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1.
Viruses ; 14(4)2022 03 24.
Article in English | MEDLINE | ID: covidwho-1834918

ABSTRACT

The effect of treatment with favipiravir, an antiviral purine nucleoside analog, for coronavirus disease 2019 (COVID-19) on the production and duration of neutralizing antibodies for SARS-CoV-2 was explored. There were 17 age-, gender-, and body mass index-matched pairs of favipiravir treated versus control selected from a total of 99 patients recovered from moderate COVID-19. These subjects participated in the longitudinal (>6 months) analysis of (i) SARS-CoV-2 spike protein's receptor-binding domain IgG, (ii) virus neutralization assay using authentic virus, and (iii) neutralization potency against original (WT) SARS-CoV-2 and cross-neutralization against B.1.351 (beta) variant carrying triple mutations of K417N, E484K, and N501Y. The results demonstrate that the use of favipiravir: (1) significantly accelerated the elimination of SARS-CoV-2 in the case vs. control groups (p = 0.027), (2) preserved the generation and persistence of neutralizing antibodies in the host, and (3) did not interfere the maturation of neutralizing potency of anti-SARS-CoV-2 and neutralizing breadth against SARS-CoV-2 variants. In conclusion, treatment of COVID-19 with favipiravir accelerates viral clearance and does not interfere the generation or maturation of neutralizing potency against both WT SARS-CoV-2 and its variants.


Subject(s)
Antibodies, Neutralizing , COVID-19 , SARS-CoV-2 , Amides/therapeutic use , Antibodies, Neutralizing/metabolism , Antibodies, Viral , COVID-19/drug therapy , Humans , Immunoglobulin G , Neutralization Tests , Pyrazines/therapeutic use , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
2.
Viruses ; 14(4):670, 2022.
Article in English | MDPI | ID: covidwho-1762631

ABSTRACT

The effect of treatment with favipiravir, an antiviral purine nucleoside analog, for coronavirus disease 2019 (COVID-19) on the production and duration of neutralizing antibodies for SARS-CoV-2 was explored. There were 17 age-, gender-, and body mass index-matched pairs of favipiravir treated versus control selected from a total of 99 patients recovered from moderate COVID-19. These subjects participated in the longitudinal (>6 months) analysis of (i) SARS-CoV-2 spike protein's receptor-binding domain IgG, (ii) virus neutralization assay using authentic virus, and (iii) neutralization potency against original (WT) SARS-CoV-2 and cross-neutralization against B.1.351 (beta) variant carrying triple mutations of K417N, E484K, and N501Y. The results demonstrate that the use of favipiravir: (1) significantly accelerated the elimination of SARS-CoV-2 in the case vs. control groups (p = 0.027), (2) preserved the generation and persistence of neutralizing antibodies in the host, and (3) did not interfere the maturation of neutralizing potency of anti-SARS-CoV-2 and neutralizing breadth against SARS-CoV-2 variants. In conclusion, treatment of COVID-19 with favipiravir accelerates viral clearance and does not interfere the generation or maturation of neutralizing potency against both WT SARS-CoV-2 and its variants.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329837

ABSTRACT

In this randomized, observer-blinded, phase 2/3 study, we assessed S-268019-b—a recombinant spike protein vaccine. We analyzed the noninferiority of S-268019-b (n=103), versus tozinameran (n=103), when given as a booster ≥6 months after the 2-dose tozinameran regimen in Japanese adults without prior COVID-19 infection. Interim results showed that S-268019-b was noninferior to tozinameran in co-primary endpoints: geometric mean titer (GMT) (126.42 versus 108.20;adjusted-GMT ratio [95% CI], 1.17 [0.96-1.42];noninferiority P -value, <0.0001) and seroresponse rate (both 100%;noninferiority P -value, 0.0004) for neutralizing antibodies on day 29. Both vaccines elicited anti-spike protein immunoglobulin G antibodies, and produced T-cell response (n=30/group) and neutralized Delta and Omicron pseudovirus variants (n=24/group) in subgroups. Most participants reported low-grade reactogenicity on days 1 and 2, the most frequent being fatigue, fever, myalgia, and injection-site pain. No serious adverse events were reported. S-268019-b safety and robust immunogenicity as a booster, supporting its use as COVID-19 booster vaccine. JRCT ID jRCT2031210470 Highlights Third COVID-19 vaccine dose (booster) enhances immune response Interim phase 2/3 data for booster ≥6 months after the 2nd dose in Japan are shown S-268019-b and tozinameran were safe and equal in inducing neutralizing antibodies Both boosters neutralized Delta and Omicron pseudovirus and induced T-cell response Results: support use of S-268019-b as a booster in vaccinated adults

