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1.
Lancet ; 396(10250): 535-544, 2020 08 22.
Article in English | MEDLINE | ID: covidwho-2106188

ABSTRACT

BACKGROUND: Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level. METHODS: 35 883 households were selected from municipal rolls using two-stage random sampling stratified by province and municipality size, with all residents invited to participate. From April 27 to May 11, 2020, 61 075 participants (75·1% of all contacted individuals within selected households) answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors, received a point-of-care antibody test, and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay. Prevalences of IgG antibodies were adjusted using sampling weights and post-stratification to allow for differences in non-response rates based on age group, sex, and census-tract income. Using results for both tests, we calculated a seroprevalence range maximising either specificity (positive for both tests) or sensitivity (positive for either test). FINDINGS: Seroprevalence was 5·0% (95% CI 4·7-5·4) by the point-of-care test and 4·6% (4·3-5·0) by immunoassay, with a specificity-sensitivity range of 3·7% (3·3-4·0; both tests positive) to 6·2% (5·8-6·6; either test positive), with no differences by sex and lower seroprevalence in children younger than 10 years (<3·1% by the point-of-care test). There was substantial geographical variability, with higher prevalence around Madrid (>10%) and lower in coastal areas (<3%). Seroprevalence among 195 participants with positive PCR more than 14 days before the study visit ranged from 87·6% (81·1-92·1; both tests positive) to 91·8% (86·3-95·3; either test positive). In 7273 individuals with anosmia or at least three symptoms, seroprevalence ranged from 15·3% (13·8-16·8) to 19·3% (17·7-21·0). Around a third of seropositive participants were asymptomatic, ranging from 21·9% (19·1-24·9) to 35·8% (33·1-38·5). Only 19·5% (16·3-23·2) of symptomatic participants who were seropositive by both the point-of-care test and immunoassay reported a previous PCR test. INTERPRETATION: The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial proportion of people with symptoms compatible with COVID-19 did not have a PCR test and at least a third of infections determined by serology were asymptomatic. These results emphasise the need for maintaining public health measures to avoid a new epidemic wave. FUNDING: Spanish Ministry of Health, Institute of Health Carlos III, and Spanish National Health System.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Antibodies, Viral/blood , Betacoronavirus/immunology , COVID-19 , Child , Child, Preschool , Female , Humans , Immunoassay , Immunoglobulin G/blood , Immunoglobulin M/blood , Infant , Infant, Newborn , Male , Middle Aged , Pandemics , Point-of-Care Testing , Prevalence , Risk Factors , SARS-CoV-2 , Seroepidemiologic Studies , Spain/epidemiology , Young Adult
2.
Acta Biochim Biophys Sin (Shanghai) ; 54(4): 556-564, 2022 Apr 25.
Article in English | MEDLINE | ID: covidwho-1862958

ABSTRACT

Age has been found to be one of the main risk factors for the severity and outcome of COVID-19. However, differences in SARS-CoV-2 specific antibody responses among COVID-19 patients of different age groups remain largely unknown. In this study, we analyzed the IgG/IgM responses to 21 SARS-CoV-2 proteins and 197 peptides that fully cover the spike protein against 731 sera collected from 731 COVID-19 patients aged from 1 to We show that there is no overall difference in SARS-CoV-2 antibody responses in COVID-19 patients in the 4 age groups. By antibody response landscape maps, we find that the IgG response profiles of SARS-CoV-2 proteins are positively correlated with age. The S protein linear epitope map shows that the immunogenicity of the S-protein peptides is related to peptide sequence, disease severity and age of the COVID-19 patients. Furthermore, the enrichment analysis indicates that low S1 IgG responses are enriched in patients aged <50 and high S1 IgG responses are enriched in mild COVID-19 patients aged >60. In addition, high responses of non-structural/accessory proteins are enriched in severe COVID-19 patients aged >70. These results suggest the distinct immune response of IgG/IgM to each SARS-CoV-2 protein in patients of different age, which may facilitate a deeper understanding of the immune responses in COVID-19 patients.


