Prediction of SARS-CoV-2 antibody titer

Two effective vaccines against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) are currently in circulation, but global vaccine deployments lag behind ongoing infections and are severe. Unvaccinated individuals with COVID-19 symptoms require urgent treatment. Passive immunotherapy, in which SARS-CoV-2 neutralizing antibody (nAbs) from the plasma of convalescent patients is administered to patients in the acute phase, is a promising strategy for COVID-19 treatment in severe cases. For example, recent Phase II Clinical trial In Argentina, convalescent plasma with high levels of nAb, especially when given early in COVID-19 symptoms to older people who do not yet require hospitalization, is critical, as measured by keeping people away from hospitalization. It has been shown to have had some beneficial health effects. However, not all SARS-CoV-2 infected individuals show a strong neutralizing antibody response, so screening donor plasma for SARS-CoV-2 neutralizing antibody activity and which convalescent patients are appropriate nAb You need to determine if you are a donor. These neutralization assays are difficult and require a high level of biosafety containment. Alternatively, identifying correlations for high nAb titers can eliminate the need for time-consuming and slow screening procedures and streamline plasma donor selection, but clinically predict high SARS-CoV-2 nAb titers. The factor is still unknown.

Scientists at the University of Washington and Fred Hatchin are studying nAbs from patients recovering from COVID-19 to find out which clinical factors predict better passive immunotherapy donors.In recent publications Clinical research journal, Dr. Jim Boonyaratanakornkit, Vaccines and Infectious Diseases Researchers and Physicians), and Koel Lab (University of Washington), SARS-CoV-2-nAb titers in plasma of 250 individuals were measured by PCR-confirmed SARS-CoV-2. Team members from the Department of Clinical Laboratory Medicine and Pathology, University of Washington, have studied fast, high-throughput, off-the-shelf SARS-CoV-2 antibody tests in parallel with the nAb assay, and are a good surrogate for the tedious nAb assay. We have identified a test that has characteristics. .. The nAb titer was then correlated with clinical or demographic data such as age, gender, comorbidities, and severity of COVID-19 disease. This comparison showed that increased age, male gender, and severe COVID-19 symptoms such as dyspnea and fever were correlated with higher nAb titers. In addition, the longer period between SARS-CoV-2 infection and antibody screening correlated with reduced nAb titers. Taken together, these results indicate that severe COVID-19 disease may produce higher levels of nAb than less severe disease, and blood anti-SARS-CoV-2 antibody titers may decline over time. It suggests that.

Since the outbreak of SARS-CoV-2 began, understanding the longevity of antibody-immunity caused by natural infections has been a top priority. To further investigate the initial finding that time from COVID-19 symptoms correlates with decreased nAb titers, Dr. Boonyaratanakornkit and colleagues collected follow-up plasma samples from 41 original study participants. To further support previous data, all but four patients had reduced nAb titers by the second visit, with an average nAb half-life of 66 days. This is because SARS-CoV-2 nAb may not provide long-term sterile immunity, and after SARS-CoV-2 infection, the window contains enough nAb for clinically effective metastasis to an individual’s plasma. It suggests that it may be limited.

Interestingly, 7% or about 3% of PCR-confirmed SARS-CoV-2 infection study participants did not have detectable nAb in plasma. To further investigate the immune response in these seronegative individuals, T cells from the blood of these participants were cultured with the SARS-CoV-2 peptide, which covers the major structural proteins of the virus. However, serum-negative individual T cells behaved similarly to healthy donor T cells and did not produce inflammatory cytokines, whereas serum-positive donor T cells did, and lack of seroconversion was SARS. -Suggests that it correlates with T cells that do not respond to CoV-2. .. Dr. Koel commented on this discovery:[age] The proportion of people with documented COVID-19 is seronegative and lacks a post-recovery T cell response. This highlights the puzzle that it appears that the infection can be removed without inducing acquired immunity. “

This study shows that factors such as age and severity of illness can be used to predict which convalescent COVID-19 patients are suitable for providing plasma for passive immunotherapy. These correlations may replace the need for traditional nAb assays. “COVID-19 is [be] It’s one of a group of infectious diseases, probably with more viruses, so the more antigens around it, the higher the level of antibodies, “says Dr. Koelle. However, this finding seems paradoxical, as a stronger immune response should limit SARS-CoV-2 replication and COVID-19 disease.Dr. Koel said the plausible cause of this discrepancy was “immune response. [in those with both severe disease and high nAb titers] Obviously, it wasn’t “effective” in time to stop the illness. This indicates the potential for temporary “competition” between viral replication and host inflammation, and adaptive immunity. Viruses and inflammation come to the fore, provoke an immune response, and look stronger in retrospect. “

In the future, Koelle Lab will ask why some people fail to seroconvert after SARS-CoV-2 infection and whether lack of seroconversion is associated with low virus vaccination at the onset of infection or successful innate immune defense. I want to understand. In addition, the laboratory is interested in understanding how antibody levels at the site of infection of the respiratory mucosa are compared to plasma nAb kinetics. The lab is also interested in whether “after spontaneous infection, there are certain levels of neutralizing antibodies that correlate with protection from reinfection,” Dr. Koel said, “currently in vaccines, we You may never know! “

This work was supported by the Fred Hutchinson National Cancer Institute, the National Institute of Allergy and Infectious Diseases, the Fred Hutchinson Joel Meyer Foundation, and the American Society for Transplant Cell Therapy.

Keith Jerome and David Koelle, members of the UW / Fred Hutch Cancer Consortium, contributed to this work.

Boonyaratanakornkit J, Morishima C, Selke S, Zamora D, McGuffin SA, Shapiro AE, Campbell VL, McClurkan CL, Jing L, Gross R, Liang J, Postnikova E, Mazur S, Lukin VV, Chaudhary A, Das MK, Fink SL , Brian A, Gleninger AL, Jerome KR, Holbrook MR, Garnsheimer TB, Wener MH, Wald A, Koel DM.. Clinical, , and temporal predictors of neutralizing antibodies against SARS-CoV-2 in COVID-19 convalescent plasma donor candidates. J Clin Invest.. December 15, 2020; 144930. Doi: 10.1172 / JCI 144930. Online before printing.