scholarly journals Relative COVID-19 viral persistence and antibody kinetics

Author(s):  
Chung-Guei Huang ◽  
Ching-Tai Huang ◽  
Avijit Dutta ◽  
Pi-Yueh Chang ◽  
Mei-Jen Hsiao ◽  
...  

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.

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247797
Author(s):  
Renee L. Higgins ◽  
Stephen A. Rawlings ◽  
Jamie Case ◽  
Florence Y. Lee ◽  
Clarence W. Chan ◽  
...  

Since the initial identification of the novel coronavirus SARS-CoV-2 in December of 2019, researchers have raced to understand its pathogenesis and begun devising vaccine and treatment strategies. An accurate understanding of the body’s temporal immune response against SARS-CoV-2 is paramount to successful vaccine development and disease progression monitoring. To provide insight into the antibody response against SARS-CoV-2, plasma samples from 181 PCR-confirmed COVID-19 patients collected at various timepoints post-symptom onset (PSO) were tested for the presence of anti-SARS-CoV-2 IgM and IgG antibodies via lateral flow. Additionally, 21 donors were tracked over time to elucidate patient-specific immune responses. We found sustained levels of anti-SARS-CoV-2 antibodies past 130 days PSO, with 99% positivity observed at 31–60 days PSO. By 61–90 days PSO, the percentage of IgM-/IgG+ results were nearly equal to that of IgM+/IgG+ results, demonstrating a shift in the immune response with a decrease in IgM antibody levels. Results from this study not only provide evidence that the antibody response to COVID-19 can persist for over 4 months, but also demonstrates the ability of Easy Check™ to monitor seroconversion and antibody response of patients. Easy Check was sufficiently sensitive to detect antibodies in patient samples as early as 1–4 days PSO with 86% positivity observed at 5–7 days PSO. Further studies are required to determine the longevity and efficacy of anti-SARS-CoV-2 antibodies, and whether they are protective against re-infection.


2012 ◽  
Vol 56 (04) ◽  
pp. 337-342 ◽  
Author(s):  
KEE-BUM PARK ◽  
BYUNG-KWAN LIM ◽  
MICHAEL B. YE ◽  
SOO-YOUNG CHUNG ◽  
JAE-HWAN NAM

2021 ◽  
Author(s):  
Lela Kardava ◽  
Nicholas Rachmaninoff ◽  
William Lau ◽  
Clarisa Buckner ◽  
Krittin Trihemasava ◽  
...  

SARS-CoV-2 mRNA vaccines are highly effective, although weak antibody responses are seen in some individuals with correlates of immunity that remain poorly understood. Here we longitudinally dissected antibody, plasmablast, and memory B cell (MBC) responses to the two-dose Moderna mRNA vaccine in SARS-CoV-2-uninfected adults. Robust, coordinated IgA and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses, but earlier and more intensely after dose two. Distinct antigen-specific MBC populations also emerged post-vaccination with varying kinetics. We identified antigen non-specific pre-vaccination MBC and post-vaccination plasmablasts after dose one and their spike-specific counterparts early after dose two that correlated with subsequent antibody levels. These baseline and response signatures can thus provide early indicators of serological efficacy and explain response variability in the population.


2021 ◽  
Author(s):  
Yosuke Hirotsu ◽  
Toshiharu Tsutsui ◽  
Yumiko Kakizaki ◽  
Yoshihiro Miyashita ◽  
Fumiaki Iwase ◽  
...  

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.


2021 ◽  
Vol 8 ◽  
Author(s):  
Cun Liu ◽  
Yanhan Liu ◽  
Xiubo Li ◽  
Lin Liang ◽  
Shangjin Cui

In order to evaluate the pathogenicity of Senecavirus A (SVA) to weaned piglets preliminarily, 28-day-old weaned piglets were challenged with SVA by intramuscular injection. The clinical manifestations, antibody levels, and tissue viral load of infected piglets were detected. The results indicated that the piglets challenged with SVA CH/FuJ/2017 showed drowsiness, lameness, oral blisters, diarrhea, and other clinical signs. Lesions on the hooves were observed. Red spots or plaques were initially observed on the hoof and then developed into blisters that cracked and gradually formed scab. The symptoms and signs were relieved after 8 days post-infection (dpi). The sentinel piglet, feeding together with the challenged piglets, showed similar clinical signs with the challenged piglets after 3 dpi. Monitoring of antibody levels showed that anti-SVA antibody could be detected at 5 dpi by competition enzyme-linked immunosorbent assay (cELISA) method, and neutralizing antibody could be detected after 7 dpi. Analysis of viral tissue distribution and viral load indicated that SVA could replicate in the liver, spleen, lung, kidney, and lymph node. In all, Senecavirus disease was successfully replicated by SVA CH/FuJ/2017 isolate, which verified the clinical manifestations of SVA infection in weaned piglets, and provided a foundation for further SVA pathogenesis and vaccine development.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3132-3132
Author(s):  
Jianghua Wu ◽  
Heng Mei ◽  
Jianwei Li ◽  
Jingpeng Zhang ◽  
Lu Tang ◽  
...  