Subject(s)
Age Factors , Antibody Formation , COVID-19 , Aged , Antibodies, Viral/blood , COVID-19/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Middle Aged , Peptides , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
3.
J Transl Med ; 20(1): 129, 2022 03 16.
Article in English | MEDLINE | ID: covidwho-1745447

ABSTRACT

Autoimmunity has emerged as a characteristic of the post-COVID syndrome (PCS), which may be related to sex. In order to further investigate the relationship between SARS-CoV-2 and autoimmunity in PCS, a clinical and serological assessment on 100 patients was done. Serum antibody profiles against self-antigens and infectious agents were evaluated by an antigen array chip for 116 IgG and 104 IgM antibodies. Thirty pre-pandemic healthy individuals were included as a control group. The median age of patients was 49 years (IQR: 37.8 to 55.3). There were 47 males. The median post-COVID time was 219 (IQR: 143 to 258) days. Latent autoimmunity and polyautoimmunity were found in 83% and 62% of patients, respectively. Three patients developed an overt autoimmune disease. IgG antibodies against IL-2, CD8B, and thyroglobulin were found in more than 10% of the patients. Other IgG autoantibodies, such as anti-interferons, were positive in 5-10% of patients. Anti-SARS-CoV-2 IgG antibodies were found in > 85% of patients and were positively correlated with autoantibodies, age, and body mass index (BMI). Few autoantibodies were influenced by age and BMI. There was no effect of gender on the over- or under-expression of autoantibodies. IgG anti-IFN-λ antibodies were associated with the persistence of respiratory symptoms. In summary, autoimmunity is characteristic of PCS, and latent autoimmunity correlates with humoral response to SARS-CoV-2.


Subject(s)
Autoimmunity , COVID-19 , Adult , Antibodies, Viral/blood , Humans , Immunoglobulin M/blood , Male , Middle Aged , SARS-CoV-2
6.
J Med Virol ; 94(4): 1711-1716, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1718398

ABSTRACT

The persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is a matter of importance regarding the coronavirus disease 19 (COVID-19) pandemic. To observe antibody dynamics, 105 blood donors, positive for SARS-CoV-2 antibodies by a lateral flow test within a seroprevalence study, were included in this study. Thirty-nine (37%) of 105 the donors were confirmed positive by a total Ig Wantai enzyme-linked immunosorbent assay (ELISA). Three (8%) in this group of 39 reported severe and 26/39 (67%) mild to moderate COVID-19 symptoms. By further ELISA-testing, 33/39 (85%) donors were initially positive for IgG antibodies, 31/39 (79%) for IgA, and 32/39 (82%) for IgM, while 27/39 (69%) were positive for all three isotypes. Persistence of IgG, IgA, and IgM was observed in 73%, 79%, and 32% of donors, respectively, after 6-9 months of observation. For IgM antibodies, the decline in the proportion of positive donors was statistically significant (p = 0.002) during 12 months observation, for IgG only the decline at 3 months was statistically significant (p = 0.042). Four donors exhibited notable increases in antibody levels. In conclusion, persistent SARS-CoV-2 IgA antibodies and IgG antibodies at 6-9 months are present in approximately three of four individuals with previous mild to moderate COVID-19.


Subject(s)
Antibodies, Viral/blood , Blood Donors/statistics & numerical data , COVID-19/immunology , SARS-CoV-2/immunology , Adult , COVID-19/blood , COVID-19/epidemiology , Denmark/epidemiology , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Kinetics , Male , Reinfection/blood , Reinfection/epidemiology , Reinfection/immunology , Seroepidemiologic Studies , Severity of Illness Index , Young Adult
7.
Microbiol Spectr ; 10(1): e0084521, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1709405

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the stimulatory levels of cellular-mediated immunity, which plays an essential role in controlling SARS-CoV-2 infection. In fact, several studies have shown the association of lymphopenia with severe COVID-19 in patients. The aim of this study is to investigate the response of the immune system, including cell-mediated immunity and antibody production, during different stages of SARS-CoV-2 infection. Peripheral blood and serum samples were collected from patients with moderate infection, patients under medication (hospitalized), patients who had recovered, and healthy individuals (n = 80). Flow cytometry analysis was performed on peripheral blood samples to determine the cellular immunity profile of each patient. The data showed a significant reduction in the levels of CD3+, CD4+, and CD8+ T cells and CD45+ cells in the moderate and under-medication groups, suggesting lymphopenia in those patients. Also, enzyme-linked immunosorbent assay (ELISA) was conducted on the serum samples to measure the levels of antibodies, including IgM and IgG, in each patient. The results revealed a significant increase in the levels of IgM in the moderate infection and under-medication patients, thus indicating the production of IgM during the first week of infection. Furthermore, changes in the levels of IgG were significantly detected among recovered patients, indicating therefore a remarkable increase during the recovery stage of SARS-CoV-2 infection and thus a strong humoral-mediated immunity. In summary, the results of this study may help us to understand the main role of the cellular immune responses, including CD3+, CD4+, and CD8+ T cells, against SARS-CoV-2 infection. This understanding might support the development of SARS-CoV-2 treatments and vaccines in the near future. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 in China. This virus is a serious threat to people not only in China but also worldwide, where it has been detected in over 222 countries. It has been reported that ∼3.4% of SARS-CoV-2-infected patients have died. The significance of our study relies on the fact that an enzyme-linked immunosorbent assay and flow cytometry were used to measure the levels of antibodies and cellular immune response, respectively, from clinical samples of patients infected with SARS-CoV-2.


