Impact of Treatment Regimens on Antibody Response to the SARS-CoV-2 Coronavirus

The coronavirus disease 2019 (COVID-19) is widely spread and remains a global pandemic. Limited evidence on the systematic evaluation of the impact of treatment regimens on antibody responses exists. Our study aimed to analyze the role of antibody response on prognosis and determine factors influencing the IgG antibodies’ seroconversion. A total of 1,111 patients with mild to moderate COVID-19 symptoms admitted to Leishenshan Hospital in Wuhan were retrospectively analyzed. A serologic SARS-CoV-2 IgM/IgG antibody test was performed on all the patients 21 days after the onset of symptoms. Patient clinical characteristics were compared. In the study, 42 patients progressed to critical illness, with 6 mortalities reported while 1,069 patients reported mild to moderate disease. Advanced age (P = 0.028), gasping (P < 0.001), dyspnea (P = 0.024), and IgG negativity (P = 0.006) were associated with progression to critical illness. The mortality rate in critically ill patients with IgG antibody was 6.45% (95% CI 1.12–22.84%) and 36.36% (95% CI 12.36–68.38%) in patients with no IgG antibody (P = 0.003). Symptomatic patients were more likely to develop IgG antibody responses than asymptomatic patients. Using univariable analysis, fever (P < 0.001), gasping (P = 0.048), cancer (P < 0.001), cephalosporin (P = 0.015), and chloroquine/hydroxychloroquine (P = 0.021) were associated with IgG response. In the multivariable analysis, fever, cancer, cephalosporins, and chloroquine/hydroxychloroquine correlated independently with IgG response. We determined that the absence of SARS-CoV-2 antibody IgG in the convalescent stage had a specific predictive role in critical illness progression. Importantly, risk factors affecting seropositivity were identified, and the effect of antimalarial drugs on antibody response was determined.

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Characterization of Anopheles gambiae D7 salivary proteins as markers of human–mosquito bite contact

Parasites & Vectors ◽

10.1186/s13071-021-05130-5 ◽

2022 ◽

Vol 15 (1) ◽

Author(s):

Brenda Oseno ◽

Faith Marura ◽

Rodney Ogwang ◽

Martha Muturi ◽

James Njunge ◽

...

Keyword(s):

Antibody Response ◽

Vector Control ◽

Anopheles Gambiae ◽

Control Strategies ◽

Antibody Responses ◽

Salivary Proteins ◽

Igg Antibody ◽

Biomarkers Of Exposure ◽

The Impact

Abstract Background Malaria is transmitted when infected Anopheles mosquitoes take a blood meal. During this process, the mosquitoes inject a cocktail of bioactive proteins that elicit antibody responses in humans and could be used as biomarkers of exposure to mosquito bites. This study evaluated the utility of IgG responses to members of the Anopheles gambiae D7 protein family as serological markers of human–vector contact. Methods The D7L2, D7r1, D7r2, D7r3, D7r4 and SG6 salivary proteins from An. gambiae were expressed as recombinant antigens in Escherichia coli. Antibody responses to the salivary proteins were compared in Europeans with no prior exposure to malaria and lifelong residents of Junju in Kenya and Kitgum in Uganda where the intensity of malaria transmission is moderate and high, respectively. In addition, to evaluate the feasibility of using anti-D7 IgG responses as a tool to evaluate the impact of vector control interventions, we compared responses between individuals using insecticide-treated bednets to those who did not in Junju, Kenya where bednet data were available. Results We show that both the long and short forms of the D7 salivary gland antigens elicit a strong antibody response in humans. IgG responses against the D7 antigens reflected the transmission intensities of the three study areas, with the highest to lowest responses observed in Kitgum (northern Uganda), Junju (Kenya) and malaria-naïve Europeans, respectively. Specifically, the long form D7L2 induced an IgG antibody response that increased with age and that was lower in individuals who slept under a bednet, indicating its potential as a serological tool for estimating human–vector contact and monitoring the effectiveness of vector control interventions. Conclusions This study reveals that D7L2 salivary antigen has great potential as a biomarker of exposure to mosquito bites and as a tool for assessing the efficacy of vector control strategies such as bednet use. Graphical abstract

