9% (95% CI: 78.8–96.4%) and 93.2% (95% CI: 81.8–97.7%) for the BW and BW + MAT models, respectively. Our MLMs outperformed traditional acute serologic screening and can provide accurate early screening for the probable diagnosis of leptospirosis in dogs.

Detection of specific antibodies against Leishmania infantum in canine serum and oral transudate using an in-house ELISA

BackgroundCanine leishmaniosis caused by the protozoan Leishmania infantum is a complex infection due to its variable clinical signs and laboratory findings. Therefore, a broad range of techniques is available for diagnosis. Testing for specific antibodies in serum is the most commonly used technique, although the testing of other body fluids, such as oral transudate (OT), can be an alternative as its collection is non-invasive and testing can be performed by untrained personnel. The aim of this study was to assess and compare the detection of L. infantum-specific antibodies in paired samples of serum and OT collected from apparently healthy dogs and dogs with clinical leishmaniosis using an in-house enyzme-linked immunosorbent assay (ELISA).MethodsSerum and OT were collected from 407 dogs, which varied in breed, sex, age, lifestyle and clinical status, by many practicing veterinarians in Spain. The main geographical areas of sampling included Barcelona (n = 110), Mallorca (n = 94), Cadiz (n = 54) and Asturias (n = 47). The majority of infected dogs were apparently healthy (89.9%) while 41 presented clinical signs and/or clinicopathological abnormalities compatible with L. infantum infection and subsequently diagnosed with leishmaniosis (10.1%). An in-house ELISA was performed to quantify the anti-Leishmania antibodies in serum and OT.ResultsThe L. infantum infection rate determined by the in-house ELISA was 37.1% in serum samples and 32.7% in OT samples. Serum and OT ELISA results showed a positive correlation (Spearman's correlation coefficient rs = 0.6687, P < 0.0001). The percent agreement between the serum and OT ELISA results was 84%, while agreement according to Cohen's kappa statistic (κ) was substantial (0.66) when all samples were analyzed. The highest percent agreement (92.1%) between both tests was found in dogs from low endemicity regions and from sick dogs, with both groups presenting almost perfect agreement according to Cohen’s κ agreement test (0.84). Few seronegative dogs (n = 23) tested positive by the OT ELISA. The agreement between serum and OT went from almost perfect to moderate when the geographical distribution and clinical status were analyzed.ConclusionsThe results of this study demonstrated an almost perfect to moderate agreement between OT and serum samples tested using the in-house ELISA. These results are particularly promising in sick dogs with high antibody levels while the results seem less optimal in apparently healthy dogs with low antibody levels.Graphical

State-wide random seroprevalence survey of SARS-CoV-2 past infection in a southern US State, 2020.

The purpose of this cross-sectional study was to estimate the proportion of Arkansas residents who were infected with the SARS-CoV-2 virus between May and December 2020 and to assess the determinants of infection. To estimate seroprevalence, a state-wide population-based random-digit dial sample of non-institutionalized adults in Arkansas was surveyed. Exposures were age, sex, race/ethnicity, education, occupation, contact with infected persons, comorbidities, height, and weight. The outcome was past COVID-19 infection measured by serum antibody test. We found a prevalence of 15.1% (95% CI: 11.1%, 20.2%) by December 2020. Seropositivity was significantly elevated among participants who were non-Hispanic Black, Hispanic (prevalence ratio [PRs]:1.4 [95% CI: 0.8, 2.4] and 2.3 [95% CI: 1.3, 4.0], respectively), worked in high-demand essential services (PR: 2.5 [95% CI: 1.5, 4.1]), did not have a college degree (PR: 1.6 [95% CI: 1.0, 2.4]), had an infected household or extra-household contact (PRs: 4.7 [95% CI: 2.1, 10.1] and 2.6 [95% CI: 1.2, 5.7], respectively), and were contacted in November or December (PR: 3.6 [95% CI: 1.9, 6.9]). Our results indicate that by December 2020, one out six persons in Arkansas had a past SARS-CoV-2 infection.

