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1.
Preprint in English | EuropePMC | ID: ppcovidwho-294894

ABSTRACT

Background: Neopterin (NP) is a biomarker for activated cellular immunity and is elevated in diseases including viral and bacterial infections, autoimmune diseases, and cancer. However, the clinical assessment of neopterin has not been used for these disorders because the physiological significance of measuring NP is obscure. It would be important to compare the NP profiles with those of other inflammation markers to reveal the significance of NP measurements in pathological states.Methods: Plasma NP, CRP, and IL-6 levels were measured in 46 patients with Coronavirus Disease 2019 (COVID-19) and 13 patients with non-COVID-19 respiratory disorders. The correlations between these markers were analyzed in the COVID-19 and non-COVID-19 patients independently.Results: The NP levels were significantly higher in the COVID-19 patients than in the non-COVID-19 patients, while both CRP and IL-6 were not changed significantly. Among the COVID-19 patients, all three values increased with the severity of symptoms. NP levels were not correlated with CRP or IL-6 levels in COVID-19 patients but were correlated with IL-6 levels in non-COVID-19 patients. The CRP levels were correlated with those of IL-6 in both the COVID-19 and non-COVID-19 patients.Conclusions: The elevation of NP levels was distinct from those of CRP and IL-6 in COVID-19 patients. Our data suggest that NP is produced in different signaling pathways and/or cells than CRP and IL-6. Further study on the signaling pathway to induce NP is expected

2.
J Infect Chemother ; 2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1531583

ABSTRACT

Lymphoma has been reported to worsen the prognosis of COVID-19 partly because it disturbs the normal production of antibodies. We treated a man with mantle cell lymphoma treated with rituximab, who developed severe COVID-19 with viral shedding that lasted for 78 days. He stayed in the intensive care unit for 28 days and did not respond to any treatment against COVID-19. His increased oxygen demand at rest eventually resolved despite the absence of anti-SARS-CoV-2-IgG. This case illustrates that recovery from COVID-19 can occur without antibody production, and that even patients with an inability to produce antibodies can recover from severe COVID-19. It also illustrates that lymphoma patients who develop severe COVID-19 while on rituximab therapy can recover from a prolonged viral shedding state if the acute lung injury can be overcome.

4.
J Infect Chemother ; 27(12): 1713-1715, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1351750

ABSTRACT

BACKGROUND: Vaccination is one of the most important tools to control the COVID-19 pandemic. However, there is little information on the antibody response in humans after the COVID-19 vaccination. METHODS: This single-center, prospective study was conducted in Yokohama, Japan. We included health care workers who had received two doses of COVID-19 vaccination (BNT162b2) 21 days apart. We measured serum immunoglobulin G (IgG) to nucleoprotein and spike protein of SARS-CoV-2 with commercially available kits before and 7, 14, and 35 days after the first dose of vaccination. RESULTS: A total of 104 workers participated in this study. Of these, 7 participants were seropositive with antibodies to spike protein at baseline and 4 of the 7 seropositive participants had COVID-19 history. The mean level of IgG to spike protein (QT) was 45.2, 1219, 2845, and 23489 AU/mL at baseline, on days 7, 14, and 35, respectively, although the values for nucleoprotein (NG) were 0.2, 0.21, 0.22, and 0.19 S/C, respectively. On day 7, QT in seropositive participants at baseline was elevated, whereas it was not elevated in seronegative participants at baseline until day 14. CONCLUSIONS: QT was elevated over the cutoff in all the participants at day 35, but NG did not change between baseline and day 35.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , Antibody Formation , Health Personnel , Humans , Japan , Pandemics , Prospective Studies , SARS-CoV-2
5.
PLoS One ; 16(7): e0254640, 2021.
Article in English | MEDLINE | ID: covidwho-1308183

