scholarly journals Active immunization by COVID-19 mRNA vaccine results in rapid antibody response and virus reduction in breakthrough infection by Delta (B.1.617.2)

2021 ◽  
Author(s):  
Yosuke Hirotsu ◽  
Toshiharu Tsutsui ◽  
Yumiko Kakizaki ◽  
Yoshihiro Miyashita ◽  
Fumiaki Iwase ◽  
...  
Keyword(s):  
Viral Load ◽  
Antibody Response ◽  
Viral Antigen ◽  
Severe Disease ◽  
High Viral Load ◽  
Active Immunization ◽  
Breakthrough Infection ◽  
Serological Data ◽  
Antibody Levels ◽  
Rapid Antibody

Abstract Vaccination is expected to suppress COVID-19 infection. However, breakthrough infections have increased following vaccination because of the spread of variants of concern, notably Delta (B.1.617.2 lineage). Virological and serological data pertaining to post-vaccination infections are limited. Here, we conducted genome analysis determined the viral lineages that infected patients following vaccination. Changes in viral load, antibody levels, and viral antigen levels following infection were analyzed. At the time of infection, Delta-infected patients had a 6.2-fold and 12.3-fold higher viral load compared with Alpha and other lineages, respectively. Viral lineages (Delta:Alpha:Other) of infection were 0:12:0 in the fully vaccinated group, 1:11:0 in the partially vaccinated group, 9:16:0 in the shortly after vaccination group, and 254:229:165 in the unvaccinated group. Breakthrough infections occurred regardless of retention of high antibody titers following vaccination. At the time of diagnosis, Delta-infected patients showed high viral load with or without vaccination. However, no fully vaccinated patients developed severe disease, and the rapid increase in anti-spike antibodies occurred approximately 1 week after onset of symptoms. Concomitantly, a decrease in viral antigen levels was observed in fully vaccinated patients, shortening the time to negative result by approximately 2 days compared with unvaccinated patients. Collectively, even if breakthrough infection occurs, the rapid antibody response in fully vaccinated individuals contributes to prevention of severe disease, possibly because of suppression of viral replication.

scholarly journals Evaluation of Antibody Response in Sows after Vaccination with Senecavirus A Vaccine and the Effect of Maternal Antibody Transfer on Antibody Dynamics in Offspring

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1066
Author(s):  
Fan Yang ◽  
Zixiang Zhu ◽  
Huanan Liu ◽  
Weijun Cao ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Low Dose ◽  
Active Immunization ◽  
High Dose ◽  
Booster Immunization ◽  
Substantial Problem ◽  
Antibody Levels ◽  
And Control ◽  
Antibody Dynamics

Senecavirus A (SVA) is a newly porcine virus that has been detected in many countries since its first detection in pigs in Canada in 2007, and it remains endemic in many countries in Asia and America, which has become a substantial problem for the pig industry. Vaccination is a potentially effective strategy for the prevention and control of SVA infection. Our lab has developed a SVA vaccine candidate previously. In this study, the antibody response to the prepared vaccine in sows and their offspring was evaluated. Vaccination of sows with inactivated SVA vaccines during pregnancy elicited SVA-specific virus-neutralizing antibodies. Vaccination with a high dose of SVA vaccine followed a booster immunization contributed to a long-term duration of the persistence of maternally derived neutralizing antibodies (MDAs) in the milk of the sows (>14 days). In contrast, vaccination with a single low dose of SVA vaccine resulted in a short-term persistence of MDAs in the milk (2–7 days). The MDAs could be efficiently transferred from the sows to their offspring through the colostrum/milk but not the umbilical cord blood. The antibody titers and the duration of the persistence of MDAs in the offspring are highly associated with the antibody levels in the milk from the sows. Vaccination of sows with a booster dose of SVA vaccine resulted in a longer-lasting MDAs in their offspring (persisted for at least 90 days). However, vaccination with the single low dose of vaccine only brought about 42 days of MDAs persistence in their offspring. The effect of MDAs on active immunization with SVA vaccine in offspring was further evaluated, which showed that vaccination of the SVA vaccine in the presence of MDAs at the titer of ≈1:64 or less could overcome the MDAs’ interference and give rise to effective antibody response. This will help for establishing the optimal times and schedules for SVA vaccination in pigs.

scholarly journals Persistent pulmonary pathology after COVID-19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase-9

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tøri Vigeland Lerum ◽  
Niklas Nyboe Maltzahn ◽  
Pål Aukrust ◽  
Marius Trøseid ◽  
Katerina Nezvalova Henriksen ◽  
...  
Keyword(s):  
Viral Load ◽  
Matrix Metalloproteinase ◽  
Hospital Admission ◽  
Randomised Clinical Trial ◽  
High Viral Load ◽  
Chest Ct ◽  
Ct Findings ◽  
High Prevalence ◽  
Negative Effect ◽  
Antibody Levels