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296006

ABSTRACT

Introduction: Blood tests and computed tomography (CT) findings at diagnosis are widely used in daily clinical practice and can offer useful prognostic factors for coronavirus disease 2019. Methods: : We retrospectively evaluated 66 patients who underwent a blood test and CT between January 1 and May 31, 2020, and performed a propensity score-matched case-control study. Cases and controls were a severe respiratory failure group (non-rebreather mask, nasal high-flow, positive-pressure ventilation) and a non-severe respiratory failure group, matched at a ratio of 1:3 by propensity scores constructed by age, sex, and medical history. We compared groups for maximum body temperature up to diagnosis, laboratory findings, and CT findings in the matched cohort. Two-tailed P-values <0.05 were considered statistically significant. Results: : Nine cases and 27 controls were included in the matched cohort. Significant differences were seen in maximum body temperature up to diagnosis (p=0.0043), the number of shaded lobes (p=0.0434), amount of ground-glass opacity (GGO) in the total lung field (p=0.0071), amounts of GGO (p=0.0001), and consolidation (p=0.0036) in the upper lung field, and pleural effusion (p=0.0117). Conclusions: : Fever and CT findings (such as GGO and consolidation) may be prognostic indicators that can be easily measured at diagnosis.

5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292710

ABSTRACT

Amid pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination is hailed as one of the most effective preventive measures. An mRNA vaccine termed BNT162b2 showed satisfactory safety and efficacy in the clinical trials but several issues including variability in the individual immune response or determination of target antibody titre that exerts sufficient immune protection needs to be assessed for planning a more efficient vaccination strategy. By monitoring IgG titres before and two months after the initial administration of BNT162b2 in 655 healthcare workers by Abbott IgG II quant that detects IgG against the receptor-binding domain in S protein of SARS-CoV-2, we confirmed that hypertension, dyslipidaemia, chronic kidney disease and use of immune suppressant in addition to male gender, advanced age, and absence of previous infection were significantly associated with low antibody response to the vaccination.

6.
J Exp Med ; 218(12)2021 12 06.
Article in English | MEDLINE | ID: covidwho-1467277

ABSTRACT

Adaptive immunity is a fundamental component in controlling COVID-19. In this process, follicular helper T (Tfh) cells are a subset of CD4+ T cells that mediate the production of protective antibodies; however, the SARS-CoV-2 epitopes activating Tfh cells are not well characterized. Here, we identified and crystallized TCRs of public circulating Tfh (cTfh) clonotypes that are expanded in patients who have recovered from mild symptoms. These public clonotypes recognized the SARS-CoV-2 spike (S) epitopes conserved across emerging variants. The epitope of the most prevalent cTfh clonotype, S864-882, was presented by multiple HLAs and activated T cells in most healthy donors, suggesting that this S region is a universal T cell epitope useful for booster antigen. SARS-CoV-2-specific public cTfh clonotypes also cross-reacted with specific commensal bacteria. In this study, we identified conserved SARS-CoV-2 S epitopes that activate public cTfh clonotypes associated with mild symptoms.


Subject(s)
COVID-19/immunology , Epitopes, T-Lymphocyte/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes, Helper-Inducer/immunology , Adult , Antibodies, Viral/immunology , Female , HLA Antigens/immunology , Humans , Lymphocyte Activation , Male
7.
J Exp Med ; 218(12)2021 12 06.
Article in English | MEDLINE | ID: covidwho-1462245

ABSTRACT

Broadly protective vaccines against SARS-related coronaviruses that may cause future outbreaks are urgently needed. The SARS-CoV-2 spike receptor-binding domain (RBD) comprises two regions, the core-RBD and the receptor-binding motif (RBM); the former is structurally conserved between SARS-CoV-2 and SARS-CoV. Here, in order to elicit humoral responses to the more conserved core-RBD, we introduced N-linked glycans onto RBM surfaces of the SARS-CoV-2 RBD and used them as immunogens in a mouse model. We found that glycan addition elicited higher proportions of the core-RBD-specific germinal center (GC) B cells and antibody responses, thereby manifesting significant neutralizing activity for SARS-CoV, SARS-CoV-2, and the bat WIV1-CoV. These results have implications for the design of SARS-like virus vaccines.


Subject(s)
Antibodies, Viral/immunology , Broadly Neutralizing Antibodies/immunology , COVID-19/immunology , Polysaccharides/immunology , SARS Virus/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Amino Acid Motifs , Animals , COVID-19/genetics , COVID-19/prevention & control , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Female , Humans , Male , Mice , Mice, Inbred BALB C , Polysaccharides/genetics , Protein Domains , SARS Virus/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
8.
Immunity ; 54(8): 1841-1852.e4, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1293863

ABSTRACT

Antibody titers against SARS-CoV-2 slowly wane over time. Here, we examined how time affects antibody potency. To assess the impact of antibody maturation on durable neutralizing activity against original SARS-CoV-2 and emerging variants of concern (VOCs), we analyzed receptor binding domain (RBD)-specific IgG antibodies in convalescent plasma taken 1-10 months after SARS-CoV-2 infection. Longitudinal evaluation of total RBD IgG and neutralizing antibody revealed declining total antibody titers but improved neutralization potency per antibody to original SARS-CoV-2, indicative of antibody response maturation. Neutralization assays with authentic viruses revealed that early antibodies capable of neutralizing original SARS-CoV-2 had limited reactivity toward B.1.351 (501Y.V2) and P.1 (501Y.V3) variants. Antibodies from late convalescents exhibited increased neutralization potency to VOCs, suggesting persistence of cross-neutralizing antibodies in plasma. Thus, maturation of the antibody response to SARS-CoV-2 potentiates cross-neutralizing ability to circulating variants, suggesting that declining antibody titers may not be indicative of declining protection.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/immunology , Antibodies, Monoclonal/immunology , Antibody Specificity , COVID-19/epidemiology , Humans , Immunoglobulin G , Neutralization Tests , SARS-CoV-2/genetics , Viral Load
9.
Intern Med ; 60(1): 123-130, 2021.
Article in English | MEDLINE | ID: covidwho-1004553

