A cross-sectional study of SARS-CoV-2 antibodies among healthcare workers in a tertiary care hospital in Taiwan: implications for protection against the Omicron variants.

BACKGROUND: Taiwan, deeply impacted by the 2003 SARS outbreak, promptly implemented rigorous infection control and prevention (ICP) measures in January 2020 to combat the global COVID-19 pandemic. This cross-sectional serologic study was conducted among healthcare workers (HCWs) in a tertiary care hospital in Taiwan from August 1, 2022, to February 28, 2023. The study aimed to assess HCWs' antibody responses to COVID-19 vaccination against Omicron subvariants BA.1, BA.4, and BA.5, considering variations in prior infection. Additionally, it evaluated the effectiveness of ICP and vaccination policies within the hospital setting in Taiwan. METHODS: A cross-sectional serology study was conducted in Taiwan to investigate the seroprevalence rates of Omicron subvariants BA.1, BA.4, and BA.5 among HCWs. A total of 777 HCWs participated in this study. A structured questionnaire was collected to obtain the epidemiological characteristics and risk factors for potential exposure. Enzyme-linked immunosorbent assay was used to detect antibody responses. Serum samples were selected for protection against Omicron subvariants BA.1, BA.4, and BA.5 by using a pseudotyped-based neutralization assay. RESULTS: More than 99% of the participants had received SARS-CoV-2 vaccination. Overall, 57.7% had been infected with SARS-CoV-2, with some being asymptomatic. The SARS-CoV-2 Anti-Spike S1 protein IgG (Anti-S) distribution was 40,000 AU/mL for 20.2% (157/777) of participants, with a mean ± standard deviation of 23,442 ± 22,086. The decay curve for Anti-S was less than 20,000 AU/ml after 120 days. The probability curve of 50% neutralization showed an Anti-S of 55,000 AU/ml. The optimum Anti-S was 41,328 AU/mL (equal to 5,869 WHO's standard BAU/mL), with 86.1% sensitivity and 63.5% specificity. CONCLUSIONS: In this significant study, 20.2% of HCWs achieved seroprotection against Omicron subvariants BA.1, BA.4, and BA.5. Their immunity against Omicron subvariants was further reinforced through recommended vaccinations and the development of natural immunity from SARS-CoV-2 exposure, collectively enhancing their protection against Omicron.

A large family of hereditary spherocytosis and a rare case of hereditary elliptocytosis with a novel SPTA1 mutation underdiagnosed in Taiwan: A case report and literature review.

RATIONALE: Hereditary spherocytosis (HS) has a defect in the vertically connected proteins on the cell membrane of red blood cells (RBC). Hereditary elliptocytosis (HE) has a defect in proteins that connect the cell membrane horizontally. We reported two families of RBC membrane disorders in Taiwanese, one was HS and the other was HE. PATIENT CONCERNS: Case 1. A 19-year-old male student with chronic jaundice and splenomegaly. His mother, maternal uncle, grandmother, and many members of older generations also had splenomegaly and underwent splenectomy. Case 2. A 40-year-old man has experienced pallor and jaundice since the age of 20 and was found to have splenomegaly, and gall bladder stones in the older age. His younger sister also had pallor and jaundice for a long time. DIAGNOSES: In case 1, a peripheral blood smear showed 20% spherocytes. Eosin-5-maleimide labeled RBC by flow cytometry showed a result of 30.6 MCF (cutoff value: 45.5 MCF). He was diagnosed with HS. The gene analysis identified a heterozygous mutation with c.166A > G (p.Lys56Glu) in the SLC4A1 gene in this proband, his mother, and maternal uncle. In case 2, more than 40% of ellipsoid RBC present in the peripheral blood smear. He was diagnosed with HE. Genetic analysis of the SPTA1 gene identified a novel heterozygous exon2, c.86A > C, p.Gln29Prol mutation. INTERVENTIONS: The two patients had compensated anemia, clinical follow-up instead of splenectomy was done. OUTCOMES: The two patients had normal daily activities and lives. LESSONS: We reported two Taiwanese families, one was hereditary spherocytosis affected by a heterozygous mutation with c.166A > G (p.Lys56Glu) in SLC4A1, and the other was hereditary elliptocytosis caused by a novel heterozygous SPTA1 gene mutation, c. 86A > C, p.Gln29Prol. These 2 seemingly common hereditary red blood cell membrane protein defects induced by hemolysis are usually underdiagnosed or misdiagnosed.

Congenital factor V deficiency in Taiwan: identification of a novel variant p.Tyr1813 ∗ and two variants specific to East Asians.

