Very severe immune aplastic anemia after mRNA vaccination against COVID-19 responds well to immunosuppressive therapy: clinical characteristics and comparison to previous reports.

OBJECTIVE: Various hematologic side effects of the Coronavirus Disease 2019 (COVID-19) vaccination has been reported, and most of them are thought to be related to autoimmune pathways. To the best of our knowledge, only few cases of post-COVID-19 vaccination aplastic anemia (AA) have been reported and there is no reported Korean case of COVID-19 vaccine-induced AA yet. We present a case of severe immune-mediated AA that developed after the administration of a messenger ribonucleic acid (mRNA) gene-based spike protein vaccine against COVID-19, which responded well to immunosuppressive therapy, and discuss the probable pathogenesis of AA and the implication of vaccination along with a comparison of previous cases reported. METHODS: A 53-year-old Korean man developed sudden pancytopenia three months after COVID-19 vaccination. To evaluate the cause of pancytopenia, a bone marrow study was performed. RESULTS: A diagnosis of AA was made through the bone marrow study and he received triple immunosuppressive therapy (IST). After triple IST for five months, his blood cell count was improved and maintained without transfusion and his follow-up bone marrow examination showed improved cellularity. CONCLUSION: COVID-19 vaccine might be associated with the development of immune-mediated AA. Prompt hematologic evaluation should be performed when there are symptoms or signs suggestive of cytopenia after COVID-19 vaccination. Although the clinical outcome of post-vaccination AA varies, a good prognosis can be possible for patients with COVID-19 vaccination-induced AA.

Association of Lupus Anticoagulant status with Disease Course in SARS-CoV-2 (COVID-19) Infection.

Background: We investigated the importance of lupus anticoagulant (LA) in patients with SARS-CoV-2. Methods: Medical records of 41 SARS-CoV-2 infected patients were reviewed. Patients were classified into two groups according to the frequency of positive LA test results: "LA (-)" and "LA (+) ≥1" (LA positive at least once). Statistical analysis was performed to determine the association between LA presence and change in LA test results and disease course according to both hospital days (HD) and days after diagnosis (DD). Results: The prevalence of LA was 51.2%. Averagely, the first change in LA test result occurred during DD 12-13 and between HD 9-10. The second change occurred on DD 15-16 and HD 13-14. The presence of LA was associated with severe disease (P = .004) but was not associated with thrombotic complications or mortality. The change of results from negative to positive or vice versa or the frequency of the changes was not associated with disease severity, thrombotic complications, or mortality. Conclusions: LA positivity can be regarded as one of the findings suggesting more serious SARS-CoV-2 infection.

Higher intakes of nutrients are linked with a lower risk of cardiovascular diseases, type 2 diabetes mellitus, arthritis, and depression among Korean adults.

Persons with underlying noncommunicable diseases (NCDs) are more likely to acquire severe coronavirus disease 2019 disease and to die from coronavirus disease 2019. An urgent need for potential therapy to prevent and control NCDs is critical. We hypothesized that higher intakes of multiple individual nutrients, fruits, or vegetables would be linked with a low risk of NCDs in the Korean population. Thus, we aim to explore the association between NCDs, including cardiovascular diseases, type 2 diabetes mellitus (T2DM), arthritis, depression, and dietary factors. A total of 56,462 adults aged 18 years (2009-2019) were included. Dietary factors, including intakes of multiple individual nutrients, fruits, and vegetables, were assessed. Multivariable-adjusted logistic regression models were used to explore the associations between dietary factors and NCDs. Interactions were found between intakes of multiple individual nutrients and sex for T2DM, hypertension, stroke, myocardial infarction, arthritis, and osteoarthritis. Only in women was a 2-fold increase in daily multiple individual nutrient intake (vitamins A, B1, B2, B3, C; potassium, protein; phosphorus; calcium; iron; monounsaturated fatty acid and polyunsaturated fatty acid; n-3 fatty acid and n-6 fatty acid; and water) associated with a lower prevalence of T2DM, hypertension, stroke, myocardial infarction, arthritis, and osteoarthritis. In both women and men, high fruit or vegetable consumption was linked with a lower risk of T2DM, hypertension, dyslipidemia, osteoarthritis, and depression than low consumption. Our findings found higher intakes of fruits, vegetables, and multiple individual nutrients are linked with a lower risk of NCDs in the Korean adult population. Further work is needed to identify whether interactions between intake of multiple individual nutrients, vegetables, and fruits affect the presence of NCDs.

Enteric Coronavirus Infection and Treatment Modeled With an Immunocompetent Human Intestine-On-A-Chip.

Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human vascular endothelium to study host cellular and inflammatory responses to infection with NL63 coronavirus. These organoid-derived intestinal epithelial cells dramatically increased their ACE2 protein levels when cultured under flow in the presence of peristalsis-like mechanical deformations in the Intestine Chips compared to when cultured statically as organoids or in Transwell inserts. Infection of the intestinal epithelium with NL63 on-chip led to inflammation of the endothelium as demonstrated by loss of barrier function, increased cytokine production, and recruitment of circulating peripheral blood mononuclear cells (PBMCs). Treatment of NL63 infected chips with the approved protease inhibitor drug, nafamostat, inhibited viral entry and resulted in a reduction in both viral load and cytokine secretion, whereas remdesivir, one of the few drugs approved for COVID19 patients, was not found to be effective and it also was toxic to the endothelium. This model of intestinal infection was also used to test the effects of other drugs that have been proposed for potential repurposing against SARS-CoV-2. Taken together, these data suggest that the human Intestine Chip might be useful as a human preclinical model for studying coronavirus related pathology as well as for testing of potential anti-viral or anti-inflammatory therapeutics.

Association between heavy metals, high-sensitivity C-reaction protein and 10-year risk of cardiovascular diseases among adult Korean population.

The prevalence of cardiovascular diseases (CVDs) in Korea tends to be increasing. It has worsened during the COVID-19 pandemic. Increasing evidence shows heavy metals are associated with increased CVD risk. We aimed to determine the association between the serum heavy metal levels and 10-year risk of CVDs and to predict risks of CVDs based on marginal effects. Heavy metals were measured by a graphite furnace atomic absorption spectrometry and direct mercury analyzer. The results show a significant relationship between the increase in cadmium, lead, mercury, hs-CRP levels and the 10-year risk of CVD after adjustment for serum cotinine, age group, sex, body mass index, a family history of CVDs, diabetes or hyperlipidemia, high-risk drinking, physical activity, and diabetes. A doubling of serum cadmium, lead, mercury, and hs-CRP was associated with the increase in the 10-year risk of CVD by 0.14%, 0.10%, 0.11% and 0.22%, respectively. Therefore, a special concern should be given to the harmful impacts of heavy metals on the 10-year risk of CVD. It is important to develop a prevention strategy targeting the high-risk population to slow down this progression to risk factors related to heavy metals and reduce prevalence. Remarkedly, hs-CRP is the most validated and widely used inflammatory marker, and could be a potential clinical value in predicting and monitoring CVDs.

Effects of Antioxidant Vitamins, Curry Consumption, and Heavy Metal Levels on Metabolic Syndrome with Comorbidities: A Korean Community-Based Cross-Sectional Study.

The burden of metabolic syndrome (MetS) has increased worldwide, especially during the COVID-19 pandemic, and this phenomenon is related to environmental, dietary, and lifestyle risk factors. We aimed to determine the association between the levels of serum heavy metals, hs-CRP, vitamins, and curry intake and to predict risks of MetS based on marginal effects. A data set of 60,256 Koreans aged ≥ 15 years between 2009 and 2017 was used to obtain information on sociodemographic, lifestyle, family history characteristics, MetS, food intake survey, and serum heavy metals. Daily intake of vitamins was measured by a one-day 24 h recall, and curry consumption was calculated using a food frequency questionnaire. Serum heavy metal levels were quantified by graphite furnace atomic absorption spectrometry and using a mercury analyzer. We found that vitamin B1, B2, B3, C, and A intakes were significantly lower in subjects with than without MetS. In contrast, serum levels of Pb, Hg, Cd, vitamin A, E, and hs-CRP were significantly higher in subjects with MetS. The risk of MetS was significantly lower for high curry consumers than low curry consumers (adjusted odds ratio 0.85, 95%CI 0.74-0.98). The risks of MetS were reduced by 12% and 1%, when vitamin B1 and C intakes increased by one mg, respectively, but were increased by 14%, 3%, and 9%, when serum levels of Pb, Hg, and hs-CRP increased by one unit. These results show that the potential health benefits resulting from vitamin and curry intakes could protect the public against the dual burden of communicable and non-communicable diseases. Further studies are required to reduce risk factors associated with serum heavy metal levels and to determine whether interactions between vitamin and curry consumption influence the presence of MetS.

The Psychological Burden of COVID-19 Stigma: Evaluation of the Mental Health of Isolated Mild Condition COVID-19 Patients.

BACKGROUND: The objective of this article is to assess the mental health issues of the mild condition coronavirus disease 2019 (COVID-19) patients admitted to a community treatment center (CTC) in Korea. METHODS: A total of 107 patients admitted to a CTC were included as the study population, and their mental health problems including depression (patient health questionnaire-9), anxiety (generalized anxiety disorder scale-7), post-traumatic stress disorder (PTSD) (PTSD checklist-5) and somatic symptoms (by patient health questionnaire-15) were evaluated every week during their stay. The stigma related to COVID-19 infection was evaluated with an adjusted version of the Middle East respiratory syndrome (MERS) stigma scale. RESULTS: During the first week of isolation, the prevalence of more-than-moderate depression was 24.3%, more-than-moderate anxiety was 14.9%, more-than-moderate somatic symptoms was 36.5% and possible PTSD was 5.6% of total population. For depression and anxiety, previous psychiatric history and stigma of COVID-19 infection were significant risk factors. For PTSD, previous psychiatric history and stigma of COVID-19 infection as well as total duration of isolation were found to be significant risk factors. Prevalence of depression, anxiety and possible PTSD remained similar across the four weeks of observations, though the prevalence of severe depression, increased after four weeks of stay. Somatic symptoms seemed to decrease during their stay. CONCLUSION: The results suggest that social mitigation of COVID-19 related stigma, as well as care of patients with pre-existing mental health problems are important mental health measures during this crisis period. It is also important that clinical guidelines and public health policies be well balanced over the protection of the public and those quarantined to minimize the negative psychosocial consequences from isolation of the patients.