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Generation of Antibody Responses to Pneumococcal Capsular Polysaccharides Is Independent of CD1 Expression in Mice

Infection and Immunity ◽

10.1128/iai.01091-08 ◽

2009 ◽

Vol 77 (5) ◽

pp. 1976-1980 ◽

Cited By ~ 4

Author(s):

Leen Moens ◽

Axel Jeurissen ◽

Stefan Nierkens ◽

Louis Boon ◽

Luc Van Kaer ◽

...

Keyword(s):

Antibody Response ◽

The Elderly ◽

Immunoglobulin M ◽

Antibody Responses ◽

Capsular Polysaccharides ◽

Wild Type ◽

Igg Antibody ◽

Antibody Treatment ◽

Serious Infection ◽

Protection Against Infection

ABSTRACT Streptococcus pneumoniae is a bacterial microorganism that frequently causes serious infection, particularly in children and the elderly. Protection against infection with S. pneumoniae is based mainly on the generation of antibodies to the pneumococcal capsular polysaccharides (caps-PS), but the mechanisms responsible for the generation of anticapsular antibodies remain incompletely understood. The aim of the present study was to evaluate the role of CD1-restricted T cells in the antibody response to caps-PS. When immunized with Pneumo23, wild-type mice and CD1 knockout mice on BALB/c and C57BL/6 backgrounds generated immunoglobulin M (IgM) and IgG antibody responses to soluble caps-PS that were comparable. Similar results were obtained after immunization with heat-inactivated S. pneumoniae. The IgM and IgG antibody response of wild-type mice to Pneumo23 was not affected by an antagonizing monoclonal anti-CD1 antibody treatment. In summary, our data provide evidence that the antibody response to caps-PS is generated independently of CD1 expression.

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The evaluation of factors affecting antibody response after administration of the BNT162b2 vaccine: a prospective study in Japan

PeerJ ◽

10.7717/peerj.12316 ◽

2021 ◽

Vol 9 ◽

pp. e12316

Author(s):

Toshiya Mitsunaga ◽

Yuhei Ohtaki ◽

Yutaka Seki ◽

Masakata Yoshioka ◽

Hiroshi Mori ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Antibody Response ◽

Prospective Study ◽

Antibody Titer ◽

Logistic Regression Analysis ◽

Multivariate Logistic Regression Analysis ◽

Antibody Test ◽

Antibody Responses ◽

Multivariate Logistic Regression

The aim of this study was to evaluate the antibody reaction after administration of the BNT162b2 vaccine, and to reveal the factors that affect antibody production. This prospective study was carried out in the Association of EISEIKAI Medical and Healthcare Corporation Minamitama Hospital, in Tokyo, Japan, from April 15, 2021 to June 09, 2021. All our hospital’s workers who were administered the BNT162b2 vaccine as part of a routine program were included in this study. We calculated the anti-SARS-CoV-2 spike-specific antibody titter (1) before vaccination, (2) 7 to 20 days after the first vaccination, and (3) A total of 7 to 20 days after the second vaccination. The low-antibody titer group (LABG) was defined as the group having less than 25 percentiles of antibody titer. Univariate and Multivariate logistic regression analysis were performed to ascertain the effects of factors on the likelihood of LABG. A total of 374 participants were eventually included in our study, and they were divided into 94 LABG and 280 non-LABG. All samples showed significant antibody elevation in the second antibody test, with a mean value of 3,476 U/mL. When comparing the LABG and non-LABG groups, the median age, blood sugar, and HbA1c were significantly higher in the LABG group. The rates of participants with low BMI (<18.5) and high BMI (>30) were significantly higher in the LABG group. The proportion of chronic lung disease, hypertension, diabetes, dyslipidemia, autoimmune disease, and cancer were significantly higher in the LABG group. Although there was no significant difference confirmed with respect to the exercise hours per day, the proportion of participants that did not perform outdoor exercises was significantly higher in the LABG group. The time interval between the second vaccination and the second antibody test, and between the first and the second vaccination was significantly longer in the non-LABG group. In the multivariate logistic regression analysis, older than 60 years, the past history of hypertension, HbA1c higher than 6.5%, and lack of outdoor exercises were significant suppressors of antibody responses, whereas the length of days from the first to the second vaccination longer than 25 days promoted a significant antibody response. Again, our single-center study demonstrates that older than 60 years, hypertension, HbA1c higher than 6.5%, and lack of outdoor exercises were significant suppressors of antibody responses, whereas the length of days from the first to the second vaccination longer than 25 days promoted a significant antibody response. Evidence from multi-center studies is needed to develop further vaccination strategies.

