Correlation between specific antibody response to wild-type BNT162b2 booster and the risk of breakthrough infection with omicron variants: Impact of household exposure in hospital healthcare workers.

BACKGROUND: The emergence of omicron variants exhibiting antigenic changes has led to an increase in breakthrough infection among individuals with a wild-type SARS-CoV-2 vaccine booster. The correlation between post-booster spike-specific antibodies and omicron infection risk remains unclear. METHODS: This prospective cohort study included SARS-CoV-2-naive healthcare workers with three-dose BNT162b2. Post-booster spike-specific IgG and interferon-γ levels were measured. Breakthrough infection was documented during a 10-month omicron-predominant period. Household and healthcare contacts were followed to identify subsequent infections. The IgG titers were additionally measured at the end of follow-up, and the titers at exposure were estimated from the two-point titers. RESULTS: Of 333 participants, 89 developed infection, of whom 37 (41.6 %) were household contacts. Kaplan-Meier curves indicated that higher IgG titers were significantly correlated with lower cumulative infection incidence (p = 0.029), whereas the interferon-γ levels were not (p = 0.926). Multivariate Cox analysis showed that increasing IgG titers were associated with a reduced hazard ratio (HR) of 0.26 (95% CI, 0.12-0.55). Household exposure posed a greater infection risk than healthcare exposure (HRs, 11.24 [6.88-18.40] vs. 2.82 [1.37-5.44]). The difference in geometric mean IgG titers of infected and uninfected participants was significant among household contacts (20,244 AU/mL vs. 13,842 AU/mL, p = 0.031). Estimation of IgG titers at exposure showed a significantly higher infection incidence in those exposed with titers of <3,000 AU/mL than in those with higher titers (79.2 % vs. 32.3 %, p < 0.001). CONCLUSIONS: Spike-specific antibodies induced by a wild-type SARS-CoV-2 vaccine booster are suggested to be effective in protecting against omicron infection. Household exposure would be a significant source of infection for hospital healthcare workers.

No significant influence of pre-vaccination antipyretic use on specific antibody response to a BNT162b2 vaccine booster against COVID-19.

The relation between pre-vaccination antipyretic use and antibody responses to SARS-CoV-2 vaccination has been unclear. We measured the pre- and post-BNT162b2 booster spike-specific IgG titers and recorded antipyretic use and adverse reactions for SARS-CoV-2-naive hospital healthcare workers. The data of 20 cases who used antipyretics within 24 h before vaccination were compared to that of 281 controls. The post-booster geometric mean IgG titers were 15,559 AU/mL (95 % CI, 11,474-21,203) for the cases and 16,850 AU/mL (95 % CI, 15,563-18,243) for the controls (p = 0.622). No significant reduction in the frequency or severity of any of the solicited adverse reactions was found for the cases. Similar results were obtained after adjustment with propensity-score matching for demographic characteristics, baseline IgG titer, and post-vaccination antipyretic use. Antipyretic use within 24 h before vaccination would not affect mRNA COVID-19 vaccine-induced specific antibody responses and that postponement of vaccination due to pre-vaccination antipyretic use would be unnecessary.

Correlation of Postvaccination Fever With Specific Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 BNT162b2 Booster and No Significant Influence of Antipyretic Medication.

Background: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine booster elicits sufficient antibody responses that protect against coronavirus disease 2019, whereas adverse reactions such as fever have been commonly reported. Associations between adverse reactions and antibody responses have not been fully characterized, nor has the influence of antipyretic use. Methods: This is a prospective observational cohort study in Japan, following our prior investigation of BNT162b2 2-dose primary series. Spike-specific immunoglobulin G (IgG) titers were measured for SARS-CoV-2-naive hospital healthcare workers who received a BNT162b2 booster. The severity of solicited adverse reactions, including the highest body temperature, and self-medicated antipyretics were reported daily for 7 days following vaccination through a web-based self-reporting diary. Results: The data of 281 healthcare workers were available. Multivariate analysis extracted fever after the booster dose (ß = .305, P < .001) as being significantly correlated with the specific IgG titers. The analysis of 164 participants with data from the primary series showed that fever after the second dose was associated with the emergence of fever after the booster dose (relative risk, 3.97 [95% confidence interval, 2.48-6.35]); however, the IgG titers after the booster dose were not associated with the presence or degree of fever after the second dose. There were no significant differences in the IgG titers by the use, type, or dosage of antipyretic medication. Conclusions: These results suggest an independent correlation between mRNA vaccine-induced specific IgG levels and post-booster vaccination fever, without any significant influence of fever after the primary series. Antipyretic medications for adverse reactions should not interfere with the elevation of specific IgG titers.

