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1.
Sleep Science ; 15:55, 2022.
Article in English | EMBASE | ID: covidwho-1935283

ABSTRACT

Introduction: Previous studies have reported that sleep deprivation and sleep disorders may decrease the antibody response after vaccination for H1N1, influenza and hepatitis A. Since the emergence of the current pandemic, the same was wondered for vaccination against COVID-19. This possible effect would be especially relevant among older adults, who are subjected to a high prevalence of sleep disorders (mainly obstructive sleep apnea - OSA) and who are at increased risk for severe COVID-19. Objective: To evaluate the effect of OSA on IgG antibody response after vaccination against COVID-19 among older adults. Methods: This study was based on a convenience sample of older adults who underwent polysomnography at the Sleep Institute (São Paulo, Brazil). It was considered eligible those who were 60 years or older, were undergoing full night type-I polysomnography, and have been fully vaccinated against COVID-19. The following exclusion criteria was applied: previous COVID-19 diagnosis, less than 15 days between last vaccine shot and IgG testing, or CPAP use in the last 3 months. All eligible participants undergone blood sampling for anti-SARS-CoV-2 IgG analysis. The apnea-hypopnea index (AHI) was used to categorize the participants in the following groups: no/mild OSA (IAH < 15), moderate OSA (AHI ≥ 15 and < 30) and severe OSA (AHI ≥ 30). The association between IgG reactive status (seronegative or seropositive) and OSA was evaluated by a X2 test. Log-transformed IgG levels were compared among OSA severity groups using a 1-way ANOVA with Welch's correction. Statistical analyses were performed using Jamovi 1.6 and the significance level was set as p<0.05. Results: The final sample comprised 122 participants, of which 35 had no/mild OSA, 31 had moderate and 56 had severe OSA. Seronegative anti-SARS-CoV-2 IgG results were observed in 9.8% of the sample, and the median IgG levels was 273 AU/ mL (IQR: 744) with no statistically significant differences among OSA severity groups in neither case. Conclusion: OSA does not appear to affect IgG antibody response following vaccination against older adults. This is a positive result from a public health perspective, since even being at increased risk for negative COVID-19 outcomes, vaccination among individuals with OSA seems to be equally effective as among those without OSA.

2.
Archives of Razi Institute ; 77(5):1561-1565, 2022.
Article in English | EMBASE | ID: covidwho-1939566

ABSTRACT

Saliva is one of the most significant components in maintaining oral homeostasis and symbiosis. It contains antimicrobial proteins and peptides, such as mucins, lactoferrin, lysozyme, lactoperoxidase, Catherine, statins, and antibodies (secretory immunoglobin A [sIgA]). Early defenses against respiratory infections rely heavily on mucosal immunity, especially secretory sIgA, which has several features and functions that make it suitable for mucosal defense. Salivary testing has been utilized to define mucosal immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Lysozyme has muramidase, with antimicrobial activity, and high concentrations in body fluids, such as saliva and tear. This research aimed to offer an update on how saliva components suppress viral infection and sustain health. A total of 50 individuals, including 30 SARS-2 patients and 20 non-infected subjects, in the age range of 32-54 years were enrolled in this study. Saliva specimens were obtained from polymerase chain reaction (PCR)-confirmed coronavirus disease 2019 (COVID-19) patients and non-infected participants. To collect saliva, the subjects were advised to swirl water over their lips three times, and 5.0 ml of saliva was collected. Samples were centrifuged at 800 x g for 10 min. Saliva was diluted at 1:2,000 with 1 × Diluent N. The immunoglobulin A (IgA) titer in saliva was detected. A spectrophotometer was used to measure the solution's change in absorbance at 550 nm. Measurements (salivary IgA and lysozyme) were made after 7, 30, and 60 days of confirmatory PCR COVID-19 test. The mean scores of salivary IgA levels were obtained at 17.85, 15.26, and 10.73 mg/dl in patients and 9.53, 10.33, and 9.21 mg/dl in healthy individuals after 7, 30, and 60 days, respectively. The salivary lysozyme activity levels in SARS-2 patients compared to controls were 9.7, 7.3, and 4.2 mg/dl versus 2.9, 3.4, and 3.77 mg/dl, respectively. The salivary IgA level was significantly higher in patients of a confirmatory test for COVID-19 compared to healthy individuals.

3.
Archives of Razi Institute ; 77(5):1543-1548, 2022.
Article in English | EMBASE | ID: covidwho-1939565

ABSTRACT

The present study aimed to investigate some microbial infections and immunological parameters associated with Covid-19 patients admitted to the intensive care unit (ICU) of Al-Amal Specialized Hospital in AL-Najaf Governorate during February and March 2021. The study included 50 patients who were assigned to two groups: 20 patients aged ≤70 years and 30 patients aged ≥70 years. The method of microbial culture was adopted to isolate bacteria and yeasts by collecting sputum specimens and oral swabs from patients and cultivating them on diagnostic media and then confirming the diagnosis by Vitek. Moreover, serum samples were collected from patients’ blood to diagnose fungal infections. Thereafter, some immunological criteria were assessed, including Covid-19 diagnosis by measuring Immunoglobulin M (IgM) and IgG, as well as examining the concentration of cytokines (Interleukin 6 (IL-6) and IF) using the enzyme-linked immunosorbent assay (ELISA) method. The results demonstrated that bacterial species Streptococcus pneumonia (n=5;25%), Haemophilus Influenzae (n=7;35%), and Moraxella catarrhalis (n=3;15%) were isolated from the first group of patients (≤70 years). The recorded data pointed out that Streptococcus pneumonia (n=10;33.3%), Streptococcus pyogenes (n=5;16.6%), Streptococcus viridans (n=1;3.3%), Haemophilus Influenzae (n=6;20%), Mycobacterium tuberculosis (n=2;6.6%), and Pseudomonas aeruginosa (n=2;6.6%) were the isolated and identified microorganisms in the second age group (≥ 70 years). The results revealed that the isolated yeast from the first age group was Candida albicans (n=5;25%) and Candida glabrata (n=3;10%), while in the second age group, 1 (3.3%) Candida albicans was isolated. The results of this study proved that 30% and 10% of patients in the first and second age groups had invasive pulmonary aspergillosis co-infection by detecting Galactomannan (GM) in the blood serum (1.05±0.59, 1.25±0.38), respectively. The results indicated that IgM and IgG levels in the serum of patients in the first age group were 11.42±6.82 and 0.47±6.82, respectively. Moreover, the levels of IgM and IgG in the second age group were 14.84±9.21 and 0.12±0.11, respectively. Furthermore, IFϫ and IL6 levels were 98.37±65.70, and 146.12±46.35 in the first group, while IFϫ and IL6 were obtained at 110.69±47.60 and 133.28±116.94 in the second group, respectively. Elderly patients with severe COVID-19 are more frequently admitted to ICUs since the proportion of severe cases and comorbidities caused by a weakened immune system is higher among this age group. Secondary bacterial infections can also occur, especially Gram-negative bacteria which are among the most significant public health problems worldwide. Moroever, aspergillosis may infect patients hospitalized with COVID-19 and lead to death.

