How long is antibody duration in Covid 19 ? / Antibodies

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Pre-existing anti-IFN autoantibodies may worsen COVID-19 in lupus patients

11/5/20


https://www.news-medical.net/news/20201 ... ients.aspx


Researchers from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have conducted a study showing that the presence of anti-interferon-alpha (IFN-α) autoantibodies among patients with systemic lupus erythematosus (SLE) may predispose these individuals to more severe disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes coronavirus disease 2019 (COVID-19).

The team says that SLE patients who developed COVID-19 had anti-IFN-α autoantibodies prior to infection, suggesting that the presence of these pre-existing autoantibodies might increase susceptibility to the virus.

Furthermore, SLE patients who had pre-existing autoantibodies were found to have higher rates of severe disease than those who did not.

“Our observations suggest that the presence of these autoantibodies may predispose SLE patients to infection with SARS-CoV-2 with a more severe presentation and represent an additional risk factor in this patient population,” write Sarthak Gupta and colleagues from the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Maryland.

Anti-IFNα autoantibodies could therefore be a useful prognostic factor for predicting which patients with SLE might develop COVID-19 and for guiding clinical decisions about the management of these patients, adds the team.

A pre-print version of the paper is available on the server medRxiv*, while the article undergoes peer review.

Type 1 IFNs play a key role in the immune response to viral infection


Type 1 IFNs, including IFNα, play important roles in both the innate and adaptive immune responses and are essential in the host defense against viral infection.

Defects in type 1 IFN signaling pathways are known to result in immunodeficiency and it has been suggested that dysregulation in the type I IFN pathway plays a key role in the pathogenesis of the autoimmune condition SLE.

Furthermore, anti-type 1 IFN autoantibodies have been reported in patients with SLE and have also been associated with life-threatening COVID-19 among the general population.

Together, these observations led Gupta and colleagues to hypothesize that SLE patients who carried anti-IFNα autoantibodies before COVID-19 became pandemic in 2020, might be at a higher risk of developing the disease. They also proposed that the presence of these autoantibodies could help to guide management and prevention strategies.

What did the researchers do?

The team investigated whether the presence of anti-IFNα autoantibodies prior to 2020 was associated with COVID-19 in patients with SLE.

The researchers studied SLE patients (aged 26 to 57 years) who had developed COVID-19 between April 1st and October 1st, 2020.

Biobanked plasma samples that had been taken from these SLE patients and 119 age-matched healthy controls prior to 2020 were tested for anti-IFNa autoantibodies by enzyme-linked immunosorbent assay (ELISA).

To test whether these anti-IFNα autoantibodies could block IFNα signaling, the team used flow cytometry to see if they could block the signal transducer and activator of transcription 1 (STAT1) phosphorylation following stimulation with recombinant human IFNα (rhIFNα) in vitro.

What did the study find?

Of the ten SLE patients studied, seven patients had mild to moderate COVID-19 symptoms that were managed in the home setting and three had severe symptoms requiring hospitalization and oxygen supplementation.

Four of the ten SLE patients (40%) had anti-IFNα autoantibodies and six (5%) of the healthy controls also tested positive for the autoantibodies.

Longitudinal assessment of the SLE samples confirmed that the autoantibodies had been present for up to three years prior to the diagnosis of COVID-19 (as far back as 2017).

SLE patients with pre-existing anti-IFNα autoantibodies had more severe COVID-19

Patients with SLE who had pre-existing anti-IFNα autoantibodies had more severe symptoms of COVID-19.

For example, the rate of hospitalization was higher among those with anti-IFNα autoantibodies (2 out of 4) than among those who did not have the autoantibodies (1 out of 6).

Among the four SLE patients who were positive for the autoantibodies, plasma samples from two (50%) of them were able to block the activity of IFNα in vitro, through neutralization of rhIFNα induced STAT1 phosphorylation.

None of the samples from the six SLE patients who did not have the autoantibodies or from the six healthy controls who did have the autoantibodies were able to inhibit this STAT1 phosphorylation by rhIFNα.

What are the clinical implications of the findings?


The researchers say the findings suggest that the presence of ant-IFNα autoantibodies may predispose SLE patients to infection with SARS-CoV-2 that has a more severe presentation and may represent an additional risk factor among this patient population.

“Anti-IFNα autoantibodies may be pathogenic and could prove to be a helpful prognostic marker to predict which SLE patient may develop COVID-19 and inform preventive measures and management of this subset of patients,” concludes the team.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Gupta S, et al. Association between anti-interferon-alpha autoantibodies and COVID-19 in systemic lupus erythematosus. medRxiv, 2020. doi: https://doi.org/10.1101/2020.10.29.20222000, https://www.medrxiv.org/content/10.1101 ... 20222000v1
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Re: How long is antibody duration in Covid 19 ? / Antibodies

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SARS-CoV-2 antibodies wane, depending on age, symptoms and ethnicity

11/8/20


https://www.news-medical.net/news/20201 ... icity.aspx


Researchers at the University of Oxford have conducted a study of UK healthcare workers showing how antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can wane over time, depending on age, previous symptoms and ethnicity.

SARS-CoV-2 is the agent responsible for the coronavirus disease 2019 (COVID-19) pandemic that continues to sweep the globe, threatening public health and devastating the economy.

The team’s longitudinal seroprevalence study of more than 3,200 healthcare workers found that immunoglobulin G (IgG) antibodies against the SARS-CoV-2 nucleocapsid protein waned within months, falling more quickly among young people and asymptomatic individuals.

