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1.
Infect Dis (Lond) ; : 1-11, 2021 Dec 24.
Article in English | MEDLINE | ID: covidwho-1585224

ABSTRACT

BACKGROUND: Understanding the longevity of antibodies against SARS-CoV-2 infection is of utmost importance in predicting the further course of the pandemic and to plan vaccination strategies. Here we report a cohort of COVID-19 patients with different disease severities whose antibody dynamics we evaluated during one-year of follow-up. METHODS: We conducted a longitudinal study of 123 COVID-19 patients and 45 SARS CoV-2 negative outpatients with upper respiratory tract infection. We analyzed the demographic and clinical features of the patients with COVID-19 in relation to different disease severities according to the WHO classification. The antibody response was evaluated by a Luciferase Immunoprecipitation System (LIPS) assay at 3, 6, and 12 months after the acute infection. RESULTS: Amongst the enrolled COVID-19 patients, 15 (12%) had mild, 42 (34%) had moderate, 39 (32%) had severe and 27 (22%) had critical disease courses; 79% of the patients were hospitalized. During follow-up, all patients had anti-SARS RBD-IgG levels above the cut-off value on all visits, but the antibody levels varied significantly between the different disease severity groups. Between the six- and 12-month follow-up visits, 41% of patients were vaccinated, which enhanced their antibody levels significantly. CONCLUSION: Our data demonstrate sustained antibody levels at one-year after moderate and severe COVID-19 infection. Vaccination of patients with the mild disease is important to raise the antibody levels to a protective level.

2.
Preprint in English | Other preprints | ID: ppcovidwho-295564

ABSTRACT

Background Although the SARS-CoV-2 mRNA vaccines have proven high efficacy, limited data exists on the duration of immune responses and their relation to age and side effects. Methods We studied the antibody and memory T cell responses to Spike protein after the two-dose Comirnaty mRNA vaccine in 122 volunteers up to 3 months and correlated the findings with age and side effects. Findings We found a robust antibody response after the second vaccination dose. However, the antibody levels declined at 6 and 12 weeks postvaccination, indicating a waning of the immune response. Regardless, the average levels remained higher compared to pre-vaccination or in COVID-19 convalescent individuals. The antibodies efficiently blocked ACE2 receptor binding to Spike protein of four variants of concern at one week but this was decreased at three months, in particular with B.1.351 and P1 isolates. 87% of individuals developed Spike-specific memory T cell responses, which were lower in individuals with increased proportions of immunosenescent CD8+ TEMRA cells. We found a decreased vaccination efficacy but fewer adverse events in older individuals, suggesting a detrimental impact of age on outcome. Interpretation The mRNA vaccine induces a strong antibody response to four variants at 1 week postvaccination but decreases thereafter, in particular among older individuals. T cell responses, although detectable in the majority, were lower in individuals with immunosenescence. The deterioration of vaccine response needs to be monitored to define the optimal time for the revaccination. Funding The Estonian Research Council, Icosagen Cell Factory, and SYNLAB Estonia. Research in context Evidence before this study The first studies addressing the immune responses in older individuals after the administration of SARS-CoV-2 mRNA vaccines have been published. We searched PubMed and medRxiv for publications on the immune response of SARS-CoV-2-mRNA vaccines, published in English, using the search terms “SARS-CoV-2”, “COVID-19”, “vaccine response”, “mRNA vaccine”, up to May 20th, 2021. To date, most mRNA vaccine response studies have not been peer-reviewed, and data on the dynamics of antibody response, role of age and side effects on SARS-CoV-2-mRNA vaccines in real vaccination situations is limited. Some studies have found a weaker immune response in older individuals after the first dose and these have been measured at a relatively short period (within one to two weeks) after the first dose but little longer-term evidence exists on the postvaccination antibody persistence. Added value of this study In this study, we assessed the antibody response up to three months after the full vaccination with Pfizer-BioNTech Comirnaty mRNA vaccine in 122 individuals. Our findings show strong Spike RBD antibody responses one week after the second dose with the capacity to block ACE2-Spike protein interaction, however, the antibodies declined significantly at three months after the second dose. The inhibition of ACE2-Spike interaction was weaker with South African (B.1.351) and Brazilian (P.1) than with Wuhan and UK (B.1.1.7) SARS-CoV-2 isolates. At three months 87% of vaccinated individuals developed either CD4+ or CD8+ T cell responses. Those negative for Spike-specific T cell response also tended to have lower Spike-specific antibody levels. In addition, CD4+ T cell response was decreased among vaccinated individuals with elevated levels of senescent CD8+ TEMRA cells. We found a weaker antibody response and faster waning of antibodies in older vaccinated individuals, which correlated with fewer side effects at the time of vaccinations. Implications of all the available evidence Our results show that two doses of Pfizer-BioNTech Comirnaty mRNA vaccine induce a strong antibody and T cell responses to Spike RBD region but the antibody levels are declined at three months after the second dose. Nevertheless, even at three months, the anti-Spike RBD antibody levels tay significantly higher than at prevaccination, after the first dose of vaccine, or in Covid-19 postinfection. Our findings implicate older individuals to have fewer vaccination adverse effects and weaker immune response after the vaccination and point to the need for more individualized vaccination protocols, in particular among older people.