Subject(s)
CD3 Complex/blood , CD4-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/cytology , COVID-19/immunology , Immunoglobulin G/blood , Immunoglobulin M/blood , Adult , Aged , Aged, 80 and over , COVID-19/blood , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Humans , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Young Adult
8.
Nat Commun ; 13(1): 915, 2022 02 17.
Article in English | MEDLINE | ID: covidwho-1703249

ABSTRACT

Quantitative or qualitative differences in immunity may drive clinical severity in COVID-19. Although longitudinal studies to record the course of immunological changes are ample, they do not necessarily predict clinical progression at the time of hospital admission. Here we show, by a machine learning approach using serum pro-inflammatory, anti-inflammatory and anti-viral cytokine and anti-SARS-CoV-2 antibody measurements as input data, that COVID-19 patients cluster into three distinct immune phenotype groups. These immune-types, determined by unsupervised hierarchical clustering that is agnostic to severity, predict clinical course. The identified immune-types do not associate with disease duration at hospital admittance, but rather reflect variations in the nature and kinetics of individual patient's immune response. Thus, our work provides an immune-type based scheme to stratify COVID-19 patients at hospital admittance into high and low risk clinical categories with distinct cytokine and antibody profiles that may guide personalized therapy.


Subject(s)
Antibodies, Viral/blood , COVID-19/pathology , Cytokines/blood , SARS-CoV-2/immunology , Severity of Illness Index , Aged , Coronavirus Nucleocapsid Proteins/immunology , Disease Progression , Female , Hospitalization , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Immunophenotyping/methods , Machine Learning , Male , Middle Aged , Phosphoproteins/immunology
9.
PLoS One ; 17(2): e0262911, 2022.
Article in English | MEDLINE | ID: covidwho-1700320

ABSTRACT

BACKGROUND: COVID-19 pandemic resulted in about 165 million infections and 3.4 million deaths all over the world across 15 months. The most severe clinical presentation of COVID-19 diseases is interstitial pneumonia. METHODS: In this paper we describe clinical outcomes based on radiological features as well as the pattern of haematochemical parameters and IgG/IgM antibodies in 75 patients hospitalized due to COVID-related interstitial pneumonia not requiring intensive care assistance. Each patient underwent routine laboratory tests, including inflammatory markers and coagulation profile at baseline. Computed Tomography (CT) was performed at baseline and after 3 months to assess the persistence of radiological sequelae. A Generalized Linear Model (GLM) was used to test for each patient the association between individual haematochemical parameters at the time of hospital admission and the subsequent radiological features after three months. The presence of IgG antibodies was quantitatively determined in 70 patients at the time of hospital admission and after 3 months. A subgroup of 49 and 21 patients underwent additional dosage of IgG after 6 and 12 months, respectively. IgM serological antibodies were available for 17 patients at baseline and 61 at T3, with additional follow-up for 51 and 20 subjects after 6 and 12 months, respectively. RESULTS: Only 28 out of 75 patients discharged from the hospital were totally healed after 3 months, while 47 patients (62.7%) still presented radiological sequelae. According to the GLM model, specific haematochemical baseline parameters-such as IL-6, GPT, platelets and eosinophil count-showed a statistically significant association with the presence of radiological sequelae at month 3 highlighting an OR = 0.5, thus meaning that subjects completely healed after 3 months presented half levels of IL-6 at baseline compared to patients with sequelae. In general, IgG serum levels were always higher than IgM at the time of hospitalization (75% at T0; n = 12 out of 16 patients with data available in both visits), after 3 months (72.1%; n = 44 out of 61 pts.), after 6 months (56.8%; 25 out of 44 pts.), and one year after hospitalization (60%; 12 out of 20 pts.). Overall, IgG and IgM serum levels presented a statistically significant decreasing trend from the baseline to month 3, 6 and 12. One patient presented an increase in IgM between baseline and month 3 but negative PCR test for SARS-COV2 on throat swab. CONCLUSIONS: As supported by our findings on 75 patients, COVID-related interstitial pneumonia triggers early IgG levels (higher than IgM) that gradually decrease over 12 months. Mid-term sequelae are still detectable at lung Computed Tomography after 3 months from the hospital admission. Occasionally, it is possible to observe increase of IgM levels in presence of low concentrations of IgG and negative PCR ELISA tests for SARS-COV2 RNA. Baseline levels of IL-6 could be proposed as predictor of radiological mid/long-term sequelae after COVID-related interstitial pneumonia.


