How long is antibody duration in Covid 19 ? / Antibodies

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SARS-CoV-2 immunity can sustain for at least eight months, study finds

11/26/20


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


How long does immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) last after initial infection? This is one of the important and difficult questions scientists are grappling with today. Fully understanding this central issue has an enormous bearing on the future of public health, the course of the pandemic as well as the efficacy and longevity of future vaccines.

Lasting immunity to SARS-CoV-2, the agent that causes the coronavirus disease 2019 (COVID-19), is questioned because serum antibodies decline during convalescence. However, functional immunity is mediated by long-lived memory T and B cells.

A new study by researchers at Monash University, Australia, has revealed that people who have been infected with COVID-19 showed sustained protection against reinfection for at least eight months.

The study, which was published on the open-source medRxiv* preprint server, shows robust evidence for the likelihood that vaccines will work for long periods.

Although some of the antibodies seem to wane with time, the body retained the ability to remember the virus and generate the response needed to prevent serious illness. Experts believe that this type of immunological memory could last for years.

The study


There has been a steep rise in the number of COVID-19 cases, with many countries experiencing second waves of infections as many businesses and schools have reopened amid the easement of lockdown restrictions worldwide.

To date, over 60.49 million people have been infected, and more than 1.42 million have died.

Some studies have shown that after being infected with COVID-19, there is a decline in antibody response within three months.

In the current study, the researchers aimed to determine the longevity of SARS-CoV-2-specific memory B cells in COVID-19 patients.

To arrive at the study’s findings, the researchers characterized the SARS-CoV-2-specific memory B cell compartment using unique sets of the receptor-binding domain (RBD) and nucleoprotein (NCP) antigens.

The team recruited 25 COVID-19 patients and collected 36 blood samples from day four after infection up to day 242. They measured the systemic memory B cell response to SARS-CoV-2 infection.

The team emphasized that from vaccination studies in mice and humans, local systemic memory B cells are phenotypically different. It was also shown that influenza-specific memory B cells persist in the lungs of mice and play an essential role in protection from reinfection.

“As knowledge of SARS-CoV-2 and human lung immunology evolve, we will gain insight into what is required for a protective response to this respiratory virus. However, we propose that the establishment of systemic immunity will prevent severe systemic COVID-19, and reinfection may be limited to a mild or asymptomatic upper respiratory tract infection,” the researchers explained in the study.

Memory B cells

Circulating RBD- and NCP-specific memory B cells were detected early after infection and persisted over 242 days after the symptoms appeared.

Further, it appeared that early after being exposed, the Ag-specific cells expressed immunoglobulin M (IgM) over time, followed by the predominance of immunoglobulin G (IgG) antibodies.

The antibodies against the virus started to drop after 20 days post-infection. However, all patients continued to retain memory B cells that recognize one of two components of SARS-CoV-2, the spike and nucleocapsid proteins. These virus-specific memory B cells were detected up to eight months after infection.

Studying the SARS-CoV-2-specific memory B cells could potentially be used as a backup marker of humoral immunity in vaccination studies. At present, COVID-19 vaccine trials explore SARS-CoV-2 specific and neutralizing antibodies as markers of vaccine efficacy.

The results of the current study gives a glimpse of hope that candidate vaccines may provide long-lasting protection against SARS-CoV-2. As antibody levels drop when the immune response contracts, IgG memory B cells remain present, showing that SARS-CoV-2 infection triggers long-term humoral immunity.

The authors said that the study results give hope to the efficacy of vaccines against the virus.


“These results are important because they show, definitively, that patients infected with the COVID-19 virus do retain immunity against the virus and the disease,” Menno van Zelm, associate professor at Monash University, said.

“This has been a black cloud hanging over the potential protection that could be provided by any COVID-19 vaccine and gives real hope that, once a vaccine or vaccines are developed, they will provide long-term protection,” he added.
*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.

Source:

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:


Hartley, G., Edwards, E., Aui, P., van Zelm, M., et al. (2020). Rapid and lasting generation of B-cell memory to SARS-CoV-2 spike and nucleocapsid proteins in COVID-19 disease and convalescence. medRxiv. doi: https://doi.org/10.1101/2020.11.17.20233544, https://www.medrxiv.org/content/10.1101 ... 20233544v1
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Re: How long is antibody duration in Covid 19 ? / Antibodies

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Study shows antibody responses persisting 10 months after SARS-CoV-2 infection

2/24/21


https://www.news-medical.net/news/20210 ... ction.aspx


Researchers in Italy have conducted a study showing that patients who had tested positive for infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still had neutralizing antibodies against the virus 10 months later.