The team also observed higher antibody titers and moderate evidence of longer antibody half-lives among Asian healthcare workers, compared with White healthcare workers.

“Relatively short-term antibody responses have two epidemiological consequences,” says Sheila Lumley and colleagues.

Firstly, seroprevalence testing could miss previous infections, particularly among younger people who had an asymptomatic or mild infection. Secondly, testing may be unable to determine whether SARS-CoV-2 has circulated historically, within a particular geographic region, for example.


“Antibody dynamics have significant implications for the course and management of pandemic,” say the researchers. “Ongoing longitudinal studies are required to determine the long-term kinetics of antibody-mediated response to SARS-CoV-2, and responses to re-exposure.”

A preprint version of the paper is available on the server medRxiv* server, while the article undergoes peer review.

Previous estimates of antibody duration vary

Antibodies against SARS-CoV-2, which are generally detectable within 1 to 3 weeks, can be assayed to help estimate the proportion of a population that has been exposed to or infected with the virus.

Serological responses can also provide some information about the risk and severity of future infection.

“Most epidemiological outbreak models assume that SARS-CoV-2 infection leads to the development of post-infection immunity for a defined duration,” writes Lumley and colleagues.

However, measurable IgG antibodies against SARS-CoV-2 antigens do not always develop following infection, and previous estimates of the duration of antibody responses vary.

What did the current study involve?

Now, Lumley and the team have presented findings from a longitudinal seroprevalence study of 3,217 UK healthcare workers who underwent quantitative serial measurements of IgG antibodies against SARS-CoV-2 nucleocapsid protein.

Polymerase chain reaction (PCR) testing and antibody testing were offered to both symptomatic workers (from March 27th onwards) and asymptomatic workers (from April 23rd onwards) by the Oxford University Hospitals NHS Foundation Trust across all four of its teaching hospitals in Oxfordshire, UK.

“39% of HCWs [healthcare workers] were asymptomatic throughout, and therefore our data also represent an important contribution to the literature, which to date has mainly focused on trajectories following symptomatic infection,” write the researchers.

A Bayesian statistical model was used to investigate the trajectory of SARS-CoV-2 IgG antibody levels and any association with age, ethnicity, previous symptoms and gender.

What did the study find?

Among this cohort of working-age healthcare workers (up to 69 years), antibody levels peaked 24 days following the first positive PCR test, before then beginning to fall.

“By following quantitative antibody responses, we could separately analyze changes in initial antibody levels and rates of waning,” says the team.

Among 452 IgG-seropositive healthcare workers tested over a median of 121 days, the estimated mean antibody half-life was 85 days and the estimated mean time until loss of seropositivity was 137 days.

Higher maximum IgG levels were correlated with longer estimated IgG half-lives (a slower fall in IgG over time).

Associations between antibody duration and age, ethnicity, symptoms


The team reports that older age was associated with higher maximum IgG titers and longer IgG half-lives.

“This study highlights that sero-epidemiological surveys performed several months into this pandemic are likely to underestimate prior exposure in younger adults, as they tend to lose detectable antibody faster,” says the researchers.

Healthcare workers of Asian ethnicity had higher maximum antibody levels, compared with their White counterparts, along with marginal evidence for longer antibody half-lives.

Prior self-reported symptoms were associated with a higher maximum antibody level, but not with changes in antibody half-lives.

No associations were observed between gender and maximum antibody levels or half-lives.

What are the implications of the study?


“We demonstrate that the half-life of SARS-CoV-2 anti-nucleocapsid IgG antibody responses in a cohort of adult HCWs [healthcare workers] is 85 days and varies between individuals by age, ethnicity and prior symptom history,” say Lumley and team.

“The extent and duration of immunity to SARS-CoV-2 infection following COVID-19 and its association with antibody titers remains a key question to be answered.”

The researchers point out that the durability of immunity following infection or vaccination will dictate the overall course of the current COVID-19 pandemic.

“Longitudinal cohorts with baseline immunology are required to determine immune correlates of protection, to determine whether measurement of the current antibody status is enough to infer whether an individual have functional immunity or not, whether waning IgG titers are representative of waning immune protection, or whether protection remains even after an individual seroreverts,” concludes the team.

*Important Notice


medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:


Lumley S, et al. The duration, dynamics and determinants of SARS-CoV-2 antibody responses in individual healthcare workers. medRxiv, 2020. doi: https://doi.org/10.1101/2020.11.02.20224824, https://www.medrxiv.org/content/10.1101 ... 20224824v1
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Re: How long is antibody duration in Covid 19 ? / Antibodies

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Pre-existing antibodies created during COVID-19 may protect children against new pandemic strain

11/9/20


https://www.news-medical.net/news/20201 ... train.aspx

Researchers at the Francis Crick Institute and University College London have found that some antibodies, created by the immune system during infection with common cold coronaviruses, can also target SARS-CoV-2 and may confer a degree of protection against the new viral strain.

In response to infection with a virus, the immune system creates antibodies to help fight it. These antibodies remain in the blood for a period after infection, and in the case of re-infection, they are able to tackle the virus again.

In their paper, published in Science today (Friday 6 November), the scientists found that some people, notably children, have antibodies reactive to SARS-CoV-2 in their blood, despite not ever having being infected with the virus.

These antibodies are likely the result of exposure to other coronaviruses, which cause a common cold and which have structural similarities with SARS-CoV-2.

The researchers made this discovery while developing highly sensitive antibody tests for COVID-19. To see how well their assay tests were performing, they compared the blood of patients with COVID-19 to patients who had not had the disease.

