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1.
Jpn J Infect Dis ; 75(4): 419-422, 2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-1957581

ABSTRACT

The detection of other pathogens in patients with hospitalized coronavirus disease (COVID-19) are not frequent. Considering that data from Japan are limited, we conducted an observational study including patients with hospitalized COVID-19 at the National Center for Global Health and Medicine from January to September 2020. In total, 247 patients with COVID-19 were included in the study. Rapid diagnostic tests, such as immunochromatography, were performed in 31 patients (12.6%). The Film Array Respiratory Panel was performed in 18 (7.3%) patients, and none of the tests were positive for pathogens other than severe acute respiratory syndrome coronavirus 2. Respiratory bacterial culture was performed in 66 (26.7%) patients, with gram-positive bacteria, gram-negative bacteria and normal flora being detected in eight (12.1%), seven (10.6%), and 63 (95.5%) patients, respectively. Patients for whom cultures were performed were older, more severely ill, and more likely to have radiological evidence of pneumonia on admission. Culture was performed more frequently in the early than in the later period of the epidemic, without any differences being observed in bacterial detection rates. The proportion of viral and bacterial detection among hospitalized patients with COVID-19 in tertiary care hospitals in Japan was low. A larger cohort study is necessary to evaluate the effect of each pathogen on the clinical course of COVID-19.


Subject(s)
COVID-19 , COVID-19/diagnosis , Cohort Studies , Humans , Japan/epidemiology , SARS-CoV-2 , Tertiary Care Centers
2.
J Infect Chemother ; 28(7): 971-974, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1828865

ABSTRACT

Corticosteroids are widely used to treat severe COVID-19, but in immunocompromised individuals, who are susceptible to persistent infection, long term corticosteroid use may delay viral clearance. We present a case of prolonged SARS-CoV-2 infection in a man with significantly impaired B-cell immunity due to non-Hodgkin lymphoma which had been treated with rituximab. SARS-CoV-2 shedding persisted, despite treatment with remdesivir. Viral sequencing confirmed the persistence of the same viral strain, ruling out the possibility of reinfection. Although SARS-CoV-2 IgG, IgA and IgM remained negative throughout the treatment period, after reduction of the corticosteroid dose, PCR became negative. Long-term corticosteroid treatment, especially in immunocompromised individuals, may result in suppression of cell-mediated immunity and prolonged SARS-CoV-2 infection.


Subject(s)
COVID-19 , Antibodies, Viral , COVID-19/drug therapy , Humans , Immunocompromised Host , Male , Rituximab/adverse effects , SARS-CoV-2
3.
Intern Med ; 61(6): 913-916, 2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1745229

ABSTRACT

A 33-year-old woman with a fever, cough, and pharyngitis was admitted after left-sided pleural effusion was detected. The fever and upper respiratory symptoms were confirmed, and she was diagnosed with coronavirus disease (COVID-19) after showing a positive polymerase chain reaction (PCR) test. After thoracentesis, pleural fluid revealed elevated adenosine deaminase values and a positive QuantiFeron test; tuberculous pleurisy was thus suspected. Subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR and anti-SARS-CoV-2 Spike IgG tests were negative, suggesting that the initial PCR result had been erroneous. However, we were unable to confirm this. Data concerning COVID-19 diagnostics are insufficient at present. It is important to make comprehensive judgments regarding the diagnosis and treatment of patients as well as public health.


Subject(s)
COVID-19 , Pleural Effusion , Tuberculosis, Pleural , Adenosine Deaminase/analysis , Adult , COVID-19/diagnosis , Comorbidity , Female , Humans , Pleural Effusion/diagnosis , SARS-CoV-2 , Tuberculosis, Pleural/diagnosis
4.
J Diabetes Investig ; 13(6): 1086-1093, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1685350