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Significantly Low Levels of IgG Antibodies Against Oncogenic Merkel Cell Polyomavirus in Sera From Females Affected by Spontaneous Abortion

Frontiers in Microbiology ◽

10.3389/fmicb.2021.789991 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chiara Mazziotta ◽

Giulia Pellielo ◽

Mauro Tognon ◽

Fernanda Martini ◽

John Charles Rotondo

Keyword(s):

Antibody Response ◽

Spontaneous Abortion ◽

Viral Infections ◽

Merkel Cell Polyomavirus ◽

Enzyme Linked Immunosorbent Assay ◽

Merkel Cell ◽

Igg Antibodies ◽

Igg Antibody ◽

The Impact

Merkel cell polyomavirus (MCPyV) is a small DNA tumor virus ubiquitous in humans. MCPyV establishes a clinically asymptomatic lifelong infection in healthy immunocompetent individuals. Viral infections are considered to be risk factors for spontaneous abortion (SA), which is the most common adverse complication of pregnancy. The role of MCPyV in SA remains undetermined. Herein, the impact of MCPyV infection in females affected by SA was investigated. Specifically, an indirect enzyme-linked immunosorbent assay (ELISA) method with two linear synthetic peptides/mimotopes mimicking MCPyV antigens was used to investigate immunoglobulin G (IgG) antibodies against MCPyV in sera from 94 females affected by SA [mean ± standard deviation (SD) age 35 ± (6) years] and from 96 healthy females undergoing voluntary pregnancy interruption [VI, mean (±SD) age 32 ± (7) years]. MCPyV seroprevalence and serological profiles were analyzed. The overall prevalence of serum IgG antibodies against MCPyV was 35.1% (33/94) and 37.5% (36/96) in SA and VI females, respectively (p > 0.05). Notably, serological profile analyses indicated lower optical densities (ODs) in females with SA compared to those undergoing VI (p < 0.05), thus indicating a reduced IgG antibody response in SA females. Circulating IgGs were identified in sera from SA and VI females. Our immunological findings indicate that a relatively reduced fraction of pregnant females carry serum anti-MCPyV IgG antibodies, while SA females presented a more pronounced decrease in IgG antibody response to MCPyV. Although yet to be determined, this immunological decrease might prompt an increase in MCPyV multiplication events in females experiencing abortive events. The role of MCPyV in SA, if present, remains to be determined.

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SELECTIVE ROLES OF THYMUS-DERIVED LYMPHOCYTES IN THE ANTIBODY RESPONSE

Journal of Experimental Medicine ◽

10.1084/jem.140.1.239 ◽

1974 ◽

Vol 140 (1) ◽

pp. 239-252 ◽

Cited By ~ 67

Author(s):

Tomio Tada ◽

Toshitada Takemori

Keyword(s):

