Clinical impact of clonal hematopoiesis on severe COVID-19 patients without canonical risk factors.

Not available.

Diagnostic Performance, Stability, and Usability of Self-Collected Combo Swabs and Saliva for Coronavirus Disease 2019 Diagnosis: A Case-Control Study.

BACKGROUND: Self-sampling procedures to detect severe acute respiratory syndrome coronavirus 2 is important for patients who have difficulty visiting the hospital and may decrease the burden for health care workers (HCWs). The objective of this study was to evaluate the diagnostic performance, stability and usability of self-collected nasal and oral combo swabs and saliva specimens. MATERIALS AND METHODS: We conducted a case-control study with 50 patients with coronavirus disease 2019 (COVID-19) and 50 healthy volunteers from March, 2021 to June, 2021. We performed real-time reverse-transcription polymerase chain reaction to compare the diagnostic performance of self-collected specimens using positive percent agreements (PPAs). RESULTS: The PPAs between self-collected and HCW-collected specimens were 77.3 - 81.0% and 80.5 -86.7% for the combo swabs and saliva specimens, respectively. The PPAs increased to 88.9 - 89.2% and 81.2 - 82.1% with a cycle threshold value ≤30. CONCLUSION: The diagnostic performance of self sampling was comparable to that of HCW sampling in patients with high viral loads and may thus assist in the early diagnosis of COVID-19.

Performance of STANDARD™ M10 SARS-CoV-2 Assay for the Diagnosis of COVID-19 from a Nasopharyngeal Swab.

The STANDARD™ M10 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) assay (M10 assay) (SD Biosensor Inc., Suwon, Korea) is a rapid, fully-automated, cartridge-type molecular diagnostic assay that detects SARS-CoV-2 RNA using primers and probes for each target gene (ORF1ab gene, E gene). This study evaluated its performance by assessing its concordance with the approved SARS-CoV-2 real-time PCR assay. Tests were performed on 80 nasopharyngeal samples. The sensitivity and specificity of the M10 assay were 100%. The M10 assay effectively diagnosed SARS-CoV-2 infection, and it was comparable to the approved SARS-CoV-2 real-time PCR assay. It is a viable point-of-care test due to its short turnaround time.

Comprehensive Rehabilitation in Severely Ill Inpatients With COVID-19: A Cohort Study in a Tertiary Hospital.

BACKGROUND: This study aimed to investigate the effects of comprehensive rehabilitation management on functional recovery and examine the correlation between clinical parameters and improvements in functional outcomes in severe-to-critical inpatients with coronavirus disease 2019 (COVID-19) in a tertiary hospital. METHODS: Post-acute COVID-19 patients who had a World Health Organization (WHO) ordinal scale of 5-7, underwent intensive care, and received comprehensive rehabilitation management, including exercise programs, nutritional support, dysphagia evaluation, and psychological care were included. The appendicular skeletal muscle mass index (SMI), Medical Research Council sum score, handgrip strength, number of repetitions in the 1-minute sit-to-stand test, gait speed, Berg Balance Scale (BBS), and Functional Ambulation Classification (FAC) were evaluated at hospital stay, discharge, and 1-month follow-up. The correlation between the rehabilitation dose and improvement in each outcome measure was analyzed. RESULTS: Overall, 37 patients were enrolled, of whom 59.5% and 32.4% had a score of 6 and 7 on the WHO ordinal scale, respectively. Lengths of stay in the intensive care unit and hospital were 33.6 ± 23.9 and 63.8 ± 36.5 days. Outcome measures revealed significant improvements at discharge and 1-month follow-up. The SMI was significantly increased at the 1-month follow-up (6.13 [5.24-7.76]) compared with that during the hospital stay (5.80 [5.39-7.05]). We identified dose-response associations between the rehabilitation dose and FAC (ρ = 0.46) and BBS (ρ = 0.50) scores. Patients with older age, longer hospitalization, longer stay at the intensive care unit, longer duration of mechanical ventilation, tracheostomy, a more depressive mood, and poorer nutritional status revealed poorer improvement in gait speed at the 1-month follow-up. CONCLUSION: Comprehensive rehabilitation management effectively improved muscle mass, muscle strength, and physical performance in severe-to-critical COVID-19 patients. Dose-response relationship of rehabilitation and functional improvement emphasizes the importance of intensive post-acute inpatient rehabilitation in COVID-19 survivors. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05104411.

The generation of stem cell-like memory cells early after BNT162b2 vaccination is associated with durability of memory CD8+ T cell responses.