Surprisingly, they found that some people who had not been exposed to SARS-CoV-2 had antibodies in their blood which would recognize the virus.

To confirm their findings, they analysed over 300 blood samples collected before the pandemic, between 2011 and 2018.

Nearly all samples had antibodies that reacted with common cold coronaviruses, which was expected given how everyone has been exposed to these viruses at some point in their lives.

However, a small fraction of adult donors, about 1 in 20, also had antibodies that cross-reacted with SARS-CoV-2, and this was not dependent on recent infection with a common cold coronavirus.

Notably, such cross-reactive antibodies were found much more frequently in blood samples taken from children aged 6 to 16.

" Our results show that children are much more likely to have these cross-reactive antibodies than adults. More research is needed to understand why this is, but it could be down to children being more regularly exposed to other coronaviruses. These higher levels we observed in children could also help explain why they are less likely to become severely ill with COVID-19. There is no evidence yet, however, that these antibodies prevent SARS-CoV-2 infection or spread."

- Kevin Ng, Lead author and post-graduate student, Retroviral Immunology Laboratory at the Crick

In the lab, the researchers tested the antibodies they found in blood from uninfected people to confirm they are able to neutralize SARS-CoV-2. They found the cross-reactive antibodies target the S2 subunit of the spike protein on the surface of the virus.

" The spike of this coronavirus is made of two parts or subunits, performing different jobs. The S1 subunit allows the virus to latch onto cells and is relatively diverse among coronaviruses, whereas the S2 subunit lets the virus into cells and is more similar among these viruses. Our work shows that the S2 subunit is sufficiently similar between common cold coronaviruses and SARS-CoV-2 for some antibodies to work against both. It was previously thought that only antibodies to the S1 could block infection, but there is now good evidence that some antibodies to S2 can be just as effective. This is exciting as understanding the basis for this activity could lead to vaccines that work against a range of coronaviruses, including the common cold strains, as well as SARS-CoV-2 and any future pandemic strains. But it is important to stress that there are still many unknowns which require further research. For example, exactly how is immunity to one coronavirus modified by exposure to another? Or why does this activity decline with age? It is not the case that people who have recently had a cold should think they are immune to COVID-19."

A large study is now underway, in partnership with researchers at Imperial College London and University College London, to uncover the role that different antibodies and other immune defenses play in protection against COVID-19 and how severely ill people become.

Source:

The Francis Crick Institute

Journal reference:


Ng, K. W., et al. (2020) Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science. doi.org/10.1126/science.abe1107.
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Re: How long is antibody duration in Covid 19 ? / Antibodies

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Study of SARS-CoV-2 antibodies in >5,000 healthcare workers

11/9/20


https://www.news-medical.net/news/20201 ... rkers.aspx


The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the causative agent for coronavirus disease 2019 (COVID-19) – has claimed nearly 50,000 lives in the United Kingdom alone. The UK is now seeing a steep rise in cases once again as it experiences a ‘second wave’ of infections nationwide, with over 1.2 million confirmed COVID-19 cases overall. Controlling the transmission of the virus is vital to stem the tide of the pandemic.

While the common risk factors among the general population are well-described, the uncertainty and exposure of healthcare workers, who are at a higher risk of SARS-CoV-2 infection, are not explicitly known. Given the vital role that hospitals and their staff play in battling the virus and saving lives, understanding the risk factors at play for healthcare professionals and support staff will be crucial if the UK is to get on top of the pandemic.

The Study

To address this, Daniel J Cooper and his team of researchers conducted a prospective seroepidemiological study to systematically evaluate specific risk factors for healthcare workers. They used a SARS-CoV-2 immunoassay and analyzed the risk factors for seropositivity using multivariate logistic regression. This study enumerates the specific risk factors among healthcare workers. Their findings are available on the medRxiv* preprint server.

The prospective cohort in this study includes almost 6,000 healthcare workers at a large teaching hospital in the East of England. Of the 5,698 staff-tested, 410 turned positive (7·2% seroprevalence) for SARS-CoV-2 antibodies. The seroprevalence was higher in the healthcare workers who were working in designated COVID-19 areas.

It was found that the healthcare assistants and domestic and portering staff had significantly higher seroprevalence than other staff groups. For the first time, this study shows that healthcare assistants represent a key at-risk occupational group. This challenges previous findings that indicate significantly higher risk among nursing staff.

“Wider asymptomatic testing in healthcare facilities has the potential to reduce the spread of SARS-CoV-2 within hospitals, thereby reducing patient and staff risk and limiting spread between hospitals and into the wider community,” say the researchers.

This study was done after adjusting for age, sex, ethnicity and COVID-19 working location. Among the staff, the Black, Asian and minority ethnicities (BAME) individuals had a high risk of infection compared to the white staff, independent of their working area. The authors demonstrate that occupational factors alone do not account for all of the increased risks among this group. As occupational risks do not explain the increased and significant risk of COVID-19 amongst BAME staff, further evaluation is required to identify the cause.

Even though the seroprevalence among healthcare workers who do not work in areas with confirmed COVID-19 patients was only marginally higher than the general population, it suggests that an increased risk amongst healthcare workers arises through occupational exposure to confirmed cases.

The symptoms associated with seropositivity were loss of sense of taste or smell, fever and myalgia (pain in muscles). However, it is important to note that 31% of staff who tested positive reported no prior symptoms consistent with COVID-19. This emphasizes the contribution of infection transmission by an asymptomatically infected population.