AbstractThe association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.

scholarly journals Viral load and antibody levels in patients with COVID-19

2021 ◽  
Vol 8 (3) ◽  
pp. 010-018
Author(s):  
Iva Christova ◽  
Iva Trifonova ◽  
Teodora Gladnishka ◽  
Elena Dragusheva ◽  
Georgi Popov ◽  
...  
Keyword(s):  
Viral Load ◽  
High Viral Load ◽  
Igg Antibodies ◽  
Rt Pcr ◽  
Serum Samples ◽  
Weekly Basis ◽  
Specific Antibody Response ◽  
Viral Loads ◽  
Antibody Levels ◽  
Kinetics Of

Relations between viral load, antibody levels and COVID-19 severity are not well studied and results from such investigations are controversial. In this study, we investigated kinetics of viral load and antibody responses to SARS-CoV-2 in 20 patients with COVID-19 and analysed the association with disease severity. The patients were followed on weekly basis within the first month after the onset and then once per month for the next 4 months. Serum samples were tested for IgA, IgM, and IgG antibodies against SARS-CoV-2 using ELISA tests. SARS-CoV-2 viral load in nasopharyngeal swabs was measured by quantitative Realtime RT-PCR. For vast majority of the patients, the viral loads were at their highest levels at presentation and then declined gradually. Despite development of specific antibody response 7-11 days after the onset of COVID-19, SARS-CoV-2 RNA was still detected in nasopharyngeal swabs of most of the patients. There was no direct link between viral load and severity of COVID-19: some of mild and some of severe cases started with a high viral load. There was a relationship between the time from the onset of the disease and the viral load: the highest viral load was in the first days. In more severe cases, there was a tendency for slower reduction in viral load and longer detection of SARS-CoV-2 virus. Levels of the specific antibodies increased earlier and to higher levels and were present for longer time in patients with more severe manifestations of COVID-19 than in those with milder disease.

scholarly journals SARS-CoV-2 infectivity correlates with high viral loads and detection of viral antigen and is terminated by seroconversion

2021 ◽  
Author(s):  
Felix Buder ◽  
Markus Bauswein ◽  
Clara L Magnus ◽  
Franz Audebert ◽  
Henriette Lang ◽  
...  
Keyword(s):  
Viral Load ◽  
Symptom Onset ◽  
Viral Antigen ◽  
Virus Isolation ◽  
Point Of Care ◽  
High Viral Load ◽  
University Hospital ◽  
Public Health Perspective ◽  
Viral Loads ◽  
Restrictive Measures

Abstract Background From a public health perspective, effective containment strategies for SARS-CoV-2 should be balanced with individual liberties. Methods We collected 79 respiratory samples from 59 patients monitored in an outpatient center or in the intensive care unit of the University Hospital Regensburg. We analyzed viral load by quantitative real-time PCR, viral antigen by point-of-care assay, time since onset of symptoms and presence of SARS-CoV-2 IgG antibodies in the context of virus isolation from respiratory specimen. Results The odds ratio for virus isolation increased 1.9-fold for each log10 level of SARS-CoV-2 RNA and 7.4-fold with detection of viral antigen, while it decreased 6.3-fold beyond 10 days of symptoms and 20.0-fold with presence of SARS-CoV-2 antibodies. The latter was confirmed for B.1.1.7 strains. The positive predictive value for virus isolation was 60.0% for viral loads above 10 7 RNA copies/mL and 50.0% for the presence of viral antigen. Symptom onset before 10 days and seroconversion predicted lack of infectivity with 93.8% and 96.0%. Conclusions Our data support quarantining patients with high viral load and detection of viral antigen, and lifting restrictive measures with increasing time to symptom onset and seroconversion. Delay of antibody formation may prolong infectivity.

scholarly journals Relative COVID-19 viral persistence and antibody kinetics

2020 ◽  
Author(s):  
Chung-Guei Huang ◽  
Ching-Tai Huang ◽  
Avijit Dutta ◽  
Pi-Yueh Chang ◽  
Mei-Jen Hsiao ◽  
...  
Keyword(s):  
Viral Load ◽  
Antibody Response ◽  
B Cell ◽  
Vaccine Development ◽  
Cell Pool ◽  
Strong Antibody Response ◽  
Key Factor ◽  
The Absolute ◽  
Antibody Levels ◽  
Relative Persistence