ABSTRACT

AIMS/INTRODUCTION: Diabetes is associated with poor clinical outcomes of coronavirus disease 2019 (COVID-19). However, the impact of newly diagnosed diabetes on prognosis has not been clarified. The objective of this study was to show the features and outcome of COVID-19 patients with newly diagnosed diabetes in Japan. MATERIALS AND METHODS: We retrospectively analyzed 62 patients with diabetes hospitalized for COVID-19 between 1 April and 18 August 2021 at the National Center for Global Health and Medicine in Tokyo, Japan. We evaluated the worst severity of COVID-19 and plasma blood glucose levels in patients with newly diagnosed diabetes or pre-existing diabetes. RESULTS: This study included 62 confirmed COVID-19 patients with diabetes, including 19 (30.6%) patients with newly diagnosed diabetes and 43 (69.4%) patients with pre-existing diabetes. Patients with newly diagnosed diabetes significantly progressed to a critical condition more frequently during hospitalization than patients with pre-existing diabetes (52.6% vs 20.9%, P = 0.018). In addition, patients with newly diagnosed diabetes had significantly higher average plasma blood glucose levels for the first 3 days after admission than those with pre-existing diabetes. CONCLUSIONS: Our study suggests that the proportion of COVID-19 patients who are newly diagnosed with diabetes is high, and they have an increased risk of developing severe disease than those with pre-existing diabetes. It might be advisable that at the point of COVID-19 diagnosis, blood glucose and glycated hemoglobin levels be assessed in all patients.


Subject(s)
COVID-19 , Diabetes Mellitus , Hyperglycemia , Blood Glucose , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Humans , Hyperglycemia/complications , Hyperglycemia/diagnosis , Retrospective Studies , Risk Factors , SARS-CoV-2
5.
Jpn J Infect Dis ; 75(1): 36-40, 2022 Jan 24.
Article in English | MEDLINE | ID: covidwho-1650209

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be detected in the stool samples of patients with coronavirus disease 2019 (COVID-19), and this virus can be transmitted via the oral-fecal route. However, there are only few reports on the viral load in the stool samples. In this pilot study, we aimed to evaluate the clinical characteristics and viral load of SARS-CoV-2 in the stool samples of 13 patients with confirmed COVID-19 using pepper mild mottle virus as a control, which has been proposed as a potential marker of human feces contamination in the environmental water bodies. SARS-CoV-2 RNA was detected in the stool samples of four patients (31%), and among them, three exhibited symptoms of diarrhea. One patient who suffered from long-term diarrhea (22 days) exhibited highest level of viral RNA in the stool sample (8.28 log10 copies/g). However, we could not harvest SARS-CoV-2 from the stool sample of any patient, even after culturing with VeroE6/TMPRESS2 cells for four weeks. Our results suggest that SARS-CoV-2 RNA can be detected in the stool samples of patients with COVID-19 suffering from diarrhea. However, further studies elucidating the relationship between SARS-CoV-2 viral load in the stool samples and symptoms of diarrhea in large cohorts and upon adjusting other causative factors and virus infectivity are still warranted.


Subject(s)
COVID-19 , Diarrhea/epidemiology , Feces , Humans , Pilot Projects , RNA, Viral , SARS-CoV-2 , Viral Load
6.
Respir Investig ; 60(2): 241-247, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1537016

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, has been a significant concern worldwide since its outbreak in December 2019. Various treatments are being researched and developed, and there are reports that dexamethasone has reduced the mortality rate and improved the clinical course of critically ill patients with COVID-19. In this study, we examined the clinical efficacy of corticosteroid therapy for patients with COVID-19 in our hospital during the first wave of infections. METHODS: We retrospectively reviewed the medical records of patients with COVID-19 who were treated with or without corticosteroid therapy at the National Center for Global Health and Medicine in Japan between February and April 2020. The primary outcome was improvement in the patients' clinical course using a seven-category ordinal scale. We collected data on patient characteristics, treatment, and clinical course, and compared them between two groups: the steroid-using group and the non-steroid-using group. RESULTS: Between February and April 2020, 110 patients were diagnosed with COVID-19. Despite poor conditions during admission into the steroid group, there were no statistical differences in clinical course between both groups, as measured using the scale. There were no statistical differences between the two groups in the number of days to fever resolution or negative polymerase chain reaction results. CONCLUSIONS: There was no difference in the clinical course between both groups. Because of the difference in background, corticosteroids may potentially make the clinical course of severely ill patients similar to that of mildly ill patients.


