Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients

The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Antigen-specific responses are of unquestionable value for clinical management of COVID-19 patients. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized COVID-19 patients with different disease presentations (i.e., mild, moderate or severe), need for intensive care units (ICU) admission or outcomes (i.e., survival vs death). We show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Interestingly, significantly higher levels of nAbs as well as anti-S1 and -N IgG and IgM antibodies were found in patients with more severe symptoms, patients requiring admission to ICU or those with fatal outcomes. More importantly, early after symptoms onset, we found that the levels of anti-N antibodies correlated strongly with disease severity. Collectively, these findings provide new insights into the kinetics of antibody responses in COVID-19 patients with different disease severity.

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Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients

10.1101/2020.09.21.20198309 ◽

2020 ◽

Author(s):

Anwar M Hashem ◽

Abdullah Algaissi ◽

Sarah A Almahboub ◽

Mohamed A Alfaleh ◽

Turki S Abujamel ◽

...

Keyword(s):

Disease Severity ◽

Neutralizing Antibodies ◽

Disease Onset ◽

Humoral Response ◽

High Morbidity ◽

Strongly Correlated ◽

Time Period ◽

Clinical Presentations ◽

Almost All ◽

Kinetics Of

The Coronavirus Disease 2019 (COVID-19), caused by the novel SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Immunological surrogate markers, in particular antigen-specific responses, are of unquestionable value for clinical management of patients with COVID-19. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized patients with RT-PCR confirmed COVID-19 infection. Our data show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Notably, anti-S and -N IgG, peaked 20-40 day after disease onset, and were still detectable for at least up to 70 days, with nAbs observed during the same time period. Moreover, nAbs titers were strongly correlated with IgG antibodies. Significantly higher levels of nAbs as well as anti-S1 and N IgG and IgM antibodies were found in patients with more severe clinical presentations, patients requiring admission to intensive care units (ICU) or those with fatal outcomes. Interestingly, lower levels of antibodies, particularly anti-N IgG and IgM in the first 15 days after symptoms onset, were found in survivors and those with mild clinical presentations. Collectively, these findings provide new insights into the characteristics and kinetics of antibody responses in COVID-19 patients with different disease severity.

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The Kinetics of Humoral Response and its Relationship with the Disease Severity in COVID-19

10.21203/rs.3.rs-35381/v1 ◽

2020 ◽

Author(s):

Lili Ren ◽

Lulu Zhang ◽

De Chang ◽

Li Guo ◽

Junwen Wang ◽

...

Keyword(s):

Disease Severity ◽

Neutralizing Antibodies ◽

Late Onset ◽

Humoral Response ◽

Spike Protein ◽

Appearance Time ◽

Global Pandemic ◽

Antibody Titers ◽

Kinetics Of

Abstract Coronavirus Disease 2019 (COVID-19) has caused global pandemic. Here we profiled the humoral response against SARS-CoV-2 by measuring immunoglobulin (Ig) A, IgM and IgG against nucleocapsid, spike proteins and IgM, IgG antibodies against receptor-binding domain (RBD) of the spike protein along with total neutralizing antibodies. We tested 279 plasma samples collected from 176 COVID-19 patients. We demonstrate more severe cases have a late onset in the humoral response compared to mild/moderate infections. All the antibody titers continue to rise in patients with COVID-19 over the disease course. However, these levels are mostly unrelated to the disease severity. The appearance time and titers of neutralizing antibodies showed significant positive correlation to the antibodies against spike protein. Our results suggest late onset of antibody response as a risk factor for disease severity, however there is a limited role of antibody titers in predicting disease severity of COVID-19.

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Kinetics of antibody responses dictate COVID-19 outcome

10.1101/2020.12.18.20248331 ◽

2020 ◽

Author(s):

Carolina Lucas ◽

Jon Klein ◽

Maria Sundaram ◽

Feimei Liu ◽

Patrick Wong ◽

...

