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1.
Journal of Clinical and Experimental Medicine ; 279(9):864-868, 2021.
Article in Japanese | Ichushi | ID: covidwho-1609967
3.
EClinicalMedicine ; 32: 100734, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1385450

ABSTRACT

BACKGROUND: To develop an effective vaccine against a novel viral pathogen, it is important to understand the longitudinal antibody responses against its first infection. Here we performed a longitudinal study of antibody responses against SARS-CoV-2 in symptomatic patients. METHODS: Sequential blood samples were collected from 39 individuals at various timepoints between 0 and 154 days after onset. IgG or IgM titers to the receptor binding domain (RBD) of the S protein, the ectodomain of the S protein, and the N protein were determined by using an ELISA. Neutralizing antibody titers were measured by using a plaque reduction assay. FINDINGS: The IgG titers to the RBD of the S protein, the ectodomain of the S protein, and the N protein peaked at about 20 days after onset, gradually decreased thereafter, and were maintained for several months after onset. Extrapolation modeling analysis suggested that the IgG antibodies were maintained for this amount of time because the rate of reduction slowed after 30 days post-onset. IgM titers to the RBD decreased rapidly and disappeared in some individuals after 90 days post-onset. All patients, except one, possessed neutralizing antibodies against authentic SARS-CoV-2, which they retained at 90 days after onset. The highest antibody titers in patients with severe infections were higher than those in patients with mild or moderate infections, but the decrease in antibody titer in the severe infection cohort was more remarkable than that in the mild or moderate infection cohort. INTERPRETATION: Although the number of patients is limited, our results show that the antibody response against the first SARS-CoV-2 infection in symptomatic patients is typical of that observed in an acute viral infection. FUNDING: The Japan Agency for Medical Research and Development and the National Institutes of Allergy and Infectious Diseases.

4.
Respir Investig ; 60(1): 68-81, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1382762

ABSTRACT

BACKGROUND: This review aimed to investigate whether bronchoalveolar lavage (BAL) is safe in patients with severe acute respiratory failure (ARF). METHODS: We searched the MEDLINE, CENTRAL, and other databases up to June 2, 2021 for studies that examined BAL for severe ARF. We included all cohort studies and randomized or non-randomized trials, while we excluded case-control studies, case reports, and case series. We evaluated the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: We included 17 studies (1085 patients) in the meta-analysis. The integrated frequency of death was 0.000% (95% confidence interval [CI]: 0.000-0.045%, I2 = 0.0%). The pooled risk of severe complications of respiratory system, cardiovascular system, and major bleeding was 1.32% (95% CI: 0.000-4.41%, I2 = 84.8%), 0.040% (95% CI: 0.000-0.71%, I2 = 9.3%), and 0.000% (95% CI: 0.000-0.27%, I2 = 0.0%), respectively. In the subgroup analysis with mechanical ventilation during BAL, there were few severe complications of the respiratory system (3/717 patients in 13 studies) and almost no heterogeneity (I2 = 0.0%). CONCLUSIONS: Our study suggests that severe complications of BAL for severe ARF are probably rare, particularly in patients receiving mechanical ventilation. After considering the risks and benefits, it would be worthwhile to consider performing BAL in patients with severe ARF of unknown etiology to pursue its cause. TRIAL REGISTRATION: The protocol was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000040600).


Subject(s)
Respiratory Distress Syndrome , Respiratory Insufficiency , Bronchoalveolar Lavage , Cohort Studies , Humans , Respiration, Artificial , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy
5.
Proc Natl Acad Sci U S A ; 118(27)2021 07 06.
Article in English | MEDLINE | ID: covidwho-1276013

ABSTRACT

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role in viral infectivity. It is also the major antigen stimulating the host's protective immune response, specifically, the production of neutralizing antibodies. Recently, a new variant of SARS-CoV-2 possessing multiple mutations in the S protein, designated P.1, emerged in Brazil. Here, we characterized a P.1 variant isolated in Japan by using Syrian hamsters, a well-established small animal model for the study of SARS-CoV-2 disease (COVID-19). In hamsters, the variant showed replicative abilities and pathogenicity similar to those of early and contemporary strains (i.e., SARS-CoV-2 bearing aspartic acid [D] or glycine [G] at position 614 of the S protein). Sera and/or plasma from convalescent patients and BNT162b2 messenger RNA vaccinees showed comparable neutralization titers across the P.1 variant, S-614D, and S-614G strains. In contrast, the S-614D and S-614G strains were less well recognized than the P.1 variant by serum from a P.1-infected patient. Prior infection with S-614D or S-614G strains efficiently prevented the replication of the P.1 variant in the lower respiratory tract of hamsters upon reinfection. In addition, passive transfer of neutralizing antibodies to hamsters infected with the P.1 variant or the S-614G strain led to reduced virus replication in the lower respiratory tract. However, the effect was less pronounced against the P.1 variant than the S-614G strain. These findings suggest that the P.1 variant may be somewhat antigenically different from the early and contemporary strains of SARS-CoV-2.


Subject(s)
COVID-19/virology , SARS-CoV-2/physiology , SARS-CoV-2/pathogenicity , Virus Replication , Animals , Antibodies, Neutralizing , COVID-19/diagnostic imaging , COVID-19/pathology , Cricetinae , Humans , Immunogenicity, Vaccine , Lung/pathology , Mesocricetus , Mice , Spike Glycoprotein, Coronavirus/genetics , X-Ray Microtomography
6.
Viruses ; 12(12)2020 12 10.
Article in English | MEDLINE | ID: covidwho-970091

ABSTRACT

Reverse transcription-quantitative PCR (RT-qPCR)-based tests are widely used to diagnose coronavirus disease 2019 (COVID-19). As a result that these tests cannot be done in local clinics where RT-qPCR testing capability is lacking, rapid antigen tests (RATs) for COVID-19 based on lateral flow immunoassays are used for rapid diagnosis. However, their sensitivity compared with each other and with RT-qPCR and infectious virus isolation has not been examined. Here, we compared the sensitivity among four RATs by using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolates and several types of COVID-19 patient specimens and compared their sensitivity with that of RT-qPCR and infectious virus isolation. Although the RATs read the samples containing large amounts of virus as positive, even the most sensitive RAT read the samples containing small amounts of virus as negative. Moreover, all RATs tested failed to detect viral antigens in several specimens from which the virus was isolated. The current RATs will likely miss some COVID-19 patients who are shedding infectious SARS-CoV-2.


Subject(s)
Antigens, Viral/analysis , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Point-of-Care Systems , SARS-CoV-2/isolation & purification , False Negative Reactions , Humans , Immunoassay , Real-Time Polymerase Chain Reaction , SARS-CoV-2/immunology , Sensitivity and Specificity , Specimen Handling
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