Subject(s)
COVID-19 , Adrenal Cortex Hormones , Global Health , Humans , Retrospective Studies , SARS-CoV-2
7.
Lancet Respir Med ; 9(12): 1365-1376, 2021 12.
Article in English | MEDLINE | ID: covidwho-1472211

ABSTRACT

BACKGROUND: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19. METHODS: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 µg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475. FINDINGS: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group. INTERPRETATION: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo. FUNDING: The National Institute of Allergy and Infectious Diseases (USA).


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19 , Interferon beta-1a/therapeutic use , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/therapeutic use , COVID-19/drug therapy , Double-Blind Method , Female , Humans , Japan , Male , Mexico , Middle Aged , Oxygen , Oxygen Saturation , Republic of Korea , SARS-CoV-2 , Singapore , Treatment Outcome , United States
8.
Glob Health Med ; 3(4): 236-239, 2021 Aug 31.
Article in English | MEDLINE | ID: covidwho-1417546

ABSTRACT

We investigated possible sources of newly infected patients with coronavirus disease (COVID-19) after the fourth wave in order to explore unknown sources. Retrospective chart review on all the confirmed patients with COVID-19 admitted to the National Center for Global Health and Medicine (NCGM) in Tokyo, Japan was conducted from May 22 through June 29, 2021. Among the 22 participants, 14 (64%) had a history of known high-risk infection behaviors. Of those, 12 reported that their activities involved eating and drinking. In addition, there were 24 high-risk situations, of those, 21 (88%) were related to indoor dining, and masks were not worn in 22 situations (92%). New source of infection has not been identified. In situations with a high known risk of infection, many cases were related to eating and drinking, and insufficient use of masks was evident. Raising risk awareness on infection prevention and control of COVID-19 is urgently needed.

9.
J Infect Chemother ; 27(11): 1669-1673, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1356307

ABSTRACT

INTRODUCTION: The automated quantitative antigen test (QAT), which detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is suitable for mass screening. However, its diagnostic capability differentiated by time from onset and potential contribution to infectivity assessment have not been fully investigated. METHODS: A retrospective, observational study using nasopharyngeal swab specimens from coronavirus disease (COVID-19) inpatients was conducted using LumipulseⓇ SARS-CoV-2 antigen test. Diagnostic accuracy was examined for the early (up to 10 days after onset) and late (over 10 days after onset) stages. Time-course QAT changes and reverse-transcription quantitative polymerase chain reaction tests results were displayed as locally estimated scatterplot smoothing curve, and receiver operating characteristic curve (ROC) analysis was used to determine the appropriate cutoff value for differentiating the early and late stages. RESULTS: We obtained 100 specimens from 68 COVID-19 patients, including 51 early-stage and 49 late-stage specimens. QAT sensitivity and specificity were 0.82 (0.72-0.90) and 0.95 (0.75-0.99) for all periods, 0.93 (0.82-0.98) and 1.00 (0.39-1.00) for the early stage, and 0.66 (0.48-0.82) and 0.93 (0.69-0.99) for the late stage, respectively. The ROC analysis indicated an ideal cutoff value of 6.93 pg/mL for distinguishing early-from late-stage specimens. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting the late stage were 0.76 (0.61-0.87), 0.76 (0.63-0.87), 0.76 (0.61-0.87), and 0.76 (0.63-0.87). CONCLUSIONS: QAT has favorable diagnostic accuracy in the early COVID-19 stages. In addition, an appropriate cutoff point can potentially facilitate rapid identification of noncontagious patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Immunologic Tests , Nasopharynx , Retrospective Studies , Sensitivity and Specificity
10.
Intern Med ; 60(14): 2297-2300, 2021 Jul 15.
Article in English | MEDLINE | ID: covidwho-1311331

ABSTRACT

We herein report a 67-year-old kidney transplant patient who died of COVID-19. He was treated with hydroxychloroquine and azithromycin and received mechanical ventilation that temporarily improved his respiratory status. Despite our efforts, however, he later developed respiratory failure and died 43 days after the disease onset. The autopsy revealed prominent organization of alveoli and alveolar ducts, with a massive accumulation of macrophages in the lungs. A few severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-positive cells were detected in the lung, suggesting delayed virus clearance owing to his long-term immunosuppressed state, leading to constant lung damage and ultimately respiratory failure.


