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1.
Front Immunol ; 12: 708523, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220870

RESUMO

Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , SARS-CoV-2/imunologia , Idoso , Formação de Anticorpos/imunologia , COVID-19/terapia , Convalescença , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Fatores de Tempo
2.
Front Immunol ; 12: 704773, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220867

RESUMO

Background: Hemodialysis patients are at high risk for severe COVID-19. SARS-CoV-2 vaccination related safety and immunogenicity data in these patients are rare. Methods: In this observational study SARS-CoV-2-seronegative hemodialysis patients were vaccinated with two doses of the Pfizer/BioNTech mRNA-BNT162b2 vaccine (COMIRNATY® 30 µg) and followed for 90 days. Local and systemic side effects were assessed at every dialysis session during the first post-vaccination week after the first and second vaccine dose. Immunogenicity was determined four weeks after vaccination by quantifying anti-SARS-CoV-2 spike protein IgG antibodies (LIAISON® SARS-CoV-2-TrimericS IgG chemiluminescent immunoassay) expressed in binding activity units per milliliter (BAU/mL) adapted to the WHO International standard. Results: Fifty patients (32% women, 68% men) with a mean (SD) age of 67.6 (14.8) years were included. Mild local reactions occurred in 38% after the first injection, and in 29.2% with mild, in 2.1% with moderate and in 2.1% with severe degree after the second injection. Systemic reactive events occurred less often, with diarrhea (4% mild, 4% moderate) and fatigue (8% mild) being the most frequent ones. After the first injection 42% of the patients developed a positive response using the assay specific cut-off value of 33.8 binding activity units per milliliter (BAU/mL) with a median (Q1, Q3) anti-SARS-CoV-2 spike IgG concentration of 20.0 (11.7, 51.0) BAU/mL. After the second injection the percentage of seropositive patients increased to 97.9% with an anti-SARS-CoV-2 spike IgG concentration of 1075 (290.8, 1735) BAU/mL. Higher age and immunosuppression were associated with lower, calcitriol treatment and prior seroconversion to hepatitis B vaccination with significantly higher antibody concentration. Conclusions: The mRNA-BNT162b2 SARS-CoV-2 vaccine appears to be safe and well-tolerated and shows a high immunogenicity in hemodialysis patients.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Imunogenicidade da Vacina/imunologia , Diálise Renal , SARS-CoV-2/imunologia , Idoso , Envelhecimento , Anticorpos Neutralizantes/sangue , COVID-19/imunologia , COVID-19/prevenção & controle , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Glicoproteína da Espícula de Coronavírus/imunologia
3.
Vet Microbiol ; 259: 109155, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34197977

RESUMO

Turkey coronavirus (TCoV) can cause a highly contagious enteric disease in turkeys with severe economic losses in the global turkey industry. To date, no commercial vaccines are available for control of the disease. In the present study, we isolated a field strain (NC1743) of TCoV and evaluated its pathogenicity in specific-pathogen-free (SPF) turkey poults to establish a TCoV disease model. The results showed that the TCoV NC1743 isolate was pathogenic to turkey poults with a minimal infectious dose at 106 EID50/bird. About 50 % of one-day-old SPF turkeys infected with the virus's minimal infectious dose exhibited typical enteric disease signs and lesions from 6 days post-infection (dpi) to the end of the experiment (21 dpi). In contrast, fewer than 20 % of older turkeys (1- or 2-week-old) infected with the same amount of TCoV displayed enteric disease signs, which disappeared after 15-18 dpi. Although all infected turkeys, regardless of age, shed TCoV, the older turkeys shed less virus than the younger birds, and 50 % of the 2-week-old birds even cleared the virus at 21 dpi. Furthermore, the viral infection caused day-old turkeys more body-weight-gain reduction than older birds. The overall data demonstrated that the TCoV NC1743 isolate is a highly pathogenic strain and younger turkeys are more susceptible to TCoV infection than older birds. Thus, one-day-old turkeys infected with the minimal infectious dose of TCoV NC1743 could be used as a TCoV disease model to study the disease pathogenesis, and the TCoV NC1743 strain could be used as a challenge virus to evaluate a vaccine protective efficacy.