SARS-CoV-2 is the agent responsible for the coronavirus disease 2019 (COVID-19) pandemic that continues to pose a global public health threat and has now claimed the lives of more than 2.49 million people.

The researchers evaluated antibody responses over the course of 10 months among 30 people who were diagnosed with SARS-CoV-2 infection in the Umbria region of Italy between the 1st and 30th March 2020.

At ten months post-infection, 19 (63%) of the individuals still had detectable levels of neutralizing immunoglobulin G (IgG) antibodies against SARS-CoV-2.

Furthermore, no cases of reinfection occurred among any of the participants, despite a surge in daily infections with mutant strains occurring in the Umbria region during the study period.

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

Concerns surrounding antibody responses to SARS-CoV-2


Since the COVID-19 outbreak began in Wuhan, China, in late December 2019, studies have shown that humoral (antibody) responses among recovered patients can last anywhere from three months to more than eight months.

The SARS-CoV-2 virus expresses four key structural proteins, among which the spike (S) protein and nucleocapsid (N) protein are the most immunogenic.

The spike protein is the main structure the virus uses to bind to and gain entry to host cells.

As the initial stage of the infection process, the spike binds to the host cell receptor angiotensin-converting enzyme 2 (ACE-2) via its receptor-binding domain (RBD).

The spike RBD is the main target of SARS-CoV-2 neutralizing antibodies, which can be detected as soon as six days following confirmation of infection by polymerase chain reaction (PCR).

Studies published in 2020 have raised concerns regarding the duration of immunity provided by these neutralizing antibodies, warning that “rapidly waning immunity” could lead to false-negative immunoassay results.


“Improved understanding of immunity offered by the antibodies developed against SARS-CoV-2 is critical,” writes Puya Dehgani-Mobaraki from Associazione Naso Sano in Umbria, Italy and colleagues.

What did the researchers do?

The researchers conducted a longitudinal observational analysis of 114 patients in the Umbria region who had tested positive for SARS-CoV-2 by real-time quantitative PCR between the 1st and 30th March.

They conducted sequential serological tests over a ten-month period among 30 of the participants who attended all of the follow-up visits.

Blood samples were collected at six different time (T) points, with the first sample taken two months post-infection in the month of May (T0). Further samples were then taken one month (T1), three months (T2), five months (T3), six months (T4) and eight months (T5) after T0.

The presence and persistence of SARS-CoV-2-specific antibodies were assessed using two commercial chemiluminescence immunoassays (CLIA), with the CLIA positivity cut-off set at >1.01.

The participants were divided into those with mild disease (n=17) and those with a moderate-to-severe disease (n=13).

What did the study find?

The team reports that anti-spike-RBD IgG was detected in 19 (63.3%) of the 30 participants at T5 – ten months after infection was initially confirmed.

Among both the mild disease group and the moderate-to-severe disease group the trend of SAR-CoV-2-specifc IgM titers stayed below the CLIA positivity cut-off (>1.01) and significantly decreased over the ten-month period.

By contrast, the IgG titer trend stayed above the CLIA positivity cut-off in both groups and no significant changes in titer were observed.

Furthermore, “our study reported zero cases of reinfection despite the fact that the Umbria region currently is experiencing a surge in daily cases with mutant strains,” 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:


Dehgani-Mobaraki P, et al. Neutralizing antibody responses 10 months after mild and moderately-severe SARS-CoV-2 infection. medRxiv, 2021. doi: https://doi.org/10.1101/2021.02.22.21252225, https://www.medrxiv.org/content/10.1101 ... 21252225v1
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Re: How long is antibody duration in Covid 19 ? / Antibodies

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COVID-19 antibodies can protect against reinfection for at least eight months

3/23/21


https://www.news-medical.net/news/20210 ... onths.aspx


Seroconversion occurs in up to 99% of people following infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen that is responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. The question, however, is how long these antibodies persist and how far they protect against reinfection. A new study released on the medRxiv* preprint server offers hope that recovered patients are largely immune to reinfection for at least eight months.

The absence of testing in the early stages of the pandemic, as well as the high incidence of asymptomatic infection, led to estimated seropositivity rates of less than 10%. Reinfection, meanwhile, has been reported in a rarity of cases and has mostly resulted in mild symptoms, indicating a high degree of protective immunity following recovery from COVID-19.

Study details

The current study takes advantage of the two waves of COVID-19 that occurred in Switzerland, the first peaking in March and the second in November, 2020. The city of Geneva had a high incidence of confirmed SARS-CoV-2 infections, at about 8,600/100,000 people.

The researchers looked at the risk of reinfections in a situation with high community transmission. The two groups they compared either had or did not have detectable antibodies to SARS-CoV-2. The aim was to estimate the infection rate in either group.

