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1.
J Infect Chemother ; 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38518846

ABSTRACT

BACKGROUND: Gram-positive bacteria are frequently resistant to empirical beta-lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer. METHODS: Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia. RESULTS: Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130-14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366-11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059-0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218-0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia. CONCLUSIONS: Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer.

2.
J Med Virol ; 95(2): e28558, 2023 02.
Article in English | MEDLINE | ID: mdl-36755360

ABSTRACT

The fourth vaccination dose confers additional protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with no prior coronavirus disease-19 (COVID-19). However, its immunological benefit against currently circulating BA.4/5 is unclear in individuals who have received a booster shot and been infected with Omicron variant BA.1/2. We analyzed immune responses in whom had been boosted once and did not have COVID-19 (n = 16), boosted once and had COVID-19 when BA.1/2 was dominant in Korea (Hybrid-6M group, n = 27), and boosted twice and did not have COVID-19 (Vx4 group, n = 15). Antibody binding activities against RBDo BA.1 and RBDo BA.4/5 , antigen-specific memory CD4+ and CD8+ T-cell responses against BA.4/5, and B-cell responses against SARS-CoV-2 wild-type did not differ statistically between the Hybrid-6M and Vx4 groups. The humoral and cellular immune responses of the Hybrid-6M group against BA.4/5 were comparable to those of the Vx4 group. Individuals who had been boosted and had an Omicron infection in early 2022 may not have high priority for an additional vaccination.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Immunity, Cellular , B-Lymphocytes , Antibodies, Neutralizing , Antibodies, Viral
3.
J Med Virol ; 95(11): e29199, 2023 11.
Article in English | MEDLINE | ID: mdl-37916645

ABSTRACT

Despite the importance of antigen-specific T cells in infectious disease, characterizing and tracking clonally amplified T cells during the progression of a patient's symptoms remain unclear. Here, we performed a longitudinal, in-depth single-cell multiomics analysis of samples from asymptomatic, mild, usual severe, and delayed severe patients of SARS-CoV-2 infection. Our in-depth analysis revealed that hyperactive or improper T-cell responses were more aggressive in delayed severe patients. Interestingly, tracking of antigen-specific T-cell receptor (TCR) clonotypes along the developmental trajectory indicated an attenuation in functional T cells upon severity. In addition, increased glycolysis and interleukin-6 signaling in the cytotoxic T cells were markedly distinct in delayed severe patients compared to usual severe patients, particularly in the middle and late stages of infection. Tracking B-cell receptor clonotypes also revealed distinct transitions and somatic hypermutations within B cells across different levels of disease severity. Our results suggest that single-cell TCR clonotype tracking can distinguish the severity of patients through immunological hallmarks, leading to a better understanding of the severity differences in and improving the management of infectious diseases by analyzing the dynamics of immune responses over time.


Subject(s)
COVID-19 , Humans , COVID-19/diagnosis , SARS-CoV-2 , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes, Cytotoxic , B-Lymphocytes
4.
J Korean Med Sci ; 38(23): e180, 2023 Jun 12.
Article in English | MEDLINE | ID: mdl-37309699

ABSTRACT

The personal protective equipment (PPE) used to minimize exposure to hazards can hinder healthcare workers from performing sophisticated procedures. We retrospectively reviewed 77,535 blood cultures (202,012 pairs) performed in 28,502 patients from January 2020 to April 2022. The contamination rate of all blood cultures was significantly elevated in the coronavirus disease 2019 ward at 4.68%, compared to intensive care units at 2.56%, emergency rooms at 1.13%, hematology wards at 1.08%, and general wards at 1.07% (All of P < 0.001). This finding implies that wearing PPE might interfere with adherence to the aseptic technique. Therefore, a new PPE policy is needed that considers the balance between protecting healthcare workers and medical practices.