COVID-19 vaccines elicit humoral and cellular immune responses. Durable maintenance of vaccine-induced immunity is required for long-term protection of the host. Here, we examine activation and differentiation of vaccine-induced CD8+ T cells using MHC class I (MHC-I) multimers and correlations between early differentiation and the durability of CD8+ T cell responses among healthcare workers immunized with two doses of BNT162b2. The frequency of MHC-I multimer+ cells is robustly increased by BNT162b2 but decreases 6 months post-second vaccination to 2.4%-65.6% (23.0% on average) of the peak. MHC-I multimer+ cells dominantly exhibit phenotypes of activated effector cells 1-2 weeks post-second vaccination and gradually acquire phenotypes of long-term memory cells, including stem cell-like memory T (TSCM) cells. Importantly, the frequency of TSCM cells 1-2 weeks post-second vaccination significantly correlates with the 6-month durability of CD8+ T cells, indicating that early generation of TSCM cells determines the longevity of vaccine-induced memory CD8+ T cell responses.

Changes in Anxiety Level and Personal Protective Equipment Use Among Healthcare Workers Exposed to COVID-19.

BACKGROUND: The relationship between changes in anxiety levels and personal protective equipment (PPE) use is yet to be evaluated. The present study assessed this relationship among healthcare workers (HCWs) involved in the care of patients with coronavirus disease 2019 (COVID-19). METHODS: An online survey was conducted in a municipal hospital with 195 nationally designated negative pressure isolation units in Korea. Anxiety level was measured using the self-rating anxiety scale (SAS), and changes in anxiety levels were assessed based on the time when COVID-19 vaccine was introduced in March 2021 in Korea. Monthly PPE usage between June 2020 and May 2021 was investigated. RESULTS: The mean SAS score (33.25 ± 5.97) was within normal range and was lower than those reported in previous studies conducted before COVID-19 vaccination became available. Among the 93 HCWs who participated, 64 (68.8%) answered that their fear of contracting COVID-19 decreased after vaccination. The number of coveralls used per patient decreased from 33.6 to 0. However, a demand for more PPE than necessary was observed in situations where HCWs were exposed to body fluids and secretions (n = 38, 40.9%). Excessive demand for PPE was not related to age, working experience, or SAS score. CONCLUSION: Anxiety in HCWs exposed to COVID-19 was lower than it was during the early period of the pandemic, and the period before vaccination was introduced. The number of coveralls used per patient also decreased although an excessive demand for PPE was observed.

Are coveralls required as personal protective equipment during the management of COVID-19 patients?

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.

Usefulness of ELISA Using Total Antibody against Plant-Expressed Recombinant Nucleocapsid Protein of SARS-CoV-2.

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.

Clonal hematopoiesis is associated with risk of severe Covid-19.

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.

Impact of Public Health Interventions on Seasonal Influenza Activity During the COVID-19 Outbreak in Korea.

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.

Predication of oxygen requirement in COVID-19 patients using dynamic change of inflammatory markers: CRP, hypertension, age, neutrophil and lymphocyte (CHANeL).

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.

Can reactogenicity predict immunogenicity after COVID-19 vaccination?

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.

Early rehabilitation in a critically ill inpatient with COVID-19.

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.

Stereotypic neutralizing VH antibodies against SARS-CoV-2 spike protein receptor binding domain in patients with COVID-19 and healthy individuals.

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.

Psychological Consequences of Survivors of COVID-19 Pneumonia 1 Month after Discharge.

As the coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, there are growing concerns about patients' mental health. We investigated psychological problems in COVID-19 patients assessed with self-reported questionnaires including the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 scale, and Impact of Event Scale-Revised Korean version. Ten patients who recovered from COVID-19 pneumonia without complications underwent self-reported questionnaires about 1 month after discharge. Of them, 10% reported depression and posttraumatic stress disorder (PTSD) while 50% had depression during the treatment. Perceived stigma and history of psychiatric treatment affected PTSD symptom severity, consistent with previous emerging infectious diseases. Survivors also reported that they were concerned about infecting others and being discriminated and that they chose to avoid others after discharge. Further support and strategy to minimize their psychosocial difficulties after discharge should be considered.

Clonal hematopoiesis is associated with risk of severe Covid-19.

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. 1-4 These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. 2,5,6 A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. 7,8 Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 515 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we found that CH was associated with severe Covid-19 outcomes (OR=1.9, 95%=1.2-2.9, p=0.01). We further explored the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH was significantly associated with risk of Clostridium Difficile (HR=2.0, 95% CI: 1.2-3.3, p=6×10 -3 ) and Streptococcus/Enterococcus infections (HR=1.5, 95% CI=1.1-2.1, p=5×10 -3 ). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.

Waning Antibody Responses in Asymptomatic and Symptomatic SARS-CoV-2 Infection.

We investigated the kinetics of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in 7 asymptomatic persons and 11 patients with pneumonia. The geometric mean titer of neutralizing antibodies declined from 219.4 at 2 months to 143.7 at 5 months after infection, indicating a waning antibody response.