Subject(s)
Antibodies, Viral/blood , COVID-19 , Hospitalization , Immunoglobulin G/blood , Immunoglobulin M/blood , Interleukin-6/blood , SARS-CoV-2/metabolism , Tomography, X-Ray Computed , Adult , COVID-19/blood , COVID-19/drug therapy , COVID-19/therapy , Female , Follow-Up Studies , Humans , Male
10.
Front Immunol ; 13: 821218, 2022.
Article in English | MEDLINE | ID: covidwho-1690442

ABSTRACT

We analyzed the serum from COVID-19 patients and vaccinated subjects, and found that the specific IgA titer level could be used to assist COVID-19 diagnosis, especially in China.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Immunoglobulin A/blood , SARS-CoV-2/immunology , COVID-19 Vaccines/immunology , China , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood
11.
Front Immunol ; 13: 829665, 2022.
Article in English | MEDLINE | ID: covidwho-1686487

ABSTRACT

Background: Understanding the long-term kinetic characteristics of SARS-CoV-2 antibodies and the impact of inactivated vaccines on SARS-CoV-2 antibodies in convalescent patients can provide information for developing and improving vaccination strategies in such populations. Methods: In this cohort, 402 convalescent patients who tested positive for SARS-CoV-2 by RT-PCR from 1 January to 22 June 2020 in Jiangsu, China, were enrolled. The epidemiological data included demographics, symptom onset, and vaccination history. Blood samples were collected and tested for antibody levels of specific IgG, IgM, RBD-IgG, S-IgG, and neutralizing antibodies using a the commercial magnetic chemiluminescence enzyme immunoassay. Results: The median follow-up time after symptom onset was 15.6 months (IQR, 14.6 to 15.8). Of the 402 convalescent patients, 44 (13.84%) received an inactivated vaccine against COVID-19. A total of 255 (80.19%) patients were IgG-positive and 65 (20.44%) were IgM-positive. The neutralizing antibody was 83.02%. Compared with non-vaccinated individuals, the IgG antibody levels in vaccinated people were higher (P=0.007). Similarly, antibody levels for RBD-IgG, S-IgG, and neutralizing antibodies were all highly increased in vaccinated individuals (P<0.05). IgG levels were significantly higher after vaccination than before vaccination in the same population. IgG levels in those who received 'single dose and ≥14d' were similar to those with two doses (P>0.05). Similar conclusions were drawn for RBD-IgG and the neutralizing antibody. Conclusion: 15.6 months after symptom onset, the majority of participants remained positive for serum-specific IgG, RBD-IgG, S-IgG, and neutralizing antibodies. For convalescent patients, a single dose of inactivated vaccine against COVID-19 can further boost antibody titres.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Child , China , Cohort Studies , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , SARS-CoV-2/immunology , Vaccines, Inactivated/immunology , Young Adult
12.
Lett Appl Microbiol ; 74(6): 863-872, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1685383

ABSTRACT

Flow cytometry has emerged as a promising technique for detection of SARS-CoV-2 antibodies. In this study, we developed an innovative strategy for simultaneous detection of immunoglobulin G (IgG), IgM and IgA. The SARS-CoV-2 nucleocapsid protein was covalently bound to functional beads surface applying sulpho-SMCC chemistry. BUV395 anti-IgG, BB515 anti-IgM, biotinylated anti-IgA1/IgA2 and BV421 streptavidin were used as fluorophore conjugated secondary antibodies. Serum and antibodies reaction conditions were optimized for each antibody isotype detection and a multiplexed detection assay was developed. This new cell-free assay efficiently discriminate COVID-19 negative and positive samples. The simultaneous detection of IgG, IgM and IgA showed a sensitivity of 88·5-96·2% and specificity of 100%. This novel strategy opens a new avenue for flow cytometry-based diagnosis.