ABSTRACT

BACKGROUND: This study aimed to clarify how SARS-CoV-2 RNAemia is related to COVID-19 critical condition development and mortality in comparison with other predictive markers and scoring systems. METHODS: This is a retrospective cohort study conducted at Yokohama Municipal Citizen's Hospital and National Institute of Infectious Diseases. We recruited adult patients with COVID-19 admitted between March 2020 and January 2021. We compared RNAemia with clinical status on admission including scoring systems such as the 4C Mortality, CURB-65, and A-DROP, as well as the Ct value of the nasopharyngeal PCR, in predicting COVID-19 mortality and critical condition development. RESULTS: Of the 92 recruited patients (median age, 58; interquartile range, 45-71 years), 14 (14.9%) had RNAemia. These patients had an older age (median, 68 years vs. 55.5 years; p = 0.011), higher values of lactated dehydrogenase (median, 381 U/L vs. 256.5 U/L, p < 0.001), C-reactive protein (median, 10.9 mg/dL vs. 3.8 mg/dL; p < 0.001), D-dimer (median, 2.07 µg/mL vs. 1.28 µg/mL; p = 0.015), lower values of lymphocyte (median, 802/µL vs. 1007/µL, p = 0.025) and Ct of the nasopharyngeal PCR assay (median, 20.59 vs. 25.54; p = 0.021) than those without RNAemia. Univariate analysis showed RNAemia was associated with mortality (odds ratio [OR], 18.75; 95% confidence interval [CI], 3.92-89.76; area under the receiver operating characteristic curve [AUC], 0.7851; p = 0.002) and critical condition (OR, 72.00; 95% CI, 12.98-399.29; AUC, 0.8198; p < 0.001). Plus, multivariate analysis also revealed the association of RNAemia with critical condition (adjusted OR, 125.71; 95% CI, 11.47-1377.32; p < 0.001). CONCLUSION: On-admission SARS-CoV-2 RNAemia is a potent predictive marker of COVID-19 critical condition and mortality. The adjusted OR for critical condition was as high as 125.71.


Subject(s)
COVID-19 Nucleic Acid Testing/standards , COVID-19/diagnosis , RNA, Viral/analysis , Aged , Biomarkers/analysis , COVID-19/mortality , COVID-19 Nucleic Acid Testing/methods , Female , Humans , Male , Middle Aged , Nasal Mucosa/virology , Patient Admission , Prognosis , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Viral Load
6.
Sci Rep ; 11(1): 13431, 2021 06 28.
Article in English | MEDLINE | ID: covidwho-1286474

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.


Subject(s)
COVID-19/pathology , Iron/blood , Adult , Aged , COVID-19/complications , COVID-19/virology , Female , Ferritins/blood , Hospitalization , Humans , Iron/metabolism , Logistic Models , Male , Middle Aged , Respiratory Insufficiency/etiology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Transferrin/analysis
7.
Cell Rep Med ; 2(6): 100311, 2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1230816

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a major global public health concern. Although rapid point-of-care testing for detecting viral antigen is important for management of the outbreak, the current antigen tests are less sensitive than nucleic acid testing. In our current study, we produce monoclonal antibodies (mAbs) that exclusively react with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and exhibit no cross-reactivity with other human coronaviruses, including SARS-CoV. Molecular modeling suggests that the mAbs bind to epitopes present on the exterior surface of the nucleocapsid, making them suitable for detecting SARS-CoV-2 in clinical samples. We further select the optimal pair of anti-SARS-CoV-2 nucleocapsid protein (NP) mAbs using ELISA and then use this mAb pair to develop immunochromatographic assay augmented with silver amplification technology. Our mAbs recognize the variants of concern (501Y.V1-V3) that are currently in circulation. Because of their high performance, the mAbs of this study can serve as good candidates for developing antigen detection kits for COVID-19.