Subject(s)
Blood Culture , COVID-19 , Humans , COVID-19 Drug Treatment , Retrospective Studies , Personal Protective Equipment
5.
J Korean Med Sci ; 38(16): e129, 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-37096312

ABSTRACT

BACKGROUND: Alpha-toxin (AT), a major virulence factor of Staphylococcus aureus, is an important immunotherapeutic target to prevent or treat invasive S. aureus infections. Previous studies have suggested that anti-AT antibodies (Abs) may have a protective role against S. aureus bacteremia (SAB), but their function remains unclear. Therefore, we aimed to investigate the association between serum anti-AT Ab levels and clinical outcomes of SAB. METHODS: Patients from a prospective SAB cohort at a tertiary-care medical center (n = 51) were enrolled in the study from July 2016 to January 2019. Patients without symptoms or signs of infection were enrolled as controls (n = 100). Blood samples were collected before the onset of SAB and at 2- and 4-weeks post-bacteremia. Anti-AT immunoglobin G (IgG) levels were measured using an enzyme-linked immunosorbent assay. All clinical S. aureus isolates were tested for the presence of hla using polymerase chain reaction. RESULTS: Anti-AT IgG levels in patients with SAB before the onset of bacteremia did not differ significantly from those in non-infectious controls. Pre-bacteremic anti-AT IgG levels tended to be lower in patients with worse clinical outcomes (7-day mortality, persistent bacteremia, metastatic infection, septic shock), although the differences were not statistically significant. Patients who needed intensive care unit care had significantly lower anti-AT IgG levels at 2 weeks post-bacteremia (P = 0.020). CONCLUSION: The study findings suggest that lower anti-AT Ab responses before and during SAB, reflective of immune dysfunction, are associated with more severe clinical presentations of infection.


Subject(s)
Bacteremia , Staphylococcal Infections , Humans , Staphylococcus aureus , Prospective Studies , Antibody Formation , Bacteremia/drug therapy , Staphylococcal Infections/drug therapy , Immunoglobulin G , Anti-Bacterial Agents/therapeutic use
6.
J Infect Dis ; 226(7): 1224-1230, 2022 09 28.
Article in English | MEDLINE | ID: mdl-35299253

ABSTRACT

BACKGROUND: Humoral immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may wane rapidly in persons recovered from mild coronavirus disease 2019 (COVID-19), but little is known about the longevity. METHODS: Serum samples were obtained 8, 12, and 18 months after infection from 20 patients with mild COVID-19. The binding activities of serum antibodies (immunoglobulin [Ig]A, IgG, and IgM) against SARS-CoV-2 antigens of the Wuhan-1 reference strain (wild-type) and the B.1.1.7, P.1, B.1.167.2, and B.1.1.529 variants were measured by enzyme-linked immunosorbent assays. Neutralizing antibody titers were measured using a cytopathic effect-based live virus neutralization assay. RESULTS: Serum IgA and IgG antibodies against spike or receptor-binding domain (RBD) protein of wild-type SARS-CoV-2 were detected for up to 18 months, and neutralizing antibodies persisted for 8 to 18 months after infection. However, any significant antibody responses against RBD proteins of SARS-CoV-2 variants were not observed, and median neutralizing antibody titers against the Delta variant at 8, 12, and 18 months were 8- to 11-fold lower than against wild-type viruses (P<.001). CONCLUSIONS: Humoral immunity persisted for up to 18 months after SARS-CoV-2 infection in patients with mild COVID-19. However, humoral immune activity against more recently circulating variants was reduced in this population.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Antibody Formation , Humans , Immunoglobulin A , Immunoglobulin G , Immunoglobulin M , Spike Glycoprotein, Coronavirus
7.
Clin Infect Dis ; 75(4): 596-603, 2022 09 10.
Article in English | MEDLINE | ID: mdl-34893799

ABSTRACT

BACKGROUND: Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a zoonotic betacoronavirus. The development of effective vaccines and control measures requires a thorough understanding of the immune response to this viral infection. METHODS: We investigated cellular immune responses up to 5 years after infection in a cohort of 59 MERS survivors by performing enzyme-linked immunospot assay and intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with synthetic viral peptides. RESULTS: Memory T-cell responses were detected in 82%, 75%, 69%, 64%, and 64% of MERS survivors from 1-5 years post-infection, respectively. Although the frequency of virus-specific interferon gamma (IFN-γ)-secreting T cells tended to be higher in moderately/severely ill patients than in mildly ill patients during the early period of follow-up, there was no significant difference among the different clinical severity groups across all time points. While both CD4+ and CD8+ T cells were involved in memory T-cell responses, CD4+ T cells persisted slightly longer than CD8+ T cells. Both memory CD4+ and CD8+ T cells recognized the E/M/N proteins better than the S protein and maintained their polyfunctionality throughout the period examined. Memory T-cell responses correlated positively with antibody responses during the initial 3-4 years but not with maximum viral loads at any time point. CONCLUSIONS: These findings advance our understanding of the dynamics of virus-specific memory T-cell immunity after MERS-coronavirus infection, which is relevant to the development of effective T cell-based vaccines.