Subject(s)
Antibodies, Viral , COVID-19 , SARS-CoV-2 , Antibodies, Viral/blood , COVID-19/diagnosis , Flow Cytometry , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Nucleocapsid Proteins , SARS-CoV-2/immunology , Sensitivity and Specificity
13.
Front Immunol ; 13: 811952, 2022.
Article in English | MEDLINE | ID: covidwho-1674342

ABSTRACT

Numerous studies have suggested that the titers of antibodies against SARS-CoV-2 are associated with the COVID-19 severity, however, the types of antibodies associated with the disease maximum severity and the timing at which the associations are best observed, especially within one week after symptom onset, remain controversial. We attempted to elucidate the antibody responses against SARS-CoV-2 that are associated with the maximum severity of COVID-19 in the early phase of the disease, and to investigate whether antibody testing might contribute to prediction of the disease maximum severity in COVID-19 patients. We classified the patients into four groups according to the disease maximum severity (severity group 1 (did not require oxygen supplementation), severity group 2a (required oxygen supplementation at low flow rates), severity group 2b (required oxygen supplementation at relatively high flow rates), and severity group 3 (required mechanical ventilatory support)), and serially measured the titers of IgM, IgG, and IgA against the nucleocapsid protein, spike protein, and receptor-binding domain of SARS-CoV-2 until day 12 after symptom onset. The titers of all the measured antibody responses were higher in severity group 2b and 3, especially severity group 2b, as early as at one week after symptom onset. Addition of data obtained from antibody testing improved the ability of analysis models constructed using a machine learning technique to distinguish severity group 2b and 3 from severity group 1 and 2a. These models constructed with non-vaccinated COVID-19 patients could not be applied to the cases of breakthrough infections. These results suggest that antibody testing might help physicians identify non-vaccinated COVID-19 patients who are likely to require admission to an intensive care unit.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/blood , COVID-19/blood , SARS-CoV-2/immunology , Severity of Illness Index , Antibody Formation/immunology , COVID-19/immunology , COVID-19/pathology , COVID-19 Vaccines/immunology , Coronavirus Nucleocapsid Proteins/immunology , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Machine Learning , Protein Domains/immunology , Spike Glycoprotein, Coronavirus/immunology , Time Factors , Vaccination
14.
Sci Rep ; 12(1): 1885, 2022 02 03.
Article in English | MEDLINE | ID: covidwho-1671623

ABSTRACT

At-home sampling is key to large scale seroprevalence studies. Dried blood spot (DBS) self-sampling removes the need for medical personnel for specimen collection but facilitates specimen referral to an appropriately accredited laboratory for accurate sample analysis. To establish a highly sensitive and specific antibody assay that would facilitate self-sampling for prevalence and vaccine-response studies. Paired sera and DBS eluates collected from 439 sero-positive, 382 sero-negative individuals and DBS from 34 vaccine recipients were assayed by capture ELISAs for IgG and IgM antibody to SARS-CoV-2. IgG and IgM combined on DBS eluates achieved a diagnostic sensitivity of 97.9% (95%CI 96.6 to 99.3) and a specificity of 99.2% (95% CI 98.4 to 100) compared to serum, displaying limits of detection equivalent to 23 and 10 WHO IU/ml, respectively. A strong correlation (r = 0.81) was observed between serum and DBS reactivities. Reactivity remained stable with samples deliberately rendered inadequate, (p = 0.234) and when samples were accidentally damaged or 'invalid'. All vaccine recipients were sero-positive. This assay provides a secure method for self-sampling by DBS with a sensitivity comparable to serum. The feasibility of DBS testing in sero-prevalence studies and in monitoring post-vaccine responses was confirmed, offering a robust and reliable tool for serological monitoring at a population level.