4.
Russian Open Medical Journal ; 11(2), 2022.
Article in English | EMBASE | ID: covidwho-1928925

ABSTRACT

Study objective - assessment of the humoral and cell-mediated immunity features in COVID-19 convalescents three months after their discharge from the hospital. Material and Methods - The study involved 78 COVID-19 convalescents who, depending on the profile of specific IgM and IgG antibodies to SARS-CoV-2, were divided into three groups. The control group consisted of 50 volunteers. Detection of IgM and IgG in blood serum was performed by ELISA. Determination of CRP concentration was conducted using the immunoturbidimetric assay. To determine the levels of IL-6, a sandwich version of the solid-phase ELISA was employed. Immunophenotyping of lymphocytes was performed via flow cytometry. Results - Of 78 COVID-19 convalescents three months after their discharge from the hospital, 30.8% of them had a profile of specific antibodies IgM(+)IgG(+), 37.2% had IgM(-)IgG(+), and 32.0% were characterized by IgM(-)IgG (-). COVID-19 convalescents with an IgM()IgG(-) profile had the highest levels of NK cells, T helper cells, B lymphocytes (p<0.001) and were characterized by hyperproduction of proinflammatory IL-6 (p<0.001). COVID-19 convalescents with an IgM(+)IgG(+) specific antibody profile were characterized by the highest levels of cytotoxic T lymphocytes (p<0.001). In a COVID-19 convalescent with an IgM(-)IgG(+) specific antibody profile, we observed an increase in the number of lymphocytes expressing late activation/apoptosis molecules (p<0.001). Conclusion - The collected data is of potential importance in clinical practice for developing a prognosis for epidemiological situation development, as well as for planning preventive measures to COVID-19.

5.
Chinese Journal of Microbiology and Immunology (China) ; 42(1):16-22, 2022.
Article in Chinese | EMBASE | ID: covidwho-1928714

ABSTRACT

Objective To detect the serum levels of SARS-CoV-2-specific IgM and IgG antibodies in patients infected with SARS-CoV-2 and recipients of inactivated vaccine in different periods for understanding their variation patterns in vivo. Methods Chemiluminescence immunoassay was used to detect the levels of SARS-CoV-2-specific IgM and IgG antibodies in 144 serum samples of 44 COVID-19 patients, 381 serum samples of 118 asymptomatic infected cases and 398 serum samples of 273 inactivated vaccine recipients collected at different periods. The results were statistically analyzed together with basic characteristics and vaccination status. Results The positive rates of IgM antibody in COVID-19 patients, asymptomatic infected cases and inactivated vaccine recipients were 52. 27% (23 / 44), 23. 73% (28 / 118) and 14. 29% (39 / 273). The positive rate of IgM antibody was higher in COVID-19 patients than in asymptomatic infected cases and vaccine recipients (χ2 = 12. 106, P = 0. 001;χ2 = 34. 755, P<0. 001). The positive rates of IgG antibody in the three populations were 100. 00% (44 / 44), 97. 46% (115 / 118) and 98. 81% (166 / 168), and the differences were not statistically significant (χ2 = 2. 944, P = 0. 229). In COVID-19 patients, the concentration of IgM antibody in <40 years old group was lower than that in ≥40 years old group (Waldχ2 = 6. 609, P = 0. 010), and the concentration of IgG antibody in patients with vaccination was higher than that in patients without vaccination (Waldχ2 = 12. 402,P<0. 001). In asymptomatic infected cases, the concentration of IgG antibody was higher in people with vaccination than in those without vaccination (Waldχ2 = 4. 530, P = 0. 033). In SARS-CoV-2 vaccine recipients, the concentration of IgG antibody in <40 years old group was higher than that in ≥40 years old group (Waldχ2 = 9. 565, P = 0. 002). Dynamic analysis of antibody levels showed that from week 1 to week 9, the concentrations of IgM and IgG antibodies in COVID-19 patients were higher than those in asymptomatic infected cases and vaccine recipients. Conclusions The concentrations of IgM and IgG antibodies in COVID-19 patients were higher than those in asymptomatic infected cases and inactivated vaccine recipients. COVID-19 patients aged ≥40 years had higher level of IgM antibody. COVID-19 patients and asymptomatic infected cases who had received vaccination had higher concentration of IgG antibody. Inactivated vaccine showed good immunogenicity after whole course of immunization, and the IgG antibody level in <40 years old group was higher.