Assuntos
Infecções por Coronavirus/veterinária , Coronavirus do Peru/patogenicidade , Doenças das Aves Domésticas/prevenção & controle , Perus/virologia , Animais , Anticorpos Antivirais/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Coronavirus do Peru/classificação , Modelos Animais de Doenças , Doenças das Aves Domésticas/sangue , Doenças das Aves Domésticas/virologia , Organismos Livres de Patógenos Específicos
4.
Viruses ; 13(6)2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198719

RESUMO

Humoral immunity has emerged as a vital immune component against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nevertheless, a subset of recovered Coronavirus Disease-2019 (COVID-19) paucisymptomatic/asymptomatic individuals do not generate an antibody response, constituting a paradox. We assumed that immunodiagnostic assays may operate under a competitive format within the context of antigenemia, potentially explaining this phenomenon. We present a case where persistent antigenemia/viremia was documented for at least 73 days post-symptom onset using 'in-house' methodology, and as it progressively declined, seroconversion took place late, around day 55, supporting our hypothesis. Thus, prolonged SARS-CoV-2 antigenemia/viremia could mask humoral responses, rendering, in certain cases, the phenomenon of 'non-responders' a misnomer.


Assuntos
Anticorpos Antivirais/sangue , Antígenos Virais/sangue , Antígenos Virais/imunologia , Teste Sorológico para COVID-19/normas , COVID-19/diagnóstico , SARS-CoV-2/imunologia , Anticorpos Antivirais/metabolismo , Antígenos Virais/metabolismo , Sítios de Ligação de Anticorpos , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Teste Sorológico para COVID-19/estatística & dados numéricos , Humanos , Imunidade Humoral/imunologia , Imunoglobulina G/sangue , Masculino , Sensibilidade e Especificidade , Soroconversão , Adulto Jovem
5.
Viruses ; 13(6)2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34200070

RESUMO

The World Health Organisation recommends monitoring the circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated anti-SARS-CoV-2 total immunoglobulin (IgT) antibody seroprevalence and in vitro sero-neutralization in Nancy, France, in spring 2020. Individuals were randomly sampled from electoral lists and invited with household members over 5 years old to be tested for anti-SARS-CoV-2 (IgT, i.e., IgA/IgG/IgM) antibodies by ELISA (Bio-rad); the sero-neutralization activity was evaluated on Vero CCL-81 cells. Among 2006 individuals, the raw seroprevalence was 2.1% (95% confidence interval 1.5 to 2.9), was highest for 20- to 34-year-old participants (4.7% (2.3 to 8.4)), within than out of socially deprived area (2.5% vs. 1%, p = 0.02) and with than without intra-family infection (p < 10-6). Moreover, 25% of participants presented at least one COVID-19 symptom associated with SARS-CoV-2 positivity (p < 10-13), with highly discriminant anosmia or ageusia (odds ratio 27.8 [13.9 to 54.5]); 16.3% (6.8 to 30.7) of seropositive individuals were asymptomatic. Positive sero-neutralization was demonstrated in vitro for 31/43 seropositive subjects. Regarding the very low seroprevalence, a preventive effect of the lockdown in March 2020 can be assumed for the summer, but a second COVID-19 wave, as expected, could be subsequently observed in this poorly immunized population.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Teste Sorológico para COVID-19 , Criança , Pré-Escolar , Controle de Doenças Transmissíveis , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Estudos Soroepidemiológicos , População Suburbana/estatística & dados numéricos , Adulto Jovem
6.
Viruses ; 13(6)2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200766

