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1.
Infect Chemother ; 53(4): 786-791, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1596564

ABSTRACT

In preparation for the surge of coronavirus disease 2019 (COVID-19), it is crucial to allocate medical resources efficiently for distinguishing people who remain asymptomatic until the end of the disease. Between January 27, 2020, and April 21, 2020, 517 COVID-19 cases from 13 healthcare facilities in Gyeonggi province, Korea, were identified out of which the epidemiologic and clinical information of 66 asymptomatic patients at the time of diagnosis were analyzed retrospectively. An exposure-diagnosis interval within 7 days and abnormal aspartate aminotransferase levels were identified as characteristic symptom development in asymptomatic COVID-19 patients. If asymptomatic patients without these characteristics at the time of diagnosis could be differentiated early, more medical resources could be secured for mild or moderate cases in this COVID-19 surge.

2.
J Korean Med Sci ; 36(50): e343, 2021 Dec 27.
Article in English | MEDLINE | ID: covidwho-1594418

ABSTRACT

As hospitals cater to elderly and vulnerable patients, a high mortality rate is expected if a coronavirus disease 2019 (COVID-19) outbreak occurs. Consequently, policies to prevent the spread of COVID-19 in hospital settings are essential. This study was conducted to investigate how effectively national and international guidelines provide recommendations for infection control issues in hospitals. After selecting important issues in infection control, we performed a systematic review and analysis of recommendations and guidelines for preventing COVID-19 transmission within medical institutions at national and international levels. We analyzed guidelines from the World Health Organization, Centers for Disease Control and Prevention, European Centre for Disease Prevention and Control, and Korea Disease Control and Prevention Agency. Recent guidelines do not provide specific solutions to infection control issues. Therefore, efforts need to be made to devise consistent advice and guidelines for COVID-19 control.


Subject(s)
COVID-19/prevention & control , Infection Control/methods , Practice Guidelines as Topic , SARS-CoV-2 , Health Personnel , Humans
4.
Open forum infectious diseases ; 8(Suppl 1):S316-S317, 2021.
Article in English | EuropePMC | ID: covidwho-1564302

ABSTRACT

Background Infection control measures against the coronavirus disease 2019 (COVID-19) within a hospital often rely on expert experience and intuition due to the lack of clear guidelines. This study surveyed current strategies for the prevention of the spread of COVID-19 in medical institutions. Methods Upon systematic review of the guidelines at the national level, 14 key topics were selected. Six hospitals were provided an open survey that assessed their responses to these topics between August 11 and 25, 2020. Using these data, an online questionnaire was developed and sent to the infection control teams of 46 hospitals in South Korea. The survey was conducted between January 31, 2021, and February 20, 2021. Results All 46 hospitals responded to the survey, and 24 hospitals (52.2%) had treated 100 or more cases of COVID-19. All hospitals operated screening clinics, and the criteria were respiratory symptoms (100%), fever (97.8%), and epidemiological association (93.5%). It was found that 89.1% (41/46) of hospitals allowed symptomatic patients to visit their general outpatient clinics if fever or respiratory symptoms were not associated with COVID-19. Most hospitals (87.2%;34/39) conducted polymerase chain reaction (PCR) tests for all hospitalized patients. Moreover, 76.1% (35/46) of hospitals implemented preemptive isolation policies for hospitalized patients, of which 97.1% (34/35) were released from isolation after a single negative PCR test. A little over half of the hospitals (58.7%;27/46) treated patients that met the national criteria for release from isolation but consistently had positive PCR results. Of these hospitals, 63% (17/27) used N95/KF94 masks, and 40.7% (11/27) used surgical masks without other personal protective equipment for treating them. Most hospitals (76.9%;20/26) accommodated them in shared rooms when the cycle threshold value of the PCR test was more than a certain value (34.6%;9/26), or after a certain period that satisfied the national criteria (26.9%;7/26). Finally, 76.1% (35/46) of hospitals performed emergency procedures or operations on suspected patients. Table 1. Screening and selective treatment policy to prevent COVID-19 patients from entering the hospital Note Values are presented as number (%) Abbreviations: COVID-19, coronavirus disease 2019;PCR, polymerase chain reaction 1 This question requested the respondent to select multiple items. 2 Suspected cases of COVID-19 include fever, respiratory symptoms, and epidemiological associations with COVID-19 patients. Note Values are presented as number (%) Abbreviations: COVID-19, coronavirus disease 2019;PCR, polymerase chain reaction;PAPR, powered air-purifying respirator;Ct, cycle threshold 1 This question requested the respondent to select multiple items. 2 It includes infectious diseases, pulmonology, and the infection control and prevention office. 3 One hospital that wrote a non-categorical answer for the question was excluded. The hospital made a decision after discussing it with an infectious diseases specialist. Conclusion Various guidelines were being applied by each medical institution, but there was a lack of an explicit set of national guidelines to support them. Disclosures All Authors: No reported disclosures