Relation of fever intensity and antipyretic use with specific antibody response after two doses of the BNT162b2 mRNA vaccine.

BACKGROUND: The reactogenicity of BNT162b2 COVID-19 vaccine has been commonly reported and antipyretic medications are often used for mitigating adverse reactions. Possible associations between the reactogenicity events and specific antibody responses have not been fully investigated, nor has the influence of using antipyretics. METHODS: Serum samples were collected from hospital healthcare workers with no COVID-19 history and the SARS-CoV-2 spike-specific IgG titer after two doses was measured. Degree of solicited adverse reactions in a day, including the highest body temperature, were reported using a self-reporting diary for five days after each dose. The highest body temperature during the five days was divided into three grades (<37.0 °C, 37.0-37.9 °C, or ≥ 38.0 °C). Self-medicated antipyretics were reported using a questionnaire. RESULTS: The data of 335 participants were available for analysis. Multivariate analysis extracted the fever grade after the second dose (standardized coefficient beta = 0.301, p < 0.0001), female sex (beta = 0.196, p = 0.0014), and age (beta = -0.119, p = 0.0495) as being significantly correlated with the IgG titers. The positive correlation of the fever grade after the second dose with the IgG titers was also observed when analyzed by sex and age. The use of antipyretics did not interfere with the IgG titers irrespective of the fever grade. CONCLUSIONS: The fever intensity after the second dose was associated with the IgG titer and antipyretic medications may be beneficial to mitigate the suffering from adverse reactions, without interfering with the acquisition of sufficient antibody responses.

Delays in Presentation Time Under the COVID-19 Epidemic in Patients With Transient Ischemic Attack and Mild Stroke: A Retrospective Study of Three Hospitals in a Japanese Prefecture.

Background: Coronavirus Disease 2019 (COVID-19) has spread worldwide with collateral damage and therefore might affect the behavior of stroke patients with mild symptoms seeking medical attention. Methods: Patients with ischemic stroke who were admitted to hospitals within 7 days of onset were retrospectively registered. The clinical characteristics, including onset-to-door time (ODT), of patients with a transient ischemic attack (TIA)/mild stroke (National Institutes of Health Stroke Scale [NIHSS] score of ≤ 3 on admission) or moderate/severe stroke were compared between those admitted from April 2019 to March 2020 (pre-COVID-19 period) and from April to September 2020 (COVID-19 period). Multivariable regression analysis was performed to identify factors associated with the ODT. Results: Of 1,100 patients (732 men, median age, 73 years), 754 were admitted during the pre-COVID-19 period, and 346 were admitted during the COVID-19 period. The number and proportion of patients with TIA/minor stroke were 464 (61.5%) in the pre-COVID-19 period and 216 (62.4%) during the COVID-19 period. Among patients with TIA/mild stroke, the ODT was longer in patients admitted during the COVID-19 period compared with that of the pre-COVID-19 period (median 864 min vs. 508 min, p = 0.003). Multivariable analysis revealed the COVID-19 period of admission was associated with longer ODT (standardized partial regression coefficient 0.09, p = 0.003) after adjustment for age, sex, route of arrival, NIHSS score on admission, and the presence of hypertension, diabetes mellitus, and wake-up stroke. No significant change in the ODT was seen in patients with moderate/severe stroke. Conclusions: The COVID-19 epidemic might increase the ODT of patients with TIA/mild stroke.

[A case of cerebral embolism with Coronavirus disease 2019].

A 63-year-old man, who had persistent fever for a month, was admitted to the hospital with sudden left arm palsy with a National Institutes of Health Stroke Scale score of 3. Consequently, brain MRI showed hyperintensity of the bilateral occipital, right parietal, and right frontal lobes on diffusion-weighted imaging. Moreover, FLAIR presented hyperintensity of the left occipital lobe. Magnetic resonance angiography detected the deficit of the blood-flow signal of the horizontal segment of the middle cerebral artery. He was diagnosed with acute ischemic stroke. In addition, chest CT showed ground-glass opacities, and test to detect SARS-CoV-2 was positive. Cerebral embolism was suspected. However, the source was unknown. His ischemic stroke was possibly associated with coagulation abnormality caused by coronavirus disease 2019.