RESUMO

SARS-CoV-2 infection fatality ratios (IFR) remain controversially discussed with implications for political measures. The German county of Tirschenreuth suffered a severe SARS-CoV-2 outbreak in spring 2020, with particularly high case fatality ratio (CFR). To estimate seroprevalence, underreported infections, and IFR for the Tirschenreuth population aged ≥14 years in June/July 2020, we conducted a population-based study including home visits for the elderly, and analyzed 4203 participants for SARS-CoV-2 antibodies via three antibody tests. Latent class analysis yielded 8.6% standardized county-wide seroprevalence, a factor of underreported infections of 5.0, and 2.5% overall IFR. Seroprevalence was two-fold higher among medical workers and one third among current smokers with similar proportions of registered infections. While seroprevalence did not show an age-trend, the factor of underreported infections was 12.2 in the young versus 1.7 for ≥85-year-old. Age-specific IFRs were <0.5% below 60 years of age, 1.0% for age 60-69, and 13.2% for age 70+. Senior care homes accounted for 45% of COVID-19-related deaths, reflected by an IFR of 7.5% among individuals aged 70+ and an overall IFR of 1.4% when excluding senior care home residents from our computation. Our data underscore senior care home infections as key determinant of IFR additionally to age, insufficient targeted testing in the young, and the need for further investigations on behavioral or molecular causes of the fewer infections among current smokers.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , COVID-19/mortalidade , Vigilância da População/métodos , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/imunologia , Feminino , Alemanha/epidemiologia , Humanos , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estações do Ano , Estudos Soroepidemiológicos , Inquéritos e Questionários , Adulto Jovem
7.
Viruses ; 13(6)2021 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204732

RESUMO

The COVID-19 pandemic caused by SARS-CoV-2 has posed a global threat to human lives and economics. One of the best ways to determine protection against the infection is to quantify the neutralizing activity of serum antibodies. Multiple assays have been developed to validate SARS-CoV-2 neutralization; most of them utilized lentiviral or vesicular stomatitis virus-based particles pseudotyped with the spike (S) protein, making them safe and acceptable to work with in many labs. However, these systems are only capable of measuring infection with purified particles. This study has developed a pseudoviral assay with replication-dependent reporter vectors that can accurately quantify the level of infection directly from the virus producing cell to the permissive target cell. Comparative analysis of cell-free and cell-to-cell infection revealed that the neutralizing activity of convalescent sera was more than tenfold lower in cell cocultures than in the cell-free mode of infection. As the pseudoviral system could not properly model the mechanisms of SARS-CoV-2 transmission, similar experiments were performed with replication-competent coronavirus, which detected nearly complete SARS-CoV-2 cell-to-cell infection resistance to neutralization by convalescent sera. These findings suggest that the cell-to-cell mode of SARS-CoV-2 transmission, for which the mechanisms are largely unknown, could be of great importance for treatment and prevention of COVID-19.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Convalescença , Testes de Neutralização/métodos , SARS-CoV-2/imunologia , Genes Reporter/genética , Células HEK293 , Humanos , Testes de Neutralização/normas , SARS-CoV-2/genética
8.
Viruses ; 13(6)2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205134

RESUMO

This observational study evaluated SARS-CoV-2 IgG seroprevalence and related clinical, demographic, and occupational factors among workers at the largest tertiary care University-Hospital of Northwestern Italy and the University of Turin after the first pandemic wave of March-April 2020. Overall, about 10,000 individuals were tested; seropositive subjects were retested after 5 months to evaluate antibodies waning. Among 8769 hospital workers, seroprevalence was 7.6%, without significant differences related to job profile; among 1185 University workers, 3.3%. Self-reporting of COVID-19 suspected symptoms was significantly associated with positivity (Odds Ratio (OR) 2.07, 95%CI: 1.76-2.44), although 27% of seropositive subjects reported no previous symptom. At multivariable analysis, contacts at work resulted in an increased risk of 69%, or 24% for working in a COVID ward; contacts in the household evidenced the highest risk, up to more than five-fold (OR 5.31, 95%CI: 4.12-6.85). Compared to never smokers, being active smokers was inversely associated with seroprevalence (OR 0.60, 95%CI: 0.48-0.76). After 5 months, 85% of previously positive subjects still tested positive. The frequency of SARS-COV-2 infection among Health Care Workers was comparable with that observed in surveys performed in Northern Italy and Europe after the first pandemic wave. This study confirms that infection frequently occurred as asymptomatic and underlines the importance of household exposure, seroprevalence (OR 0.60, 95%CI: 0.48-0.76).


Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , COVID-19/imunologia , Pessoal de Saúde/estatística & dados numéricos , Imunoglobulina G/sangue , Centros de Atenção Terciária/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Monitoramento Epidemiológico , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Estudos Soroepidemiológicos , Inquéritos e Questionários
9.
Sci Rep ; 11(1): 13780, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215811

RESUMO

Most patients infected with SARS-CoV-2 are asymptomatic or mildly symptomatic. However, the early and late antibody kinetics, and the association between antibody levels, clinical symptoms, and disease phase in these patients have not yet been fully defined. Confirmed SARS-CoV-2 patients and their household contacts were evaluated over a period four months. The evaluation procedure included symptom monitoring, viral load and serology analysis every ten days. A total of 1334 serum samples were collected from 135 patients and analyzed using three assays for IgG-N, IgG-S and IgM antibodies. Of the study participants, 97% were seropositive during the study, and two distinct clusters were identified. These clusters were significantly different in their inflammatory related symptoms. Peak IgG-S was 40.0 AU/ml for the non-inflammatory cluster and 71.5 AU/ml for the inflammatory cluster (P = 0.006), whereas IgG-N peaks were 4.3 and 5.87 (P = 0.023) respectively. Finally, a decision tree model was designed to predict the disease phase based on the serological titer levels, and had an overall accuracy of 80.7%. The specific profile of seroconversion and decay of serum antibodies can be used to predict the time-course from the acute infection.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , COVID-19/sangue , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Carga Viral
10.
Arch Iran Med ; 24(5): 427-433, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34196209

RESUMO

BACKGROUND: Real-time polymerase chain reaction (RT-PCR) of virus nucleic acid test (NAT) has become the standard method to diagnose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, there are still many limitations, especially the problem of the high false negative rate. Therefore, the aim of this study was to investigate the positive rate of SARS-CoV-2 NAT and evaluate the diagnostic performance of SARS-CoV-2 IgM and IgG antibody detection in novel coronavirus infection. METHODS: A total of 10309 suspected or high-risk cases of infection with SARS-CoV-2 in Wuhan Hubei, China, were tested for virus NAT by RT-PCR. Among those cases, 762 COVID-19 patients and 143 patients with non-COVID-19 who were tested for SARS-CoV-2 IgM and IgG during the NAT period were screened. The difference between the two test methods was analyzed using the chi-square test. RESULTS: The positive rate of 10309 cases was about 36% (95% CI: 33.39%-39.67%). SARS-CoV-2 was present in various types of specimens, and alveolar lavage fluid had the highest positive rate [52.38% (95% CI: 31.02-73.74)]. The clinical sensitivity of serum SARS-CoV-2 IgM and IgG was 77.17% (588/762) and 94.88% (723/762), respectively, and the clinical specificity was 93.71% (134/143) and 90.21% (129/143). The area under the curve (AUC) of SARS-CoV-2 IgG and combination of IgG with IgM were equally larger than IgM [0.973 (95% CI: 0.964-0.983) vs 0.930 (95% CI: 0.910-0.949)]. IgG antibody had the highest specificity [100.0% (95% CI: 100.00%-100.00%)] and sensitivity [94.0% (95% CI: 92.45%-95.55%)] when detected alone or in combination with IgM antibody. The total coincidence rate of SARS-CoV-2 antibodies detection and SARS-CoV-2 NAT for the diagnosis of SARS-CoV-2 infection was 92.04% (833/905). Among the 34 SARS-CoV-2 NAT-negative patients with clinical symptoms and CT imaging features, 29 (85.29%) patients were positive for SARS-CoV-2 IgM, and 31 (91.76%) were positive for IgG. CONCLUSION: SARS-CoV-2 NAT should be considered for many types of specimens, and the combined test of SARS-CoV-2 IgM and IgG can make up for the problem of missed NAT in COVID-19 patients.