T Cells ◽

B Cells ◽

Antibody Response ◽

Suppressive Effect ◽

Antibody Responses ◽

Cell Transfer ◽

Spleen Cells ◽

Igg Antibody ◽

Igm Antibody

Passively transferred thymocytes and spleen cells from donors primed with keyhole limpet hemocyanin (KLH) exerted differential suppressive effect on IgM and IgG antibody responses of syngeneic recipients immunized with DNP-KLH depending primarily on the time when KLH-primed cells were transferred. This was demonstrated by the decrease in the numbers of DNP-specific direct and indirect PFC in the spleen of the recipients given KLH-primed cells at different times during primary and secondary immunization. Whereas the cell transfer simultaneously with or 2 days after the primary immunization produced only slight suppression of the peak IgM antibody response, it caused profound suppression of late IgM and IgG antibody responses. By contrast, the cell transfer 3 days after the immunization produced immediate suppression of the ongoing IgM antibody response resulting in its earlier termination, while being unable to prevent the induction of IgG antibody response. KLH-primed cells could moderately suppress the secondary anti-DNP antibody response, in which IgG antibody response was found to be slightly more sensitive than IgM antibody response to the suppressive influence of KLH-primed cells. The suppressive effect of the KLH-primed spleen cells was completely eliminated by the in vitro treatment of the cells with anti-θ and C before cell transfer, indicating that cells responsible for the suppression are, in fact, T cells. The suppression of DNP-specific antibody response by KLH-primed T cells was achieved only if the recipients were immunized with DNP-KLH but not with DNP-heterologous carrier, suggesting that direct interaction between T and B cells is necessary for the suppression of the antibody response. It is concluded that susceptibility of B cells to the specific suppressive influence of T cells is inherently different depending on the differentiation stage of B cells and on the immunoglobulin class they are destined to produce.

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Antibody Responses against Enterovirus Proteases are Potential Markers for an Acute Infection

Viruses ◽

10.3390/v12010078 ◽

2020 ◽

Vol 12 (1) ◽

pp. 78

Author(s):

Niila V. V. Saarinen ◽

Virginia M. Stone ◽

Minna M. Hankaniemi ◽

Magdalena A. Mazur ◽

Tytti Vuorinen ◽

...

Keyword(s):

Antibody Response ◽

Respiratory Infections ◽

Acute Infection ◽

Diagnostic Odds Ratio ◽

Antibody Responses ◽

Structural Proteins ◽

Igg Antibody ◽

Potential Marker ◽

Igm Elisa ◽

Immunological Assays

Background: Enteroviruses are a group of common non-enveloped RNA viruses that cause symptoms ranging from mild respiratory infections to paralysis. Due to the abundance of enterovirus infections it is hard to distinguish between on-going and previous infections using immunological assays unless the IgM fraction is studied. Methods: In this study we show using Indirect ELISA and capture IgM ELISA that an IgG antibody response against the nonstructural enteroviral proteins 2A and 3C can be used to distinguish between IgM positive (n = 22) and IgM negative (n = 20) human patients with 83% accuracy and a diagnostic odds ratio of 30. Using a mouse model, we establish that the antibody response to the proteases is short-lived compared to the antibody response to the structural proteins in. As such, the protease antibody response serves as a potential marker for an acute infection. Conclusions: Antibody responses against enterovirus proteases are shorter-lived than against structural proteins and can differentiate between IgM positive and negative patients, and therefore they are a potential marker for acute infections.

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SARS-CoV-2 IgG antibody responses in rt-PCR positive cases: first report from India

10.1101/2020.11.13.20229716 ◽

2020 ◽

Author(s):

Girish Chandra Dash ◽

Debaprasad Parai ◽

Hari Ram Choudhary ◽

Annalisha Peter ◽

Usha Kiran Rout ◽

...

Keyword(s):

Antibody Response ◽

Infected Individual ◽

Antibody Responses ◽

Rt Pcr ◽

Serum Samples ◽

Igg Antibody ◽

Ct Value ◽

Significant Difference ◽

The Mean ◽

The Relationship

AbstractThe SARS-CoV-2 antibody responses remain poorly understood and the clinical utility of serological testing is still unclear. As it is thought to confer some degree of immunity, this study is carried out to know the relationship between demographics and ct value of confirmed rt-PCR patients. A total of 384 serum samples were collected between 4-6 weeks after confirmed SARS-CoV-2 infection. IgG positivity was found to be 80.2% (95% CI, 76.2 – 84.2). The IgG positivity increased with the decrease in the ct value, with highest of 87.6% positivity in individuals with <20 ct value. The mean (± SD) ct value of IgG positives and og IgG negatives was 23.34 (± 6.09) and 26.72 (± 7.031) respectively. There was no significant difference found between the demographic characteristics such as age, sex, symptoms and antibody response. The current study is first of its kind wherein we have assessed the correlation of ct of RT-PCR with development of IgG against SARS-CoV-2. Our study showed that although Ct value might not have any relation with severity of the diseases but is associated with the antibody response among the SARS-CoV-2 infected individual.