6.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927844

ABSTRACT

RATIONALE: Over 400,000 individuals are estimated to have been exposed to the fallout of the World Trade Center (WTC) disaster. The incidence of acquired allergy and lung injury among rescue and cleanup workers exposed to the WTC fallout has been established. Briefly, rescue and cleanup workers exposed to the WTC fallout had a high incidence of allergic hypersensitivity and permanent small airways dysfunction characterized by distal airways narrowing and airway hyperresponsiveness. The current study sought to quantify the utilization of allergy/immunology services among rescue and cleanup workers exposed to the WTC fallout. METHODS: Subjects (N=65) were referred from the WTC Health Program to a multispecialty allergy/immunology and pulmonology clinic for provision of allergy-immunology specialty services. Electronic health records of all subjects were retrospectively reviewed from the date of first referral to March 2020-when routine care was interrupted due to the coronavirus disease 2019 pandemic-to quantify utilization of allergy/immunology and pulmonology services;10 subjects were excluded from analysis due to incomplete health records. RESULTS: On average, time to referral for allergy-immunology services by the WTC Health Program was 15.2 years (SD=1.7). The majority of the subjects were male (89.1%), police officers (67.3%) who never smoked (65.5%) and had no history of allergic or respiratory disease prior to being exposed to the WTC fallout. Most were found to have environmental allergies (83.6%);the most common comorbidities were allergic rhinitis (89.1%), asthma (67.3%), and chronic sinusitis (63.6%). All subjects underwent environmental allergy testing. Most subjects-35 of 55 (63.6%)-were prescribed an epinephrine autoinjector for environmental allergies. Regarding allergic immunotherapy (IT), 33 of 55 (60.0%) received IT;additionally, 7 subjects (12.7%) were determined to be IT candidates but did not receive IT. The most common monoclonal antibody therapy used in this cohort was omalizumab (18.2%). Only 11 (20.0%) and 3 (5.5%) underwent serum IgE and IgG testing, respectively. CONCLUSION: Rescue and cleanup workers referred to a multispecialty allergy/immunology and pulmonology practice from the WTC Health Program not only had a high incidence of acquired allergies to environmental allergens, but the majority were prescribed and epinephrine autoinjector and either received or were candidates to receive allergy immunotherapy. Given that hundreds of thousands of individuals were exposed to the WTC fallout and exposure is an independent risk factor for developing allergic disease, this research may have identified ways we may be falling short in providing allergy/immunology services to exposed individuals.

7.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927826

ABSTRACT

Introduction: Encephalopathy in a transplant recipient is a challenging clinical presentation that requires a broad differential (both infectious and noninfectious) and consideration of exposures. West Nile Virus (WNV) encephalitis is a rare etiology of encephalopathy in a transplant recipient with controversial management. Case: A man in his seventies presented due to encephalopathy in September 2021. Medical history was significant for deceased donor kidney transplant in September 2020 and myasthenia gravis. Immunosuppression consisted of tacrolimus, mycophenolic acid, and prednisone 10 mg daily. He was on fluconazole for coccidioidomycosis prophylaxis. Symptoms consisted of worsening weakness over five days and headaches for two days. On admission, he was febrile to 38.1° C and had altered mental status. He was started on empiric meningitis treatment with ampicillin, vancomycin, cefepime, and acyclovir, and was given doxycycline for atypical coverage. He developed worsening encephalopathy and was intubated for airway protection. CSF profile revealed 255/mm3 WBC (77% neutrophils, 20% lymphocytes, 3% monocytes), 45/mm3 RBC, 61 glucose mg/dL (serum 126 mg/dL), and 96.1 mg/dL protein. Exposure history was significant for visiting family in central Arizona several weeks prior to presentation where he was exposed to mosquitos and two cats. He ate at a fast-food restaurant two days prior to presentation. He received three doses of COVID-19 vaccine. He was born and raised in Arizona and has remote travel to Mexico. Extensive studies (considering the risk factors above) identified the etiology of his encephalopathy as WNV encephalitis with positive serum PCR, elevated serum and CSF IgM with normal IgG. Unfortunately, the patient expired despite aggressive therapy. Discussion: This case represents three interesting challenges that we feel will be of interest to the conference attendees. The first is encephalopathy in a transplant recipient within one year of transplant requires a broad differential including donor-derived infections, opportunistic organisms that can cause meningoencephalitis, as well as knowledge of local and seasonal pathogens on the rise. With the monsoon season in 2021, Arizona rose to become one of the top ten states in the country with WNV cases. The second is management of a critically ill patient with meningitis and myasthenia gravis, since multiple agents for empiric therapy have been associated with worsening of or precipitating myasthenic crisis. Finally, supportive care is the mainstay of the management of WNV encephalitis and IVIG and adjustments in immunosuppression is controversial.

8.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927766

ABSTRACT

Systemic capillary leak syndrome (SCLS or Clarkson's disease) is a rare condition characterized by episodes of vascular hyperpermeability. The extravasation of plasma to the interstitial space results in hemoconcentration, hypoalbuminemia, hypovolemia and compartment syndrome of the extremities. The disease can be idiopathic or secondary to causes including viral infections or chemotherapeutic toxicity. We present a fatal case of idiopathic SCLS which rapidly deteriorated to multiple organ failure despite initial improvement with methylene blue. A 57-year-old male presented for worsening back pain over one month. He described a flulike illness 2 weeks prior. Testing for respiratory viruses including SARS-CoV-2 was negative. He received intravenous crystalloid fluids acutely developed respiratory distress and hypotension requiring emergent intubation and initiation of norepinephrine infusion. CT angiography of the chest demonstrated pulmonary edema. Early during his hospitalization urine output ceased and body weight increased by 10 kg, developing tense anasarca. Hematocrit concentrated from 42.7 to 54.4%. Serum albumin dropped from 4.6 to 2.5 g/dL. C1 esterase inhibitor level and IgM were normal. Ferritin was elevated at 2515 ng/ml. He received cefepime and vancomycin, though infectious workup returned unremarkable. Continuous renal replacement therapy and stress dose steroids were initiated. Vasopressor requirement worsened until he was on three vasopressors at one point. Given the constellation of hemoconcentration, hypoalbuminemia, and shock a diagnosis was made of idiopathic SCLS. Treatment was started with methylene blue, montelukast, and the β-adrenergic agonist terbutaline. Blood pressure improved and patient came off pressors and lactate improved from 13 to 4. However, he later developed rising creatine kinase continued to climb to >40,000 U/L. He developed rhabdomyolysis with concern for compartment syndrome of the extremities due to third spacing of fluids. Orthopedic surgery was consulted;but did not believe a fasciotomy was indicated due to rapid decline. Lactic acidosis rose to 18 mmol/L. His family decided to transition to comfort measures. He passed with family at bedside on Day 4 of hospitalization. There are fewer than 500 cases of SCLS reported since initial discovery in 1960. Given the overlap in presentation with common causes of plasma leakage such as sepsis, it is likely that many cases are unrecognized. Patients are often mismanaged;development of severe hypovolemia despite fluids and compartment syndrome is overlooked. This case builds on our evolving recognition of this disease, and the potential for the use of methylene blue to help acute exacerbations of the disease.