Assuntos
Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19 , COVID-19/diagnóstico , SARS-CoV-2/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , China , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
11.
Viruses ; 13(6)2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198530

RESUMO

The goal of this study was to develop a mathematical model to simulate the actions of drugs that target SARS-CoV-2 virus infection. To accomplish that goal, we have developed a mathematical model that describes the control of a SARS-CoV-2 infection by the innate and adaptive immune components. Invasion of the virus triggers the innate immunity, whereby interferon renders some of the target cells resistant to infection, and infected cells are removed by effector cells. The adaptive immune response is represented by plasma cells and virus-specific antibodies. The model is parameterized and then validated against viral load measurements collected in COVID-19 patients. We apply the model to simulate three potential anti-SARS-CoV-2 therapies: (1) Remdesivir, a repurposed drug that has been shown to inhibit the transcription of SARS-CoV-2, (2) an alternative (hypothetical) therapy that inhibits the virus' entry into host cells, and (3) convalescent plasma transfusion therapy. Simulation results point to the importance of early intervention, i.e., for any of the three therapies to be effective, it must be administered sufficiently early, not more than a day or two after the onset of symptoms. The model can serve as a key component in integrative platforms for rapid in silico testing of potential COVID-19 therapies and vaccines.


Assuntos
Imunidade Adaptativa , COVID-19/tratamento farmacológico , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Imunidade Inata , Modelos Teóricos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Anticorpos Antivirais/sangue , Antivirais/uso terapêutico , COVID-19/imunologia , COVID-19/terapia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunização Passiva/métodos , Internalização do Vírus/efeitos dos fármacos
12.
PLoS One ; 16(7): e0254367, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34242356

RESUMO

COVID-19 serological test must have high sensitivity as well as specificity to rule out cross-reactivity with common coronaviruses (HCoVs). We have developed a quantitative multiplex test, measuring antibodies against spike (S) proteins of SARS-CoV-2, SARS-CoV, MERS-CoV, and common human coronavirus strains (229E, NL63, OC43, HKU1), and nucleocapsid (N) protein of SARS-CoV viruses. Receptor binding domain of S protein of SARS-CoV-2 (S-RBD), and N protein, demonstrated sensitivity (94% and 92.5%, respectively) in COVID-19 patients (n = 53), with 98% specificity in non-COVID-19 respiratory-disease (n = 98), and healthy-controls (n = 129). Anti S-RBD and N antibodies appeared five to ten days post-onset of symptoms, peaking at approximately four weeks. The appearance of IgG and IgM coincided while IgG subtypes, IgG1 and IgG3 appeared soon after the total IgG; IgG2 and IgG4 remained undetectable. Several inflammatory cytokines/chemokines were found to be elevated in many COVID-19 patients (e.g., Eotaxin, Gro-α, CXCL-10 (IP-10), RANTES (CCL5), IL-2Rα, MCP-1, and SCGF-b); CXCL-10 was elevated in all. In contrast to antibody titers, levels of CXCL-10 decreased with the improvement in patient health suggesting it as a candidate for disease resolution. Importantly, anti-N antibodies appear before S-RBD and differentiate between vaccinated and infected people-current vaccines (and several in the pipeline) are S protein-based.


Assuntos
Anticorpos Antivirais , COVID-19 , Quimiocinas , Proteínas do Nucleocapsídeo de Coronavírus , Imunoglobulina G , Imunoglobulina M , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Adulto , Animais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/sangue , COVID-19/imunologia , Quimiocinas/sangue , Quimiocinas/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/sangue , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Macaca mulatta , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/sangue , Fosfoproteínas/imunologia , Coelhos , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/sangue , Glicoproteína da Espícula de Coronavírus/imunologia
15.
Nat Commun ; 12(1): 4048, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193869

RESUMO

The ongoing SARS-CoV-2 pandemic necessitates the fast development of vaccines. Recently, viral mutants termed variants of concern (VOC) which may escape host immunity have emerged. The efficacy of spike encoding mRNA vaccines (CVnCoV and CV2CoV) against the ancestral strain and the VOC B.1.351 was tested in a K18-hACE2 transgenic mouse model. Naive mice and mice immunized with a formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA-immunized mice develop elevated SARS-CoV-2 RBD-specific antibody and neutralization titers which are readily detectable, but significantly reduced against VOC B.1.351. The mRNA vaccines fully protect from disease and mortality caused by either viral strain. SARS-CoV-2 remains undetected in swabs, lung, or brain in these groups. Despite lower neutralizing antibody titers compared to the ancestral strain BavPat1, CVnCoV and CV2CoV show complete disease protection against the novel VOC B.1.351 in our studies.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Linhagem Celular , Chlorocebus aethiops , Genoma Viral/genética , Humanos , Camundongos , Camundongos Transgênicos , SARS-CoV-2/genética , Células Vero
16.
Nat Commun ; 12(1): 4043, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193870