To mitigate and reduce the risk of occupational SARS-CoV-2 infection, the factors aiding the risks need to be methodically identified. This study reports healthcare worker specific risk factors based entirely on seroprevalence data, identifying two main factors: increased risk when caring for confirmed COVID-19 cases and among those identifying as being within specific ethnic groups (BAME staff).

It is important to understand how population-level risk factors influence occupational risk in defined demographic groups.

Summing Up

The authors conclude that the risk of SARS-CoV-2 infection amongst healthcare workers is heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. And increased risk amongst BAME staff cannot be accounted for solely by occupational factors.

This study prioritizes efforts to reduce the risk of SARS-CoV-2 infection among healthcare workers; the meticulous focus is imperative. Hand hygiene, better access to high quality personal protective equipment (PPE), and frequent asymptomatic testing must be well-placed mechanisms for healthcare workers, the researchers argue.

As the UK is presently witnessing another surge in COVID-19 diagnoses, protecting healthcare workers by identifying risk factors for SARS-CoV-2 infection is paramount - this study is aligned towards this goal.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Cooper, Daniel J. (2020) A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital. medRxiv, doi: https://doi.org/10.1101/2020.11.03.20220699, https://www.medrxiv.org/content/10.1101 ... 20220699v1
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Re: How long is antibody duration in Covid 19 ? / Antibodies

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After SARS-CoV-2 antibodies fade B and T-cells persist

11/9/20


https://www.news-medical.net/news/20201 ... rsist.aspx


Amid the coronavirus disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is still unclear how long an immune response against SARS-CoV-2 lasts. Recent studies have shown that the immune response may last up to about four months, which could help in the development of potential vaccines against the virus.

Now, an international team of thirty researchers from Sweden, Italy, Germany, the USA, and China aimed to determine the longevity of the immune response against SARS-CoV-2, particularly the specific memory B-cell and T-cell responses over time in convalescent COVID-19 patients.

The team has found that the levels of specific Immunoglobulin M (IgM) and Immunoglobulin A (IgA) antibodies declined after one month. In contrast, specific Immunoglobulin G (IgG) levels remained stable for up to six months after infection. Further, the team detected anti-SARS-CoV-2 IgG antibodies in serum samples collected six to eight months after the onset of symptoms.

The study


The SARS-CoV-2 emerged in Wuhan City, China, in late December 2019. Since then, many developments have been made in finding out more about the virus, how it spreads, and if it induces a long-lasting immune response. However, it remains unclear whether the antibody titer is a marker for protective immunity against COVID-19.

A robust adaptive immune response and spike-specific neutralizing antibodies, circulating follicular helper T cells, and memory B cells have been detected in patients who recovered from COVID-19. It remains a mystery how long the adaptive immunity lasts after the natural infection.

To arrive at the study findings, which appeared on the pre-print server bioRxiv*, the researchers tested a cluster of patients from the Lombardy region, the hardest-hit region in the first wave pandemic in Italy. These patients experienced mild to critical illness due to COVID-19. Along with them are Swedish volunteers with mild symptoms.

The team detected the presence of elevated anti-spike (anti-S) and anti-receptor binding domain (anti-RBD) antibody levels over eight months. Also, specific memory B cell and T cell responses were evaluated in some patients.

What the team found

The research revealed that an anti-SARS-CoV-2 antibody response exists in most COVID-19 patients as early as two weeks after the start of their symptoms. Further, the level of anti-S and anti-RBD IgG remained stable for about six months after being diagnosed, followed by declining levels between six and eight months. However, the decline in anti-S and anti-RBD IgA and IgM levels were seen from one to three months after disease onset.

“Our results are in line with previous studies showing a similar longevity and pattern of anti-SARS-CoV-2 antibody response with antibody levels reaching a peak at 23 days following symptom onset and being maintained for at least 4 months,” the researchers explained.

The team also observed that men had higher anti-RBD IgG antibody titers, especially those who were more severely ill with COVID-19. Meanwhile, 7 percent of patients who developed severe illness did not develop or had an extremely low level of antibodies after being infected. This means that these patients’ immune systems exhibited a weaker response.

“The presence of high level of SARS-CoV-2 specific memory B and T cells in the majority of patients, 6- 8 months after infection, suggests that immunity after infection could be at least transiently protective and that development of long-term protective immunity through vaccination might be possible,” the researchers concluded.

Determining the longevity of the body’s immune response is crucial in the development of effective vaccines. With a longer immunity against SARS-CoV-2, the vaccines being developed will be more effective in inducing an immune response.

Currently, there are over 200 candidate vaccines against SARS-CoV-2. Of these, 47 are undergoing trials to test the vaccines’ efficacy and safety. Ten vaccines are in the last phase of human trials.

To date, there are have been over 50.8 million confirmed infections with SARS-CoV-2 worldwide, and at least 1.26 million deaths. More than 33.23 million have already recovered. However, a second wave of the outbreak is happening in many countries across the globe, which is likely to raise the numbers considerably in the coming weeks.

*Important Notice


bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Sources:

World Health Organization (WHO). (2020). https://www.who.int/publications/m/item ... e-vaccines
COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU) - https://gisanddata.maps.arcgis.com/apps ... 7b48e9ecf6

Journal reference:

Sherina, N., Piralla, A., Du, L. et al. (2020). Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection. bioRxiv. https://www.biorxiv.org/content/10.1101 ... 6.371617v1
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Identifying SARS-CoV-2 spike protein mutations resistant to antibodies

11/10/20


https://www.news-medical.net/news/20201 ... odies.aspx


Using a set of different monoclonal antibodies, researchers determined different mutations in the SARS-CoV-2 spike protein that leads to resistance. Understanding these resistant mutations is important in developing effective therapeutic strategies.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, infects host cells via the spike proteins on the virus surface. The N-terminal subunit (S1) plays a role in receptor binding and the C-terminal subunit (S2) helps in the virus-host cell membrane fusion.