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The Effect of Chronic and Inhospital Exposure to Renin-Angiotensin System Inhibitors on the Outcome and Inflammatory State of Coronavirus Disease 2019 Adult Inpatients

International Journal of Hypertension ◽

10.1155/2021/5517441 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Pedro Gaspar ◽

Inês Parreira ◽

Pedro Antunes Meireles ◽

Filipe Bessa ◽

Virgílio Dias Silva ◽

...

Keyword(s):

Inflammatory Response ◽

Invasive Mechanical Ventilation ◽

Multivariable Analysis ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin ◽

Icu Admission ◽

Risk Of Death ◽

Asymptomatic Patients ◽

The Impact

Background. Controversies exist about the effect of renin-angiotensin system inhibitors (RASi) on coronavirus disease 2019 (COVID-19) outcome. The inhospital use of RASi and its effect on inflammatory sate are still poorly studied during the COVID-19 pandemic. Objectives. We aimed to compare the impact of previous and inhospital RASi exposure on the outcome and inflammatory response of COVID-19 patients. Methods. Single-centre, ambispective analysis of hospitalized adult COVID-19 patients at Hospital de Santa Maria, Lisbon, between March and August 2020 was performed. We excluded asymptomatic patients and those admitted due to another disease. The primary outcome was inhospital all-cause mortality. Illness severity was assessed based on the development of acute respiratory distress syndrome/acute lung injury (ARDS/ALI), intensive care unit (ICU) admission, and need for invasive mechanical ventilation (IMV). We used C-reactive protein (CRP), ferritin, and interleukin 6 (IL-6) as surrogate markers of the inflammatory response. Results. From a total of 432 patients, 279 were selected, among whom 133 (47.7%) were receiving a RASi. Chronic treatment with RASi was not associated with the risk of death (OR 1.24, 95% CI 0.66–2.31, p = 0.500 ), ARDS/ALI development (OR 1.12, 95% CI 0.67–1.86, p = 0.676 ), ICU admission (OR 1.11, 95% CI 0.67–1.84, p = 0.686), and IMV need (OR 1.03, 95% CI 0.58–1.84, p = 0.917 ) in a univariable and multivariable analysis. Inhospital RASi withdrawing was associated with the risk of death (OR 4.38, 95% CI 1.11–17.21, p = 0.035 ) and ARDS/ALI development (OR 4.33, 95% CI 1.49–12.6, p = 0.007 ), the latter remaining significant after adjustment. Previous exposure to RASi was associated with lower CRP levels at admission ( p = 0.018 ). IL-6 levels were significantly higher in those patients whose RASi were stopped ( p = 0.024 ). Conclusion. Previous and inhospital exposure to RASi was not associated with mortality nor severity of COVID-19. This study supports current guidance on RASi management during the COVID-19 pandemic.

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Detection of Anti-SARS-CoV-2-S2 IgG Is More Sensitive Than Anti-RBD IgG in Identifying Asymptomatic COVID-19 Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.724763 ◽

2021 ◽

Vol 12 ◽

Author(s):