9.
Sleep ; 45(SUPPL 1):A310, 2022.
Article in English | EMBASE | ID: covidwho-1927437

ABSTRACT

Introduction: Sleep disorders and sleep deprivation induces decreased antibody response following vaccination for different viral diseases (including H1N1, influenza and hepatitis A). The same has been speculated for COVID-19. This study aimed to assess whether obstructive sleep apnea (OSA) reduces antibody levels after COVID-19 vaccination among older adults. Methods: This was a convenience-sample study composed of older adults (≥60 years old). Those who underwent polysomnography at the Sleep Institute (São Paulo, Brazil) and received complete COVID-19 vaccination schedule were considered eligible. Individuals with previous diagnosis of COVID-19, less than 15 days between vaccination and IgG testing, or CPAP use in the last 3 months were excluded. Anti-SARS-CoV-2 IgG levels were measured using a chemiluminescence assay. The participants were distributed in the following groups, according to their apneahypopnea index (AHI): no/mild OSA (AHI<15), moderate OSA (AHI≥15 and <30) and severe OSA (AHI≥30). The effects of OSA on IgG levels (ANOVA), the correlation between IgG levels and AHI (Spearman's correlation test) and the association between serostatus (positive vs. negative) and OSA severity levels (X2 test) were analysed. Results were considered as statistically significant when p<0.05. Results: The sample included 122 older adults (median age 72.0 - IQR: 5.7), of whom 35 (28.6%) had AHI no/mild OSA;31 (25.4%) had moderate OSA, and 56 (45.9%) had severe OSA. Oxford/ AstraZeneca was the most referred vaccine (n=111, 91.0%), followed by CoronaVac (n=9, 9.0%). Seropositive status (IgG count ≥50.0 AU/mL) was observed in 90.2% of the participants and the median IgG levels in the complete sample was 273.0 AU/ML (IQR: 744.0). No/mild, moderate and severe OSA groups presented IgG levels of 482.0 (IQR: 677.0), 285 (IQR: 884.0) and 181.0 (IQR: 598.0), respectively, with no statistical difference them (p=0.606). There was no statistically significant correlation between AHI index and IgG levels (Spearman's rho=-0.169, p=0.063) and no significant association between serostatus and OSA severity groups (X2=0.912;p=0.634). Conclusion: Anti-SARS-CoV-2 IgG levels after vaccination are not significantly affected by OSA among older adults. Thus, despite being at higher risk for severe cases, OSA does not decrease the antibody response following vaccination against COVID-19.

10.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925420

ABSTRACT

Objective: To describe the occurrence of acute cerebellar ataxia after COVID-19 infection in a 5- year-old boy. Background: Neurologic manifestations can occur in many adult patients with COVID-19 but are less frequently described in the literature than the respiratory or inflammatory effects of the disease. There are even fewer reports of the neurologic manifestations of the disease in children. Design/Methods: A 5-year-old boy with type I diabetes mellitus was exposed to a COVID-19 positive classmate in school. He tested positive for the SARS-CoV-2 virus and developed mild symptoms including rhinorrhea and decreased energy. Eight days later he developed acute ataxia, double vision, tremor and dysmetria. He was admitted to the hospital for further evaluation. Results: He had hyperglycemia at presentation, however labs were not consistent with diabetic ketoacidosis. Nasopharyngeal swab for SARS-CoV-2 was positive by polymerase chain reaction, and SARS-CoV-2 IgG nucleocapsid antibody testing was positive in serum. Cerebrospinal fluid showed white blood cells 8 cells/uL, red blood cells 0 cells/uL, protein 20 mg/dL and glucose 110 mg/dL. Other infectious testing in the CSF was negative including CSF testing for SARS-CoV-2. Brain magnetic resonance imaging with and without contrast was normal. The patient was treated with supportive care and discharged home after 4 days. Symptoms gradually improved and resolved at 2 month follow up. Conclusions: Acute cerebellar ataxia can be seen in children, often following a viral infection. Rare reports have described acute ataxia in adults recovering from COVID-19. Only one case report has previously described acute cerebellar ataxia in a pediatric patient of 13 years (Tomar et al 2021). Providers should be aware of acute cerebellar ataxia as a possible sequela in pediatric patients recovering from COVID-19.

11.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925368

ABSTRACT

Objective: We present two patients with neurological complications following COVID-19 mRNA vaccination. Background: Post-vaccinal myelitis and demyelination is well described. We investigated two patients presenting inflammatory demyelination following mRNA based vaccination against COVID-19. Design/Methods: Patients were referred to the treating neurologist for a second opinion as possible cases of multiple sclerosis. Clinical neurological evaluation, MRI imaging of brain and spine as well as serum and cerebrospinal fluid (CSF) analysis was performed. Results: In case 1, the patient developed left-side numbness and difficulty walking six weeks post-second dose of the Moderna mRNA COVID-19 vaccine. She was found to have an enhancing thoracic cord lesion on MRIs, and CSF ELISA studies showed highly elevated IgG levels against the spike protein receptor-binding domain (S1-RBD) of COVID 19. In case 2, the patient began to hiccup and vomit, developed diplopia, and right-side weakness and numbness around two days post-second dose of the Moderna vaccine. MRIs showed two lesions on her brain and a C4 enhancing lesion on her spinal cord. CSF showed oligoclonal bands. However, further analysis of her spinal fluid showed highly elevated IgG antibodies to the S1-RBD. Conclusions: Initially, case 1 was diagnosed with transverse myelitis and possible multiple sclerosis, and case 2 with multiple sclerosis. Both patients likely would have received long-term immunosuppressive therapy had vaccine complications not been suspected. The presence of CSF antibodies to the S1-RBD protein suggests an immune response to the mRNA COVID-19 vaccinations crossing over to the CNS as the likely cause of these neurological complications. In patients developing acute neurological complaints in the period following vaccination, even with the presence of oligoclonal bands, CSF should be analyzed for reactivity against the S1-RBD. Further investigation is required to explain the mechanism of this response and subsequent complications. Both patients are clinically improving and will continue to be managed by a neurologist.