Modified diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score including deep white matter lesions predicts symptomatic intracerebral hemorrhage following intravenous thrombolysis.

The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used for the assessment of early ischemic changes (EICs) before thrombolysis. However, for symptomatic intracerebral hemorrhage (sICH) following intravenous recombinant tissue plasminogen activator (rt-PA), the prediction abilities of CT-ASPECTS, diffusion-weighted imaging (DWI)-ASPECTS, and DWI-ASPECTS including EICs in deep white matter (DWI-ASPECTS + W) are unclear. We investigated associations between each score and sICH following intravenous rt-PA. Data from consecutive patients who received intravenous rt-PA for acute ischemic stroke from 2005 to 2015 in four hospitals were retrospectively screened. We included data from patients who had undergone both CT and magnetic resonance imaging before thrombolysis and without evidence of posterior circulation stroke. We analyzed the ability of CT-ASPECTS, DWI-ASPECTS, and DWI-ASPECTS + W to predict sICH, accompanied by an increase in the National Institutes of Health Stroke Scale (NIHSS) score of ≥ 4 within the initial 36 h. Of 455 patients (273 men, median 75 years old), sICH occurred in 15 patients (3.3%). Receiver operating characteristics curve analysis showed that the optimal cut-offs of CT-ASPECTS, DWI-ASPECTS, and DWI-ASPECTS + W for predicting sICH were ≤ 9 (sensitivity 60.0%, specificity 59.8%, c-statistic 0.625), ≤ 6 (sensitivity 53.3%, specificity 80.9%, c-statistic 0.718), and ≤ 8 (sensitivity 86.7%, specificity 55.9%, c-statistic 0.756), respectively. A DWI-ASPECTS + W of ≤ 8 was independently associated with sICH (odds ratio 5.21, 95% confidence interval 1.30-35.31) after adjustment for pretreatment with antithrombotic agents, pretreatment NIHSS score, and large artery occlusions. DWI-ASPECTS + W predicted sICH in patients with acute anterior circulation stroke receiving intravenous rt-PA.

Differences between predictive factors for early neurological deterioration due to hemorrhagic and ischemic insults following intravenous recombinant tissue plasminogen activator.

Early neurological deterioration (END) following intravenous recombinant tissue plasminogen activator (rt-PA) treatment is a serious clinical event that can be caused by hemorrhagic or ischemic insult. We investigated the differences in predictive factors for END due to hemorrhagic and END due to ischemic insults. Consecutive patients from four hospitals who received 0.6 mg/kg intravenous rt-PA for acute ischemic stroke were retrospectively recruited. END was defined as a National Institutes of Health Stroke Scale (NIHSS) score ≥ 4 points within 24 h compared with baseline. END was classified into those due to hemorrhagic (ENDh) or ischemic (ENDi) insult based on computed tomography (CT) or magnetic resonance imaging. Risk factors associated with ENDh and ENDi were investigated by comparison with non-END cases. A total of 744 patients (452 men, median 75 years old) were included. END was observed in 79 patients (10.6%), including 22 ENDh (3.0%) and 57 ENDi (7.7%), which occurred within a median of 7 h after treatment. Multivariate analyses showed that higher pretreatment NIHSS score (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.00-1.13) and pretreatment with antiplatelets (OR 2.84, 95% CI 1.08-7.72) were associated with ENDh. Extensive early ischemic change (Alberta Stroke Program Early CT Score ≤ 7 on CT or ≤ 6 on diffusion-weighted imaging; OR 2.80, 95% CI 1.36-5.64) and large artery occlusions (OR 3.09, 95% CI 1.53-6.57) were associated with ENDi. Distinct factors were predictive for the END subtypes. These findings could help develop preventative measures for END in patients with the identified risk factors.