5.
Antimicrob Resist Infect Control ; 10(1): 164, 2021 11 27.
Article in English | MEDLINE | ID: covidwho-1538091

ABSTRACT

OBJECTIVES: Few studies have investigated the contamination of personal protective equipment (PPE) during the management of patients with severe-to-critical coronavirus disease (COVID-19). This study aimed to determine the necessity of coveralls and foot covers for body protection during the management of COVID-19 patients. METHODS: PPE samples were collected from the coveralls of physicians exiting a room after the management of a patient with severe-to-critical COVID-19 within 14 days after the patient's symptom onset. The surface of coveralls was categorized into coverall-only parts (frontal surface of the head, anterior neck, dorsal surface of the foot cover, and back and hip) and gown-covered parts (the anterior side of the forearm and the abdomen). Sampling of the high-contact surfaces in the patient's environment was performed. We attempted to identify significant differences in contamination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between the coverall-only and gown-covered parts. RESULTS: A total of 105 swabs from PPEs and 28 swabs from patient rooms were collected. Of the PPE swabs, only three (2.8%) swabs from the gown-covered parts were contaminated with SARS-CoV-2. However, 23 of the 28 sites (82.1%) from patient rooms were contaminated. There was a significant difference in the contamination of PPE between the coverall-only and gown-covered parts (0.0 vs 10.0%, p = 0.022). CONCLUSIONS: Coverall contamination rarely occurred while managing severe-to-critical COVID-19 patients housed in negative pressure rooms in the early stages of the illness. Long-sleeved gowns may be used in the management of COVID-19 patients.