12.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925308

ABSTRACT

Objective: To describe antibody and T-cell responses to the three SARS-CoV-2 vaccines available in the United States (U.S.) in patients with relapsing multiple sclerosis (RMS) on ozanimod or other disease modifying therapies (DMTs). Background: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel, zoonotic coronavirus that emerged in late 2019 in patients with pneumonia of unknown cause;the disease caused by SARS-CoV-2 is termed COVID-19 (coronavirus disease 2019). Recent reports have suggested that RMS patients on certain DMTs may have a blunted humoral response to the available COVID-19 vaccinations. Sphingosine-1-phosphate (S1P) receptor modulators may control RMS via sequestration of circulating lymphocytes, thus raising questions about vaccination response in RMS on ozanimod and other S1P receptor modulators. Design/Methods: Prospective observational trial following patients with RMS who are going to be vaccinated against COVID-19. The primary endpoint is the proportion of subjects treated with ozanimod with SARS-CoV-2 anti-spike IgG positivity (Elecsys® Anti-SARS-CoV-2) 4 weeks after full vaccination as compared to pre-vaccination levels. To ensure a geographic distribution across the U.S., RMS patients were recruited online (under the care of various neurologists), and all study-related proceures were performed at the patient's home. Results: Descriptive statistics of antibody and T-cell response for sixty subjects (30 treated with ozanimod and 30 treated with various other FDA-approved RMS DMTs) assessed prior to and 28 days after full vaccination will be presented. Additionally, all subjects will complete follow-up questionnaires every 3 months until a year has passed from the second (or only) vaccine dose Conclusions: In this study, RMS patients treated with ozanimod had an antibody and T-cell response to the three available COVID-19 vaccines in the U.S. This trial is ongoing, with 48- weeks of follow-up expected in December 2022.

13.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925269

ABSTRACT

Objective: To report a pediatric case of severe, treatment-resistant, COVID-19-associated acute longitudinally extensive transverse myelitis (LETM). Background: Since the COVID-19 global pandemic, there is evolving literature reporting the neurological manifestations of the novel coronavirus. COVID-19-associated acute LETM was first reported in an elderly Asian man with lower-extremity weakness <1-week after onset of fever and respiratory distress. In childhood, this is rarely reported with only few reports of COVID-19-associated acute LETM. Design/Methods: We reviewed clinical and radiographic reports of our patient. We searched PubMed for literature using terms “transverse myelitis & COVID-19” and “pediatric transverse myelitis&COVID-19.” Results: A 5-year-old previously healthy boy presented with altered mental status. Prior to admission, he was exposed to COVID-19 and had consumed an unknown quantity of sertraline and risperidone tablets. Thereafter, he stated that he could not feel his legs, fell, and hit his head. In the emergency department, he was intubated. EKG revealed QTc prolongation (486-ms). SARS-CoV-2-PCR positive. Thereafter, flaccid quadriparesis, bulbar dysfunction, left-sided numbness, and hyperreflexia were noted;he communicated by eye blinking. MRI-spine revealed C1-C4 hyperintensity (T2-weighted) consistent with LETM;DWI negative for acute stroke. CSF basic labs, viral and MS panels, and ACE unremarkable. Serum anti-aquaporin-4 and myelin-oligodendrocyte-glycoprotein antibodies negative. Serum West Nile-IgM-IgG negative. Mycoplasma pneumoniae IgM-reactive, IgG-positive;confirmatory IgM immunofluorescence assay-negative. He received IV-methylprednisolone ×5-days, plasmapheresis ×10-sessions, pulsed steroid ×3-days. Minimal neurological improvement was noted. Repeat MRI-spine 2-weeks later unchanged. Tracheostomy and gastric tube were placed. He was transferred to a neurology topic. Conclusions: COVID-19-associated acute LETM in childhood can have a rapid, devastating clinical course. Clinicians should maintain a high-index of suspicion for LETM in COVID-19 pediatric patients presenting with neurological manifestations and consider alternative strategies for severe, treatment-resistant cases.

14.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925168

ABSTRACT

Objective: Assess the SARS-CoV2 Spike antibody response in multiple sclerosis (MS) patients on high efficacy immunotherapies. Background: There is limited knowledge about SARS-CoV2 mRNA vaccine response in MS patients on immunotherapy. Design/Methods: Patients with MS, aged 18-65, on fingolimod, siponimod, ofatumumab, or ocrelizumab for at least 3 months prior to first mRNA SARS-CoV2 vaccine (Pfizer or Moderna) were offered enrollment. A cohort of healthy controls who received the mRNA vaccines were also enrolled. Blood samples for the SARS-CoV2 Spike antibody (Anti-SARS-CoV2 S, RocheElecsys) were collected 2-3 months after the second mRNA vaccine. The proportion who seroconverted (antibody>0.4 U/ml), and SARS-CoV2 Spike antibody levels were assessed. Results: A total of 39 MS patients (6 fingolimod, 33 ocrelizumab) and 31 controls were included in this interim analysis. 33%(13/39) of MS patients seroconverted, compared to 100%(31/31) in the control group, with an estimated risk difference of -0.67,(95% confidence interval: -0.81, -0.52;Fisher's exact test, p=9.0∗10-10 ). There was no difference in seroconversion rates between MS patients who received the Pfizer (34%, 10/29) versus the Moderna vaccine (30%, 3/10) (95% confidence interval -0.38, 0.29;Fisher's exact test=1). Seroconversion was found in 100% (31/31) of controls, 66.7% (4/6) of fingolimod-treated patients, and 27.3% (9/33) of ocrelizumab-treated patients (three group comparison, Fisher's exact test p-value =2.7∗10 -10). The median Spike antibody level was <0.4 U/ml in MS patients, and 1,663 U/ml in controls (Wilcoxon rank sum test, p-value= 1.0∗10-12 ). The median Spike antibody level in the ocrelizumab group was <0.4 U/ml, 3.45 U/ml in the fingolimod group, and 1,663 U/ml in the control group (Kruskal Wallis test, p-value=5.9∗10-12 ). Total IgG correlated with Spike antibody levels in the ocrelizumab-treated group only (Spearman correlation, p=0.025). Conclusions: MS patients on ocrelizumab and fingolimod have significantly lower rates of seroconversion, and lower median Spike antibody levels in response to the mRNA SARS-CoV2 vaccines compared to controls.

