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1.
J Nippon Med Sch ; 88(4): 380-383, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1551292

ABSTRACT

We assessed the association of severity of coronavirus disease 2019 (COVID-19) with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) load, IgG antibody level, and prognostic indicators.Twenty-one patients hospitalized with COVID-19 were classified as having severe or mild disease on the basis of average respiratory rate during hospitalization (severe: ≥22 breaths/min; mild: <22 breaths/min). Viral load in nasopharyngeal samples, blood levels of C-reactive protein (CRP), lymphocytes, and D-dimer on admission and plasma immunoglobulin G (IgG) index on Day 7±2 after symptom onset were compared in relation to disease severity. Seven patients had severe disease and 14 had mild disease. Those with severe disease had a significantly higher IgG index (median: 3.75 vs 0.56, p=0.01) and CRP (median: 8.6 vs 1.0 mg/dL, p<0.001) and D-dimer levels (median: 1.65 vs 0.75 µg/mL; p=0.002) and a significantly lower lymphocyte count (median: 1,176 vs 666 cells/µL, p=0.005) and viral load (median: 8.7×106 vs 2.3×104 copies/mL, p=0.005). Furthermore, time from symptom onset to virus disappearance was significantly longer in severe patients (median: 24 vs 17 days, p=0.03). A high IgG index in the early phase of the disease was associated with severe disease and might serve as a prognostic indicator.


Subject(s)
Antibodies, Viral/blood , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , COVID-19/diagnosis , Immunoglobulin G/blood , SARS-CoV-2/pathogenicity , Viral Load , Adult , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/drug therapy , COVID-19/therapy , COVID-19/virology , Female , Hospitalization , Host-Pathogen Interactions , Humans , Japan , Male , Middle Aged , Oxygen Inhalation Therapy , Predictive Value of Tests , Prognosis , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Severity of Illness Index , Time Factors
2.
Hum Vaccin Immunother ; 17(10): 3551-3553, 2021 10 03.
Article in English | MEDLINE | ID: covidwho-1242090

ABSTRACT

Neutralizing antibodies are the basis of almost all approved prophylactic vaccines and the foundation of effective protection from pathogens, including the recently emerging SARS Coronavirus 2 (SARS-CoV-2). However, the contribution of antibodies to protection and to the course of the disease during first-time exposure to a pathogen is unknown. We analyzed the antibodies and B cell responses in severe and mild COVID-19 patients. Despite our primary assumption that high antibody titers contribute to a mild disease, we found that severe COVID-19 illness, and not mild infection, correlates with strong anti-viral antibody and memory B cell responses. This phenomenon was also demonstrated for anti-Mycobacterium tuberculosis inhibiting antibodies that we recently isolated from an actively infected Tuberculosis-sick donor. This correlation between disease severity and antibody responses can be explained by the fact that high viral loads drive B cell stimulation and generation of high-affinity antibodies that will be protective upon future encounter with the particular pathogen.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Antibody Formation , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
3.
J Med Virol ; 93(4): 2227-2233, 2021 04.
Article in English | MEDLINE | ID: covidwho-1217375

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, little is known about the durability of the antibody response during COVID-19 convalescent phase. We investigated the prevalence of anti-SARS-CoV-2 specific antibodies including immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and the dynamic changes in antibody levels in convalescent COVID-19 patients. A total of 159 blood samples were collected from 52 recovered COVID-19 patients up to six months after symptom onset for longitudinal serological tests. The positive rate of IgG and IgM antibodies was 92.3% and 90.4% in the first month after symptom onset, and the seropositivity of IgG antibody remained high at all follow-up time points, whereas the seropositivity of IgM antibody decreased to 22.73% by the sixth months after symptom onset. The level of IgG antibody was stable, the level of IgM antibody decreased slightly in the early convalescent phase and was detected in only five patients in the sixth month after symptom onset. The level of IgG antibody was higher in the severe and critical group than in the moderate group. The anti-SARS-CoV-2 specific antibodies have a long-term persistence in convalescent COVID-19 patients, whether they have long-term protection need to be further investigated.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Viral/biosynthesis , Antibody Formation , COVID-19/blood , COVID-19/diagnosis , COVID-19 Testing/methods , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Serologic Tests/methods
4.
PLoS One ; 16(4): e0249449, 2021.
Article in English | MEDLINE | ID: covidwho-1171683