AbstractImportanceThe COVID-19 antibody response is a critical indicator for evaluating immunity and also serves as the knowledge base for vaccine development. The picture is still not clear because of many limitations including testing tools, time of sampling, and the unclear impact of varying clinical status. In addition to these problems, antibody levels may not be equivalent to protective capacity.ObjectiveTo define the key factor for the different patterns of COVID-19 antibody response.DesignWe elucidated the antibody response with time-series throat and serum samples for viral loads and antibody levels, then used a neutralization test to evaluate protectiveness.SettingA medical center that typically cares for patients with moderate to severe diseases. Because of the low prevalence of COVID-19 in Taiwan and local government policy, however, we also admit COVID-19 patients with mild disease or even those without symptoms for inpatient care.ParticipantsRT-PCR-confirmed COVID-19 patients.ResultsWe found that only patients with relative persistence of virus at pharynx displayed strong antibody responses that were proportional to the pharyngeal viral load. They also had proportional neutralization titers per unit of serum. Although antibody levels decreased around 2 weeks after symptom onset, the neutralization efficacy per unit antibody remained steady and even continued to increase over time. The antibody response in patients with rapid virus clearance was weak, but the neutralization efficacy per unit antibody in these patients was comparable to those with persistent presence of virus. The deceased were with higher viral load, higher level of antibody, and higher neutralization titers in the serum, but the neutralization capacity per unit antibody is relatively low.Conclusions and RelevanceStrong antibody response depends on the relative persistence of the virus, instead of the absolute virus amount. The antibody response is still weak if large amount of virus is cleared quickly. The neutralization efficacy per unit antibody is comparable between high and low antibody patterns. Strong antibody response contains more inefficient and maybe even harmful antibodies. Low antibody response is also equipped with a capable B cell pool of efficient antibodies, which may expand with next virus encounter and confer protection.Key pointsQuestionThe key factor for the different “patterns” of COVID-19 antibody response.FindingsStrong antibody response depends on the relative persistence of the virus, instead of the absolute virus amount. The antibody response is still weak if large amount of virus is cleared quickly. The neutralization efficacy per unit antibody is comparable between high and low antibody patterns. High antibody level contains more inefficient antibodies.MeaningStrong response contains inefficient and maybe harmful antibodies. Low antibody response is also equipped with a capable B cell pool of efficient antibodies, which may expand with next virus encounter and confer protection.

scholarly journals Distinct SARS-CoV-2 antibody reactivity patterns elicited by natural infection and mRNA vaccination

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Rafael Assis ◽  
Aarti Jain ◽  
Rie Nakajima ◽  
Algis Jasinskas ◽  
Saahir Khan ◽  
...  
Keyword(s):  
Antibody Response ◽  
Orange County ◽  
Medical Center ◽  
Natural Infection ◽  
Severe Disease ◽  
Vaccination Campaign ◽  
Cross Reactivity ◽  
Before And After ◽  
Finger Stick ◽  
Antibody Levels

AbstractWe analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8476 finger stick blood specimens were collected before and after a vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing antigens from SARS-CoV-2, SARS, MERS, Common CoV, and Influenza. Twenty-six percent of specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive; out of 852 seropositive individuals 77 had symptoms and 9 sought medical care. The antibody response was predominantly against nucleocapsid (NP), full length, and S2 domain of spike. Anti-receptor binding domain (RBD) reactivity was low and not cross-reactive against SARS S1 or SARS RBD. A vaccination campaign at the University of California Irvine Medical Center (UCIMC) started on December, 2020 and 6724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% pre-vaccination to 79% post-vaccination in January, 93% in February, and 99% in March. mRNA vaccination induced higher antibody levels than natural exposure, especially against the RBD domain and cross-reactivity against SARS RBD and S1 was observed. Nucleocapsid protein antibodies can be used to distinguish vaccinees to classify pre-exposure to SARS-CoV-2 Previously infected individuals developed higher antibody titers to the vaccine than non pre-exposed individuals. Hospitalized patients in intensive care with severe disease reach significantly higher antibody levels than mild cases, but lower antibody levels compared to the vaccine. These results indicate that mRNA vaccination rapidly induces a much stronger and broader antibody response than SARS-CoV-2 infection.

scholarly journals Is Higher Viral Load in SARS-CoV-2 Associated With Death?

2020 ◽  
Author(s):  
Klinger Soares Faico-Filho ◽  
Victor Cabelho Passarelli ◽  
Nancy Bellei
Keyword(s):  
Cohort Study ◽  
Viral Load ◽  
Disease Severity ◽  
Prognostic Marker ◽  
Patient Outcomes ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Severe Disease ◽  
High Viral Load ◽  
Nasopharyngeal Swab

There is no proven prognostic marker or adequate number of studies in patients hospitalized for Coronavirus Disease-2019 (COVID-19). We conducted a retrospective cohort study of patients hospitalized with COVID-19 from March 14 to June 17, 2020, at Sao Paulo Hospital. SARS-CoV-2 viral load was assessed using the cycle threshold (Ct) values obtained from an RTPCR assay applied to the nasopharyngeal swab samples. Disease severity and patient outcomes were compared. Among the 875 patients, 50.1% (439/875) had mild, 30.4% (266/875) moderate, and 19.5% (170/875) severe disease. A Ct value of <25 (472/875) indicated a high viral load, which was independently associated with mortality (OR: 0,34; 95% CI: 0,217 to 0,533; p < 0.0001). Admission SARS-CoV-2 viral load is an important surrogate biomarker of infectivity and is independently associated with mortality among patients hospitalized with COVID-19.