6.
Microbiol Spectr ; : e0067221, 2021 Nov 24.
Article in English | MEDLINE | ID: covidwho-1532977

ABSTRACT

Here, we aimed to investigate the diagnostic value of a serological assay using the nucleocapsid protein developed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection and evaluated its performance using three commercial enzyme-linked immunosorbent assays (ELISAs), namely, Standard E 2019 novel coronavirus disease (COVID-19) total antibody (Ab) ELISA (SD Biosensor), and EDI novel coronavirus COVID-19 IgG and IgM ELISA. A recombinant nucleocapsid protein (rNP) was expressed from plants and Escherichia coli for the detection of serum total Ab. We prospectively collected 141 serum samples from 32 patients with reverse transcription-PCR (RT-PCR)-confirmed COVID-19 and determined the sensitivity and dynamics of their total Ab response. Specificity was evaluated using 158 prepandemic samples. To validate the assays, we evaluated the performance using two different cutoff values. The sensitivity and specificity for each assay were as follows: 92.91% and 94.30% (plant-rNP), 83.69% and 98.73% (SD Biosensor), 75.89% and 98.10% (E. coli-rNP), 76.47% and 100% (EDI-IgG), and 80.39% and 80% (EDI-IgM). The plant-based rNP showed the highest sensitivity and area under the receiver operating characteristic (ROC) curve (0.980) among all the assays (P < 0.05). The seroconversion rate for total Ab increased sequentially with disease progression, with a sensitivity of 100% after 10 to 12 days of post-symptom onset (PSO) for both rNP-plant-based and SD Biosensor ELISAs. After 2 weeks of PSO, the seroconversion rates were >80% and 100% for EDI-IgM and EDI-IgG ELISA, respectively. Seroconversion occurred earlier with rNP plant-based ELISA (5 days PSO) compared with E. coli-based (7 days PSO) and SD Biosensor (8 days PSO) ELISA. We determined that rNP produced in plants enables the robust detection of SARS-CoV-2 total Abs. The assay can be used for serosurvey and complementary diagnosis of COVID-19. IMPORTANCE At present, the principal diagnostic methods for COVID-19 comprise the identification of viral nucleic acid by genetic approaches, including PCR-based techniques or next-generation sequencing. However, there is an urgent need for validated serological assays which are crucial for the understanding of immune responses against SARS-CoV-2. In this study, a highly sensitive and specific serological antibody assay was developed for the detection of SARS-CoV-2 with an overall accuracy of 93.56% using a recombinant nucleoprotein expressed from plants.

7.
Nat Commun ; 12(1): 5975, 2021 10 13.
Article in English | MEDLINE | ID: covidwho-1467103

ABSTRACT

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 525 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we show that CH is associated with severe Covid-19 outcomes (OR = 1.85, 95%=1.15-2.99, p = 0.01), in particular CH characterized by non-cancer driver mutations (OR = 2.01, 95% CI = 1.15-3.50, p = 0.01). We further explore the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH is significantly associated with risk of Clostridium Difficile (HR = 2.01, 95% CI: 1.22-3.30, p = 6×10-3) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15-2.13, p = 5×10-3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.


Subject(s)
COVID-19/etiology , COVID-19/pathology , Clonal Hematopoiesis/genetics , Hematopoietic Stem Cells/virology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/immunology , Child , Child, Preschool , Clonal Hematopoiesis/immunology , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Mutation/immunology , Neoplasms/genetics , Risk Factors , SARS-CoV-2 , Severity of Illness Index
8.
BJPsych Open ; 7(6): e183, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1443808

ABSTRACT

Background: Mental illness among survivors of coronavirus disease 2019 (COVID-2019) during the post-illness period is an emerging and important health issue. Aims: We aimed to investigate the prevalence of mental illness and the associated factors for its development among COVID-2019 survivors. Method: From 1 January to 4 June 2020, data were extracted from the National Health Insurance Service COVID-19 database in South Korea. Patients with COVID-19 were defined as those whose test results indicated that they had contracted the infection, regardless of disease severity. COVID-19 survivors were defined as those who recovered from the infection. The primary end-point was the development of mental illness, which was evaluated between 1 January and 1 December 2020. Results: A total 260 883 individuals were included in this study, and 2.36% (6148) were COVID-19 survivors. The COVID-19 survivors showed higher prevalence of mental illness than the control group (12.0% in the COVID-19 survivors v. 7.7% in the control group; odds ratio (OR) = 2.40, 95% CI 2.21-2.61, P < 0.001). Additionally, compared with the control group, the no specific treatment for COVID-19 group (OR = 2.23, 95% CI 2.03-2.45, P < 0.001) and specific treatment for COVID-19 group (OR = 3.27, 95% CI 2.77-3.87, P < 0.001) showed higher prevalence of mental illness among survivors. Conclusions: In South Korea, COVID-19 survivors had a higher risk of developing mental illness compared with the rest of the populations. Moreover, this trend was more evident in COVID-19 survivors who experienced specific treatment in the hospital.