RESUMO

Memory T cells contribute to rapid viral clearance during re-infection, but the longevity and differentiation of SARS-CoV-2-specific memory T cells remain unclear. Here we conduct ex vivo assays to evaluate SARS-CoV-2-specific CD4+ and CD8+ T cell responses in COVID-19 convalescent patients up to 317 days post-symptom onset (DPSO), and find that memory T cell responses are maintained during the study period regardless of the severity of COVID-19. In particular, we observe sustained polyfunctionality and proliferation capacity of SARS-CoV-2-specific T cells. Among SARS-CoV-2-specific CD4+ and CD8+ T cells detected by activation-induced markers, the proportion of stem cell-like memory T (TSCM) cells is increased, peaking at approximately 120 DPSO. Development of TSCM cells is confirmed by SARS-CoV-2-specific MHC-I multimer staining. Considering the self-renewal capacity and multipotency of TSCM cells, our data suggest that SARS-CoV-2-specific T cells are long-lasting after recovery from COVID-19, thus support the feasibility of effective vaccination programs as a measure for COVID-19 control.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Memória Imunológica/imunologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Vacinas contra COVID-19/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Interferon gama/sangue , Vacinação
17.
Nat Commun ; 12(1): 4144, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230476

RESUMO

To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 64.3% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Receptores Virais/imunologia , SARS-CoV-2/imunologia , Adulto , Animais , Doadores de Sangue , COVID-19/terapia , Linhagem Celular , China , Chlorocebus aethiops , Convalescença , Feminino , Humanos , Imunidade Humoral/imunologia , Imunização Passiva , Memória Imunológica/imunologia , Estudos Longitudinais , Masculino , Fatores Sexuais , Glicoproteína da Espícula de Coronavírus/imunologia , Células Vero
18.
Front Immunol ; 12: 684014, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194438

RESUMO

T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4+ and CD8+ T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8+ T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8+ T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.


Assuntos
Anafilatoxinas/metabolismo , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/fisiopatologia , Progressão da Doença , ELISPOT , Feminino , Citometria de Fluxo , Humanos , Imunidade Humoral , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente
19.
PLoS One ; 16(7): e0253977, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214116

RESUMO

SARS-CoV-2 pandemic is causing high morbidity and mortality burden worldwide with unprecedented strain on health care systems. To investigate the time course of the antibody response in relation to the outcome we performed a study in hospitalized COVID-19 patients. As comparison we also investigated the time course of the antibody response in SARS-CoV-2 asymptomatic subjects. Study results show that patients produce a strong antibody response to SARS-CoV-2 with high correlation between different viral antigens (spike protein and nucleoprotein) and among antibody classes (IgA, IgG, and IgM and neutralizing antibodies). The antibody peak is reached by 3 weeks from hospital admission followed by a sharp decrease. No difference was observed in any parameter of the antibody classes, including neutralizing antibodies, between subjects who recovered or with fatal outcome. Only few asymptomatic subjects developed antibodies at detectable levels.


Assuntos
Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Infecções Assintomáticas , COVID-19/imunologia , SARS-CoV-2/imunologia , Idoso , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , COVID-19/mortalidade , Comorbidade , Feminino , Hospitalização , Humanos , Imunoglobulina A/biossíntese , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/biossíntese , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Estudos Retrospectivos
20.
Dtsch Med Wochenschr ; 146(13-14): 904-907, 2021 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-34256405

RESUMO

From an infectious disease perspective, there have been outstanding findings since January 2020 far beyond the knowledge gained about SARS-CoV, which hopefully will help us to manage future pandemics. Positive highlights include the increased public awareness of infectious disease epidemiology, the increase in immunological knowledge, and the successful use of existing vaccine development platforms and technologies. This article presents a personal selection of interesting developments in recent months.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/imunologia , Infectologia , SARS-CoV-2/imunologia , COVID-19/complicações , COVID-19/prevenção & controle , Humanos , Interferon Tipo I/sangue
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