Congenital coagulation factor V deficiency (FVD) is a rare, autosomal recessive bleeding disorder. We characterized the clinical presentations, laboratory features, and genetic alterations of Taiwanese patients with FVD. From 1983 to 2010, five women, one man, and one boy diagnosed with FVD were enrolled in this study. The factor V coagulant activity was determined using a one-stage prothrombin time-based test. The factor V antigen level was measured in an ELISA. Sanger sequencing was performed for genetic analyses of F5 , the gene responsible for the disease. One novel and de novo F5 genetic variant, p.Tyr1813 ∗ , was identified. Based on the presence of a premature termination codon with a resultant truncated factor V-protein lacking an intact light chain fragment, the variant is pathogenic. In addition, we identified seven variants previously found to cause FVD. Among them, p.Gly420Cys and p.Asp96His were repeatedly detected in five and four patients, respectively. Both variants are found to be specific to the East Asian populations. Various FVD-associated bleeding manifestations were observed, predominantly mucocutaneous bleeding and hypermenorrhea. All patients exhibited very low factor V coagulant activity (<1-2.5 IU/dl, reference range: 60-133 IU/dl). The factor V antigen level was less than 2% in six patients (reference range: 75-157%). The novel F5 genetic variant p.Tyr1813 ∗ and two distinct, East Asians-specific, recurrent variants p.Gly420Cys and p.Asp96His were identified among seven index patients with FVD in Taiwan. Our clinical and laboratory findings support the reported features of FVD.

Characterization of congenital factor XII deficiency in Taiwanese patients: identification of one novel and one common mutation.

BACKGROUND: Factor XII (FXII) deficiency is an interesting condition that causes prolonged activated partial thromboplastin time without bleeding diathesis. FXII may be not important in hemostasis, but still plays roles in thrombosis and inflammation. In order to raise clinical awareness about this condition, we studied patients with severe FXII deficiency and their relatives. METHODS: Consecutive severely FXII deficient patients presenting from 1995 to 2020 were recruited from two medical centers in Taiwan. Index patients and their families were tested for FXII function, antigen and F12 gene. F12 variants were constructed into the pIRES-hrGFP vector and expressed on human embryonic kidney cells (HEK293T). FXII antigen and activity were analyzed. RESULTS: We found five severely FXII deficient patients, three women and two men, aged 44-71 years. FXII antigen results ranged from undetectable to 43.7%. Three different mutations were identified: c.1681C>A (p.Gly542Ser), c.1561G>A (p.Glu502Lys), and a novel mutation c.1556T>A (p.Leu500Gln). HEK293T cells expressed consistently low FXII activity with all mutations. FXII antigen expression was similar to the wild type in c.1681C>A (p.Gly542Ser), but reduced in c.1556T>A (p.Leu500Gln) and c.1561G>A (p.Glu502Lys). CONCLUSIONS: We report five unrelated patients with severe FXII deficiency, one of whom carried a novel, cross-reacting material negative mutation c.1556T>A (p.Leu500Gln).

Critical Test Result Recall Supporting System (CTR RSS) Improves Follow-Up among Patients in the Community.

Follow-up care of patients in the community is an important topic for improving patient outcomes, especially when medical personnel receives a notification of the critical test result (CTR) when the CTR becomes available after patients have been out of hospital; how to recall the patient back to the hospital and follow-up treatment is essential for preventing the healthcare risk of neglecting or delayed intervention with respect to the patient's CTR. We are concerned that the follow-up of CTR and timely recall of our patients in the community improves and facilitates patient safety. We built the CTR Recall Supporting System (RSS) to follow up and recall our patients in the community. Measures were introduced to evaluate the effectiveness of CTR RSS; the rate of return of patients within 7 days increased from 58.5% to 88.8%, an increase of 30.3%, the patients in the community's return follow-up interval days decreased from 10.9 days to 6.2 days, reduced by 4.7 days (p < 0.001), and the mortality rate of the patients in the community within 48 h decreased from 8.0% to 1.9%, a decrease of 6.1%, p < 0.001. The implementation of the CTR RSS significantly increases the discharged patient in he community's CTR return follow-up within 7 days rate, decreases CTR return follow-up interval days, and reduces the CTR mortality rate within 48 h. This effectively improves the effects of CTR on return follow-up visits and provides a prototype system for hospitals that intend to improve this issue.

Clinical features and genetic defect in six index patients with congenital fibrinogen disorders: Three novel mutations with one common mutation in Taiwan's population.

INTRODUCTION: Congenital fibrinogen disorders (CFDs) are caused by mutations in fibrinogen-encoding genes, FGA, FGB, and FGG, which lead to quantitative or qualitative abnormalities of fibrinogen. Although the diagnosis of CFDs is based on antigenic and functional level of fibrinogen, few genotypes are clearly correlated with phenotype. METHODS: In this study, we investigated all of the referred patients diagnosed as CFDs in Taiwan's population between 1995 and 2020. Clinical features, laboratory data and genetic defects were analysed. Functional fibrinogen level was determined by the Clauss method. Antigenic fibrinogen was measured by an enzyme-linked immunosorbent assay. Fibrinogen genes were assessed for mutations by polymerase chain reaction and sequencing. RESULTS: A total of 18 patients from six unrelated families with CFDs were identified. One patient from a consanguineous family was diagnosed as afibrinogenemia type 1A with a novel homozygous frameshift mutation in FGB exon 4. The other five (83.3 %) index patients were all diagnosed as dysfibrinogenemia type 3A caused by two novel and one known mutation. Six (33.3 %) patients from three families had a novel mutation in FGB exon 8. The clinical features and laboratory data were highly variable among these patients with the same mutation. CONCLUSIONS: Three novel mutations of CFDs causing afibrinogenemia and dysfibrinogenemia were identified. The point mutation in FGB exon 8 is also a common mutation in Taiwan's population. Considerable phenotypic variability among the patients with an identical mutation was observed.

