COVID-19 neutralizing antibodies predict disease severity and survival

García-Beltrán, Wilfredo F.; Lam, Evan C.; Astudillo, Michael; Yang, Diane; Miller, Tyler E.; Feldman, Jared; Hauser, Blake M.; Caradonna, Timothy M.; Clayton, Kiera; Nitido, Adam; Murali, Mandakolathur R.; Alter, Galit; Charles, Richelle C.; Dighe, Anand S.; Branda, John A.; Lennerz, Jochen K.; Lingwood, Daniel; Schmidt, Aaron; Iafrate, A. John; Balazs, Alejandro B.

doi:10.1101/2020.10.15.20213512

“…The cohort consists primarily (91.69%) of patients with mild COVID-19 therefore representing the predominant clinical course of this disease 6 . Since higher disease severity was shown to correlate with higher antibody responses 14,42 , cohorts mainly composed of hospitalized individuals have limited applicability on the majority of COVID-19 cases 20,35,43,44 . Moreover, to our knowledge this is the most comprehensive study (n=963), in which neutralizing antibody activity has been reported to date with the next largest study having analyzed 4-5 fold less individuals at a single time point 45 .…”

Section: Discussionmentioning

confidence: 99%

Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2

Vanshylla

¹

,

Cristanziano

²

,

Kleipass

³

et al. 2021

Preprint

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A detailed understanding of antibody-based SARS-CoV-2 immunity has critical implications for overcoming the COVID-19 pandemic and for informing on vaccination strategies. In this study, we evaluated the dynamics of the SARS-CoV-2 antibody response in a cohort of 963 recovered individuals over a period of 10 months. Investigating a total of 2,146 samples, we detected an initial SARS-CoV-2 antibody response in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of recovered patients demonstrated exceptional SARS-CoV-2 neutralizing activity, defining them as ‘elite neutralizers’. These individuals also possessed effective cross-neutralizing IgG antibodies to SARS-CoV-1 without any known prior exposure to this virus. By applying multivariate statistical modeling, we found that sero-reactivity, age, time since disease onset, and fever are key factors predicting SARS-CoV-2 neutralizing activity in mild courses of COVID-19. Investigating longevity of the antibody response, we detected loss of anti-spike reactivity in 13% of individuals 10 months after infection. Moreover, neutralizing activity had an initial half-life of 6.7 weeks in serum versus 30.8 weeks in purified IgG samples indicating the presence of a more stable and long-term memory IgG B cell repertoire in the majority of individuals recovered from COVID-19. Our results demonstrate a broad spectrum of the initial SARS-CoV-2 neutralizing antibody response depending on clinical characteristics, with antibodies being maintained in the majority of individuals for the first 10 months after mild course of COVID-19.

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“…The D614G mutation causes an allosteric change in the spike RBD (61,62), and exhibits efficient replication in vitro and transmission in animal models (63,64); however there are no indications thus far of higher clinical severity or mortality (65). Additionally, D614G mutant pseudovirus is neutralized by both convalescent patient sera and vaccine-elicited immune sera (66,67). Minkassociated variants are not associated with rapid spread or increased disease severity among humans, and preliminary serology assessments show that convalescent sera with varying antibody titers neutralize both wildtype and mink-variant virus suggesting that it is unlikely that these mutations will jeopardize the effects of vaccines or therapeutics (68,69).…”

Section: Breadth Of Immune Coverage Of Emerging Sars-cov-2 Variantsmentioning

confidence: 99%

“…Potent neutralizing antibodies against SARS-CoV-2 appear to increase survival and may protect against reinfection with variants of SARS-CoV-2. In a cohort of 113 patients infected with SARS-CoV-2 stratified by disease severity and outcomes (i.e., non-hospitalized, hospitalized, intubated, immunosuppressed, and deceased), anti-RBD antibody levels, neutralization titers, and neutralization potency indices predicted disease severity and survival (66). Comprehensive immunophenotyping of peripheral blood in 42 individuals with divergent clinical trajectories of SARS-CoV-2 infection and COVID-19 (moderate n = 7, severe n = 28, recovered n = 7) showed perturbations in multiple leukocyte populations, which distinguished cases of severe COVID-19 from healthy donors, cases of moderate COVID-19, and from patients who have recovered from COVID-19 (44).…”

Section: Systems Serology and Systems Immunologymentioning

confidence: 99%

Immunity to SARS-CoV-2: Lessons Learned

Fergie

¹

,

Srivastava

²

2021

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In the year since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and with understanding of the etiology of the coronavirus disease 2019 (COVID-19) pandemic, it has become clear that most infected individuals achieve some form of immunity against the virus with relatively few reported reinfections. A number of vaccines have already achieved emergency use authorization based on data from large phase 3 field efficacy clinical trials. However, our knowledge about the extent and durability of this immunity, and the breadth of vaccine coverage against SARS-CoV-2 variants is still evolving. In this narrative review, we summarize the latest and rapidly developing understanding of immunity to SARS-CoV-2 infection, including what we have learned about the key antigens of SARS-CoV-2 (i.e., the spike protein and its receptor-binding domain), their importance in vaccine development, the immediate immune response to SARS-CoV-2, breadth of coverage of emerging SARS-CoV-2 variants, contributions of preexisting immunity to related coronaviruses, and duration of immunity. We also discuss lessons from newer approaches, such as systems serology, that provide insights into molecular and cellular immune responses elicited and how they relate to the trajectory of infection, and potentially inform immune correlates of protection. We also briefly examine the limited research literature on immune responses in special populations, such as pregnant women and children.