Subject(s)
Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Humans , Immunologic Memory , Leukocytes, Mononuclear , Memory T Cells , Survivors
8.
Oncologist ; 27(12): e931-e937, 2022 12 09.
Article in English | MEDLINE | ID: mdl-36218350

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic affected millions of individuals, and patients with cancer are known to be more susceptible. Vaccines against SARS-CoV-2 have been developed and used for patients with cancer, but scarce data are available on their efficacy in patients under active anti-cancer therapies. MATERIALS AND METHODS: In this study, we semi-quantitatively measured the titers of the immunoglobulin G against the anti-spike protein subunit 1 of SARS-CoV-2 after vaccination of patients with early breast cancer undergoing concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments. RESULTS: Standard doses of COVID-19 vaccines provided sufficient immune responses in patients with early breast cancer, regardless of the type of anticancer therapies. However, the post-vaccination serum anti-spike antibody titers were significantly lower in the patients under cytotoxic chemotherapy. CONCLUSION: Our study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations.


Subject(s)
Breast Neoplasms , COVID-19 , Humans , Female , SARS-CoV-2 , COVID-19 Vaccines/therapeutic use , Breast Neoplasms/drug therapy , COVID-19/prevention & control , Patients
9.
Anal Chem ; 94(49): 17186-17194, 2022 12 13.
Article in English | MEDLINE | ID: mdl-36399654

ABSTRACT

A high-throughput, accurate screening is crucial for the prevention and control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current methods, which involve sampling from the nasopharyngeal (NP) area by medical staffs, constitute a fundamental bottleneck in expanding the testing capacity. To meet the scales required for population-level surveillance, self-collectable specimens can be used; however, its low viral load has hindered its clinical adoption. Here, we describe a magnetic nanoparticle functionalized with synthetic apolipoprotein H (ApoH) peptides to capture, concentrate, and purify viruses. The ApoH assay demonstrates a viral enrichment efficiency of >90% for both SARS-CoV-2 and its variants, leading to an order of magnitude improvement in analytical sensitivity. For validation, we apply the assay to a total of 84 clinical specimens including nasal, oral, and mouth gargles obtained from COVID-19 patients. As a result, a 100% positivity rate is achieved from the patient-collected nasal and gargle samples, which exceeds that of the traditional NP swab method. The simple 12 min pre-enrichment assay enabling the use of self-collectable samples will be a practical solution to overcome the overwhelming diagnostic capacity. Furthermore, the methodology can easily be built on various clinical protocols, allowing its broad applicability to various disease diagnoses.


Subject(s)
COVID-19 , Humans , COVID-19/diagnosis , SARS-CoV-2 , beta 2-Glycoprotein I , COVID-19 Testing , Nasopharynx , Specimen Handling/methods , Peptides
10.
BMC Med ; 20(1): 181, 2022 05 04.
Article in English | MEDLINE | ID: mdl-35508998

ABSTRACT

BACKGROUND: Practical guidance is needed regarding the vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals in resource-limited countries. It includes the number of vaccine doses that should be given to unvaccinated patients who experienced COVID-19 early in the pandemic. METHODS: We recruited COVID-19 convalescent individuals who received one or two doses of an mRNA vaccine within 6 or around 18 months after a diagnosis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Their samples were assessed for IgG-binding or neutralizing activity and cell-mediated immune responses against SARS-CoV-2 wild-type and variants of concern. RESULTS: A total of 43 COVID-19 convalescent individuals were analyzed in the present study. The results showed that humoral and cellular immune responses against SARS-CoV-2 wild-type and variants of concern, including the Omicron variant, were comparable among patients vaccinated within 6 versus around 18 months. A second dose of vaccine did not significantly increase immune responses. CONCLUSION: One dose of mRNA vaccine should be considered sufficient to elicit a broad immune response even around 18 months after a COVID-19 diagnosis.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Testing , COVID-19 Vaccines , Humans , Immunity, Cellular , RNA, Messenger/genetics , SARS-CoV-2/genetics , Vaccination , Vaccines, Synthetic , mRNA Vaccines
11.
J Korean Med Sci ; 37(29): e238, 2022 Jul 25.
Article in English | MEDLINE | ID: mdl-35880508