3.
Front Immunol ; 12: 709759, 2021.
Article in English | MEDLINE | ID: covidwho-1450807

ABSTRACT

The clinical features of SARS-CoV-2 infection range from asymptomatic to severe disease with life-threatening complications. Understanding the persistence of immune responses in asymptomatic individuals merit special attention because of their importance in controlling the spread of the infections. We here studied the antibody and T cell responses, and a wide range of inflammation markers, in 56 SARS-CoV-2 antibody-positive individuals, identified by a population screen after the first wave of SARS-CoV-2 infection. These, mostly asymptomatic individuals, were reanalyzed 7-8 months after their infection together with 115 age-matched seronegative controls. We found that 7-8 months after the infection their antibodies to SARS-CoV-2 Nucleocapsid (N) protein declined whereas we found no decrease in the antibodies to Spike receptor-binding domain (S-RBD) when compared to the findings at seropositivity identification. In contrast to antibodies to N protein, the antibodies to S-RBD correlated with the viral neutralization capacity and with CD4+ T cell responses as measured by antigen-specific upregulation of CD137 and CD69 markers. Unexpectedly we found the asymptomatic antibody-positive individuals to have increased serum levels of S100A12, TGF-alpha, IL18, and OSM, the markers of activated macrophages-monocytes, suggesting long-term persistent inflammatory effect associated with the viral infection in asymptomatic individuals. Our results support the evidence for the long-term persistence of the inflammation process and the need for post-infection clinical monitoring of SARS-CoV-2 infected asymptomatic individuals.


Subject(s)
Antibodies, Viral/blood , Asymptomatic Infections , CD4-Positive T-Lymphocytes/immunology , COVID-19/pathology , Inflammation Mediators/blood , SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CD4 Lymphocyte Count , Coronavirus Nucleocapsid Proteins/immunology , Humans , Inflammation/immunology , Interleukin-18/blood , Macrophages/immunology , Monocytes/immunology , Oncostatin M/blood , Phosphoproteins/immunology , Protein Domains/immunology , S100A12 Protein/blood , Spike Glycoprotein, Coronavirus/immunology , Transforming Growth Factor alpha/blood
4.
Lancet Reg Health Eur ; 10: 100208, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1404792

ABSTRACT

Background: SARS-CoV-2 mRNA vaccines have proven high efficacy, however, limited data exists on the duration of immune responses and their relation to age and side effects. Methods: We studied the antibody and memory T cell responses after the two-dose BNT162b2 vaccine in 122 volunteers up to 6 months and correlated the findings with age and side effects. Findings: We found a robust antibody response to Spike protein after the second dose. However, the antibody levels declined at 12 weeks and 6 months post-vaccination, indicating a waning of the immune response over time. At 6 months after the second dose, the Spike antibody levels were similar to the levels in persons vaccinated with one dose or in COVID-19 convalescent individuals. The antibodies efficiently blocked ACE2 receptor binding to SARS-CoV-2 Spike protein of five variants of concern at one week but this was decreased at three months. 87% of individuals developed Spike-specific memory T cell responses, which were lower in individuals with increased proportions of immunosenescent CD8+ TEMRA cells. We found antibody response to correlate negatively with age and positively with the total score of vaccination side effects. Interpretation: The mRNA vaccine induces a strong antibody response to SARS-CoV-2 and five VOCs at 1 week post-vaccination that decreases thereafter. T cell responses, although detectable in the majority, were lower in individuals with higher T cell immunosenescence. The deterioration of vaccine response suggests the need to monitor for the potential booster vaccination.

5.
Vaccine ; 39(38): 5376-5384, 2021 09 07.
Article in English | MEDLINE | ID: covidwho-1340875

ABSTRACT

PURPOSE: In Estonia, during the first wave of COVID-19 total number of cases confirmed by PCR was 13.3/10,000, similar in most regions, including capital Tallinn, but in the hotspot of Estonian epidemic, an island Saaremaa, the cumulative incidence was 166.1/10,000. We aimed to determine the prevalence of SARS-CoV-2 IgG antibodies in these two regions, symptoms associated with infection and factors associated with antibody concentrations. METHODS: Participants were selected using stratified (formed by age decades) random sampling and recruited by general practitioners. IgG or neutralizing antibodies were determined from sera by four assays. Symptoms associated with seropositivity were analyzed by multiple correspondence analysis, antibody concentrations by multiple linear regression. RESULTS: Total of 3608 individual were invited and 1960 recruited from May 8 to July 31, 2020. Seroprevalence was 1.5% (95% confidence interval (CI) 0.9-2.5) and 6.3% (95% CI 5.0-7.9), infection fatality rate 0.1% (95% CI 0.0-0.2) and 1.3% (95% CI 0.4-2.1) in Tallinn and Saaremaa, respectively. Of seropositive subjects 19.2% (14/73) had acute respiratory illness. Fever, diarrhea and the absence of cough and runny nose were associated with seropositivity in individuals aged 50 or more years. IgG, but not neutralizing antibodies concentrations were higher if fever, difficulty breathing, shortness of breath, chest pain or diarrhea was present, or hospitalization required. CONCLUSION: Similarly to other European countries the seroprevalence of SARS-CoV-2 in Estonia was low even in the hotspot region Saaremaa suggesting that majority of population is susceptible to SARS-CoV-2. Focusing only on respiratory symptoms may delay accurate diagnosis of SARS-CoV-2 infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Estonia/epidemiology , Humans , Immunoglobulin G , Prevalence , Seroepidemiologic Studies
8.
Sci Rep ; 10(1): 20533, 2020 11 25.
Article in English | MEDLINE | ID: covidwho-947550