ABSTRACT

OBJECTIVES: To determine the seroprevalence of anti-SARS-CoV-2 IgG and IgM antibodies in symptomatic Japanese COVID-19 patients. METHODS: Serum samples (n = 114) from 34 COVID-19 patients with mild to critical clinical manifestations were examined. The presence and titers of IgG antibody for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were determined by a chemiluminescent microparticle immunoassay (CMIA) using Alinity i SARS-CoV-2 IgG and by an immunochromatographic (IC) IgM/IgG antibody assay using the Anti-SARS-CoV-2 Rapid Test. RESULTS: IgG was detected by the CMIA in 40%, 88%, and 100% of samples collected within 1 week, 1-2 weeks, and 2 weeks after symptom onset in severe and critical cases, and 0%, 38%, and 100% in mild/moderate cases, respectively. In severe and critical cases, the positive IgG detection rate with the IC assay was 60% within one week and 63% between one and two weeks. In mild/moderate cases, the positive IgG rate was 17% within one week and 63% between one and two weeks; IgM was positive in 80% and 75% of severe and critical cases, and 42% and 88% of mild/moderate cases, respectively. On the CMIA, no anti-SARS-CoV-2 IgG antibodies were detected in COVID-19 outpatients with mild symptoms within 10 days from onset, whereas 50% of samples from severe inpatients were IgG-positive in the same period. The IC assay detected higher IgM positivity earlier from symptom onset in severe and critical cases than in mild/moderate cases. CONCLUSIONS: A serologic anti-SARS-CoV-2 antibody analysis can complement PCR for diagnosing COVID-19 14 days after symptom onset.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19 , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/metabolism , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , Female , Humans , Immunoassay , Japan/epidemiology , Male , Middle Aged
5.
Viral Immunol ; 34(3): 201-209, 2021 04.
Article in English | MEDLINE | ID: covidwho-1114816

ABSTRACT

For the assessment of vaccine-induced immune response and to understand the role of antibodies in neutralization, it is necessary to assess dynamics of various antibodies in patients with different clinical manifestations. This study aims to quantitate circulating levels of IgA/IgG and IgG subtypes induced at different days postonset of symptoms, in severe and nonsevere patients. For this, serum or plasma samples (n = 146) collected from 79 COVID-19 patients were used. Indirect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific IgA, IgG, and IgG subtype specific enzyme-linked immunosorbent assays (ELISAs) were performed. Antibody titers between severe and nonsevere patients were compared at different times postonset of clinical symptoms. Titers in ELISA were compared to neutralizing antibody (Nab) titers determined by plaque reduction neutralization test (PRNT). Over 75% patients were positive for IgA/IgG antibodies in the first week. The ELISA titers did not differ during the first week; however, severe disease exhibited raised titers thereafter. Nab titers correlated with the ELISA titers in mild presentation but not in severe disease. IgA and IgG1 antibodies correlated stronger with Nabs. The findings highlighted that IgA together with IgG play an important in SARS-CoV-2 neutralization. These results will prove useful in assessing efficacy of vaccines and understanding disease pathogenesis.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunoglobulin A/blood , Immunoglobulin G/blood , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Antibodies, Neutralizing/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Neutralization Tests , Young Adult
6.
Transl Res ; 232: 60-74, 2021 06.
Article in English | MEDLINE | ID: covidwho-1081356

ABSTRACT

COVID-19 patients elicit strong responses to the nucleocapsid (N) protein of SARS-CoV-2 but binding antibodies are also detected in prepandemic individuals, indicating potential crossreactivity with common cold human coronaviruses (HCoV) and questioning its utility in seroprevalence studies. We investigated the immunogenicity of the full-length and shorter fragments of the SARS-CoV-2 N protein, and the crossreactivity of antibodies with HCoV. We identified a C-terminus region in SARS-CoV2 N of minimal sequence homology with HCoV that was more specific for SARS-CoV-2 and highly immunogenic. IgGs to the full-length SARS-CoV-2 N also recognized N229E N, and IgGs to HKU1 N recognized SARS-CoV-2 N. Crossreactivity with SARS-CoV-2 was stronger for alpha- rather than beta-HCoV despite having less sequence identity, revealing the importance of conformational recognition. Higher preexisting IgG to OC43 N correlated with lower IgG to SARS-CoV-2 N in rRT-PCR negative individuals, reflecting less exposure and indicating a potential protective association. Antibodies to SARS-CoV-2 N were higher in patients with more severe and longer duration of symptoms and in females. IgGs remained stable for at least 3 months, while IgAs and IgMs declined faster. In conclusion, N protein is a primary target of SARS-CoV-2-specific and HCoV crossreactive antibodies, both of which may affect the acquisition of immunity to COVID-19.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Antibodies, Viral/blood , Cross Reactions , Female , Humans , Immunoglobulin G/immunology , Male , Rhinovirus/immunology , Seroepidemiologic Studies
7.
Rev Recent Clin Trials ; 16(2): 138-145, 2021.
Article in English | MEDLINE | ID: covidwho-771653