A Case Report of a 3-Year-Old Child With Anaphylactic Shock After a Diclofenac Suppository Confirmed by Serial Tryptase and a Basophil Activation Test.

Diclofenac is one of the most commonly used non-steroidal anti-inflammatory drug (NSAID) agents for fever management by general practitioners. Anaphylaxis due to suppository of diclofenac sodium (Voltaren) is extremely rare in children. We report the case of a 3-year-old girl with anaphylactic shock after a diclofenac suppository with confirmation by serial tryptase and a basophil activation test.

A family with an MYH9-related disorder with different phenotypes masquerading as immune thrombocytopaenia: an underreported disorder in Taiwan.

A 66-year-old woman had experienced abnormal bleeding since the age of 7. Thrombocytopenia was not detected until she was 48, and immune thrombocytopenia was diagnosed at age 66. She also reported experiencing hearing disturbance since the age of 30 and acute renal failure since the age of 61 but reported no visual disturbance. Her younger son, who was 40 years old, also experienced abnormal bleeding since the age of 6, but immune thrombocytopenia was diagnosed as late as age 35. He had no other associated disorders. Laboratory examinations of both mother and son revealed a low platelet count (8000 and 29,000 µL, respectively), giant platelets and Döhle body-like granulocyte inclusion bodies. The mother had a high creatinine level (15.4 mg/dL) and normal liver enzyme levels. MYH9 genetic analysis identified a heterozygous mutation, c.101T>A, p.Val34Glu at exon 2 in both patients. These clinical and laboratory findings were consistent with a diagnosis of an MYH9-related disorder with different phenotypes observed in the same family. MYH9-related disorders were recognised in 2003, but were often misdiagnosed as immune thrombocytopenia, and hence, they have rarely been reported in Taiwan.

Characterization of hereditary factor XI deficiency in Taiwanese patients: identification of three novel and two common mutations.

Hereditary coagulation factor XI (FXI) deficiency is a rare bleeding disorder, but information on FXI deficiency in Taiwanese patients remains scarce. We evaluated clinical and genetic features of severe FXI deficiency patients in Taiwan. We collected clinical information and performed coagulation laboratory tests and genetic studies in ten unrelated Taiwanese families with severe FXI deficiency. FXI coagulation activity was assayed using a one-stage method. FXI antigen was determined using enzyme-linked immunosorbent assay. Underlying genetic mutations were evaluated using direct sequencing methods. Ten unrelated Taiwanese patients with hereditary FXI deficiency and variable bleeding tendencies were analyzed. Half of the patients were male. The most common bleeding manifestations were easy bruising (40%), bleeding after dental procedures (40%), and postoperative bleeding (33%). Two patients (20%) were asymptomatic. No correlation was found between bleeding manifestations and baseline FXI levels. Three novel mutations were identified: c.1322delT p.Lys442Cysfs*8, c.599G > C p.Cys200Ser, and IVS4 c.325 + 2del124. Two common mutations, c.1107C > T p.Tyr369* (40%) and c.841C > T p.Gln281* (30%), were also found. No correlation existed between bleeding and FXI activity, highlighting the difficulty in predicting FXI deficiency-related bleeding. Three novel FXI genetic mutations and two common mutations were identified, contributing to the known spectrum of FXI deficiency-related mutations.

Absence of hypercoagulability in acute Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis syndrome with the striking feature of cardiovascular involvement. Endothelial cell (EC) damage has been suggested to predispose individuals to the development of coronary vascular disorders. When EC are perturbed, prethrombotic complications ensue. The purpose of this study was to examine the clinical relevance of EC activation and hypercoagulability in the pathogenesis of KD and to determine if plasma levels of these markers are correlated with the development of coronary aneurysms. METHODS: EC function and coagulation status were assessed in 52 patients with acute KD, 20 febrile control subjects, and 20 healthy control subjects. Biological markers of EC and hypercoagulability were measured and included thrombomodulin, tissue factor, tissue factor pathway inhibitor, von Willebrand factor (vWF), coagulation factor VII (FVII), activated factor VII, prothrombin fragment 1 + 2 (F1 + 2), and D-dimer. RESULTS: Transient dilatation of coronary arteries was the most common complication (55.8%), and coronary aneurysm was noted in five patients (9.6%). Levels of vWF, FVII, F1 + 2 and D-dimer were higher in acute KD patients compared with healthy controls but not febrile controls. Markers of EC and hypercoagulability were not different between patients with cardiac complications and those without cardiac complications. Biological and immunological assays did not demonstrate the prethrombotic state in acute KD. CONCLUSIONS: Our results suggest that hypercoagulability does not occur during the acute stage of KD. Markers of EC damage and hypercoagulability are not predictive of coronary aneurysms in KD.