9.
J Obes Metab Syndr ; 30(3): 248-260, 2021 Sep 30.
Article in English | MEDLINE | ID: covidwho-1337811

ABSTRACT

Background: During the coronavirus disease 2019 (COVID-19) pandemic, preventive measures mandated by government policies have included the closure of exercise facilities and movement restriction, which can lead to an unhealthy lifestyle. We investigated the effect of these preventive measures on metabolic parameters in individuals with cardiometabolic disorders. Methods: In this retrospective, observational study of patients who visited the hospital at least twice a year for the past 4 years, changes in cardiometabolic factors during the COVID-19 pandemic (2019-2020) were compared with changes in the same cohort at the same annual time points during the previous seasons of 2016-2019. Results: A total of 1,485 individuals with a mean age of 61.8±11.7 years were included in the analyses. During the COVID-19 pandemic, the number of patients whose metabolic syndrome worsened increased significantly by 21% compared with the 2018-2019 season. Body mass index increased by 0.09±1.16 kg/m2 in the 2019-2020 pandemic period, whereas it decreased by -0.39±3.03 kg/m2 in 2018-2019 and by -0.34±2.18 kg/m2 in 2017-2018 (both P<0.05). Systolic blood pressure increased by 2.6±18.2 mmHg in the COVID-19 pandemic period, while it decreased in the three antecedent seasons (all P<0.05). Lipid profiles worsened in the pandemic period compared with the previous years. Framingham coronary heart disease risk score also increased significantly. Conclusion: Nationwide strategies to maintain cardiometabolic health are necessary during contagious disease pandemics like COVID-19 to mitigate the adverse health effects of pandemic-preventative strategies.

10.
Clin Infect Dis ; 73(1): e132-e140, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1290937

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) was introduced in Korea early with a large outbreak in mid-February. We reviewed the public health interventions used during the COVID-19 outbreak and describe the impact on seasonal influenza activity in Korea. METHODS: National response strategies, public health interventions and daily COVID-19-confirmed cases in Korea were reviewed during the pandemic. National influenza surveillance data were compared between 7 sequential seasons. Characteristics of each season, including rate of influenza-like illness (ILI), duration of epidemic, date of termination of epidemic, distribution of influenza virus strain, and hospitalization, were analyzed. RESULTS: After various public health interventions including enforced public education on hand hygiene, cough etiquette, staying at home with respiratory symptoms, universal mask use in public places, refrain from nonessential social activities, and school closures the duration of the influenza epidemic in 2019/2020 decreased by 6-12 weeks and the influenza activity peak rated 49.8 ILIs/1000 visits compared to 71.9-86.2 ILIs/1000 visits in previous seasons. During the period of enforced social distancing from weeks 9-17 of 2020, influenza hospitalization cases were 11.9-26.9-fold lower compared with previous seasons. During the 2019/2020 season, influenza B accounted for only 4%, in contrast to previous seasons in which influenza B accounted for 26.6-54.9% of all cases. CONCLUSIONS: Efforts to activate a high-level national response not only led to a decrease in COVID-19 but also a substantial decrease in seasonal influenza activity. Interventions applied to control COVID-19 may serve as useful strategies for prevention and control of influenza in upcoming seasons.


Subject(s)
COVID-19 , Influenza, Human , Disease Outbreaks , Humans , Influenza, Human/epidemiology , Public Health , Republic of Korea , SARS-CoV-2 , Seasons
11.
Sci Rep ; 11(1): 13026, 2021 06 22.
Article in English | MEDLINE | ID: covidwho-1279902