Temporal Trends in Clinical Characteristics and Door-to-Needle Time in Patients Receiving Intravenous Tissue Plasminogen Activator: A Retrospective Study of 4 Hospitals in Japan.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (rt-PA) has become a common treatment for acute ischemic stroke and has highly time-dependent benefits. We aimed to clarify temporal trends regarding the frequency and characteristics of patients receiving rt-PA and explore factors associated with door-to-needle time (DNT) in Japanese emergency hospitals. METHODS: Consecutive patients who received intravenous rt-PA for acute ischemic stroke from October 2005 to December 2015 were retrospectively registered from 4 hospitals. Temporal trends in the frequency and characteristics of patients receiving rt-PA and factors associated with DNT were investigated. RESULTS: A total of 750 patients, including 688 (420 men, median 75 years old) with out-of-hospital stroke, were registered. The frequency of patients receiving intravenous rt-PA for acute ischemic stroke continuously increased from 1.8% in 2005 to 9.5% in 2015. The proportion of patients who were elderly or had prestroke disability increased over time, while pretreatment stroke severity declined. The DNT gradually decreased (median 105 minutes in 2005, 61 minutes in 2015). According to multivariate regression analysis with correction for multiple comparisons, activation of a code stroke system (standardized partial regression coefficient (ß) -.50, P < .001, q < .001), onset-to-door time (ß -.15, P < .001, q < .001), pretreatment with antithrombotic agents (ß .12, P < .001, q = .001), and year of treatment (ß .11, P = .007, q = .011) were associated with DNT. CONCLUSIONS: Intravenous rt-PA was widely adopted in Japanese emergency hospitals. Characteristics of patients receiving intravenous rt-PA have changed over the past decade. Several factors, including the year of treatment, were associated with DNT, which has shortened over time.

[A case of possible elderly onset rheumatoid meningitis without arthritis].

A 93-year-old man was admitted to our hospital with disturbance of consciousness. Brain magnetic resonance imaging (MRI) showed hyperintensity of the subarachnoid space in the left frontal and parietal lobes on diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR). Gadolinium-enhancement of the pia mater was also observed. We did not perform biopsy because of a high risk of perioperative complication. Although physical examination found no evidence of the rheumatoid arthritis, rheumatoid factors and anti-cyclic citrullinated peptides antibodies were elevated. He was suspected to have rheumatoid meningitis. We treated him with intravenous methylprednisolone (0.5 g/day) for 3 days. Rheumatoid meningitis often shows hyperintensity of the subarachnoid space on the DWI and FLAIR, and steroid therapy is effective.

Intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator (rt-PA) therapy for acute cerebral infarction in a patient with ANCA-associated vasculitis.

We report the case of a 68-year-old man who suddenly developed right hemiparesis. MRI of the brain revealed a new infarction in the left corona radiata, and intravenous rt-PA was administered 100 minutes after the onset of symptoms. After the rt-PA infusion was started, his consciousness declined and the CT revealed bilateral intracerebral hemorrhage. His consciousness did not improve thereafter. He was diagnosed with ANCA-associated vasculitis owing to the high levels of MPO-ANCA and urinary protein and the presence of erythrocytes without any other cause of renal damage. Although ANCA-associated vasculitis rarely involves the central nervous system, intracerebral hemorrhage as well as cerebral infarction may occur. This case provides an important opportunity to explore the implications of intravenous rt-PA therapy for acute cerebral infarction in patients with ANCA-associated vasculitis.

[Case of cerebellar and spinal cord infarction presenting with acute brachial diplegia due to right vertebral artery occlusion].

A 73-year-old man was admitted for evaluation of sudden onset of dizziness, bilateral shoulder pain, and brachial diplegia. Neurological examination revealed severe bilateral weakness of the triceps brachii, wrist flexor, and wrist extensor muscles. There was no paresis of the lower limbs. His gait was ataxic. Pinprick and temperature sensations were diminished at the bilateral C6-C8 dermatomes. Vibration and position senses were intact. An MRI of the head revealed a right cerebellar infarction and occlusion of the right vertebral artery. An MRI of the cervical spine on T2 weighted imaging (T2WI) showed cord compression at the C3/4-C5/6 level secondary to spondylotic degeneration without any intramedullary signal changes of the cord. On the following day, however, high-signal lesions on T2WI appeared in the C5-C6 spinal cord, suggesting cord infarction. Unilateral vertebral artery occlusion does not usually result in cervical cord infarction because of anastomosis of arteries. Because of the long-term mechanical compression in our case, it was likely that cervical cord ischemia was present before the onset of symptoms. On the basis of chronic cord compression, our case suggests that occlusion of a unilateral vertebral artery could cause cervical cord infarction.

[A case of subacute necrotizing lymphadenitis with recurrent aseptic meningitis associated with persistent high titer of anti-nuclear antibody occurring over a short period of time].