Subject(s)
COVID-19 , Kidney Transplantation , Respiratory Distress Syndrome , Aged , Humans , Kidney Transplantation/adverse effects , Lung , Male , SARS-CoV-2
11.
J Infect Chemother ; 27(8): 1273-1275, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1225293

ABSTRACT

Rapid antigen tests (RATs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have advantages over viral culture in terms of cost and rapidity of testing, but they have low sensitivity. In addition, RATs tend to be negative from approximately 11 days after symptom onset. To determine whether the antigen-negative state indicates a lack of infectiousness, we assessed the association between viral culture and RAT results. Viral culture, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and rapid antigen testing were performed on stored nasopharyngeal samples with threshold cycle values < 30, based on previous RT-qPCR testing. SARS-CoV-2 was isolated by viral culture from nine samples (45%) and one sample (17%) with positive and negative RAT results, respectively. The RAT and viral culture results were both associated with the viral load level and their cutoffs were similar, but the associations were not statistically significant. RAT might be a useful indicator of infectiousness, which can be helpful to control infection. However, further studies with larger sample size are warranted to confirm this observation.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Nasopharynx , Sensitivity and Specificity , Serologic Tests
12.
Jpn J Infect Dis ; 74(2): 161-165, 2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1150990

ABSTRACT

Real-time reverse transcription polymerase chain reaction (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are occasionally repeated when clinicians suspect false-negative results, but the conditions under which repeated RT-PCR testing is warranted remain unclear. We evaluated the practice of repeat RT-PCR testing for SARS-CoV-2 in 45 patients who were retested after an initial negative PCR test. Of these, the diagnosis of coronavirus disease (COVID-19) was confirmed in four patients with typical chest computed tomography (CT) findings and in one patient without typical CT findings in whom the test result was strongly suspected to be false-positive. We recommend repeat RT-PCR testing only for patients with typical CT findings of COVID-19.


Subject(s)
COVID-19 Nucleic Acid Testing/standards , COVID-19/diagnosis , Lung/diagnostic imaging , SARS-CoV-2/isolation & purification , Specimen Handling , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Nasopharynx/virology , Retrospective Studies , SARS-CoV-2/genetics , Specimen Handling/methods , Specimen Handling/standards , Sputum/virology , Tomography, X-Ray Computed , Young Adult
13.
Infect Dis (Lond) ; 53(8): 581-589, 2021 08.
Article in English | MEDLINE | ID: covidwho-1147914

ABSTRACT

BACKGROUND: The current gold standard in coronavirus disease (COVID-19) diagnostics is the real-time reverse transcription-polymerase chain reaction (RT-PCR) assay for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasopharyngeal swab (NPS) samples. Alternatively, nasal swab (NS) or saliva swab (SS) specimens are used, although available data on test accuracy are limited. We examined the diagnostic accuracy of NPS/NS/SS samples for this purpose. METHODS: Ten patients were included after being tested positive for SARS-CoV-2 RT-PCR in NPS samples according to the National Institute of Infectious Disease guidelines. In comparison with this conventional diagnostic method, NPS/NS/SS samples were tested using the cobas 6800 systems RT-PCR device. To investigate the usefulness of the cobas method and the difference among sample types, the agreement and sensitivity were calculated. Five to six samples were collected over a total period of 5-6 d from each patient. RESULTS: Fifty-seven sets of NPS/NS/SS samples were collected, of which 40 tested positive for COVID-19 by the conventional method. Overall, the concordance rates using the conventional method were 86.0%/70.2%/54.4% for NPS/NS/SS samples (cobas); however, for samples collected up to and including on Day 9 after disease onset (22 negative and one positive specimens), the corresponding rates were 95.7%/87.0%/65.2%. The overall sensitivity estimates were 100.0%/67.5%/37.5% for NPS/NS/SS samples (cobas). For samples up to 9 d after onset, the corresponding values were 100.0%/86.4%/63.6%. CONCLUSIONS: NS samples are more reliable than SS samples and can be an alternative to NPS samples. They can be a useful diagnostic method in the future.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Nasopharynx , Reverse Transcriptase Polymerase Chain Reaction , Saliva , Specimen Handling
14.
Respir Investig ; 59(3): 377-381, 2021 May.
Article in English | MEDLINE | ID: covidwho-1065554

ABSTRACT

A 70-year-old Japanese man contracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and required oxygen to maintain oxygen saturation (>90%), 5 weeks after onset of coronavirus disease 2019 (COVID-19) symptoms. Transbronchial lung cryobiopsy revealed pathological features of organizing pneumonia with alveolar epithelial injury, and prednisolone administration led to alleviation of respiratory symptoms and recovery of respiratory function. This case report is the first to demonstrate the use of corticosteroids to successfully treat post-COVID-19 respiratory failure in a patient with biopsy-proven organizing pneumonia. We propose that steroid treatment be considered for patients with persistent respiratory dysfunction as COVID-19 pneumonia sequelae.