ABSTRACT

The objective of the study was to develop and validate a prediction model that identifies COVID-19 patients at risk of requiring oxygen support based on five parameters: C-reactive protein (CRP), hypertension, age, and neutrophil and lymphocyte counts (CHANeL). This retrospective cohort study included 221 consecutive COVID-19 patients and the patients were randomly assigned randomly to a training set and a test set in a ratio of 1:1. Logistic regression, logistic LASSO regression, Random Forest, Support Vector Machine, and XGBoost analyses were performed based on age, hypertension status, serial CRP, and neutrophil and lymphocyte counts during the first 3 days of hospitalization. The ability of the model to predict oxygen requirement during hospitalization was tested. During hospitalization, 45 (41.8%) patients in the training set (n = 110) and 41 (36.9%) in the test set (n = 111) required supplementary oxygen support. The logistic LASSO regression model exhibited the highest AUC for the test set, with a sensitivity of 0.927 and a specificity of 0.814. An online risk calculator for oxygen requirement using CHANeL predictors was developed. "CHANeL" prediction models based on serial CRP, neutrophil, and lymphocyte counts during the first 3 days of hospitalization, along with age and hypertension status, provide a reliable estimate of the risk of supplement oxygen requirement among patients hospitalized with COVID-19.


Subject(s)
C-Reactive Protein/analysis , COVID-19/pathology , Hypertension/complications , Lymphocytes/cytology , Neutrophils/cytology , Oxygen Inhalation Therapy , Age Factors , Aged , Area Under Curve , Biomarkers/analysis , Biomarkers/metabolism , COVID-19/complications , COVID-19/virology , Female , Humans , Logistic Models , Lymphocytes/metabolism , Male , Middle Aged , Neutrophils/metabolism , ROC Curve , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Support Vector Machine
12.
Korean J Intern Med ; 36(6): 1486-1491, 2021 11.
Article in English | MEDLINE | ID: covidwho-1248069

ABSTRACT

BACKGROUND/AIMS: This study aimed to assess the association between local and systemic reactogenicity and humoral immunogenicity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. METHODS: Adverse events were prospectively evaluated using an electronic diary in 135 healthy adults who received a SARS-CoV-2 vaccine (AZD1222, AstraZeneca/Oxford, n = 42; or BNT162b2, Pfizer/BioNTech, n = 93). We semi-quantitatively measured anti-S1 immunoglobulin G (IgG) using an enzyme-linked immunosorbent assay at baseline, 3 weeks after the first dose of AZD1222 or BNT162b2, and 2 weeks after the second dose of BNT162b2. We evaluated the association between the maximum grade of local or systemic adverse events and the anti-S1 IgG optical density using multivariate linear regression with adjustment for age, sex, and use of antipyretics. RESULTS: The median age of the 135 vaccinees was 30 years (36 years in the AZD1222 group and 29 years in the BNT162b2 group) and 25.9% were male (9.5% in the AZD1222 group and 33.3% in the BNT162b2 group). Local and systemic adverse events were generally comparable after the first dose of AZD1222 and the second dose of BNT162b2. The grades of local and systemic adverse events were not significantly associated with anti-S1 IgG levels in the AZD1222 or BNT162b2 group. CONCLUSION: Local and systemic reactogenicity may not be associated with humoral immunogenicity after SARS-CoV-2 vaccination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adult , Humans , Male , SARS-CoV-2 , Vaccination/adverse effects
13.
Sci Rep ; 11(1): 8080, 2021 04 13.
Article in English | MEDLINE | ID: covidwho-1182872

ABSTRACT

The objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.


Subject(s)
COVID-19/pathology , Immunity , Adult , Aged , C-Reactive Protein/analysis , COVID-19/immunology , COVID-19/virology , Cluster Analysis , Female , Humans , Lymphocytes/cytology , Male , Middle Aged , Neutrophils/cytology , Risk Factors , SARS-CoV-2/isolation & purification
14.
Open Forum Infect Dis ; 8(4): ofab057, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1069299