ABSTRACT

SARS-CoV-2 infection has a risk to develop into life-threatening COVID-19 disease. Whereas age, hypertension, and chronic inflammatory conditions are risk factors, underlying host factors and markers for disease severity, e.g. requiring intensive care unit (ICU) treatment, remain poorly defined. To this end, we longitudinally profiled blood inflammation markers, antibodies, and 101 plasma proteins of hospitalized COVID-19 patients who did or did not require ICU admission. While essentially all patients displayed SARS-CoV-2-specific antibodies and virus-neutralization capacity within 12-15 days, a rapid, mostly transient upregulation of selective inflammatory markers including IL-6, CXCL10, CXCL11, IFNγ, IL-10, and monocyte-attracting CCL2, CCL7 and CCL8, was particularly evident in ICU patients. In addition, there was consistent and sustained upregulation of apoptosis-associated proteins CASP8, TNFSF14, HGF, and TGFB1, with HGF discriminating between ICU and non-ICU cohorts. Thus, COVID-19 is associated with a selective inflammatory milieu within which the apoptotic pathway is a cardinal feature with potential to aid risk-based patient stratification.


Subject(s)
Apoptosis , COVID-19 Testing/methods , COVID-19/blood , COVID-19/diagnosis , Caspase 8/blood , Chemokines/blood , Proteome , SARS-CoV-2/genetics , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/virology , Female , Hospitalization , Humans , Inflammation/blood , Intensive Care Units , Longitudinal Studies , Male , Middle Aged , Proteomics/methods , Risk Factors , Up-Regulation , Young Adult
9.
Nat Med ; 26(10): 1623-1635, 2020 10.
Article in English | MEDLINE | ID: covidwho-717130

ABSTRACT

Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. Some signature traits identify links with other settings of immunoprotection and immunopathology; others, including basophil and plasmacytoid dendritic cell depletion, correlate strongly with disease severity; while a third set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation in other COVID-19 cohorts, individual traits within this signature may collectively and individually guide treatment options; offer insights into COVID-19 pathogenesis; and aid early, risk-based patient stratification that is particularly beneficial in phasic diseases such as COVID-19.


Subject(s)
Antibodies, Viral/immunology , B-Lymphocytes/immunology , Coronavirus Infections/immunology , Cytokines/immunology , Dendritic Cells/immunology , Pneumonia, Viral/immunology , T-Lymphocytes/immunology , Aged , B-Lymphocyte Subsets/immunology , Basophils/immunology , Betacoronavirus , COVID-19 , Case-Control Studies , Cell Cycle , Chemokine CXCL10/immunology , Chemokines/immunology , Cohort Studies , Coronavirus Infections/blood , Disease Progression , Female , Flow Cytometry , Hospitalization , Humans , Immunologic Memory , Immunophenotyping , Interleukin-10/immunology , Interleukin-6/immunology , Leukocyte Count , Lymphocyte Activation/immunology , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Prognosis , SARS-CoV-2 , Severity of Illness Index , T-Lymphocyte Subsets/immunology , Up-Regulation
10.
Eur J Immunol ; 50(8): 1234-1236, 2020 08.
Article in English | MEDLINE | ID: covidwho-614139

ABSTRACT

Profiling antibodies to SARS-CoV-2 can help to assess potential immune response after COVID-19 disease. Luciferase IP system (LIPS) assay is a sensitive method for quantitative detection of antibodies to antigens in their native conformation. We here describe LIPS to detect antibody responses to SARS-CoV-2 spike (S) and nucleocapsid (N) proteins in COVID-19 patients. The antibodies targeted both S and N fragments and gave a high assay sensitivity by identifying 26 out of 26 COVID-19 patients with N antigen or with three protein fragments when combined into a single reaction. The assay correlated well with ELISA method and was specific to COVID-19 as we saw no reactivity among uninfected healthy controls. Our results show that LIPS is a rapid and measurable method to screen antibody responses against SARS-CoV-2 antigens.


Subject(s)
Antibodies, Viral , Betacoronavirus , Coronavirus Infections , Nucleocapsid Proteins , Pandemics , Pneumonia, Viral , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , Betacoronavirus/immunology , Betacoronavirus/metabolism , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/immunology , Female , Humans , Male , Middle Aged , Nucleocapsid Proteins/immunology , Nucleocapsid Proteins/metabolism , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , SARS-CoV-2
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