Subject(s)
COVID-19/drug therapy , Prednisolone/administration & dosage , Administration, Oral , Aged , Biomarkers/blood , COVID-19/diagnosis , COVID-19/pathology , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Oxygen Inhalation Therapy , Tomography, X-Ray Computed , Treatment Outcome
15.
J Infect Chemother ; 27(6): 808-813, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1065337

ABSTRACT

INTRODUCTION: Among patients with coronavirus disease 2019 (COVID-19), the factors that affect anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody production remain unclear. This study aimed to identify such factors among patients convalescing from COVID-19. METHODS: This study comprised patients who had been diagnosed with COVID-19 between January 1 and June 30, 2020 and gave consent for anti-SARS-CoV-2 spike protein antibody measurement using enzyme-linked immunosorbent assay during their acute and/or convalescent phases. Factors related to elevated antibody titers and the relationship between the days from disease onset and the development of antibody titers were assessed. RESULTS: A total of 84 participants enrolled in the study. Nineteen participants had antibody titers measured during the convalescent phase only, and 65 participants had antibody titers measured during the acute and convalescent phases. The antibody titers peaked in weeks 5 and 6. The stepwise multivariate log-normal analysis revealed that male sex (P = 0.04), diabetes mellitus (P = 0.03), and high C-reactive protein levels during the disease course (P < 0.001) were associated with elevated IgG antibodies. Glucocorticoid use was not associated with antibody titers. CONCLUSION: The study found that high values of maximum CRP levels during the acute phase, male sex, and diabetes mellitus were associated with elevated antibody titers. Antibody titers tended to be highest in the first 5 or 6 weeks after the onset of symptoms.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation , COVID-19/immunology , Adult , Aged , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Female , Humans , Immunoglobulin G/immunology , Male , Middle Aged , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
16.
J Clin Apher ; 36(3): 313-321, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-978131

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX-DHP) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive pneumonia patients. METHODS: This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS-CoV-2-positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX-DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX-DHP was performed. PMX-DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated. RESULTS: On day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine ß2-microglobulin decreased on days 4 and 8. Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty-two PMX-DHPs were performed, of which seven and five PMX-DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D-dimer and fibrin degradation product levels were high before PMX-DHP. CONCLUSIONS: Future studies are expected to determine the therapeutic effect of PMX-DHP on COVID-19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.


Subject(s)
COVID-19/therapy , Hemoperfusion/instrumentation , Hemoperfusion/methods , Polymyxin B/chemistry , Polystyrenes/chemistry , Adult , Aged , Aged, 80 and over , Arteries/metabolism , Biomarkers/urine , Blood Gas Analysis , Cytokines/blood , Endothelium, Vascular/metabolism , Female , Hospitalization , Humans , Male , Middle Aged , Oxygen/metabolism , Respiration, Artificial , Retrospective Studies , Risk , beta 2-Microglobulin/urine
17.
18.
Gene ; 766: 145145, 2021 Jan 15.
Article in English | MEDLINE | ID: covidwho-756821