ABSTRACT

Background: We compared all-cause mortality between individuals in South Korea with and without coronavirus disease 2019 (COVID-19) using propensity score (PS) matching. Methods: This population-based cohort study used data from the National Health Insurance Service COVID-19 cohort database. In the database, we included individuals (COVID-19 patients, control population, and test-negative individuals) aged 20 years or older, regardless of hospitalization. The primary end point was all-cause mortality between January 1, 2020, and August 27, 2020. Results: A total of 328 374 adults were included in the study: 7713 and 320 660 in the COVID-19 group and the control group. After PS matching, a total of 15 426 individuals (7713 per group) were included in the analysis. All-cause mortality was 3.2% (248/7713) and 1.6% (126/7713) in the COVID-19 group and the control group, respectively. In Cox regression analysis after PS matching, the risk of death in the COVID-19 group was twice as high (hazard ratio, 2.00; 95% CI, 1.61-2.48; P < .001) as that in the control group. Among patients aged ≥60 years, the COVID-19 group had a 2.32-fold higher all-cause mortality compared with the control group, while statistically significant differences were not observed in the age groups 20-39 years (P = .339) and 40-59 years (P = .562). Conclusions: In South Korea, all-cause mortality was twice as high among individuals with COVID-19 as among those with similar underlying risks, primarily because of the elevated COVID-19-associated mortality in those aged ≥60 years. Our results highlight the need for prevention of COVID-19 with respect to mortality as a public health outcome.

15.
Immunity ; 54(1): 44-52.e3, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-1065202

ABSTRACT

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Programmed Cell Death 1 Receptor/metabolism , SARS-CoV-2/immunology , Acute-Phase Reaction/immunology , Acute-Phase Reaction/virology , COVID-19/pathology , COVID-19/virology , Convalescence , Epitopes, T-Lymphocyte , Histocompatibility Antigens Class I/immunology , Humans , Immunologic Memory , Immunophenotyping , Interferon-gamma/metabolism , Lymphocyte Activation , Viral Load
16.
Eur J Phys Rehabil Med ; 56(6): 858-861, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1049276

ABSTRACT

BACKGROUND: Survivors of critical coronavirus disease 2019 (COVID-19) suffer from severe physical functional disability. Recent reports from several countries suggest that rehabilitative intervention is needed to improve physical functional decline in the challenging situation of COVID-19. CASE REPORT: A 58-year-old woman, previously without gait difficulty, was diagnosed with COVID-19 requiring endotracheal intubation and mechanical ventilation. She also developed stress-induced cardiomyopathy. After management in intensive care unit for 15 days, she could not sit on a bed without back support. After receiving short-term inpatient rehabilitation therapy, lower limb muscle strength, balance function, and gait speed had rapidly and significantly improved at the time of hospital discharge and at 1-month follow-up. CLINICAL REHABILITATION IMPACT: As COVID-19 tends to progress rapidly in the acute phase, early rehabilitation is necessary, despite challenges to its implementation. Feasible inpatient rehabilitation for patients with critical COVID-19 will pave the way to improve physical functional disability.


Subject(s)
COVID-19/epidemiology , Critical Care/methods , Critical Illness/rehabilitation , Intensive Care Units , COVID-19/rehabilitation , Comorbidity , Critical Illness/epidemiology , Female , Humans , Middle Aged , Pandemics , SARS-CoV-2
18.
Sci Transl Med ; 13(578)2021 01 27.
Article in English | MEDLINE | ID: covidwho-1007317