Keyword(s):

Disease Severity ◽

Disease Onset ◽

Humoral Response ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Delayed Response ◽

Viral Control ◽

Cross Sectional ◽

Neutralization Capacity ◽

Kinetics Of

SummaryRecent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). Yet, the exact feature of antibody responses that governs COVID-19 disease outcomes remain unclear. Here, we analysed humoral immune responses in 209 asymptomatic, mild, moderate and severe COVID-19 patients over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-Spike (S) IgG levels, length of hospitalization and clinical parameters associated with worse clinical progression. While high anti-S IgG levels correlated with worse disease severity, such correlation was time-dependent. Deceased patients did not have higher overall humoral response than live discharged patients. However, they mounted a robust, yet delayed response, measured by anti-S, anti-RBD IgG, and neutralizing antibody (NAb) levels, compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, while sera from 89% of patients displayed some neutralization capacity during their disease course, NAb generation prior to 14 days of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se, but rather with the delayed kinetics of NAb production.

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SARS-CoV-2 infection elicits a rapid neutralizing antibody response that correlates with disease severity

Scientific Reports ◽

10.1038/s41598-021-81862-9 ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Benjamin Trinité ◽

Ferran Tarrés-Freixas ◽

Jordi Rodon ◽

Edwards Pradenas ◽

Víctor Urrea ◽

...

Keyword(s):

Detection Limit ◽

Antibody Response ◽

Disease Severity ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Maximal Activity ◽

Antibody Responses ◽

Asymptomatic Individuals ◽

Rapid Kinetics ◽

Kinetics Of

AbstractThe protective effect of neutralizing antibodies in SARS-CoV-2 infected individuals is not yet well defined. To address this issue, we have analyzed the kinetics of neutralizing antibody responses and their association with disease severity. Between March and May 2020, the prospective KING study enrolled 72 COVID-19+ participants grouped according to disease severity. SARS-CoV-2 infection was diagnosed by serological and virological tests. Plasma neutralizing responses were assessed against replicative virus and pseudoviral particles. Multiple regression and non-parametric tests were used to analyze dependence of parameters. The magnitude of neutralizing titers significantly increased with disease severity. Hospitalized individuals developed higher titers compared to mild-symptomatic and asymptomatic individuals, which together showed titers below the detection limit in 50% of cases. Longitudinal analysis confirmed the strong differences in neutralizing titers between non-hospitalized and hospitalized participants and showed rapid kinetics of appearance of neutralizing antibodies (50% and 80% of maximal activity reached after 11 and 17 days after symptoms onset, respectively) in hospitalized patients. No significant impact of age, gender or treatment on the neutralizing titers was observed in this limited cohort. These data identify a clear association of humoral immunity with disease severity and point to immune mechanisms other than antibodies as relevant players in COVID-19 protection.

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Kinetics of Anti-SARS-CoV-2 Antibody Responses 3 Months Post Complete Vaccination with BNT162b2; A Prospective Study in 283 Health Workers

Cells ◽

10.3390/cells10081942 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1942

Author(s):

Evangelos Terpos ◽

Ioannis P. Trougakos ◽

Vangelis Karalis ◽

Ioannis Ntanasis-Stathopoulos ◽

Sentiljana Gumeni ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Health Workers ◽

Antibody Responses ◽

Healthy Individuals ◽

Younger Age ◽

Constant Rate ◽

Rate Of Decline ◽

A Prospective Study ◽

Kinetics Of ◽

Over Time

The aim of this study was to investigate the kinetics of neutralizing antibodies (NAbs) and anti-SARS-CoV-2 anti-S-RBD IgGs up to three months after the second vaccination dose with the BNT162b2 mRNA vaccine. NAbs and anti-S-RBD levels were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and three months after the second vaccination (D111) (NCT04743388). 283 health workers were included in this study. NAbs showed a rapid increase from D8 to D36 at a constant rate of about 3% per day and reached a median (SD) of 97.2% (4.7) at D36. From D36 to D50, a slight decrease in NAbs values was detected and it became more prominent between D50 and D111 when the rate of decline was determined at −0.11 per day. The median (SD) NAbs value at D111 was 92.7% (11.8). A similar pattern was also observed for anti-S-RBD antibodies. Anti-S-RBDs showed a steeper increase during D22–D36 and a lower decline rate during D36–D111. Prior COVID-19 infection and younger age were associated with superior antibody responses over time. In conclusion, we found a persistent but declining anti-SARS-CoV-2 humoral immunity at 3 months following full vaccination with BNT162b2 in healthy individuals.