Subject(s)
Antibodies, Viral/blood , COVID-19 Testing/methods , COVID-19/diagnosis , COVID-19/epidemiology , Dried Blood Spot Testing/methods , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Specimen Handling/methods , Biomarkers/blood , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Feasibility Studies , Female , Humans , Male , Sensitivity and Specificity , Seroepidemiologic Studies
15.
Nat Microbiol ; 7(3): 423-433, 2022 03.
Article in English | MEDLINE | ID: covidwho-1671570

ABSTRACT

Elucidating the dynamics of the neutralizing antibody (nAb) response in coronavirus disease 2019 (COVID-19) convalescents is crucial in controlling the pandemic and informing vaccination strategies. Here we measured nAb titres across 411 sequential plasma samples collected during 1-480 d after illness onset or laboratory confirmation (d.a.o.) from 214 COVID-19 convalescents, covering the clinical spectrum of disease and without additional exposure history after recovery or vaccination against SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. Forty-eight samples were also tested for neutralizing activities against the circulating variants using pseudotyped neutralization assay. Results showed that anti-RBD IgG and MN titres peaked at ~120 d.a.o. and subsequently declined, with significantly reduced nAb responses found in 91.67% of COVID-19 convalescents (≥50% decrease in current MN titres compared with the paired peak MN titres). Despite this decline, majority of the COVID-19 convalescents maintained detectable anti-RBD IgG and MN titres at 400-480 d.a.o., with undetectable neutralizing activity found in 14.41% (16/111) of the mild and 50% (5/10) of the asymptomatic infections at 330-480 d.a.o. Persistent antibody-dependent immunity could provide protection against circulating variants after one year, despite significantly decreased neutralizing activities against Beta, Delta and Mu variants. In conclusion, these data show that despite a marked decline in neutralizing activity over time, nAb responses persist for up to 480 d in most convalescents of symptomatic COVID-19, whereas a high rate of undetectable nAb responses was found in convalescents from asymptomatic infections.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/physiology , Adolescent , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Asymptomatic Infections/epidemiology , COVID-19/blood , COVID-19/epidemiology , COVID-19/virology , Child , Child, Preschool , Cohort Studies , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Male , Middle Aged , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Young Adult
16.
PLoS One ; 17(1): e0262897, 2022.
Article in English | MEDLINE | ID: covidwho-1662441

ABSTRACT

This study investigated the performance of a rapid point-of-care antibody test, the BioMedomics COVID-19 IgM/IgG Rapid Test, in comparison with a high-quality, validated, laboratory-based platform, the Roche Elecsys Anti-SARS-CoV-2 assay. Serological testing was conducted on 709 individuals. Concordance metrics were estimated. Logistic regression was used to assess associations with seropositivity. SARS-CoV-2 seroprevalence was 63.5% (450/709; 95% CI 59.8%-67.0%) using the BioMedomics assay and 71.9% (510/709; 95% CI 68.5%-75.2%) using the Elecsys assay. There were 60 discordant results between the two assays, all of which were seropositive in the Elecsys assay, but seronegative in the BioMedomics assay. Overall, positive, and negative percent agreements between the two assays were 91.5% (95% CI 89.2%-93.5%), 88.2% (95% CI 85.1%-90.9%), and 100% (95% CI 98.2%-100%), respectively, with a Cohen's kappa of 0.81 (95% CI 0.78-0.84). Excluding specimens with lower (Elecsys) antibody titers, the agreement improved with overall, positive, and negative percent concordance of 94.4% (95% CI 92.3%-96.1%), 91.8% (95% CI 88.8%-94.3%), and 100% (95% CI 98.2%-100%), respectively, and a Cohen's kappa of 0.88 (95% CI 0.85-0.90). Logistic regression confirmed better agreement with higher antibody titers. The BioMedomics COVID-19 IgM/IgG Rapid Test demonstrated good performance in measuring detectable antibodies against SARS-CoV-2, supporting the utility of such rapid point-of-care serological testing to guide the public health responses and vaccine prioritization.


Subject(s)
COVID-19 Serological Testing , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/isolation & purification , Adult , COVID-19/blood , COVID-19/genetics , COVID-19/virology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Point-of-Care Testing , Qatar , SARS-CoV-2/pathogenicity , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/genetics , Young Adult
17.
Nat Commun ; 13(1): 446, 2022 01 25.
Article in English | MEDLINE | ID: covidwho-1655574

ABSTRACT

Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS.