The receptor-binding domains (RBDs) of S1 bind to the human angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 antibodies prevent infection by targeting the RBD.

RNA viruses, like SARS-CoV-2, are present as a swarm of genome sequences around a core sequence. Variants can escape from this swarm in the presence of antibodies or drugs and become resistant.

There are now more than 2,700 mutations identified in the spike protein of the SARS-CoV-2 virus. There may be several mechanisms for these mutations, like host adaptation and immune selection during natural infection. Additional mutants could arise with the use of vaccines, therapeutic antibodies, and convalescent plasma therapy, which may reduce the effectiveness of these therapies.

Mutations that are resistant to antibodies

In a preprint paper published on the bioRxiv* server, researchers from Washington University in St. Louis, Harvard, and Mayo Clinic report on the mutational landscape of resistance in the SARS-CoV-2 RBD using a variety of monoclonal antibodies (mAbs).

They used a chimeric infectious vesicular stomatitis virus (VSV), a SARS-CoV-2 mimic, where they replaced the glycoprotein with the SARS-CoV-2 spike protein. Using the mAb 2B04, the authors determined that SARS-CoV-2 variants that were not neutralized had mutations in the RBD related to residues involved in ACE2 binding.

Further testing with nine other mAbs revealed a similar result. For the mAb 2H04, the resistance mutations were present outside the ACE2 binding site, on the side and base of the RBD. This suggests virus neutralization may occur by alternative attachment factors.

Several resistance mutations were common among the different mAbs tested, suggesting they represent important antigenic sites on the RBD.

The resistance mutations arising from the different mAbs made them resistant to the other mAbs in the chosen array of mAbs. Substitutions at S477 and E484 led to a broad resistance, while substitutions at several other sites led to resistance to more than one mAb.

Soluble human ACE2 receptors, which are not attached to cells and can compete with those on the host cell to bind to the virus, are another strategy being investigated to combat the virus. The authors tested the resistance of Vero E6 cells to human and murine soluble ACE2. The human soluble ACE2 neutralized all the escape mutants, although some mutations required higher ACE2 concentrations to be neutralized.

The authors also used serum from four convalescent COVID-19 patients to test if the serum antibodies neutralized the escape mutant viruses. They found many mutations that were resistant to neutralization by the sera. In particular, the mutation at residue E484 was resistant to all the four sera, suggesting this is a major neutralizing epitope. However, substitution at this position was quite rare and found only in about 0.05% of strains sequenced.

Resistant mutations found in virus isolates from humans

The authors also tested additional mutations, adding up to 48 different escape mutants. The team also investigated if any of these mutants are present in human isolates of SARS-CoV-2 by compiling available genome sequences of the virus and comparing them against the mutants' genome sequence. They found 27 of the 48 mutations are circulating in humans, with the most frequent mutation seen being D614G, observed in 86% of the isolates.

Substitution at S477N, which conferred a resistance to some level in all the mAbs, was the second most abundant variant in the human isolates.

The authors also note a few limitations of the study. Although the VSV is an effective mimic of the SARS-CoV-2 virus, 27 escape mutants were found only in the human isolates of the virus. They also note the few human sera tested. More human sera samples may help determine the extent of neutralization and escape mutants present.

If such variations in the virus arise after vaccination, they could limit the efficacy of treatment. "The relatively low genetic barrier to resistance combined with knowledge of the presence of relevant substitutions in clinical isolates suggests that effective mAb therapy likely will require a combination of at least two neutralizing antibodies," write the authors. Determining the residues resistant to specific antibodies could help select combinations based on non-overlapping resistant mutations.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Liu, Z. et al. (2020) Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. bioRxiv. https://doi.org/10.1101/2020.11.06.372037, https://www.biorxiv.org/content/10.1101 ... 6.372037v1
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Detectable SARS-CoV-2 antibodies 120 days post-infection in Chicago case study

11/19/20


https://www.news-medical.net/news/20201 ... study.aspx


As the coronavirus global health crisis continues, detecting the presence of serum antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent that causes the coronavirus disease 2019 (COVID-19), is crucial. In doing so, scientists can gain a better insight into both the scale of the virus's spread and a population's resistance to it after initial infection.

Serum antibodies reflect prior exposure to the virus, and some may confer protection or immunity against subsequent reinfection.

In a recent study, a team of researchers at Northwestern University, USA, had found that nearly 20 percent seroprevalence in the United States metropolitan site, Chicago, over the summer, during a period when lockdown restrictions were eased.

They found that three-quarters of seropositive individuals retained detectable antibodies for at least 120 days or four months.

The new finding supports previous studies showing people who recovered from COVID-19 developed antibodies to protect against a second bout.

The role of serum antibodies


Antibodies are produced over days to weeks after infection with the virus. An antibody response's strength depends on many factors, including nutritional status, age, certain medications, being immunocompromised and illness severity.

Antibodies are detected in the blood of people who are tested after an infection. When antibodies are present in the blood, it means that the body has generated an immune response to the infection.

A COVID-19 antibody test, known as a serology test, is a blood test that can detect if a person has developed antibodies to SARS-CoV-2. Being exposed to the virus increases antibody serum levels.

Understanding the role of antibodies and the importance of serum antibody tests can help health experts estimate the virus's extent.