ABSTRACT

COVID-19, a novel coronavirus-related illness, has spread worldwide. Patients with apparently mild/moderate symptoms can suddenly develop severe pneumonia. Therefore, almost all COVID-19 patients require hospitalization, which can reduce limited medical resources in addition to overwhelming medical facilities. To identify predictive markers for the development of severe pneumonia, a comprehensive analysis of serum chemokines and cytokines was conducted using serial serum samples from COVID-19 patients. The expression profiles were analyzed along the time axis. Serum samples of common diseases were enrolled from a BioBank to confirm the usefulness of predictive markers. Five factors, IFN-λ3, IL-6, IP-10, CXCL9, and CCL17, were identified as predicting the onset of severe/critical symptoms. The factors were classified into two categories. Category A included IFN-λ3, IL-6, IP-10, and CXCL9, and their values surged and decreased rapidly before the onset of severe pneumonia. Category B included CCL17, which provided complete separation between the mild/moderate and the severe/critical groups at an early phase of SARS-CoV-2 infection. The five markers provided a high predictive value (area under the receiver operating characteristic curve (AUROC): 0.9-1.0, p < 0.001). Low expression of CCL17 was specifically observed in pre-severe COVID-19 patients compared with other common diseases, and the predictive ability of CCL17 was confirmed in validation samples of COVID-19. The factors identified could be promising prognostic markers to distinguish between mild/moderate and severe/critical patients, enabling triage at an early phase of infection, thus avoiding overwhelming medical facilities.


Subject(s)
Biomarkers/blood , Chemokine CCL17/blood , Coronavirus Infections/blood , Coronavirus Infections/physiopathology , Pneumonia, Viral/blood , Pneumonia, Viral/physiopathology , Betacoronavirus/physiology , COVID-19 , Cytokines/blood , Hospitalization , Humans , Pandemics , SARS-CoV-2 , Severity of Illness Index
19.
Intern Med ; 59(19): 2405-2408, 2020 Oct 01.
Article in English | MEDLINE | ID: covidwho-736583

ABSTRACT

An 83-year-old man was hospitalized for coronavirus disease 2019 (COVID-19) after a 10-day history of a persistent fever. Chest computed tomography showed extensive non-segmental ground glass opacity. Despite the initiation of lopinavir and ritonavir, respiratory failure progressed. Two days of polymyxin B-immobilized fiber column-direct hemoperfusion (PMX-DHP) with adjunctive corticosteroid prevented his respiratory condition from worsening. For rapidly progressive COVID-19 cases, the early use of PMX-DHP may avoid the need for mechanical ventilation by suppressing local inflammation of the lung.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Hemoperfusion/methods , Pneumonia, Viral/complications , Polymyxin B/pharmacology , Respiratory Insufficiency/therapy , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , COVID-19 , Coronavirus Infections/epidemiology , Humans , Male , Pandemics , Pneumonia, Viral/epidemiology , Respiration, Artificial/methods , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/etiology , SARS-CoV-2 , Tomography, X-Ray Computed
20.
Crit Care Explor ; 2(8): e0170, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-703522

ABSTRACT

SUBJECTS: Early detection of coronavirus disease 2019 in patients likely to develop severe manifestations enables appropriate interventions, including rapid ICU admission. This study was conducted to determine whether noninvasive urine biomarkers can predict the clinical severity of coronavirus disease 2019. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: This is single-center study, national center hospital designated for infectious disease. Fifty-eight patients who tested positive for severe acute respiratory syndrome coronavirus 2 in respiratory specimens through real-time reverse transcription-polymerase chain reaction were retrospectively studied. Urinary ß2-microglobulin, liver-type fatty acid-binding protein were serially measured. Serum interferon-γ and monocyte chemotactic protein-1 were also evaluated. The 58 patients were assigned into three groups. Patients requiring intensive care were assigned to the severe group (n = 12). Patients treated with oxygen were assigned to the moderate group (n = 13). Other patients were assigned to the mild group (n = 33). Urine tests revealed that low ß2-microglobulin and liver-type fatty acid-binding protein levels were associated with mild disease, whereas high levels were associated with severe disease. In severe cases, liver-type fatty acid-binding protein tended to be persistently high. The resulting cutoff values were ß2-microglobulin; severe versus moderate + mild: 2,457 µg/dL (specificity 76.9% and sensitivity 90.0%, area under the receiver operating characteristic curve 85.9%), liver-type fatty acid-binding protein; severe versus moderate + mild: 22.0 µg/gCre (specificity 84.6% and sensitivity 90%, area under the receiver operating characteristic curve 91.8%). Urinary ß2-microglobulin and serum interferon-γ/monocyte chemotactic protein-1 showed a similar trend. CONCLUSIONS: Evaluating urinary biomarkers such as ß2-microglobulin and liver-type fatty acid-binding protein may allow determination of coronavirus disease 2019 patients with active cytokines and recognition of patients likely to become critically ill and requiring careful observation and early intervention.

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