ABSTRACT

INTRODUCTION: Corona virus is a group of viruses that cause diseases in mammals and birds. In humans, these families of viruses can cause respiratory infections from a mild form to fatal. It is preferably called coronavirus. Formally, it is known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or 2019 novel coronavirus (2019-nCoV) and this disease is called coronavirus disease 2019 (COVID-19). SARS-CoV-2 is infectious in humans and the world health organization has announced COVID-19 as pandemic disease. Tocilizumab is a biological agent that inhibits the cytokine, interleukin 6 (IL-6 inhibitor). As SARS-CoV-2 infection leads to the development of cytokine storm syndrome, the drug, tocilizumab, seems to have a positive effect on patients with COVID-19. AIM: To analyze and review the possible effects and efficacy of the tocilizumab (monoclonal antibody against IL-6 receptors) in SARS-CoV-2 patients. MATERIALS AND METHODS: A search was carried out for all recent review articles, which were used to study the SARS-CoV-2 disease and their characteristics. Furthermore, we have analyzed the most recent research articles on monoclonal antibody against IL-6 receptors (tocilizumab) and their possible clinical effects in COVID-19 and its' clinical trials. RESULTS: COVID-19 is a disease caused by SARS-CoV-2 infection. It is a life threatening condition, which can give rise to fatal outcomes if left untreated. However, there are no approved treatments for COVID-19 globally. Furthermore, we can conclude that SARS-CoV-2 is associated with the worsening of lung conditions, characterized by interstitial pneumonia with acute respiratory distress syndrome as a result of cytokine storm syndrome. According to available research data, tocilizumab, a recombinant humanized anti-human monoclonal antibody of IgG1τ (gamma 1, kappa), can improve patient's condition from cytokine storm syndrome by inhibiting the IL-6 (Interleukin 6) receptors. CONCLUSION: The rational use of the tocilizumab in severe and critically ill COVID-19 patients can prevent the development of irreversible lung injury and death of the patient. Three retrospective studies of Xiaoling Xu et al., Pan luo et al., and Paola Tonaiti et al. have shown the efficacy of tocilizumab in severe and critically ill COVID-19 patients. However, we need more randomized research studies with a significant number of patients which can confirm the promising results on tocilizumab treatment in COVID-19 patients. Moreover, ongoing clinical trails such as TOSCA, COVACTA results have not been published yet which are expected to give better and more significant results on tocilizumab's effectiveness and safety.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Clinical Trials as Topic , Humans , Treatment Outcome
8.
Proc Natl Acad Sci U S A ; 117(20): 10970-10975, 2020 05 19.
Article in English | MEDLINE | ID: covidwho-155000

ABSTRACT

After analyzing the immune characteristics of patients with severe coronavirus disease 2019 (COVID-19), we have identified that pathogenic T cells and inflammatory monocytes with large amount of interleukin 6 secreting may incite the inflammatory storm, which may potentially be curbed through monoclonal antibody that targets the IL-6 pathways. Here, we aimed to assess the efficacy of tocilizumab in severe patients with COVID-19 and seek a therapeutic strategy. The patients diagnosed as severe or critical COVID-19 in The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) and Anhui Fuyang Second People's Hospital were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography (CT) scan image, and laboratory examinations were retrospectively analyzed. Fever returned to normal on the first day, and other symptoms improved remarkably within a few days. Within 5 d after tocilizumab, 15 of the 20 patients (75.0%) had lowered their oxygen intake, and 1 patient needed no oxygen therapy. CT scans manifested that the lung lesion opacity absorbed in 19 patients (90.5%). The percentage of lymphocytes in peripheral blood, which decreased in 85.0% of patients (17/20) before treatment (mean, 15.52 ± 8.89%), returned to normal in 52.6% of patients (10/19) on the fifth day after treatment. Abnormally elevated C-reactive protein decreased significantly in 84.2% of patients (16/19). No obvious adverse reactions were observed. All patients have been discharged on average 15.1 d after giving tocilizumab. Preliminary data show that tocilizumab, which improved the clinical outcome immediately in severe and critical COVID-19 patients, is an effective treatment to reduce mortality.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adult , Aged , Aged, 80 and over , COVID-19 , China , Coronavirus Infections/blood , Coronavirus Infections/physiopathology , Disease Progression , Female , Humans , Interleukin-6/antagonists & inhibitors , Interleukin-6/blood , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Treatment Outcome
9.
J Transl Med ; 18(1): 164, 2020 04 14.
Article in English | MEDLINE | ID: covidwho-52547

ABSTRACT

A severe pneumonia-associated respiratory syndrome caused by a new coronavirus was identified in December 2019 (COVID-19), spread rapidly and has become a world-wide public health challenge. About 25% of COVID-19 patients experienced severe complications including acute respiratory distress syndrome (ARDS), and even progressed into an intensive care unit (ICU) admission and died. The exploration for the mortality causes and advancing novel therapeutic development of severe COVID-19 is crucial at the moment. The biopsy samples analysis at autopsy suggested that increased alveolar exudate caused by aberrant host immune response and inflammatory cytokine storm probably impedes alveolar gas exchange and contributes to the high mortality of severe COVID-19 patients. Our research has identified that pathogenic T cells and inflammatory monocytes incite inflammatory storm with large amount of interleukin 6, therefore monoclonal antibody that targets the IL-6 pathways may potentially curb inflammatory storm. Moreover, Tocilizumab treatment that blocking IL-6 receptors showed inspiring clinical results including temperature returned to normal quickly and respiratory function improved. Therefore, we suggest that Tocilizumab is an effective treatment in severe patients of COVID-19 to calm the inflammatory storm and reduce mortality.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , COVID-19 , Coronavirus Infections/immunology , Humans , Interleukin-6/antagonists & inhibitors , Pandemics , Pneumonia, Viral/immunology , SARS-CoV-2 , Severity of Illness Index
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