Decoding the temporal nature of brain GR activity in the NFκB signal transition leading to depressive-like behavior.

The fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.

Limited Benefit of Facility Isolation and the Rationale for Home Care in Children with Mild COVID-19.

Considering the mild degree of coronavirus disease 2019 (COVID-19) in children and the enormous stress caused by isolation in unfamiliar places, policies requiring mandatory isolation at medical facilities should be reevaluated especially given the impact of the pandemic on the availability of hospital beds. In this study, we assessed the usefulness of facility isolation and the transmissibility of severe acute respiratory syndrome coronavirus 2 by infected children to uninfected caregivers in isolation units at a hospital and a residential treatment center in Seoul during August-November 2020. Fifty-three children were included and median age was 4 years (range, 0-18). All were mildly ill or asymptomatic and isolated for a median duration of 12 days. Thirty percent stayed home longer than 2 days before entering isolation units from symptom onset. Among 15 uninfected caregivers, none became infected when they used facemasks and practiced hand hygiene. The results suggest children with mild COVID-19 may be cared safely at home by a caregiver in conditions with adherence to the preventive measures of wearing facemasks and practicing hand hygiene.

Information Technology-Based Management of Clinically Healthy COVID-19 Patients: Lessons From a Living and Treatment Support Center Operated by Seoul National University Hospital.

BACKGROUND: South Korea took preemptive action against coronavirus disease (COVID-19) by implementing extensive testing, thorough epidemiological investigation, strict social distancing, and rapid treatment of patients according to disease severity. The Korean government entrusted large-scale hospitals with the operation of living and treatment support centers (LTSCs) for the management for clinically healthy COVID-19 patients. OBJECTIVE: The aim of this paper is to introduce our experience implementing information and communications technology (ICT)-based remote patient management systems at a COVID-19 LTSC. METHODS: We adopted new electronic health record templates, hospital information system (HIS) dashboards, cloud-based medical image sharing, a mobile app, and smart vital sign monitoring devices. RESULTS: Enhancements were made to the HIS to assist in the workflow and care of patients in the LTSC. A dashboard was created for the medical staff to view the vital signs and symptoms of all patients. Patients used a mobile app to consult with their physician or nurse, answer questionnaires, and input self-measured vital signs; the results were uploaded to the hospital information system in real time. Cloud-based image sharing enabled interoperability between medical institutions. Korea's strategy of aggressive mitigation has "flattened the curve" of the rate of infection. A multidisciplinary approach was integral to develop systems supporting patient care and management at the living and treatment support center as quickly as possible. CONCLUSIONS: Faced with a novel infectious disease, we describe the implementation and experience of applying an ICT-based patient management system in the LTSC affiliated with Seoul National University Hospital. ICT-based tools and applications are increasingly important in health care, and we hope that our experience will provide insight into future technology-based infectious disease responses.

Selecting coronavirus disease 2019 patients with negligible risk of progression: early experience from non-hospital isolation facility in Korea.

BACKGROUND/AIMS: As the novel coronavirus (coronavirus disease 2019 [COVID-19]) outbreak progresses rapidly, staying home is recommended for suspected patients; however, the safety of this recommendation is uncertain. In Korea, non-hospital facilities called "living and treatment centers (LTCs)" have been established since 5 March 2020. The LTCs provided a unique opportunity to evaluate the safety of selection criteria for low-risk groups. METHODS: Between 5 March and 9 April 2020, patients with COVID-19 who met the following criteria were admitted to the LTC; alert, age below 65 years old, no underlying disease or well-controlled underlying disease, body temperature below 38.0°C, whether taking antipyretics or not, and no dyspnea. Patients were closely observed by doctors or nurses' interviews twice a day and transferred to hospitals when symptoms worsened. RESULTS: A total of 113 patients were admitted to the LTC; 52.2% were female, with a median age of 25 years (interquartile range, 21.5 to 39.5). Of 113 patients, 54 (47.8%) were asymptomatic at diagnosis, and 15 (13.3%) had no symptoms until they were released from isolation. During the follow-up period, two (1.8%) patients were transferred to a hospital but did not progress to severe status during hospitalization. CONCLUSION: The risk of progression was negligible in COVID-19 patients who met the admission criteria for LTC at the time of diagnosis. LTCs could be a safe alternative considering shortage of hospital beds.