The study matched each individual in the seropositive group to two seronegative controls. The sociodemographic characteristics of each group were comparable. So were the body mass index, and type and number of comorbidities in each group.

The follow-up continued for 36 and 25 weeks in the seropositive and seronegative groups, respectively. The testing rate was slightly higher among the seronegatives, at 1.52 per person vs. 1.39 in the seropositives.

However, the positive test fraction was lower in the seropositive group, at 2.4% vs. 11% in the seronegative group.

What were the results?


Only seven of 448 seropositive individuals had a positive polymerase chain reaction test for the virus. Five were likely to be reinfections, the other two probably not.

Conversely, 16% of seronegative individuals were positive, which indicates an incidence of 5 per 1,000 person-weeks. Over the entire follow-up period, the chances of being infected were 94% less for seropositive individuals compared to the other group.

What are the implications?

The study provides strong evidence that the presence of antibodies to SARS-CoV-2 is associated with strong protection against reinfection, as indicated by a positive test, at eight or more months following the first positive test.

Earlier reports have also shown that among over 1,200 seropositive healthcare workers in the UK, only two infections were detected after six months of follow-up. Both were asymptomatic. This yields an incidence rate ratio of 0.12.

The sample in the above study was composed of healthy participants of working age, and the period of the study was one of low incidence, with only 1 positive test per 10,000 days at risk. In contrast, the current study was carried out over a period with six-fold higher incidence.

A Qatar study, including over 1,30,000 confirmed infections, showed that reinfection was detected in only 0.05% of them. In this case, reinfection was determined on the basis of a positive PCR test at 45 or more days from the first positive swab.

This was, however, a study in a country that had only one wave of COVID-19, and where young workers were chiefly affected during the early phase, which was characterized by the rapid, extensive spread. Here, the infections dropped steeply following August 2020.

Strengths of this study

The current study covers a more representative sample, including many elderly individuals. Moreover, the follow-up period extended into the second wave, several months after seroconversion, with a high incidence of infection.

Thus, this supports the hypothesis that SARS-CoV-2 infection is followed by robust and durable antibody-mediated protection against reinfection. The degree of protection matches, at least, the preliminary results reported following vaccination with lipid nanoparticle-mRNA-based vaccines, at 90%.

Some degree of underestimation of actual reinfection is inevitable, perhaps, given that reinfections are milder in clinical presentation, and also because seropositive patients are aware that they have already had and recovered from the infection.

This is likely to be low, because testing was extensively carried out in the second wave, more so than in the first, with the ratio of undetected cases to detected ones falling from about 12 to 3, respectively. Secondly, both seropositive and seronegative subjects had similar testing rates, but a drastically lower positive test rate in the former.

Conclusion

Documented SARS-CoV-2 reinfections were exceedingly rare, with an incidence of 0.3 infections for every 1000 persons-week, and none were severe.”

The risk of reinfection is apparently reduced ten-fold by seroconversion after SARS-CoV-2 infection, as recorded at eight or more months after initial infection. These findings will help shape vaccination policies to provide maximum coverage while allowing appropriate relaxations of non-pharmaceutical interventions as soon as possible.

The extent of protection against variants of concern such as the UK variant cannot be estimated from this study, since these were present in very low numbers at that time. Further research may explore the correlation, if any, between antibody titers and the risk of reinfection, and the percentage of persistent seropositivity with prolonged monitoring.

*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:

Leidi, A. et al. (2021). Risk of reinfection after seroconversion to SARS-CoV-2: A population-based propensity-score matched cohort study. medRxiv preprint. doi: https://doi.org/10.1101/2021.03.19.21253889, https://www.medrxiv.org/content/10.1101 ... 21253889v1
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Re: How long is antibody duration in Covid 19 ? / Antibodies

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Recovered COVID-19 patients show signs of long-term immunity

4/28/21


https://www.news-medical.net/news/20210 ... unity.aspx


A study conducted by researchers in the United States has found that most patients who recovered from coronavirus disease 2019 (COVID-19) showed signs of long-lasting immunity against the causative agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The longitudinal analysis of 254 COVID-19 patients found that most convalescent individuals mounted durable SARS-CoV-2-specific antibody, B cell and T cell responses that are likely to confer long-lived immunity.

“Because the cohort will be followed for 2 to 3 more years, we can build on these results to define the progression to long-lived immunity against this novel human coronavirus, which can guide rational responses when future outbreaks occur,” writes Kristen Cohen from the Fred Hutchinson Cancer Research Center in Seattle, Washington and colleagues.