Subject(s)
Antibodies, Viral/immunology , COVID-19/complications , COVID-19/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Viral/blood , COVID-19/blood , COVID-19/diagnosis , Cohort Studies , Cough/blood , Cough/complications , Cough/immunology , Dyspnea/blood , Dyspnea/complications , Dyspnea/immunology , Fatigue/blood , Fatigue/complications , Fatigue/immunology , Female , Fever/blood , Fever/complications , Fever/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , ROC Curve , SARS-CoV-2/physiology
18.
Nat Med ; 26(6): 845-848, 2020 06.
Article in English | MEDLINE | ID: covidwho-1641979

ABSTRACT

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.


Subject(s)
Antibodies, Viral/blood , Antibody Formation/drug effects , Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adult , Aged , Antibody Formation/immunology , Antiviral Agents/therapeutic use , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/immunology , Coronavirus Infections/virology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Pandemics/prevention & control , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2
19.
Nat Commun ; 13(1): 320, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1632529

ABSTRACT

Pregnant women represent a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Here we show that SARS-CoV-2 infection during pregnancy primarily induces unique inflammatory responses at the maternal-fetal interface, which are largely governed by maternal T cells and fetal stromal cells. SARS-CoV-2 infection during pregnancy is also associated with humoral and cellular immune responses in the maternal blood, as well as with a mild cytokine response in the neonatal circulation (i.e., umbilical cord blood), without compromising the T-cell repertoire or initiating IgM responses. Importantly, SARS-CoV-2 is not detected in the placental tissues, nor is the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and emphasizes the rarity of placental infection.


Subject(s)
COVID-19/immunology , Immunity/immunology , Infectious Disease Transmission, Vertical , Placenta/immunology , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , Adult , COVID-19/blood , COVID-19/virology , Cytokines/blood , Cytokines/immunology , Cytokines/metabolism , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Infant, Newborn , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/virology , RNA, Viral/genetics , RNA, Viral/metabolism , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Young Adult
20.
Microbiol Spectr ; 10(1): e0118121, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1632412

ABSTRACT

To fight severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), mass vaccination has begun in many countries. To investigate the usefulness of a serological assay to predict vaccine efficacy, we analyzed the levels of IgG, IgM, and IgA against the receptor-binding domain (RBD) of SARS-CoV-2 in the sera from BNT162b2 vaccinated individuals in Japan. This study included 219 individuals who received two doses of BNT162b2. The levels of IgG, IgM, and IgA against RBD were measured by enzyme-linked immunosorbent assay before and after the first and second vaccination, respectively. The relationship between antibody levels and several factors, including age, gender, and hypertension were analyzed. Virus-neutralizing activity in sera was measured to determine the correlation with the levels of antibodies. A chemiluminescent enzyme immunoassay (CLEIA) method to measure IgG against RBD was developed and validated for the clinical setting. The levels of all antibody isotypes were increased after vaccination. Among them, RBD-IgG was dramatically increased after the second vaccination. The IgG levels in females were significantly higher than in males. There was a negative correlation between age and IgG levels in males. The IgG levels significantly correlated with the neutralizing activity. The CLEIA assay measuring IgG against RBD showed a reliable performance and a high correlation with neutralizing activity. Monitoring of IgG against RBD is a powerful tool to predict the efficacy of SARS-CoV-2 vaccination and provides useful information in considering a personalized vaccination strategy for COVID-19. IMPORTANCE Mass vaccination campaigns using mRNA vaccines against SARS-CoV-2 have begun in many countries. Serological assays to detect antibody production may be a useful tool to monitor the efficacy of SARS-CoV-2 vaccination in individuals. Here, we reported the induction of antibody isotype responses after the first and second dose of the BNT162b2 vaccine in a well-defined cohort of employees in Japan. We also reported that age, gender, and hypertension are associated with differences in antibody response after vaccination. This study not only provides valuable information with respect to antibody responses after BNT162b2 vaccination in the Japanese population but also the usefulness of serological assays for monitoring vaccine efficacy in clinical laboratories to determine a personalized vaccination strategy for COVID-19.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , Adult , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Japan , Male , Middle Aged , Neutralization Tests , Vaccines, Synthetic/immunology , Young Adult , /immunology
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