A 35-year-old woman developed recurrent aseptic meningitis three times over a period of 16 months. Each episode followed swelling of her cervical lymph nodes. During the third episode, microscopic findings of biopsied specimens from a cervical lymph node indicated subacute necrotizing lymphadenitis (SNL). While she responded poorly to NSAIDs, steroids rapidly improved her fever, headache and swollen lymph nodes. Since the first episode, anti-nuclear antibody (ANA) and anti-SS-A antibody was positive and the titer of ANA increased with each episode. SNL is a benign and self-limited disease, and the appearance of autoantibodies is usually transient. It is possible that a persistent immune abnormality is related to recurrences of aseptic meningitis with SNL.

[A case of MELAS presenting juvenile-onset hyperglycemic chorea-ballism].

We report herein the case of a 28-year-old man presenting with hyperglycemic chorea-ballism (HCB) in addition to mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). He was admitted to a local hospital due to weight loss, general fatigue and thirst. The patient had diabetes mellitus, with a blood glucose level of 738 mg/dl and HbA1c of 19.8%. Although insulin therapy improved hyperglycemia, he noticed involuntary movements in the right upper and lower limbs, which subsequently extended to the left side. The patient was thus transferred to our hospital. He displayed short stature (154 cm) and emaciation, and a maternal family history of diabetes mellitus was elicited. He had no history of stroke-like episode, headache, vomiting and seizure. Neurological examination revealed low intelligence (IQ 57), mild sensorineural deafness, and chorea-ballism in the extremities and head without ptosis or eye movement disturbance. Brain computed tomography (CT) demonstrated areas of high density, while T1-weighted magnetic resonance imaging (MRI) revealed extreme hyperintensity and T2-weighted MRI showed hyperintensity in bilateral caudate nuclei, putamina and globi pallidus. HCB was diagnosed. In, CSF, lactate level was increased to 43.9 mg/dl (n, 4-16), pyruvate level was 1.65 mg/dl (n, 0.3-0.9) and total protein concentration was 59 mg/dl. Histological examination of a biopsy sample from the biceps brachii muscle demonstrated ragged-red fibers. An A3243G point mutation in the tRNA(Leu(UUR)) gene was detected, indicating the presence of MELAS. Involuntary movements improved on treatment with haloperidol up to 4.5 mg/day. HCB usually appears in elderly individuals, and cases less than 40-years-old are very rare. The mitochondrial dysfunction in MELAS may accelerate development of HCB.

[An elder case of neurosarcoidosis associated with brain infarction].

A 75-year-old woman with sarcoidosis developed sudden weakness of the left upper and lower limbs. Neurological examination revealed left-sided hemiplegia, hyperreflexia with pathological reflexes and hypesthesia. She was disoriented and euphoric. Diffusion-weighted brain MRI showed high intensity lesions in the right parietooccipital lobes. Electroencephalogram showed diffuse slowing of the background activity. Serum lysozyme increased to 18.4 mg/ml, CSF protein to 51 mg/dl. After admission, she presented psychotic manifestation followed by a progressive disturbance of consciousness. Epithelioid granulomas without caseous necrosis were present in the biopsied lymph node and specimens from the occipital cortex, indicating neurosarcoidosis. Necrosis was also present in the sampled brain tissue. The psychotic symptoms and consciousness disturbance rapidly ameliorated after the treatment with oral prednisolone, 40 mg/day. Neurosarcoidosis should be considered even in an elder case of sarcoidosis complicated with a stroke.

[Spinal epidural hematoma: relationship between imaging findings and neurological outcomes].

PURPOSE: The purpose of this study was to evaluate the usefulness of CT or MR imaging findings in patients with spinal epidural hematoma (SEH) for predicting neurological outcome. MATERIALS AND METHODS: MR images of our six patients with SEH were evaluated retrospectively: complete recovery was achieved in two patients; paresis remained in two patients; and paraplegia remained in two patients. The ratio of the maximum anteroposterior diameter of the SEH to that of the spinal canal was calculated in each patient on midline on axial images in our six patients and 23 previously reported patients. RESULTS: Among our six patients, the ratio was less than 60% in two patients with total recovery, whereas all four patients with remaining motor impairment had ratios of 60% or more. Of 29 cases, 18 of 22 patients without residual motor impairment had ratios of less than 60%, but five of seven patients with residual motor deficits had ratios of 60% or more (p = 0.023). CONCLUSION: The degree of spinal cord compression by hematoma may be a prognostic factor in SEH.