ABSTRACT

Despite the low prevalence of secondary bacterial infection in coronavirus disease 2019 (COVID-19) patients, most of them were administered antibiotic therapy empirically. However, the prognostic impact of empirical antibiotic therapy has not been evaluated. We conducted retrospective propensity score-matched case-control study of 233 COVID-19 patients with moderate to severe illnesses who required oxygen therapy and evaluated whether empirical antibiotic therapy could improve clinical outcomes. Empirical antibiotic therapy did not improve clinical outcomes including length of stay, days with oxygen requirement, the proportion of patients with increased oxygen demand, the proportion of patients who required mechanical ventilation, and overall mortality. This finding implies that routine administration of antibiotics for the treatment of COVID-19 is not essential and should be restricted.


Subject(s)
COVID-19 , Anti-Bacterial Agents/therapeutic use , Case-Control Studies , Humans , Oxygen/therapeutic use , Retrospective Studies
12.
J Korean Med Sci ; 37(8): e67, 2022 Feb 28.
Article in English | MEDLINE | ID: mdl-35226425

ABSTRACT

We investigated the kinetics of the neutralizing antibody responses to the severe acute respiratory syndrome-coronavirus-2 delta variant over the course of 1 year in 16 patients infected at the beginning of the pandemic. In patients with severe disease, neutralizing responses to the delta variant were detectable, albeit at lower levels than responses to the wild type. Neutralizing responses to the delta variant were undetectable, however, in asymptomatic persons. This finding implies that the vaccination strategy for persons with past natural infection should depend on the severity of the previous infection.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Female , Humans , Kinetics , Male , Middle Aged , Severity of Illness Index , Vaccination , Young Adult
13.
J Korean Med Sci ; 37(32): e252, 2022 Aug 15.
Article in English | MEDLINE | ID: mdl-35971766

ABSTRACT

BACKGROUND: The clinical features of coronavirus disease 2019 (COVID-19) patients in the COVID-19 vaccination era need to be clarified because breakthrough infection after vaccination is not uncommon. METHODS: We retrospectively analyzed hospitalized COVID-19 patients during a delta variant-dominant period 6 months after the national COVID-19 vaccination rollout. The clinical characteristics and risk factors for severe progression were assessed and subclassified according to vaccination status. RESULTS: A total of 438 COVID-19 patients were included; the numbers of patients in the unvaccinated, partially vaccinated and fully vaccinated groups were 188 (42.9%), 117 (26.7%) and 133 (30.4%), respectively. The vaccinated group was older, less symptomatic and had a higher Charlson comorbidity index at presentation. The proportions of patients who experienced severe progression in the unvaccinated and fully vaccinated groups were 20.3% (31/153) and 10.8% (13/120), respectively. Older age, diabetes mellitus, solid cancer, elevated levels of lactate dehydrogenase and chest X-ray abnormalities were associated with severe progression, and the vaccination at least once was the only protective factor for severe progression. Chest X-ray abnormalities at presentation were the only predictor for severe progression among fully vaccinated patients. CONCLUSION: In the hospitalized setting, vaccinated and unvaccinated COVID-19 patients showed different clinical features and risk of oxygen demand despite a relatively high proportion of patients in the two groups. Vaccination needs to be assessed as an initial checkpoint, and chest X-ray may be helpful for predicting severe progression in vaccinated patients.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , Humans , Retrospective Studies , SARS-CoV-2 , Vaccination
14.
J Korean Med Sci ; 37(49): e353, 2022 Dec 19.
Article in English | MEDLINE | ID: mdl-36536547