ABSTRACT

Stereotypic antibody clonotypes exist in healthy individuals and may provide protective immunity against viral infections by neutralization. We observed that 13 of 17 patients with COVID-19 had stereotypic variable heavy chain (VH) antibody clonotypes directed against the receptor binding domain (RBD) of SARS-CoV-2 spike protein. These antibody clonotypes were composed of immunoglobulin heavy variable 3-53 (IGHV3-53) or IGHV3-66 and immunoglobulin heavy joining 6 (IGHJ6) genes. These clonotypes included IgM, IgG3, IgG1, IgA1, IgG2, and IgA2 subtypes and had minimal somatic mutations, which suggested swift class switching after SARS-CoV-2 infection. The different IGHV chains were paired with diverse light chains resulting in binding to the RBD of SARS-CoV-2 spike protein. Human antibodies specific for the RBD can neutralize SARS-CoV-2 by inhibiting entry into host cells. We observed that one of these stereotypic neutralizing antibodies could inhibit viral replication in vitro using a clinical isolate of SARS-CoV-2. We also found that these VH clonotypes existed in 6 of 10 healthy individuals, with IgM isotypes predominating. These findings suggest that stereotypic clonotypes can develop de novo from naïve B cells and not from memory B cells established from prior exposure to similar viruses. The expeditious and stereotypic expansion of these clonotypes may have occurred in patients infected with SARS-CoV-2 because they were already present.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin Heavy Chains/immunology , Immunoglobulin Variable Region/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Neutralizing/isolation & purification , COVID-19/blood , COVID-19/virology , Clone Cells , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G/blood , Mutation/genetics , Protein Binding , Protein Domains , Recombinant Proteins/metabolism , Spike Glycoprotein, Coronavirus/genetics
19.
BMC Infect Dis ; 20(1): 901, 2020 Nov 30.
Article in English | MEDLINE | ID: covidwho-1005880

ABSTRACT

BACKGROUND: Staphylococcus aureus bacteremia (SAB) presents heterogeneously, owing to the differences in underlying host conditions and immune responses. Although Toll-like receptor 2 (TLR2) is important in recognizing S. aureus, its function during S. aureus infection remains controversial. We aimed to examine the association of TLR2 expression and associated cytokine responses with clinical SAB outcomes. METHODS: Patients from a prospective SAB cohort at two tertiary-care medical centers were enrolled. Blood was sampled at several timepoints (≤5 d, 6-9 d, 10-13 d, 14-19 d, and ≥ 20 d) after SAB onset. TLR2 mRNA levels were determined via real-time PCR and serum tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-10 levels were analyzed with multiplex-high-sensitivity electrochemiluminescent ELISA. RESULTS: TLR2 levels varied among 59 SAB patients. On days 2-5, TLR2 levels were significantly higher in SAB survivors than in healthy controls (p = 0.040) and slightly but not significantly higher than non-survivors (p = 0.120), and SAB patients dying within 7 d had lower TLR2 levels than survivors (P = 0.077) although statistically insignificant. IL-6 and IL-10 levels were significantly higher in non-survivors than in survivors on days 2-5 post-bacteremia (P = 0.010 and P = 0.021, respectively), and those dying within 7 d of SAB (n = 3) displayed significantly higher IL-10/TNF-α ratios than the survivors did (P = 0.007). CONCLUSION: TLR2 downregulation and IL-6 and IL-10 concentrations suggestive of immune dysregulation during early bacteremia may be associated with mortality from SAB. TLR2 expression levels and associated cytokine reactions during early-phase SAB may be potential prognostic factors in SAB, although larger studies are warranted.


Subject(s)
Bacteremia/metabolism , Bacteremia/mortality , Cytokines/metabolism , Down-Regulation/genetics , Staphylococcal Infections/metabolism , Staphylococcal Infections/mortality , Staphylococcus aureus/isolation & purification , Toll-Like Receptor 2/genetics , Adult , Aged , Aged, 80 and over , Cytokines/analysis , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Staphylococcal Infections/microbiology , Staphylococcus aureus/metabolism , Survivors , Tertiary Care Centers
20.
Immunity ; 54(1): 44-52.e3, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-988082

ABSTRACT

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Programmed Cell Death 1 Receptor/metabolism , SARS-CoV-2/immunology , Acute-Phase Reaction/immunology , Acute-Phase Reaction/virology , COVID-19/pathology , COVID-19/virology , Convalescence , Epitopes, T-Lymphocyte , Histocompatibility Antigens Class I/immunology , Humans , Immunologic Memory , Immunophenotyping , Interferon-gamma/metabolism , Lymphocyte Activation , Viral Load
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