Efficacy and Safety of Vitamin D Supplementation to Prevent COVID-19 in Frontline Healthcare Workers. A Randomized Clinical Trial

BackgroundAssociations between vitamin D (VD) deficiency and the risk of SARS-CoV-2 infection have been documented in cross-sectional population studies. Intervention studies in patients with moderate to severe COVID-19 have failed to consistently document a beneficial effect.ObjectiveTo determine the efficacy and safety of VD-supplementation in the prevention of SARS-CoV-2 infection in highly exposed individuals.MethodsA double-blind, parallel, randomized trial was conducted. Frontline healthcare workers from four hospitals in Mexico City, who tested negative for SARS-CoV-2 infection, were enrolled between July 15 and December 30, 2020. Participants were randomly assigned to receive 4,000 IU VD (VDG) or placebo (PG) daily for 30 d. RT-PCR tests were taken at baseline and repeated if COVID-19 manifestations appeared during follow-up. Serum 25-hydroxyvitamin D3 and antibody tests were measured at baseline and at day 45. Per-protocol and intention-to-treat analysis were conducted.ResultsOf 321 recruited subjects, 94 VDG and 98 PG completed follow-up. SARS-CoV-2 infection rate was lower in VDG than in PG (6.4 vs. 24.5%, p <0.001). The risk of acquiring SARS-CoV-2 infection was lower in the VDG than in the PG (RR: 0.23; 95% CI: 0.09–0.55) and was associated with an increment in serum levels of 25-hydroxyvitamin D3 (RR: 0.87; 95% CI: 0.82–0.93), independently of VD deficiency. No significant adverse events were identified.ConclusionsOur results suggest that VD-supplementation in highly exposed individuals prevents SARS-CoV-2 infection without serious AEs and regardless of VD status.

Meta-analysis of the robustness of COVID-19 diagnostic kit performance during the early pandemic

BackgroundAccurate detection of SARS-CoV-2 is necessary to mitigate the COVID-19 pandemic. However, the test reagents and assay platforms are varied and may not be sufficiently robust to diagnose COVID-19.MethodsWe reviewed...

A point-of-care diagnostic test for aquaporin-4 antibody seropositive neuromyelitis optica

BackgroundGiven the need for specialized laboratory techniques, diagnostic testing for serum antibodies to aquaporin-4, a protein associated with neuromyelitis optica spectrum disorder (NMOSD), is not globally accessible. We aimed to evaluate a novel point-of-care, filter paper-based test for serum AQP4 antibodies (AQP4-Ab). MethodsAdults with AQP4-Ab seropositive NMOSD and seronegative controls (with other central nervous system demyelinating diagnoses) used lancets to place blood drops (∼1 mL) on filter paper cards. Samples were analyzed after an average of 9.4 days using transfected AQP4-GFP HEK293 cells, and results were compared to participants’ prior serum AQP4-Ab test results by blinded laboratory staff. ResultsOf 40 participants (mean age 53.7 years; 83% female), 25 were cases and 15 were controls. The most common diagnosis of controls was multiple sclerosis (73%). The average NMOSD disease duration was 6.3 years. All AQP4-Ab seropositive participants were on disease modifying therapies at the time of participation. The point-of-care test yielded a sensitivity of 80% and specificity of 93% (positive and negative predictive values 95% and 74%). ConclusionThis point-of-care AQP4-Ab testing method may become a pragmatic option to diagnose AQP4-Ab seropositive NMOSD in difficult-to-reach settings. This method should be confirmed with other testing parameters and field tested in new populations.

Combined Prospective Seroconversion and PCR Data of Selected Cohorts Indicate a High Rate of Subclinical SARS-CoV-2 Infections-an Open Observational Study in Lower Saxony, Germany.