The study findings

To arrive at the study findings, the researchers used dried blood spots (DBS) that are easily collected at home using a simple finger prick method.

The team had previously described the development and sensitivity of a DBS test to measure immunoglobulin G (IgG) to the receptor-binding domain of the SARS-CoV-protein using a laboratory-based enzyme-linked immunosorbent assay (ELISA).

The participant base included a mix of people who were split into two categories. The first group was categorized as "essential," which meant they needed to work outside of their homes during the shelter-in-placer order; the second, "non-essential," were those who worked from home during the same period.

The researchers recruited the participants through two methods. First, community-based participants were recruited from ten zip codes in Chicago through social media advertising and news articles. Second, employees, students and faculty members from the Northwestern University Feinberg School of Medicine in Chicago were sent an email describing the study with a link to the website.

The participants were asked to complete a questionnaire about general health status and COVID-19 symptoms. The team provided the community participants with materials for DBS collection who returned their samples using a courier service provided by the research team.

Both Chicago and other places within Illinois were under a stay-at-home order from March 21 until May 30.

The researchers started sampling in late June 2020, a period when lockdown orders were lifted. The collection of samples went on through September 6.

Overall, the researchers found that the seroprevalence of IgG was 19.8 percent, with similar seroprevalence among samples obtained from the mail and those through an onsite DBS kit distribution.

Further, the team also noted no difference between seroprevalence in people who were known as "essential" and those who are "non-essential."

"These data underscore the importance of a self-collected, quantitative assay with adequate sensitivity to detect antibodies at the lower levels among non-hospitalized persons with community-acquired exposure to COVID-19," the researchers concluded in the study.

COVID-19 spread

The coronavirus pandemic continues to spread across the globe, with over 56.49 million cases confirmed. The virus has already claimed more than 1.35 million lives.

The United States reports the highest number of confirmed cases, reaching 11.55 million. India, Brazil, France, and Russia record increasing numbers of also, with over 8.95 million, 5.94 million, 2.11 million, and 1.99 million cases confirmed, respectively.
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Re: How long is antibody duration in Covid 19 ? / Antibodies

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SARS-CoV-2 immunity can last over six months, study finds

11/19/20


https://www.news-medical.net/news/20201 ... finds.aspx


At present, over 56.56 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), which has led to over 1.35 million deaths.

On the other hand, over 39.35 million people have recovered from the infection. The question currently baffling researchers is the longevity or duration of immunity against reinfection among those recovered.

US-based scientists – from the La Jolla Institute for Immunology, University of California, San Diego and Icahn School of Medicine at Mount Sinai – have released a study on preprint server bioRxiv*, titled “Immunological memory to SARS-CoV-2 assessed for greater than six months after infection,” contributing to the enormous research effort currently underway in this area.

Background


As the researchers note, to understand the efficacy of vaccines currently in development, it is important to know the longevity of immunological memory against SARS-CoV-2. This would also help develop better diagnostic methods for the infection, they added.

Overall, the future course of the pandemic could be more accurately predicted if the individual immune reaction to SARS-CoV-2 infection can be quantified and its longevity defined.

Antibodies

The viral infection is known to release SARS-CoV-2-specific antibodies and stimulate the CD4+ T cells and CD8+ T cells. This T cell response leads to less severe disease, and thus, “CD4+ T cell and CD8+ T cell responses may be important for control and resolution of primary SARS-CoV-2 infection,” write the researchers.

The neutralizing antibodies against the infection are capable of protecting against secondary infection with SARS-CoV-2. When these neutralizing antibodies were given passively – through convalescent plasma transfusion, for example – infection severity was found to be much less severe in lab animals. However, in humans, if this passive transfer of neutralizing antibodies provided after the infection had already started, the infection severity could not be significantly controlled. This means that the T cells within the infected person play a significant role in protecting against secondary infection rather than the antibodies alone, write the researchers.

Circulating memory T cells and memory B cells may take several days to reactivate when exposed to the infection again, and this reactivation can trigger “recall T cell responses and/or anamnestic antibody responses,” write the researchers.

“COVID-19 vaccine development is closely tied to the topic of immunological memory.” This study was undertaken to assess the immune memory of the “three branches of adaptive immunity (CD4+ T cell, CD8+ T cell, and humoral immunity),” they add.

Study design

This study analyzed the immune memory against SARS-CoV-2 in 185 recovered COVID-19 cases for over 6 months after recovery from the infection. 43 percent of the participants were male, and 57 percent were female. The participants had a wide range of severity of disease, from asymptomatic to severe. They were recruited from multiple sites. Of the patients, 7 percent had needed hospitalization and some needed intensive care unit (ICU) care.

Adults with confirmed infection were included and their disease was scored from 0 to 10 using a numerical scoring system based on the NIH ordinal scale. The team explains that “asymptomatic” cases had a score of 1, those with “mild symptoms” has scores of 2 or 3, those with “moderate symptoms or disease” had scores of 4 or 5 and those with “severe disease” had scores 6 and over. Those over scores of 4 had needed hospitalization.

Blood samples were collected for antibody analysis as well as for SARS-CoV-2-specific CD4+ T cells and CD8+ T cell assays and memory B cell assays. Spike receptor-binding domain (RBD) IgG was also measured. SARS-CoV-2-specific memory B cells were identified using fluorescently labeled multimerized probes.

Most of the participants provided blood samples at 6 days post-onset-of-symptoms and then against at 240 days post-onset-of-symptoms. A total of 41 samples were obtained at over 6 months post-onset-of-symptoms (178 days or longer). A total of 38 participants provided samples at 2 to 4 points over the study period.