ABSTRACT

Case 1: A 65-year-old man with novel coronavirus infection (COVID-19) complicated with acute respiratory failure. On admission, the patient was started on favipiravir and corticosteroid. However, due to a lack of significant improvement, he was introduced to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Although iliopsoas hematoma occurred as a complication, the patient recovered. Case 2: A 49-year-old man with COVID-19 had been started on favipiravir and corticosteroid. Due to progressive respiratory failure, the patient underwent mechanical ventilation and ECMO. The patient recovered without complications. We successfully treated these severe cases with a multimodal combination of pharmacological and non-pharmacological supportive therapy.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Amides/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/therapy , Extracorporeal Membrane Oxygenation , Methylprednisolone/therapeutic use , Pyrazines/therapeutic use , Respiration, Artificial , Aged , COVID-19/complications , Humans , Male , Middle Aged , Respiratory Insufficiency/therapy , Respiratory Insufficiency/virology , SARS-CoV-2
10.
Intern Med ; 60(1): 31-37, 2021 Jan 01.
Article in English | MEDLINE | ID: covidwho-902223

ABSTRACT

Objective We aimed to clarify clinical and laboratory characteristics of coronavirus disease 2019 (COVID-19) patients, and further explore the features to detect COVID-19 pneumonia at the first visit to community-based hospitals. Methods Diagnoses of COVID-19 were based on positive results from real-time reverse-transcription polymerase chain reaction testing of nasopharyngeal-swab specimens. We retrospectively reviewed the medical records of patients showing positive results. The clinical characteristics and results of blood tests were compared between the patients with and without pneumonia. The risk factors associated with pneumonia were then evaluated by a multivariable analysis. Results The study cohort comprised 154 patients, including 117 patients (76.0%) with pneumonia at first visit. Significant differences were seen in age, the frequency of fever, tachycardia, desaturation (peripheral oxygen saturation ≤95%), any comorbidity, neutrocyte count and fraction, lymphocyte count and fraction, platelet count, lactate dehydrogenase (LDH), C-reactive protein (CRP), and fibrinogen between the patients with and without pneumonia. Using a multivariable analysis, CRP ≥0.3 mg/dL and fibrinogen >400 mg/dL were found to be associated with the presence of pneumonia. Conclusion Community-based settings for screening COVID-19 patients should perform chest X-ray and blood tests for white blood cell fractions, fibrinogen, LDH, and CRP. Of these, elevations in the CRP and fibrinogen levels could be critically associated with the presence of COVID-19 pneumonia.


Subject(s)
COVID-19/diagnosis , Adult , Age Factors , C-Reactive Protein/analysis , COVID-19/blood , COVID-19 Nucleic Acid Testing , Female , Fever/virology , Fibrinogen/metabolism , Humans , Japan , L-Lactate Dehydrogenase/blood , Leukocyte Count , Lymphocyte Count , Male , Middle Aged , Neutrophils , Oximetry , Platelet Count , Retrospective Studies , Risk Factors , SARS-CoV-2 , Tachycardia/virology
11.
J Infect Chemother ; 27(2): 379-383, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-844273

ABSTRACT

A 49-year-old Japanese male was managed by mechanical ventilation due to coronavirus disease 2019 (COVID-19) pneumonia. Favipiravir as an antiviral therapy, and anti-inflammatory treatment were administered. SARS-CoV-2 RNA was detected in serum by the loop-mediated isothermal amplification (LAMP) method on Day 9; favipiravir treatment was continued. On Day 13, negative serum RNA was confirmed, followed by mechanical ventilation was removed. On Day 23, LAMP negative was confirmed in nasopharynx, after that the patient discharged on Day 27. We could treat successfully for severe COVID-19 pneumonia based on the LAMP method. We consider this method will be useful in COVID-19 treatment.


Subject(s)
Amides/administration & dosage , Antiviral Agents/administration & dosage , COVID-19/drug therapy , Pyrazines/administration & dosage , RNA, Viral/blood , SARS-CoV-2/isolation & purification , COVID-19/diagnosis , COVID-19 Testing/methods , Humans , Male , Middle Aged , Molecular Diagnostic Techniques/methods , Nasopharynx/virology , Nucleic Acid Amplification Techniques/methods , Pneumonia, Viral/drug therapy , RNA, Viral/isolation & purification , Respiration, Artificial/methods , Treatment Outcome , Viremia/diagnosis
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