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Declining Levels of Neutralizing Antibodies Against SARS-CoV-2 in Convalescent COVID-19 Patients One Year Post Symptom Onset

Frontiers in Immunology ◽

10.3389/fimmu.2021.708523 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tiandan Xiang ◽

Boyun Liang ◽

Yaohui Fang ◽

Sihong Lu ◽

Sumeng Li ◽

...

Keyword(s):

Symptom Onset ◽

Neutralizing Antibodies ◽

Natural Infection ◽

Protein S ◽

Igg Antibodies ◽

Neutralizing Activity ◽

Specific Igg ◽

One Year ◽

Kinetics Of

Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.

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Cytokine Profiles and Antibody Response Associated to Choclo Orthohantavirus Infection

Frontiers in Immunology ◽

10.3389/fimmu.2021.603228 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tybbysay P. Salinas ◽

Jose L. Garrido ◽

Jacqueline R. Salazar ◽

Publio Gonzalez ◽

Nicole Zambrano ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Serum Levels ◽

Mortality Rates ◽

Antibody Responses ◽

Cytokine Profiles ◽

Th2 Cytokine ◽

Igg1 Subclass ◽

Asymptomatic Individuals

BackgroundNew World Hantaviruses (NWHs) are the etiological agent underlying hantavirus cardiopulmonary syndrome (HCPS), a severe respiratory disease with high mortality rates in humans. In Panama, infections with Choclo Orthohantavirus (CHOV) cause a much milder illness characterized by higher seroprevalence and lower mortality rates. To date, the cytokine profiles and antibody responses associated with this milder form of HCPS have not been defined. Therefore, in this study, we examined immune serological profiles associated with CHOV infections.MethodsFor this retrospective study, sera from fifteen individuals with acute CHOV-induced HCPS, were analyzed alongside sera from fifteen convalescent phase individuals and thirty-three asymptomatic, CHOV-seropositive individuals. Cytokine profiles were analyzed by multiplex immunoassay. Antibody subclasses, binding, and neutralization against CHOV-glycoprotein (CHOV-GP) were evaluated by ELISA, and flow cytometry.ResultsHigh titers of IFNγ, IL-4, IL-8, and IL-10 serum cytokines were found in the acute individuals. Elevated IL-4 serum levels were found in convalescent and asymptomatic seropositive individuals. High titers of IgG1 subclass were observed across the three cohorts analyzed. Neutralizing antibody response against CHOV-GP was detectable in few acute individuals but was strong in both convalescent and asymptomatic seropositive individuals.ConclusionA Th1/Th2 cytokine signature is characteristic during acute mild HCPS caused by CHOV infection. High expression of Th2 and IL-8 cytokines are correlated with clinical parameters in acute mild HCPS. In addition, a strong IL-4 signature is associated with different cohorts, including asymptomatic individuals. Furthermore, asymptomatic individuals presented high titers of neutralizing antibodies.

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Kinetics of Nucleocapsid, Spike and Neutralizing Antibodies, and Viral Load in Patients with Severe COVID-19 Treated with Convalescent Plasma

Viruses ◽

10.3390/v13091844 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1844

Author(s):