The study results

Overall, the study results showed that specific antibody responses against the spike protein on the virus (called the Spike IgG) were stable in convalescent patients for over 6 months. Spike protein-specific memory B cells were also abundantly present at 6 months. The number of these memory B cells was also found to be higher at 6 months post-infection recovery than at 1 month post-recovery. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells had a half-life of 3 to 5 months and showed a declining trend thereafter.

Antibody levels:

98 percent were seropositive for spike IgG at 1 month post-onset-of-symptoms (days 20 to 50)
90 percent were seropositive for spike IgG at 6 to 8 months (post-onset-of-symptoms over 178 days)
SARS-CoV-2 RBD IgG titers had a half-life of 83 days
88 percent were seropositive for RBD IgG at 6 to 8 months (post-onset-of-symptoms over 178 days)
The percentage of subjects seropositive for SARS-CoV-2 neutralizing antibodies (titer > 20) at 6 to 8 months post-onset-of-symptoms was 90 percent
Circulating RBD IgA had a half-life of 27 days

Memory B cells:

Spike-specific memory B cells in SARS-CoV-2 unexposed donors were rare. Spike-specific memory B cell rose from the first measurement at days 36 to 163 on the second measurement at days 111 to 240. Authors wrote, “Overall, based on the observations here, development of B cell memory to SARS-CoV-2 appeared to be robust and likely long-lasting.”

Memory T cells:

SARS-CoV-2 memory CD8+ T cells in 155 subjects were identified. At days 20 to 50 post symptom onset, the SARS-CoV2 memory CD8+ T cells were found in 61 percent of participants. The proportion of subjects with SARS-CoV-2 memory CD8+ T cells at post 6 months after symptom onset was 50 percent.

SARS-CoV-2 memory CD4+ T cell response was robust, say the researchers. At days 20 to 50 post symptom onset, the SARS-CoV2 memory CD4+ T cells were found in 94 percent of participants. The proportion of subjects with SARS-CoV-2 memory CD4+ T cells at post 6 months after symptom onset was 89 percent.

Conclusions and implications

The authors of the study concluded that each component of SARS-CoV-2 immune memory, including the antibody, memory B cell, CD4+ T cell and CD8+ T cell memory to SARS-CoV-2, showed a robust presence months after recovery from the infection. They write, “immune memory consisting of at least three immunological compartments was measurable in ~90% of subjects > 5 months PSO (post symptom onset), indicating that durable immunity against 2o (secondary) COVID-19 disease is a possibility in most individuals.”
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Re: How long is antibody duration in Covid 19 ? / Antibodies

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Austrian study shows robust antibody response to SARS-CoV-2 for over 6 months

11/24/20


https://www.news-medical.net/news/20201 ... onths.aspx


In the face of discouraging news about the resurgence of COVID-19, some reports offer hope of protection in the face of a robust and persistent immune response. In an encouraging report, an Austrian preprint appearing on the medRxiv* server in November 2020 suggests a high level of durable immunity to SARS-CoV-2 over at least six months. This could shape future strategies for population testing and immunization.

The COVID-19 pandemic is far from losing its strength, with a second wave being reported in many countries in Europe. Even eleven months into the pandemic, it is unclear how robust the antibody responses are, how long they persist, as well as how well they protect against reinfection.

A typical antibody response begins with immunoglobulin M (IgM) secretion followed by a switch to IgG, the latter indicating a mature and durable immune response. earlier research has shown that over 90% of SARS-CoV-2 infected individuals have a strong antibody response targeting the viral spike protein. Since this protein contains the receptor-binding domain (RBD) where the virus engages the human host cell via the angiotensin-converting enzyme 2 (ACE2), antibodies directed against it neutralize the virus.

The current study is a follow-up of a seroprevalence survey carried out in June 2020 in an Austrian town called Weißenkirchen. This town was badly hit by the infection in the first wave. The researchers performed an ELISA-based survey of anti-SARS-CoV-2 spike IgG and IgM levels, finding a 12% prevalence, 9% showing IgG and 9% IgA, respectively, and 6% showing both.

The current study repeated the testing on 121 people, of whom 68 had been tested in the first wave. The researchers found that 58% (70/121) were seropositive for Immunoglobulin A (IgA) or Immunoglobulin G (IgG), with 45% and 48% having IgG and IgA antibodies, respectively. Both antibodies were present in 36%.

Among the 68 first-wave positives, 63 (93%) remained positive for anti-SARS-CoV-2 antibodies in June, with half of them having IgG and three-quarters IgA antibodies. Both antibodies were present in 56% of the group.

In the current (October) study, 84% (57/68) of this group continued to be seropositive, with 66% and 74% displaying IgG and IgA antibodies, respectively, and 56% having both. This is only slightly down from 93% in the first round of testing, which indicates that the antibodies elicited by the infection remained remarkably stable throughout this period.

To distinguish the contribution of true antibody persistence vs. a rise in antibodies caused by new infections in hitherto naïve individuals within this subgroup, the individual antibody titers were analyzed. This showed that of the 47 people who had IgG against the virus in June 2020, 44 (94%) remained positive in the current round, while 1 of the 68 had newly developed IgG. The remaining 3 did not have IgA at the beginning and lost their IgG positivity by October.

Similarly, of the 50 IgA positives in the first round, 44 (88%) had persistent IgA antibodies, but 6 others had new IgA responses. Five of these novel IgA responses were in individuals who already had IgG antibodies in June. Therefore, the researchers found, the seropositivity is primarily due to persistent antibodies. In fact, the robust IgA persistence is unexpected since this is typically part of an early and temporary immune response, with IgG being the persistent class.