15.
Medical Immunology (Russia) ; 24(2):337-350, 2022.
Article in Russian | EMBASE | ID: covidwho-1918188

ABSTRACT

At the present time, studying humoral immunity to the new coronavirus infection is among the most important tasks. The COVID-19 infection induces a protective pool of specific antibodies determining severity and duration of such immune protection after convalescence. The antibody testing is also necessary for assessing efficiency of anti-COVID vaccines in order to defeat the SARS-CoV-2 pandemic. Despite enormous interest of scientific community in this problem seen in the literature, there is still a lack for longitudinal observations of immunological status (more than 6 months) in the patients who have undergone COVID-19. The aim of this study is a long-term monitoring (9-14 months) of development and extinction of immune response to SARS-CoV-2 infection using quantitative assessment of IgA and IgG levels in peripheral blood of the patients who had COVID-19 in anamnesis. Monitoring of anti-SARS-CoV-2 levels over time has demonstrated significant individual variability, and made it possible to divide the study participants into three groups, according to characteristic features of humoral immunity after documented COVID-19. The study describes characteristic features of humoral immune response for each of these groups. The first group (30% of the study group) exhibited classical pattern of antibody response to viral infection. The second group (40% of study participants) presented with high plasma IgA levels, and their significant excess (about 2 times) over IgG levels throughout the observation period. The third group (30% of study participants), apparently comprised the subjects with increased humoral immunity to SARS-CoV-2 infection. Their plasma antibodies remain at high levels for at least 9-10 months after the onset of infection. The data obtained confirm the pattern of plasma IgA which is not quite typical to viral infections in dynamics after a sufficiently long time period after the disease in most study participants (2nd and 3rd groups;70% of all volunteers who have recovered from COVID-19) and suggests an important role of this immunoglobulin against SARS-CoV-2 infection. The specific responses of anti-SARS-CoV-2 IgG are very similar to behavior of such antibodies in other viral infections including contacts with coronaviruses from earlier generations. Humoral immunity against SARS-CoV-2 may persist for more than 6 months, thus supporting an assumption that the naturally infected patients are able to resist re-infection for a long time.

16.
Vox Sanguinis ; 117(SUPPL 1):263, 2022.
Article in English | EMBASE | ID: covidwho-1916364

ABSTRACT

Background: Plasma collected from patients that have recovered from an infectious disease has been transfused over many decades for prophylaxis and treatment of various infectious diseases. Taking into consideration the expansion of COVID-19 pandemics, we started the COVID-19 convalescent plasma (CCP) programme. Aims: The aim of our study is to show our experience with collecting the CCP and to evaluate the SARS-CoV-2 antibody concentration in different convalescent plasma donors' subgroups. Methods: This is a prospective study performed in the Institute for Transfusion Medicine of Republic of North Macedonia since 30 April 2020 till July 2021. Antibody testing was performed at the Institute for Immunobiology and Human Genetics in Skopje using CLIA method with Snibe Maglumi SARS-CoV-2 S-RBD IgG (quantitative) with IgG cut-off larger than 5 AU/ml. All potential donor were tested for: negative RTPCR for SARSCoV-2 before donation, anti-SARS-CoV-2 antibodies, anti- HLA antibodies (where applicable), blood count, blood group, TTI and biochemistry. Preferred method for plasma collection was plasmapheresis which was performed with Terumo BCT Trima Accel and donation of whole blood, depending on the donor preference and venous access. All donors signed inform consent for donation and inclusion in the study. Results: There were 1476 potential CCP donors, but only 700(47.9%) donors fulfilled all the criteria and we obtained 793 units of CCP;639 (80.6%) units from whole blood donors and 154 (19.4%) CCP units from 61 plasmapheresis donors, 485 (69.3%) males and 215 (30.7%) females. Mean age of the donors was 40 years (range 18-63). Mean value of SARS-CoV-2 S-RBD IgG concentration was 31.05 AU/ml, (range from 5.1 AU/ml to >100 AU/ml), mean value of SARS-CoV-2 S-RBD IgG in men was 37.6 AU/ml and 28.9 AU/ml in women (p < 0.05). Distribution of CCP donors according to the ABO blood group was: 301 blood group A (43%) with median value of SARS-CoV-2 S-RBD IgG = 27.15 AU/ml, 220 blood group O (31.4%) median value of SARS-CoV-2 S-RBD IgG = 32.1 AU/ml, 116 blood group B (16.6%) median value of SARS-CoV-2 S-RBD IgG = 35.9 AU/ml and 63 donors had blood group AB (9%) median value of SARS-CoV-2 S-RBD IgG = 26.45 AU/ml. There were 69 donors that were previously hospitalized with mean value of SARS-CoV-2 S-RBD IgG = 48.6 AU/ml, and 629 that were treated at home with mean value of SARS-CoV-2 SRBD IgG = 29.1 AU/ml (p < 0.05), of which 578 had symptoms with mean value of SARSCoV- 2 S-RBD IgG = 29.1 AU/ml and 51 were asymptomatic with mean value of SARS-CoV-2 S-RBD IgG = 29.3 AU/ml. The CCP donors had the following distribution according to the age: 125 donors in the 18-29 age group with median value of SARS-CoV-2 S-RBD IgG = 23.0 AU/ml, 200 donors in the 30-39 age group with mean value of SARSCoV-2 S-RBD IgG = 28.2 AU/ml, 217 donors in the 40-49 age group with mean value of SARS-CoV-2 SRBD IgG = 32.9 AU/ml and 156 donors in the 50-63 age group mean value of SARS-CoV-2 S-RBD IgG = 38.3 AU/ml (p < 0.05). Summary/Conclusions: The collection procedures are safe and effective and collected CCP units were with high concentration and quality. The concentration of SARS-CoV-2 S-RBD IgG in CCP obtained from previously hospitalized patients was significantly larger than in ones that were treated at home. The concentration of SARS-CoV-2 S-RBD IgG was higher in men, in advanced age group and in donors with blood group B. The further studies are needed to clarify the impact of different variables on antibodies concentration/ titre in donors.