Abstract Background: As of early August 2021, more than 190 million people have developed coronavirus disease (COVID-19), a pandemic that has killed approximately 4 million people. Caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 exhibited a highly variable clinical course, ranging from a high proportion of asymptomatic and mild infections to severe and fatal disease. However, the immunological determinants underlying the heterogeneity of COVID-19 remain to be fully elucidated. Methods: To systemically analyze the immunopathogenesis of COVID-19, a multicompartment mathematical model based on both immunological principles and COVID-19-related work performed by the scientific community was built to illustrate the dynamics of host immunity after SARS-CoV-2 infection. We used ordinary differential equations (ODEs) to simulate the time-dependent functions of immunologic variations in the four compartments, which were draining lymph nodes, peripheral blood, lung and distant lymph nodes and spleen. Our model consisted of equations for 109 immunologic variations, which contained 223 parameters. K was used to characterize the adequacy of the SARS-CoV-2-specific naïve T/B cell pool; K I represented the hill coefficient of antigen-presenting cell (APC) differentiation. Further, we used method of pseudo landscape to visualize the effect of APC capacity and the SARS-CoV-2-specific naïve T/B cell pool on clinical outcomes. Results: Based on both immunologic knowledge and extensive COVID-19-related work performed by the scientific community, we constructed a knowledge-driven mathematical model that incorporated SARS-CoV-2 infection, bacterial infection, leukocyte chemotaxis, innate immunity and adaptive immunity. The model simulated and predicted the different trajectories of the viral load, bacterial load, immune cells, cytokines and infected epithelial cells in patients with different severities. A higher viral load and longer virus-shedding period were observed in patients with higher severity, along with an increase in SARS-CoV-2-infected lung epithelial cells. The trajectories of both peripheral blood IL-6 and lymphocytes predicted COVID-19 outcomes. Based on the distribution, trafficking and differentiation of immune cells after SARS-CoV-2 infection, we proposed that early-stage lymphopenia is related to lymphocyte chemotaxis. The delayed initiation of both innate and adaptive immunity resulted in elevated SARS-CoV-2 shedding and was a pivotal cause of COVID-19 severity. Spatiotemporally, viral shedding and postviral bacterial infection evoked stronger innate immunity. Viral shedding could be restrained by the rapid initiation of APC, antibody-secreting cell (ASC) and cytotoxic T cell (CTL). Moreover, our model predicted that the insufficient SARS-CoV-2-specific naïve T/B cell pools and inactive APC caused a series of chain reactions, including viral shedding, bacterial infection, sepsis and cytokine storms. Finally, pseudopotential analysis revealed that a high state characterized by severe bacterial infections and cytokine storms was a stable attractor for patients with insufficient SARS-CoV-2-specific naïve T/B cells and inactive APC (Figure 1). Conclusion: Overall, our analysis provided a comprehensive view of the dynamics of host immunity after SARS-CoV-2 infection and highlighted that the antigen-specific naïve T/B cell pool and APC ability may essentially determine COVID-19 heterogeneity from an immunological standpoint. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


Parasitology ◽  
1999 ◽  
Vol 118 (6) ◽  
pp. 635-639 ◽  
Author(s):  
P. NIE ◽  
D. HOOLE

The humoral antibody response and the number of pronephric antibody-secreting cells were examined in naturally Bothriocephalus acheilognathi-infected carp. Cyprinus carpio, and in those injected intraperitoneally with an extract of the cestode. In the extract-injected fish, specific antibody was detected 3 weeks after a second injection given 2 weeks after the primary injection, and antibody levels persisted for more than 200 days. A third injection also enhanced the antibody level in the extract-injected carp. The numbers of antibody-secreting cells were significantly higher in carp injected 3 times with the extract than in the control. In naturally-infected fish, the serum antibody levels and the number of pronephric antibody-secreting cells were higher in infected fish than in uninfected individuals although this difference was not statistically significant. The relevance of these results to immune protection against infection is discussed.


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