Thomas P. Thomopoulos ◽

Margherita Rosati ◽

Evangelos Terpos ◽

Dimitris Stellas ◽

Xintao Hu ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Rna Binding ◽

Neutralizing Antibody ◽

Binding Domain ◽

High Morbidity ◽

Viral Loads ◽

Effective Treatment Modality ◽

Meta Analyses ◽

Humoral Responses ◽

Kinetics Of

COVID-19 is an ongoing pandemic with high morbidity and mortality. Despite meticulous research, only dexamethasone has shown consistent mortality reduction. Convalescent plasma (CP) infusion might also develop into a safe and effective treatment modality on the basis of recent studies and meta-analyses; however, little is known regarding the kinetics of antibodies in CP recipients. To evaluate the kinetics, we followed 31 CP recipients longitudinally enrolled at a median of 3 days post symptom onset for changes in binding and neutralizing antibody titers and viral loads. Antibodies against the complete trimeric Spike protein and the receptor-binding domain (Spike-RBD), as well as against the complete Nucleocapsid protein and the RNA binding domain (N-RBD) were determined at baseline and weekly following CP infusion. Neutralizing antibody (pseudotype NAb) titers were determined at the same time points. Viral loads were determined semi-quantitatively by SARS-CoV-2 PCR. Patients with low humoral responses at entry showed a robust increase of antibodies to all SARS-CoV-2 proteins and Nab, reaching peak levels within 2 weeks. The rapid increase in binding and neutralizing antibodies was paralleled by a concomitant clearance of the virus within the same timeframe. Patients with high humoral responses at entry demonstrated low or no further increases; however, virus clearance followed the same trajectory as in patients with low antibody response at baseline. Together, the sequential immunological and virological analysis of this well-defined cohort of patients early in infection shows the presence of high levels of binding and neutralizing antibodies and potent clearance of the virus.

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The Slower Antibody Response in Myelofibrosis Patients after Two Doses of mRNA SARS-CoV-2 Vaccine Calls for a Third Dose

Biomedicines ◽

10.3390/biomedicines9101480 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1480

Author(s):

Fabio Fiorino ◽

Anna Sicuranza ◽

Annalisa Ciabattini ◽

Adele Santoni ◽

Gabiria Pastore ◽

...

Keyword(s):

Healthy Subjects ◽

Vaccine Dose ◽

Antibody Responses ◽

Inhibition Activity ◽

Specific Antibodies ◽

Slow Kinetics ◽

Binding Inhibition ◽

Specific Igg ◽

The Impact ◽

Kinetics Of

Immunization with mRNA SARS-CoV-2 vaccines has been highly recommended and prioritized in fragile subjects, including patients with myelofibrosis (MF). Available data on the vaccine immune response developed by MF patients and the impact of ruxolitinib treatment are still too fragmented to support an informed decision on a third dose for this category of subjects. Here, we show that 76% of MF patients develop spike-specific IgG after the second mRNA SARS-CoV-2 vaccine dose, but the response has a slower kinetics compared to healthy subjects, suggesting a reduced capability of their immune system to promptly react to vaccination. A reduced ACE2/RBD binding inhibition activity of spike-specific antibodies was also observed, especially in ruxolitinib-treated patients. Our results, showing slow kinetics of antibody responses in MF patients following vaccination with mRNA SARS-CoV-2 vaccines, support the need for a third vaccine dose.

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Immune response to SARS-CoV-2 variants of concern in vaccinated individuals

Nature Communications ◽

10.1038/s41467-021-23473-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Matthias Becker ◽

Alex Dulovic ◽

Daniel Junker ◽

Natalia Ruetalo ◽

Philipp D. Kaiser ◽

...

Keyword(s):

South African ◽

Neutralizing Antibodies ◽

Substantial Reduction ◽

Humoral Response ◽

Antibody Responses ◽

Igg Antibody ◽

Transmission Potential ◽

Know How ◽

Mutant Strains ◽

Antibody Titers

AbstractSARS-CoV-2 is evolving with mutations in the receptor binding domain (RBD) being of particular concern. It is important to know how much cross-protection is offered between strains following vaccination or infection. Here, we obtain serum and saliva samples from groups of vaccinated (Pfizer BNT-162b2), infected and uninfected individuals and characterize the antibody response to RBD mutant strains. Vaccinated individuals have a robust humoral response after the second dose and have high IgG antibody titers in the saliva. Antibody responses however show considerable differences in binding to RBD mutants of emerging variants of concern and substantial reduction in RBD binding and neutralization is observed against a patient-isolated South African variant. Taken together our data reinforce the importance of the second dose of Pfizer BNT-162b2 to acquire high levels of neutralizing antibodies and high antibody titers in saliva suggest that vaccinated individuals may have reduced transmission potential. Substantially reduced neutralization for the South African variant further highlights the importance of surveillance strategies to detect new variants and targeting these in future vaccines.

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