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

Long-lived immunity is needed to end the COVID-19 pandemic

To finally bring an end to the COVID-19 pandemic, long-lived population immunity against the causative agent SARS-CoV-2 will need to be achieved.

Multiple cross-sectional and longitudinal studies have shown that natural infection with SARS-CoV-2 induces humoral (antibody) and cellular responses that target multiple viral proteins.

However, “more comprehensive, quantitative analyses with extensive serial sampling in larger numbers of COVID-19 patients are limited, and could resolve some conflicting views about the durability of immunity,” says Cohen and the team.

Importantly, determining the frequency, immune function, specificity and duration of antibodies and memory B and T cell responses among COVID-19 patients could help researchers understand the integral components required for long-lived immunity.

What did the current study involve?

The researchers conducted a longitudinal prospective study of 254 COVID-19 patients who became infected with SARS-CoV-2 during the first surge of the pandemic.

The team evaluated participants from the point of early infection and for eight months thereafter using highly standardized or validated assays.

A sharp rise in immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies against the viral spike protein was observed during the first month of infection, after which levels of these antibodies quickly declined.

The spike protein mediates the initial stage of the SARS-CoV-2 infection process by attaching to host cells via its receptor-binding domain (RBD).

The researchers say the fast decline in IgG and IgA after one month of infection can likely be explained by the disappearance of the short-lived plasmablasts that secrete these antibodies once B cells first encounter the viral spike protein.

However, samples taken after 250 days revealed a slowing of this antibody decay towards a plateau level, indicating the generation of longer-lived plasma cells and more durable antibody responses.

“The importance of these observations is that following recovery, neutralizing antibodies may persist, albeit at low levels, and may act as the first line of defense against future encounters of SARS-CoV-2 and possibly related human coronaviruses,” writes the team.

There was an ongoing rise in both spike and RBD memory B cell responses

The potential durability of these antibody responses was further substantiated by an ongoing rise in both spike and RBD memory B cell responses after more than 3 to 5 months and a plateauing of these responses after 6 to 8 months.

The researchers say this persistence of memory B cells may be explained by their sustained production in the germinal centers of lymph nodes that drain the respiratory tract during the early months of infection. The memory B cells are then redistributed into the circulation once the germinal centers begin to recede.

“Thus, the induction and maintenance of memory B cells and, over time, long-lived plasma cells will continue to furnish higher affinity antibodies if re-exposures occur,” they write.

Polyfunctional CD4+ and CD8+ T cells were also generated and maintained

Polyfunctional SARS-CoV-2-specific CD4+ and CD8+ T cells were also generated and maintained, with an estimated half-life of 200 days.

Interestingly, the CD4+ T cells mounted a broader antigen-specific response and targeted several structural and accessory proteins, while CD8+ T cells preferentially targeted the nucleoprotein, which binds and packages viral RNA for virion assembly.

Cohen and colleagues say this finding highlights the importance of including the nucleoprotein as a potential vaccine antigen.

What are the study implications?

The team says that taken together, the findings suggest that broad and effective immunity may persist long-term in recovered COVID-19 patients.

“Thus, recovered COVID-19 patients are likely to better defend against the variants than persons who have not been infected but have been immunized with spike-containing vaccines only,” writes Cohen and colleagues.

“Nevertheless, vaccine induction of CD8+ T cells to more conserved antigens such as the nucleocapsid, rather than just to SARS-CoV-2 spike antigens, may add benefit to more rapid containment of infection as SARS-CoV-2 variants overtake the prevailing strains,” they conclude.

*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:


Cohen K, et al. Longitudinal analysis shows durable and broad immune memory after SARS-CoV-2 infection with persisting antibody responses and memory B and T cells. medRxiv, 2021. doi: https://doi.org/10.1101/2021.04.19.21255739, https://www.medrxiv.org/content/10.1101 ... 21255739v1
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Re: How long is antibody duration in Covid 19 ? / Antibodies

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SARS-CoV-2 antibodies are detectable up to a year after infection, finds study

5/3/21


https://www.news-medical.net/news/20210 ... study.aspx


A team of scientists from the United States has recently investigated the robustness and durability of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in coronavirus disease 2019 (COVID-19) patients. Their findings reveal that COVID-19 patients exhibit a strong anti-SARS-CoV-2 antibody response for up to 1 year and that the robustness of antibody response depends on the patient’s age and disease severity. The study is currently available on the medRxiv* preprint server.

Background

With more than one year into the COVID-19 pandemic, it is now known that the robustness and durability of anti-SARS-CoV-2 antibody response in COVID-19 patients is a major predictor of reinfection and vaccine response. In this context, studies have shown that even a single vaccine dose is capable of inducing a strong antibody response in individuals with prior SARS-CoV-2 infection.