ABSTRACT

Since 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide, and the coronavirus disease 2019 (COVID-19) pandemic currently continues. In response to this unprecedented pandemic, several researchers and medical staff have struggled to find appropriate treatments for COVID-19. Patients with mild symptoms can recuperate with symptomatic care, however establishing treatment for severe to critically ill patients who can have a high mortality has been essential. Accordingly, the guidelines for COVID-19 treatment have evolved through numerous trials and errors and have been relatively well established to date. In the Republic of Korea, several evidence-based guidelines for COVID-19 treatment were released and revised, reflecting various research and regional medical conditions. To date, approximately 3 years after the beginning of the COVID-19 pandemic, we are reflecting on the changes in the guidelines thus far and have summarized the treatment experience of severe to critically ill patients with COVID-19. The Korean guidelines for COVID-19 treatment have been updated continuously as the National Institutes of Health (NIH) guidelines have changed. Dexamethasone is currently used as the backbone for the treatment of severe to critically ill patients with COVID-19, and remdesivir, baricitinib, and tocilizumab can be added depending on a patient's situation. In addition, venous thromboembolism prophylaxis is one of the important adjunctive therapies for patients with severe COVID-19. In the clinical field, treatment of severely ill patients with COVID-19 based on guidelines is widely practiced by medical staff and established currently.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Critical Illness , Pandemics , COVID-19 Drug Treatment
15.
J Korean Med Sci ; 37(16): e126, 2022 Apr 25.
Article in English | MEDLINE | ID: mdl-35470600

ABSTRACT

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.


Subject(s)
COVID-19 , Personal Protective Equipment , Anxiety/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Health Personnel , Humans , SARS-CoV-2
16.
J Infect Dis ; 224(1): 39-48, 2021 07 02.
Article in English | MEDLINE | ID: mdl-33755725

ABSTRACT

BACKGROUND: Understanding the memory T-cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for assessing the longevity of protective immunity after SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination. However, the longitudinal memory T-cell response up to 8 months post-symptom onset (PSO) according to the severity of illness is unknown. METHODS: We analyzed peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with COVID-19 who experienced asymptomatic, mild, or severe illness at 2, 5, and 8 months PSO. SARS-CoV-2 spike, nucleocapsid, and membrane protein-stimulated PBMCs were subjected to flow cytometry analysis. RESULTS: A total of 24 patients (7 asymptomatic, 9 with mild disease, and 8 with severe disease) and 6 healthy volunteers were analyzed. SARS-CoV-2-specific OX40+CD137+CD4+ T cells and CD69+CD137+CD8+ T cells persisted at 8 months PSO. Also, antigen-specific cytokine-producing or polyfunctional CD4+ T cells were maintained for up to 8 months PSO. Memory CD4+ T-cell responses tended to be greater in patients who had severe illness than in those with mild or asymptomatic disease. CONCLUSIONS: Memory response to SARS-CoV-2, based on the frequency and functionality, persists for 8 months PSO. Further investigations involving its longevity and protective effect from reinfection are warranted.


Subject(s)
COVID-19/immunology , COVID-19/virology , Host-Pathogen Interactions/immunology , Immunologic Memory , SARS-CoV-2/immunology , T-Lymphocyte Subsets/immunology , Adult , Aged , Antigens, Viral , Biomarkers , COVID-19/diagnosis , COVID-19/epidemiology , Case-Control Studies , Cytokines/metabolism , Disease Management , Epitopes, T-Lymphocyte/immunology , Female , Humans , Immunity, Cellular , Immunophenotyping , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Longitudinal Studies , Male , Middle Aged , Severity of Illness Index , Symptom Assessment , T-Lymphocyte Subsets/metabolism , Time Factors
17.
Proteomics ; 21(11-12): e2000278, 2021 06.
Article in English | MEDLINE | ID: mdl-33945677

ABSTRACT

In managing patients with coronavirus disease 2019 (COVID-19), early identification of those at high risk and real-time monitoring of disease progression to severe COVID-19 is a major challenge. We aimed to identify potential early prognostic protein markers and to expand understanding of proteome dynamics during clinical progression of the disease. We performed in-depth proteome profiling on 137 sera, longitudinally collected from 25 patients with COVID-19 (non-severe patients, n = 13; patients who progressed to severe COVID-19, n = 12). We identified 11 potential biomarkers, including the novel markers IGLV3-19 and BNC2, as early potential prognostic indicators of severe COVID-19. These potential biomarkers are mainly involved in biological processes associated with humoral immune response, interferon signalling, acute phase response, lipid metabolism, and platelet degranulation. We further revealed that the longitudinal changes of 40 proteins persistently increased or decreased as the disease progressed to severe COVID-19. These 40 potential biomarkers could effectively reflect the clinical progression of the disease. Our findings provide some new insights into host response to SARS-CoV-2 infection, which are valuable for understanding of COVID-19 disease progression. This study also identified potential biomarkers that could be further validated, which may support better predicting and monitoring progression to severe COVID-19.