ABSTRACTDespite lockdown measures, intense symptom-based PCR, and antigen testing, the SARS-CoV-2 pandemic spread further. In this open observational study conducted in Lower Saxony, Germany, voluntary SARS-CoV-2 PCR tests were performed from April 2020 until June 2021, supported by serum antibody testing to prove whether PCR testing in subjects with none or few symptoms of COVID-19 is a suitable tool to manage the pandemic. In different mobile stations, 4,817 subjects from three different working fields participated in the PCR testing. Serum antibody screening using the SARS-CoV-2 ViraChip IgG (Viramed, Germany) and the Elecsys Anti-SARS-CoV-2 assay (Roche, Germany) was performed alongside virus neutralization testing. Subjects were questioned regarding comorbidities and COVID-19 symptoms. Fifty-one subjects with acute SARS-CoV-2 infection were detected of which 31 subjects did not show any symptoms possibly characteristic for COVID-19. An additional 37 subjects reported a previous SARS-CoV-2 infection (total prevalence 1.82%). Seroconversion was discovered in 58 subjects with known SARS-CoV-2 infection and in 58 subjects that never had a positive PCR test. The latter had a significantly lower Charlson Comorbidity Index, and one third of them were asymptomatic. In 50% of all seroconverted subjects, neutralizing serum antibodies (NAbs) were detectable in parallel to N/S1 (n = 16) or N/S1/S2 antigen specific antibodies (n = 40) against SARS-CoV-2. NAb titers decreased within 100 days after PCR-confirmed SARS-CoV-2 acute infection by at least 2.5-fold. A relatively high rate of subclinical SARS-CoV-2 infections may contribute to the spread of SARS-CoV-2, suggesting that in addition to other intervention strategies, systematic screening of asymptomatic persons by PCR testing may significantly enable better pandemic control.IMPORTANCE Within this open observational study, repeated PCR (n > 4,700) and antibody screening (n > 1,600) tests were offered in three different working fields. The study identified 51 subjects with acute SARS-CoV-2 infection and 37 subjects reported to have had a positive PCR test taken externally. Thirty-one of the 51 subjects did not display any symptoms prior to testing. In addition, 58 subjects without PCR-confirmed SARS-CoV-2 infection were identified by seroconversion. Subjects, that had undergone SARS-CoV-2 infection without having noticed, more often had a low grade of immunization with no NAbs, but may have relevantly contributed to the spread of the pandemic. Based on these results, we suggest that both regular PCR and rapid test screening of symptomatic and asymptomatic individuals, specifically within groups or workplaces identifiable as having close quarter contact, thus increased infection transference risk, is necessary to better assess and therefore reduce the spread of a pandemic virus.

Management of Pediatric Lyme Disease: Updates From 2020 Lyme Guidelines.

Management of Pediatric Lyme Disease: Updates From 2020 Lyme Guidelines.

Positive Predictive Value of the ICD-10 Diagnosis Code for Long-COVID.

PurposeTo examine the positive predictive value (PPV) of International Classification version 10 (ICD-10) diagnosis codes for long coronavirus disease 2019 (long-COVID) in a Danish Health registry.Patients and MethodsThis was a medical record review of all patients with a diagnosis code of long-COVID (DB948A) at all hospitals in the North Denmark Region from February 27, 2020 through June 30, 2021. Confirmed long-COVID was categorized as fulfillment of all three criteria: (1) a positive polymerase chain reaction (PCR) test for SARS-CoV-2 on a respiratory sample or a positive serum antibody test, (2) symptoms suggestive of long-COVID with no other diagnosis considered more likely, and (3) symptom duration >6 weeks.ResultsA total of 306 patients were assigned a hospital diagnosis code for long-COVID corresponding to 1.4% of all SARS-CoV-2 positive individuals during the study period (n=21,727). Next, 40 patients were excluded due to incomplete diagnostic evaluation at time of record review leaving 266 patients for analysis. The patients had a median age of 51 years (interquartile range 43–60) and 175/266 (66%) were females. Long-COVID was confirmed in 249/266 yielding an overall PPV of 94% (95%CI: 90–96) and did not differ substantially according to most age groups, sex, previous hospitalization for COVID-19, or by using 12 weeks of symptom duration as cut-off. The PPV was low for children and adolescents (n=5), the very elderly (n=9), and those included by secondary long-COVID diagnoses (n=10).ConclusionThe overall PPV of diagnosis codes for long-COVID in the North Denmark Region was high and was likely suitable for future registry-based studies of long-COVID. Caution is advised at the extremes of age and secondary diagnosis codes.