8.
Int Immunol ; 33(4): 241-247, 2021 03 31.
Article in English | MEDLINE | ID: covidwho-1066348

ABSTRACT

An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19). However, data regarding myeloid cell expansion have been collected in Europe, where the mortality rate by COVID-19 is greater than those in other regions including Japan. Thus, characteristics of COVID-19-induced myeloid cell subsets remain largely unknown in the regions with low mortality rates. Here, we analyzed cellular dynamics of myeloid-derived suppressor cell (MDSC) subsets and examined whether any of them correlate with disease severity and prognosis, using blood samples from Japanese COVID-19 patients. We observed that polymorphonuclear (PMN)-MDSCs, but not other MDSC subsets, transiently expanded in severe cases but not in mild or moderate cases. Contrary to previous studies in Europe, this subset selectively expanded in survivors of severe cases and subsided before discharge, but such transient expansion was not observed in non-survivors in Japanese cohort. Analysis of plasma cytokine/chemokine levels revealed positive correlation of PMN-MDSC frequencies with IL-8 levels, indicating the involvement of IL-8 on recruitment of PMN-MDSCs to peripheral blood following the onset of severe COVID-19. Our data indicate that transient expansion of the PMN-MDSC subset results in improved clinical outcome. Thus, this myeloid cell subset may be a predictor of prognosis in cases of severe COVID-19 in Japan.


Subject(s)
COVID-19/pathology , Interleukin-8/blood , Myeloid-Derived Suppressor Cells/immunology , Neutrophils/immunology , SARS-CoV-2/immunology , Humans , Interleukin-8/immunology , Japan , Leukocyte Count , Myeloid Cells/immunology , Neutrophil Activation/immunology
9.
Pathol Int ; 70(10): 820-824, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-721161

ABSTRACT

A 93-year-old woman was admitted with a 10-day history of cough and prostration. Thoracic computed tomography revealed extensive ground-glass opacities in both the lungs. The polymerase chain reaction test of sputum for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) was positive. She was treated with antiviral agents and steroid pulse therapy. However, her oxygen saturation gradually declined, and she died 10 days after hospitalization. The most important autopsy finding was fuzzily segmented diffuse alveolar damage (DAD) that expanded from the subpleural to the medial area. No remarkable changes were observed in organs other than the lungs. Therefore, pneumocytes were suggested as the primary target for SARS-CoV-2, which might explain why coronavirus infectious disease-19 is a serious condition. Thus, early treatment is essential to prevent viral replication from reaching a level that triggers DAD.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Aged, 80 and over , Autopsy , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/pathology , Coronavirus Infections/therapy , Fatal Outcome , Female , Humans , Japan , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/therapy , SARS-CoV-2
10.
J Infect Chemother ; 26(11): 1177-1180, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-597846

ABSTRACT

BACKGROUND: A large COVID-19 outbreak occurred on the cruise ship Diamond Princess in February 2020. Little information has been reported about the clinical characteristics of the patients. METHODS: This single-center, retrospective, observational study was conducted in Yokohama, Japan. We included symptomatic patients who were infected on the ship and admitted to our hospital between 5 and 19 February 2020. All the cases were confirmed with SARS-CoV-2 infection by polymerase chain reaction (PCR). RESULTS: We confirmed 17 cases. The average age was 69 years; 10 patients were Asian and 7 were Caucasian. Eleven patients had one or more chronic diseases. The major symptoms were cough and fever. Chest computed tomography (CT) scans found bilateral ground-glass opacities predominantly in the peripheral area, which were similar to reports from cases in China. C-reactive protein (CRP) levels were higher in severe and critical cases than in mild to moderate cases. The moderate to severe cases reached symptomatic resolution; one of the three critical cases resulted in death due to multiple organ failure. SARS-CoV-2 was detected by PCR at an average of 7 days after symptomatic resolution. CONCLUSIONS: Cough and fever, increased blood CRP levels, and CT findings of bilateral ground-glass opacities predominantly in the peripheral lung were characteristic of the COVID-19 cases in this study. These findings were compatible with those of previous reports.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Disease Outbreaks/statistics & numerical data , Pneumonia, Viral/epidemiology , Ships/statistics & numerical data , Travel-Related Illness , Aged , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/statistics & numerical data , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Female , Humans , Japan/epidemiology , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Polymerase Chain Reaction/statistics & numerical data , RNA, Viral/isolation & purification , Retrospective Studies , SARS-CoV-2
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