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“…The cohort consists primarily (91.69%) of patients with mild COVID-19 therefore representing the predominant clinical course of this disease 6 . Since higher disease severity was shown to correlate with higher antibody responses 14,42 , cohorts mainly composed of hospitalized individuals have limited applicability on the majority of COVID-19 cases 20,35,43,44 . Moreover, to our knowledge this is the most comprehensive study (n = 963), in which neutralizing antibody activity has been reported to date with the next largest study having analyzed 4-5 fold less individuals at a single time point 45 The broad spectrum of neutralizing activity developed in COVID-19 recovered individuals may impact the level of protective immunity.…”

Section: Discussionmentioning

confidence: 99%

“…NAb response presented here is comparable to recent spike-based mRNA vaccine studies in age group 18-55, where geometric mean neutralizing titers were in the range of 100-300 ID 50 (depending on dose) 1.5 months post vaccination 17,50 versus 111.3 ID 50 in this study. Recent studies have reported that age, gender and disease severity 14,36,44 can impact SARS-CoV-2 NAb titers 14,36,42,43,45 . However, a comprehensive analysis on a large representative cohort was missing.…”

Section: Discussionmentioning

confidence: 99%

Kinetics and Correlates of the Neutralizing Antibody Response to SARS-CoV-2

Vanshylla

¹

,

Cristanziano

²

,

Kleipass

³

et al. 2021

View full text Add to dashboard Cite

A detailed understanding of antibody-based SARS-CoV-2 immunity has critical implications for overcoming the COVID-19 pandemic and for informing on vaccination strategies. In this study, we evaluated the dynamics of the SARS-CoV-2 antibody response in a cohort of 963 recovered individuals over a period of 10 months. Investigating a total of 2,146 samples, we detected an initial SARS-CoV-2 antibody response in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of recovered patients demonstrated exceptional SARS-CoV-2 neutralizing activity, de ning them as 'elite neutralizers'. These individuals also possessed effective cross-neutralizing IgG antibodies to SARS-CoV-1 without any known prior exposure to this virus. By applying multivariate statistical modeling, we found that sero-reactivity, age, time since disease onset, and fever are key factors predicting SARS-CoV-2 neutralizing activity in mild courses of COVID-19. Investigating longevity of the antibody response, we detected loss of anti-spike reactivity in 13% of individuals 10 months after infection. Moreover, neutralizing activity had an initial half-life of 6.7 weeks in serum versus 30.8 weeks in puri ed IgG samples indicating the presence of a more stable and long-term memory IgG B cell repertoire in the majority of individuals recovered from COVID-19. Our results demonstrate a broad spectrum of the initial SARS-CoV-2 neutralizing antibody response depending on clinical characteristics, with antibodies being maintained in the majority of individuals for the rst 10 months after mild course of COVID-19. Main COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was rst identi ed in December 2019 1,2. Since then, the virus has rapidly spread across the globe and caused more than 90 million proven infections and over 2 million deaths. Disease severity ranges from asymptomatic infection to symptoms like cough, fever, muscle pain, and diarrhea to severe courses of infection including pneumonia with severe respiratory distress and a high risk of death 3-5. While the majority of infected individuals experience a mild course of disease, elderly or individuals with preexisting conditions are at higher risk for severe courses of COVID-19 6. In symptomatic non-hospitalized cases, the acute course of disease typically spans 7-14 days 7,8. However, a signi cant fraction of COVID-19 patients suffer long-lasting symptoms post recovery, so called 'post-COVID syndrome' 9-11 (Augustin et al., submitted). SARS-CoV-2 infects human cells by using the virus spike (S) protein 12 for targeting the angiotensin converting enzyme-2 (ACE-2) receptor 13. The S-protein carries dominant epitopes against which humoral B and T cell responses are generated upon natural infection and vaccination 14-18. Spike-speci c IgM, IgA, and IgG antibodies are detected early after infection 19,20 and IgG antibody levels and IgG memory B cells can persist post infection 21. Neutralizing antibodies (NAbs) ar...

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COVID-19 neutralizing antibodies predict disease severity and survival

Cited by 38 publications

References 65 publications

Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2

Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2

Immunity to SARS-CoV-2: Lessons Learned

Kinetics and Correlates of the Neutralizing Antibody Response to SARS-CoV-2

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