Baolin Liao ◽

Zhao Chen ◽

Peiyan Zheng ◽

Linghua Li ◽

Jianfen Zhuo ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Early Time ◽

Antibody Responses ◽

Structural Proteins ◽

Antibody Detection ◽

Igg Antibody ◽

Detection Scheme ◽

Asymptomatic Patients ◽

Asymptomatic Infections ◽

And Control

Characterizing the serologic features of asymptomatic SARS-CoV-2 infection is imperative to improve diagnostics and control of SARS-CoV-2 transmission. In this study, we evaluated the antibody profiles in 272 plasma samples collected from 59 COVID-19 patients, consisting of 18 asymptomatic patients, 33 mildly ill patients and 8 severely ill patients. We measured the IgG against five viral structural proteins, different isotypes of immunoglobulins against the Receptor Binding Domain (RBD) protein, and neutralizing antibodies. The results showed that the overall antibody response was lower in asymptomatic infections than in symptomatic infections throughout the disease course. In contrast to symptomatic patients, asymptomatic patients showed a dominant IgG-response towards the RBD protein, but not IgM and IgA. Neutralizing antibody titers had linear correlations with IgA/IgM/IgG levels against SARS-CoV-2-RBD, as well as with IgG levels against multiple SARS-CoV-2 structural proteins, especially with anti-RBD or anti-S2 IgG. In addition, the sensitivity of anti-S2-IgG is better in identifying asymptomatic infections at early time post infection compared to anti-RBD-IgG. These data suggest that asymptomatic infections elicit weaker antibody responses, and primarily induce IgG antibody responses rather than IgA or IgM antibody responses. Detection of IgG against the S2 protein could supplement nucleic acid testing to identify asymptomatic patients. This study provides an antibody detection scheme for asymptomatic infections, which may contribute to epidemic prevention and control.

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Dynamics of the Magnitude, Breadth and Depth of the Antibody Response at Epitope Level Following Dengue Infection

Frontiers in Immunology ◽

10.3389/fimmu.2021.686691 ◽

2021 ◽

Vol 12 ◽

Author(s):

Francesca Falconi-Agapito ◽

Karen Kerkhof ◽

Xiomara Merino ◽

Johan Michiels ◽

Marjan Van Esbroeck ◽

...

Keyword(s):

Antibody Response ◽

Acute Phase ◽

Dengue Infection ◽

Public Health Problem ◽

Antibody Responses ◽

Major Public Health Problem ◽

Serum Samples ◽

Igg Antibody ◽

Time Points ◽

Secondary Infections

Dengue is a major public health problem in tropical and sub-tropical regions worldwide. Since the Zika epidemic and the increased co-circulation of other arboviruses, the serology-based diagnosis of dengue has become more problematic due to the high antigenic resemblance, especially among the flavivirus family. Therefore, a more comprehensive understanding of the diversity, specificity and temporal evolution of the antibody response following dengue infection is needed. In order to close this knowledge gap, we used a high-density peptide microarray of 9,072 linear peptides covering the entire proteome diversity of dengue, Zika, yellow fever and chikungunya viruses. The IgM and IgG antibody responses were measured against the designed microarray in symptomatic dengue infected individuals from an arbovirus endemic area in Peru and in overseas travelers returning to Belgium, as representatives of multiple-exposed and primary infections, respectively. Serum samples were collected longitudinally across four time points over the period of six months in Peru and over two time points in travelers. We show that epitopes eliciting the strongest flavivirus cross-reactive antibodies, in both primary and secondary infections were concentrated in the capsid, E, NS1, NS3 and NS5 proteins. The IgG antibody responses against NS1 and NS3 followed a rise-and-fall pattern, with peak titers between two to four weeks after onset of illness. The response to the E and NS5 proteins increased rapidly in the acute phase and was maintained at stable levels until at least 6 months after illness. A more scattered IgM antibody reactivity across the viral proteome was observed in the acute phase of the disease and that persisted through the 6-month window. The magnitude, breadth (i.e. number of unique epitopes targeted) and depth (i.e. number of epitope variants recognized) of the IgG response was higher in secondary infections compared to primary infections. For IgM antibodies, the magnitude of the response was higher in primary infected individuals whereas the breadth and depth of the response was lower in this group compared with the endemic subjects. Finally, through this arboviral proteome-wide epitope mapping, we were able to identify IgM and IgG dengue-specific epitopes which can be useful serological markers for dengue diagnosis and serostatus determination.

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