Subject(s)
COVID-19 , Host-Pathogen Interactions/genetics , Proteome , Transcriptome/genetics , Aged , Biomarkers/blood , COVID-19/diagnosis , COVID-19/genetics , COVID-19/metabolism , Disease Progression , Female , Gene Expression Profiling , Humans , Longitudinal Studies , Male , Middle Aged , Prognosis , Proteome/analysis , Proteome/genetics , Proteome/metabolism , Proteomics
18.
Clin Infect Dis ; 73(3): e550-e558, 2021 08 02.
Article in English | MEDLINE | ID: mdl-32898238

ABSTRACT

BACKGROUND: Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridges this gap. METHODS: We traced antibody responses and memory B cells in peripheral blood collected from 70 recovered Middle East respiratory syndrome coronavirus (MERS-CoV) patients for 3 years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge. RESULTS: Anti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients who suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than 2-fold. Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viral loads observed during infection periods. In a transgenic mice model challenged with lethal doses of MERS-CoV, a significant reduction in viral loads and enhanced survival was observed when therapeutically treated with human plasma retaining a high neutralizing titer (> 1/5000). However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss. CONCLUSIONS: High titers of neutralizing activity are required for suppressive effect on the viral replication but may not be sufficient to reduce inflammatory lesions upon fatal infection. Therefore, immune sera with high neutralizing activity must be carefully selected for plasma therapy of zoonotic coronavirus infection.


Subject(s)
Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , Animals , Antibodies, Neutralizing , Antibodies, Viral , Coronavirus Infections/drug therapy , Humans , Mice , Republic of Korea , Spike Glycoprotein, Coronavirus
19.
Clin Infect Dis ; 73(9): e3002-e3008, 2021 11 02.
Article in English | MEDLINE | ID: mdl-33219681

ABSTRACT

BACKGROUND: Positive results from real-time reverse-transcription polymerase chain reaction (rRT-PCR) in recovered patients raise concern that patients who recover from coronavirus disease 2019 (COVID-19) may be at risk of reinfection. Currently, however, evidence that supports reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been reported. METHODS: We conducted whole-genome sequencing of the viral RNA from clinical specimens at the initial infection and at the positive retest from 6 patients who recovered from COVID-19 and retested positive for SARS-CoV-2 via rRT-PCR after recovery. A total of 13 viral RNAs from the patients' respiratory specimens were consecutively obtained, which enabled us to characterize the difference in viral genomes between initial infection and positive retest. RESULTS: At the time of the positive retest, we were able to acquire a complete genome sequence from patient 1, a 21-year-old previously healthy woman. In this patient, through the phylogenetic analysis, we confirmed that the viral RNA of positive retest was clustered into a subgroup distinct from that of the initial infection, suggesting that there was a reinfection of SARS-CoV-2 with a subtype that was different from that of the primary strain. The spike protein D614G substitution that defines the clade "G" emerged in reinfection, while mutations that characterize the clade "V" (ie, nsp6 L37F and ORF3a G251V) were present at initial infection. CONCLUSIONS: Reinfection with a genetically distinct SARS-CoV-2 strain may occur in an immunocompetent patient shortly after recovery from mild COVID-19. SARS-CoV-2 infection may not confer immunity against a different SARS-CoV-2 strain.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Female , Humans , Phylogeny , RNA, Viral/genetics , Reinfection , Young Adult
20.
Emerg Infect Dis ; 27(3): 928-931, 2021 03.
Article in English | MEDLINE | ID: mdl-33350923

ABSTRACT

Waning humoral immunity in coronavirus disease patients has raised concern over usefulness of serologic testing. We investigated antibody responses of 58 persons 8 months after asymptomatic or mildly symptomatic infection with severe acute respiratory syndrome coronavirus 2. For 3 of 4 immunoassays used, seropositivity rates were high (69.0%-91.4%).


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunity, Humoral , Adult , Asymptomatic Infections , COVID-19/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Republic of Korea , SARS-CoV-2/immunology , Young Adult
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