Similarly, there is evidence showing that the robustness of antibody response positively correlates with the severity of COVID-19. However, cases of reinfection in COVID-19 recovered patients have also been documented in the literature.

Moreover, a limited number of studies have suggested that cross-reactive immunity from seasonal human coronaviruses can provide some degree of protection against SARS-CoV-2 infection. Therefore, an in-depth understanding of the dynamics of anti-SARS-CoV-2 antibody response is particularly necessary to determine the risk of reinfection and vaccine efficacy.

In the current study, the scientists have evaluated the magnitude and durability of IgG-specific anti-SARS-CoV-2 binding and neutralizing antibodies in mild, moderate, or severe COVID-19 patients. They have also investigated whether age, disease severity, and prior immunity against seasonal coronaviruses can influence SARS-CoV-2 specific humoral immunity.

Study design

The study was conducted on laboratory-confirmed COVID-19 patients who received medical treatment at seven military hospitals in the United States. The serum samples were collected from the patients at the time of enrollment and up to one year post-enrollment.

A total of 505 patients (both hospitalized and non-hospitalized) were enrolled for the study and evaluated for anti-SARS-CoV-2 antibody response. The patients were divided into three age groups: 18 – 44 years; 45 – 64 years; and more than 65 years. The patients who had been hospitalized were considered having moderate to severe COVID-19.

The serum levels of IgG-specific anti-spike binding antibodies were estimated in 250 of 505 enrolled patients. The magnitude and durability of neutralizing antibodies were evaluated in 72 patients within 6 months after the symptom onset. The serum samples collected from 11 patients at 12-month post symptom onset were also evaluated for neutralizing antibodies.

Antibody response and disease severity


The study findings revealed that 100% of hospitalized patients were present with anti-SARS-CoV-2 antibody response even after one year of symptom onset. Among non-hospitalized patients, about 95% and 80% remained seropositive 6 months and 12 months after the symptom onset, respectively. The half-life of binding antibodies in both hospitalized and non-hospitalized patients was found to be more than 1000 days after the symptom onset. During the early infection phase, hospitalized patients exhibited significantly higher antibody levels than non-hospitalized patients. However, after 12 months of infection, this difference in antibody response was abolished.

Two different neutralization assays were carried by the scientists to determine the duration and efficacy of anti-SARS-CoV-2 neutralizing antibodies. In one experiment, the half-life of neutralizing antibodies in hospitalized and non-hospitalized patients was found to be 88 days and 77 days, respectively.

Whereas, in the other experiment, the half-life was estimated to be 106 days and 29 days in hospitalized and non-hospitalized patients, respectively. Similar to the binding antibody response, hospitalized patients exhibited higher neutralizing antibody titers than non-hospitalized patients during the early infection phase. Taken together, these findings reveal a positive correlation between disease severity and antibody response.

Antibody response and patient age


During the early infection phase, a positive correlation between the binding antibody level and age was observed in non-hospitalized patients. The highest antibody response was observed in non-hospitalized patients aged more than 65 years. Importantly, no difference in antibody response was observed after 12 months of the symptom onset.

The half-life of binding antibodies in non-hospitalized patients aged 18 – 44 years, 45 – 64 years, and more than 65 years were estimated to be 1000 days, 230 days, and 143 days, respectively. However, a half-life of 1000 days was detected in hospitalized patients across all age groups.

Regarding neutralizing antibodies, the magnitude of response was found to increase with age in non-hospitalized patients during the early infection phase. Similarly, higher levels of neutralizing antibodies were observed in non-hospitalized patients aged 45 years and above.

Overall, these findings indicate that the age-dependent increase in early antibody response is confounded by age-related disease severity.

Cross-reactive immune response

During the early infection phase, higher levels of cross-reactive antibodies against seasonal beta coronaviruses were detected in mild to severe COVID-19 patients. However, cross-reactive immune responses to seasonal coronaviruses did not show any correlation with COVID-19 severity and anti-SARS-CoV-2 neutralizing antibody response.

Study significance


The study findings reveal that the antibody-mediated immunity developed in response to natural SARS-CoV-2 infection can persist for up to one year post-infection. However, the robustness and durability of antibody response is relatively lower among younger individuals with mild COVID-19 that does not require hospitalization.

*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:


Laing E. 2021. SARS-CoV-2 antibodies remain detectable 12 months after infection and antibody magnitude is associated with age and COVID-19 severity. MedRxiv. doi: https://doi.org/10.1101/2021.04.27.21256207 https://www.medrxiv.org/content/10.1101 ... 21256207v1
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