17.
Vox Sanguinis ; 117(SUPPL 1):25-26, 2022.
Article in English | EMBASE | ID: covidwho-1916360

ABSTRACT

Background: ABO hemolytic disease of the fetus and newborn (ABOHFDN) is a frequent event, and usually a problem of the neonate rather than the fetus, however, it is difficult to predict the disease severity. Thus, there is a need to increase awareness towards ABOHFDN for optimizing care in terms of early diagnosis and adequate monitoring. Aims: To determine the frequency of ABO-incompatibility in neonates born to group O mothers and to assess the severity of ABO-HDFN in neonates and determine the neonatal outcomes. Methods: This prospective observational study was carried out from February 2020 to May 2021 after obtaining a written informed consent from the mothers. A total of 260 neonates born to blood group O mothers were recruited. The maternal red cell antibody screen (ABS) using a 3-cell panel (Diacell, Bio-Rad, Switzerland) and the neonatal direct antiglobulin test (DAT) were done by column agglutination technique (CAT). For DAT positive samples, the IgG subclass of anti-A/anti-B was determined using DAT IgG1/IgG3 screening cards (Bio-Rad, Switzerland) and a heat elution at 56°C was also performed. The maternal anti-A/anti-B IgG titers was determined by tube technique after treating the serum sample with 0.01 M di-thiothreitol (DTT). The neonatal total serum bilirubin (TSB) and other relevant parameters were also recorded. The requirement for treatment in terms of phototherapy and/or exchange transfusion (ET) and the neonatal outcome were also recorded. Due to travel restrictions during the ongoing COVID-19 pandemic, the follow-up was performed telephonically with parents 6-8 weeks after discharge. Results: Of the 260 group O mothers, none had positive ABS. Of the 260 neonates born to them as an outcome of singleton pregnancies, 84 with blood group O were excluded from the study. The overall frequency of ABO-incompatibility between mother and neonates was 67.69% (176/260). Out of 176 neonates, 77 (43.8%) were group A and 99 (56.2%) were group B, and 15 (8.5%) of them had a positive DAT. Overall, 26.7% (47/176) neonates received phototherapy and 172 (97.7%) neonates survived. The mean (±SD) duration of phototherapy (hours) was 34.17 (±25.67) hours and it ranged from 12- 120 h. Only 1 neonate required ET. None of the neonates required readmission. The median maternal IgG anti-A titre was 16 (8-64) (range: 2-512), while the IgG anti-B titre was 32 (32-64) (range: 4- 512) (p = <0.001). The maximal TSB in neonates had a significant positive association with neonatal birth weight (p = 0.045), maturity at birth (p = 0.037), positive DAT (p = 0.006) and requirement of phototherapy (p = <0.001). Neonatal DAT positivity was significantly associated with maternal IgG titers (p = <0.001), neonatal PCV (p = 0.017), maximal TSB (p = 0.006), requirement (p = <0.001) and duration of phototherapy (p = 0.024). At a cut-off of maternal IgG titre ≥64, it predicted the requirement of phototherapy with a sensitivity of 72.3% and a specificity of 72%. The relative risk (95% CI) of a DAT positive neonate requiring phototherapy was calculated to be 4.55 (3.12-6.33). Summary/Conclusions: The frequency of ABO-incompatibility in neonates born to group O mothers was 67.69% (176/260). The maternal IgG titre of anti-A/anti-B of 64 or more could be a good predictor for identifying the neonates at-risk for developing hyperbilirubinemia requiring further management and combining it with neonatal DAT further enhances the sensitivity to identify such at-risk neonates.

18.
Vox Sanguinis ; 117(SUPPL 1):64, 2022.
Article in English | EMBASE | ID: covidwho-1916337

ABSTRACT

Background: Vaccines have been an important strategy to control the SARS-CoV-2 pandemic. In The Netherlands two mRNA vaccines (BTN162b2, Pfizer-BioNTech;mRNA-1273, Moderna), and two adenovirus vector-based vaccines (ChAdOx1 nCoV-19, AstraZeneca;Ad26. COV2.S, Johnson & Johnson/Janssen) have been administered. In 2021, vaccination with the ChAdOx1 nCoV-19 was ceased in The Netherlands and other European countries due to the occurrence of thrombocytopenia and thromboembolic events. This new phenomenon was termed vaccine-induced thrombotic thrombocytopenia (VITT) and was clinically associated with thrombocytopenia and thrombosis at unusual sites, in particular cerebral venous sinus thrombosis (CVST). In addition, VITT was characterized by the presence of IgG-antibodies directed against platelet factor 4 (PF4). As PF4 appears to play a central role in the pathophysiology of VITT, it is recommended that the role of PF4 should be taken into account for VITT diagnostic testing. Aims: To characterize and define the patient population of clinically suspected VITT cases in The Netherlands from a diagnostics perspective. Methods: We describe a cohort of 283 clinically suspected VITT patients. We assessed these patients based on their clinical presentation and using an anti-PF4 IgG ELISA and a functional PF4-dependent platelet activation assay. Results: We found that when the 283 clinically suspected VITT patients were analysed in the anti-PF4 IgG ELISA: 24 (8.5%) tested positive, 248 (87.6%) tested negative, and 11 (3.9%) tested weak positive. Out of the 24 patients that tested positive in the anti-PF4 IgG ELISA, 19 (79.2%) patients also demonstrated increased PF4-dependent platelet activation. Furthermore, we observed that platelet activation was inhibited by excess levels of heparin and by a FcγRIIa-blocking antibody, indicating a role for platelet-FcγRIIa in the pathophysiology of VITT. Remarkably, we found that patients vaccinated with mRNA vaccines BTN162b2 (N = 84) and mRNA-1273 (N = 36), did not test positive in the anti-PF4 IgG ELISA. Based on these test results 19 patients (11 women) were eventually diagnosed with probable VITT, of which 13 presented with both thrombocytopenia and thrombosis and three suffered from CVST. Strikingly, discrepancies in test results were also present, including nine patients with low levels of anti-PF4 IgG but with increased PF4-dependent platelet activation, and two patients with high levels of anti-PF4 IgG but without any PF4-dependent platelet activation. Summary/Conclusions: VITT is a rare but serious complication of SARS-CoV-2 virus vaccination, particularly due to adenovirus vectorbased vaccines. Our results underline the importance of using the clinical presentation, in combination with the anti-PF4 IgG ELISA and the PF4-dependent platelet activation assay for VITT diagnostics. Discrepancies in test results, however, proved it difficult to unequivocally diagnose VITT. Therefore, it will be essential to obtain more insights into the pathophysiology of VITT in order to improve the diagnostic accuracy and identify preventive and therapeutic approaches.