scholarly journals Renal Injury in DENV-4 Fatal Cases: Viremia, Immune Response and Cytokine Profile

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 223
Author(s):  
Priscila Conrado Guerra Nunes ◽  
Lilimar da Silveira Rioja ◽  
Janice Mery Chicarino de Oliveira Coelho ◽  
Natália Gedeão Salomão ◽  
Kíssila Rabelo ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Load ◽  
Renal Injury ◽  
Mononuclear Cells ◽  
Tissue Injury ◽  
Severe Disease ◽  
Renal Involvement ◽  
High Viral Load ◽  
Renal Tissue ◽  
Cortical Region

Dengue virus (DENV) infections may result in asymptomatic cases or evolve into a severe disease, which involves multiple organ failure. Renal involvement in dengue can be potentially related to an increased mortality. Aiming to better understand the role of DENV in renal injury observed in human fatal cases, post-mortem investigations were performed in four DENV-4 renal autopsies during dengue epidemics in Brazil. Tissues were submitted to histopathology, immunohistochemistry, viral quantification, and characterization of cytokines and inflammatory mediators. Probably due the high viral load, several lesions were observed in the renal tissue, such as diffuse mononuclear infiltration around the glomerulus in the cortical region and in the medullary vessels, hyalinosis arteriolar, lymphocytic infiltrate, increased capsular fibrosis, proximal convoluted tubule (PCT) damage, edema, PCT debris formation, and thickening of the basal vessel membrane. These changes were associated with DENV-4 infection, as confirmed by the presence of DENV-specific NS3 protein, indicative of viral replication. The exacerbated presence of mononuclear cells at several renal tissue sites culminated in the secretion of proinflammatory cytokines and chemokines. Moreover, it can be suggested that the renal tissue injury observed here may have been due to the combination of both high viral load and exacerbated host immune response.

scholarly journals Elevated SARS-CoV-2 Antibodies Distinguish Severe Disease in Early COVID-19 Infection

2020 ◽  
Author(s):  
Natalie S. Haddad ◽  
Doan C. Nguyen ◽  
Merin E. Kuruvilla ◽  
Andrea Morrison-Porter ◽  
Fabliha Anam ◽  
...  
Keyword(s):  
Antibody Response ◽  
Severe Disease ◽  
Roc Curves ◽  
Multiplex Immunoassay ◽  
Specific Igg ◽  
Critical Patients ◽  
Antibody Levels ◽  
Kinetics Of

AbstractBackgroundSARS-CoV-2 has caused over 36,000,000 cases and 1,000,000 deaths globally. Comprehensive assessment of the multifaceted anti-viral antibody response is critical for diagnosis, differentiation of severe disease, and characterization of long-term immunity. Initial observations suggest that severe disease is associated with higher antibody levels and greater B cell/plasmablast responses. A multi-antigen immunoassay to define the complex serological landscape and clinical associations is essential.MethodsWe developed a multiplex immunoassay and evaluated serum/plasma from adults with RT-PCR-confirmed SARS-CoV-2 infections during acute illness (N=52) and convalescence (N=69); and pre-pandemic (N=106) and post-pandemic (N=137) healthy adults. We measured IgA, IgG, and/or IgM against SARS-CoV-2 Nucleocapsid (N), Spike domain 1 (S1), receptor binding domain (S1-RBD) and S1-N-terminal domain (S1-NTD).ResultsTo diagnose infection, the combined [IgA+IgG+IgM] or IgG for N, S1, and S1-RBD yielded AUC values −0.90 by ROC curves. From days 6-30 post-symptom onset, the levels of antigen-specific IgG, IgA or [IgA+IgG+IgM] were higher in patients with severe/critical compared to mild/moderate infections. Consistent with excessive concentrations of antibodies, a strong prozone effect was observed in sera from severe/critical patients. Notably, mild/moderate patients displayed a slower rise and lower peak in anti-N and anti-S1 IgG levels compared to severe/critical patients, but anti-RBD IgG and neutralization responses reached similar levels at 2-4 months.ConclusionThis SARS-CoV-2 multiplex immunoassay measures the magnitude, complexity and kinetics of the antibody response against multiple viral antigens. The IgG and combined-isotype SARS-CoV-2 multiplex assay is highly diagnostic of acute and convalescent disease and may prognosticate severity early in illness.One Sentence SummaryIn contrast to patients with moderate infections, those with severe COVID-19 develop prominent, early antibody responses to S1 and N proteins.

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