Of the 34 subjects with both antibody classes, 33, that is, 97%, still had both in the second round, while the IgA level fell in one person. Thus, having both the antibodies best predicted antibody persistence in this study.

Again, to rule out undetected waning of antibody levels, the researchers compared the relative titers of both antibody classes from both rounds, using semi-quantitative ELISA. This confirmed a steady level for both classes, if not an increase, indicating a durable antibody-based immune response for six months or more. This suggests that a SARS-CoV-2 vaccine should produce both IgA and IgG antibodies and that these will provide immunity for over six months.

The authors intend to continue testing this cohort with both semi-quantitative and quantitative ELISA for both IgG and IgA and to use newer tests for T cell-mediated immunity to the virus as well. These studies will also indicate whether waning of the immune response is to be expected and the risk factors for such waning, such as patient-specific factors like age, sex and habits, disease severity, and the presence of other comorbidities.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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Re: How long is antibody duration in Covid 19 ? / Antibodies

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SARS-CoV-2 spike protein antibodies can persist up to 200 days after symptom onset

11/25/20

https://www.news-medical.net/news/20201 ... finds.aspx


Researchers report SARS-CoV-2 antibodies to the spike protein (S protein) can persist 200 days after symptom onset, but that antibodies to the nucleoprotein (N protein) can reduce much more rapidly.

Studies on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the ongoing COVID-19 pandemic, have established that the spike protein of the virus is key to infection. The receptor-binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2), followed by membrane fusion with the host cell membrane and viral entry.

In response to virus infection, the host produces specific immunoglobulin (IgG) antibodies to the spike protein, RBD, and nucleoprotein, starting between six to 15 days after infection. Antibodies to the spike protein and RBD antigens are correlated with T cell response and viral neutralization in in vitro studies. However, it is unclear if reinfection can occur in patients who have mounted an immune response, although some reinfection cases have been reported. Hence, there is a need to understand and characterize the immune response after SARS-CoV-2 infection.

IgG and neutralizing antibodies to SARS-CoV – the betacoronavirus responsible for the 2002 SARS outbreak – have been known to persist for 2–3 years after infection, with recent reports showing persistence even up to 12–17 years. After MERS infection, antibodies have been seen for 34 months after infection. However, longitudinal studies of SARS-CoV-2 antibodies are limited for many reasons, including the shortness of present studies’ durations and low sample numbers.

Determining antibody dynamics over time

In a new study published on the medRxiv* preprint server, a team of UK-based researchers have reported on antibody kinetics and persistence after SARS-CoV-2 infection. In their ‘COVID-19 Staff Testing of Antibody Responses Study’ (Co-STARS) undertaken between April and October 2020, the team enrolled 3,555 UK health care workers, of which 349 were seropositive for SARS-CoV-2. The positive participants were followed for up to 7 months after symptom onset, providing 1,163 monthly serological samples. The team measured serum antibodies using MSD Chemiluminescent binding assay, while the detection of SARS-CoV-2 was done using real-time polymerase chain reaction reverse transcription (RT-PCR).

Alongside the experimental tests, the team also statistically analyzed the data and antibody dynamics, which were estimated using two gamma models to include an assumption for exponential decay of antibodies and another for a long-lived plateau of antibodies after infection.

The authors observed a faster decay in the nucleoprotein antibody compared to those of the spike protein and RBD antibodies. After 200 days of symptom onset, 75% of the participants were positive for the nucleoprotein antibodies, while 99% were still positive for the spike protein antibodies.

By modeling the data obtained, the authors estimate that 95% of people after SARS-CoV-2 infection will have spike protein antibodies until 465 days after symptom onset. This was under the most stringent assumption that spike protein antibodies decay exponentially. Under more optimistic assumptions, antibodies are predicted to remain for a long time.

Weekly measurements of the antibodies showed they increased rapidly in the first three weeks and maintained high levels four to 10 weeks after symptom onset, with peak antibody levels observed 30–40 days after symptoms developed.

The team's analysis showed that the half-lives for the nucleoprotein, RBD, and spike protein antibodies were 60 days, 102 days, and 126 days, respectively, under the gamma decay model, which assumes exponential decay of antibodies. The half-lives for the RBD and spike protein antibodies were increased to 110 days and 364 days under the gamma plateau model, which assumes long-lived antibodies.

A sigmoidal relationship between the antibody binding titers and percentage binding or ACE2 receptor blocking for the spike protein and RBD antibodies indicated that above an antibody threshold titer, there is a significant increase in binding/ACE2 receptor blocking.

Implications of antibody levels detected

Although the duration of antibodies persisting in infected individuals conflicts with some other results showing rapid decay of antibodies, the results are similar to those observed for SARS-CoV and MERS.

The lower duration of the presence of nucleoprotein antibodies is important to take into account when designing diagnostic tests and seroprevalence-based public health interventions. Since none of the positive participants in the study needed hospitalization, the authors write, the participants were a representative sample of COVID-19 patients. This is because the majority of COVID-19 cases do not need hospitalization.

Although there is no definitive understanding of the protection to SARS-CoV-2 offered by antibodies as yet, animal studies support the idea that neutralizing antibodies correlate to viral immunity. But, it still remains to be seen if the level of antibodies detected are enough to provide long-term immunity from SARS-CoV-2. Neutralization assays after a year of infection will be needed to determine this.

*Important Notice


medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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