19.
Vox Sanguinis ; 117(SUPPL 1):30, 2022.
Article in English | EMBASE | ID: covidwho-1916336

ABSTRACT

Background: Recent studies reported that individuals with ABO blood type O are underrepresented among patients infected with severe acute respiratory syndrome coronavirus SARS-CoV-2 compared with controls. Our preceding study results indicated a lower proportion of individuals with blood type O accompanied by a higher incidence of blood type AB in patients hospitalized with COVID-19 than in healthy blood donors. Thus, we hypothesized that the variable susceptibility to infection with SARS-CoV-2 might be related to interference caused by circulating ABO antibodies and further may be influenced by the antibody titers which vary widely between individuals. Aims: Therefore, we aimed to investigate ABO antibody levels, including IgM, IgG and IgA subclasses, in the serum and saliva of Caucasians (n = 187), who recovered from mild COVID-19 and to compare them with those of individuals who had never been infected with the virus. Further, a possible association between ABO antibodies and virusspecific total antibody concentrations in the COVID-19 convalescents as well as a potential relationship between the total IgA secreted in saliva and anti-A/anti-B specific IgA in saliva specimens were addressed. Methods: The convalescent study participants were recruited between June 2020 and February 2021. Individuals who had been hospitalized with COVID-19 or who were pregnant were excluded from the study. Two samples were collected within 2 months after the diagnosis (median days: 44) and approximately 2 months later (median days: 66 days). Isotype specific anti-A and anti-B were determined by flow cytometry on a FACS Canto II. The results were compared with the levels in samples from blood and saliva donors. The antibodies specific to SARS-CoV-2 as well as total IgA in saliva were tested by ELISA. Results: COVID-19 convalescents had significantly lower levels of anti-A and anti-B IgM, IgG and IgA in their serum than control subjects (p < 0.001). ABO antibody levels tested in saliva of participants who previously suffered from COVID-19 did not differ significantly from antibody levels tested in saliva controls (p ≥ 0.338). ABO antibody levels remained stable over the period considered. No significant association between the level of ABO antibodies and SARS-CoV-2-specific antibodies was observed (-0.44 < rho < 0.42, p > 0.053). Total IgA in saliva was lower in convalescents than in controls (p = 0.038). Summary/Conclusions: We observed consistently lower serum concentrations of anti-A and anti-B in COVID-19 convalescents than in healthy controls, suggesting ABO antibodies to conferring a degree of protection against SARS-CoV-2 infection. There may be an increased susceptibility to SARS-CoV-2 infection due to individual preexisting low ABO antibody levels. However, the mechanism underlying our observation of significantly reduced ABO antibodies in the serum, but not in the saliva of affected individuals remains unresolved. Further studies to better understand the molecular mechanism underlying our observation are needed.

20.
Vox Sanguinis ; 117(SUPPL 1):265, 2022.
Article in English | EMBASE | ID: covidwho-1916316

ABSTRACT

Background: The new Severe Acute Respiratory Syndrome Virus-2 (SARS-CoV-2), which is responsible coronavirus disease (COVID-19), spread worldwide from China, causing a pandemic from late December 2019. Due to the high proportion of asymptomatic or mild infections (approximately 80%), data restricted to laboratoryconfirmed cases do not capture the true extent of the spread or burden of the virus, or its infection-fatality ratio. Therefore, serological detection of specific antibodies against SARS-CoV-2 can better estimate the true number of infections. The current study aimed to estimate the seroprevalence of SARS-CoV-2 antibodies among the whole blood donors without any prior COVID-19 history or symptoms. Aims: To determine seroprevalence of SARS-CoV-2 (COVID-19) antibody (IgG and IgM) among asymptomatic healthy blood donors. Methods: This was a cross sectional study conducted between March 16 and July 10, 2021 among 300 blood donors without any prior COVID-19 history or symptoms who came to a tertiary care, multispecialty hospital in south India. Any donor who had travelled abroad or came back from abroad after January,2020 and donors who had received COVID-19 vaccine are excluded from the study. 3 ml venous blood was drawn in EDTA tube from participants and was tested by 'Access SARS CoV-2 IgG assay' and 'Access SARS CoV-2 IgM assay' by UniCel DxI 800 Immunoassay analyser (Beckman coulter). The Access SARS CoV-2 IgG assay and the Access SARS Cov-2 IgM assay detect antibodies to the Receptor Binding Domain (RBD) of the Spike Protein. Result was reported as Reactiveif Signal/Cut-off (S/CO) > 1.0 and non-Reactive if S/CO <1. Data was collected and entered into excel sheets and was analysed by using the software SPSS version 25. Results: A total of 300 healthy blood donors were included. All were males with the mean age being 26.98 years. The study reported seroprevalence of 15.3% for IgG and 4.3% for IgM (95%CI) among whole blood donors. Seroprevalence was similar across age groups, diet patterns, voluntary/ replacement donations, area of residence, ABO and Rh groups without any statistical significance. However higher IgG response was noted in the 30-45 age group and among B Positive blood group donors. Summary/Conclusions: Almost 15% of blood donors were seroconverted for COVID-19 during second wave. This is a reflection of widespread seroprevalence in the adult male population. Real-time seroprevalence studies will help to know the herd immunity among the blood donors which will assist in knowing the Covid-19 transmission dynamics, distribution of immunity levels at a particular point in time, immunity gaps, development of novel therapeutics and prioritize the vaccination programmes to high-risk individuals.

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