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

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.

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

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1390
Author(s):  
Anwar M. Hashem ◽  
Abdullah Algaissi ◽  
Sarah A. Almahboub ◽  
Mohamed A. Alfaleh ◽  
Turki S. Abujamel ◽  
...  
Keyword(s):  
Disease Severity ◽  
Neutralizing Antibodies ◽  
Humoral Response ◽  
Mortality Rates ◽  
Antibody Responses ◽  
High Morbidity ◽  
Clinical Presentations ◽  
Specific Igg ◽  
Almost All ◽  
Kinetics Of

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.

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

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.

scholarly journals Kinetics of antibody responses dictate COVID-19 outcome

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.

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

Viruses ◽  
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.

scholarly journals Patients with Multiple Myeloma on Anti-CD38 or Anti-BCMA Based Regimens and Patients with Waldenstrom's Macroglobulinemia Under Rituximab or BTK Inhibitors Have a Poor Humoral Response Following COVID-19 Vaccination

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3791-3791
Author(s):  
Evangelos Terpos ◽  
Maria Gavriatopoulou ◽  
Ioannis Ntanasis-Stathopoulos ◽  
Alexandros Briasoulis ◽  
Sentiljana Gumeni ◽  
...  
Keyword(s):  
Antibody Response ◽  
Active Treatment ◽  
Neutralizing Antibodies ◽  
Research Funding ◽  
Hematological Malignancies ◽  
Kinase Inhibitors ◽  
Viral Vector ◽  
Vaccine Dose ◽  
Humoral Response ◽  
Kinetics Of

Abstract Introduction: Recent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with hematological malignancies. Herein, we evaluated the development of neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with plasma cell neoplasms (PCNs) after vaccination with either the mRNA BNT162b2 or viral vector AZD1222 vaccine, up to 50 days post their first vaccine dose. Methods: This is an ongoing large prospective study (NCT04743388) evaluating the kinetics of anti-SARS-CoV-2 antibodies after COVID-19 vaccination in healthy subjects and in patients with hematological malignancies or solid tumors. Here we present the data on patients with PCNs in comparison to controls of similar age and gender, who were vaccinated during the same time period (January to March 2021) in Athens (Greece). Major exclusion criteria for both patients and controls included the presence of: (i) autoimmune disorder under immunosuppressive therapy or other active malignant disease; (ii) HIV or active hepatitis B and C infection, (iii) end-stage renal disease and (iv) prior diagnosis of COVID-19. Serum was collected on day 1 (D1; before the first vaccine dose), on day 22 (D22; before the second dose of the BNT162b2 or 3 weeks post the first AZD1222 dose) and on day 50 (D50; 4 weeks post second dose of the BNT162b2 or 7 weeks post the first AZD1222 dose). NAbs against SARS-CoV-2 were measured using an FDA approved-ELISA methodology (cPass™ SARS-CoV-2 NAbs Detection Kit, GenScript, Piscataway, NJ, USA). Results: We evaluated 382 patients with PCNs after vaccination with either the BNT162b2 or the AZD1222 vaccine. Patients with MM (n=213), WM (n=106), SMM (n=38) and MGUS (n=25) and 226 healthy controls were enrolled in the study. Of MM/SMM/MGUS patients, 215 (77.9%) were vaccinated with the BNT162b2 and 61 (22.1%) with the AZD1222 vaccine, while out of 106 WM patients 90 (84.9%) were vaccinated with the BNT162b2 and 16 (15.1%) with the AZD1222 vaccine. Vaccination with either two doses of the BNT162b2 or one dose of the AZD1222 vaccine led to lower production of NAbs against SARS-CoV-2 in patients compared with controls both on day 22 and on day 50 (P<0.001 for all comparisons). After the first dose of the vaccine, on D22, the patient group had lower NAb titers compared with controls: the median NAb inhibition titer was 27% (IQR: 15.3-42%) for MM/SMM/MGUS versus 20.5% (IQR: 10-37%) for WM patients versus 38.7% (IQR: 22-54.3%) for controls (P<0.001 for all comparisons). On D50 the median NAb inhibition titer was 62.8% (IQR: 26-88.9%) for MM/SMM/MGUS versus 36% (IQR: 18-78%) for WM patients versus 90% (IQR: 58-96.4%) for controls (P<0.001 for all comparisons). 57.3% MM/SMM/MGUS, 42% WM patients and 81% controls developed NAb titers ≥50% (p<0.001 for patients versus controls). Furthermore, MM patients showed an inferior NAb response compared with MGUS on day 22 (p=0.009) and on day 50 (p=0.003). Importantly, active treatment with either anti-CD38 monoclonal antibodies or belantamab mafodotin and lymphopenia at the time of vaccination were independent prognostic factors for suboptimal antibody response following vaccination in MM (p<0.05). Disease-related immune dysregulation and therapy-related immunosuppression were involved in the low humoral response in patients with WM. Importantly, active treatment with either rituximab or Bruton's Tyrosine Kinase inhibitors (BTKIs) was proven as an independent prognostic factor for suboptimal antibody response following vaccination in WM (p<0.05). Regarding adverse events, 33% and 31.6% patients reported mild reactions after the first and second dose of the BNT162b2 vaccine, respectively; 32.8% patients vaccinated with the first dose of AZD1222 also presented with local reactions. Conclusion: Patients with MM and WM have a low humoral response following SARS-CoV-2 vaccination, especially those who are under treatment with anti-CD38-, anti-BCMA-, anti-CD20- or BTKIs-based regimens. This result suggest that these patients have to continue the protective measures against SARS-CoV-2 as they are at high risk for COVID-19. Further studies on the kinetics of immune subpopulations following COVID-19 vaccination will elucidate the underlying immune landscape and determine the potential need for additional booster vaccine doses or protective administration of antibodies against SARS-CoV-2 in MM/WM patients with poor response after full vaccination. Disclosures Terpos: Janssen-Cilag: Consultancy, Honoraria, Research Funding; BMS: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Genesis: Consultancy, Honoraria, Research Funding; GSK: Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Gavriatopoulou: Janssen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria; Genesis: Honoraria; GSK: Honoraria; Amgen: Honoraria. Kastritis: Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Genesis: Honoraria; Takeda: Honoraria; Pfizer: Honoraria. Dimopoulos: Janssen: Honoraria; BeiGene: Honoraria; Takeda: Honoraria; Amgen: Honoraria; BMS: Honoraria.

scholarly journals The kinetics of humoral response and its relationship with the disease severity in COVID-19

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Lili Ren ◽  
Lulu Zhang ◽  
De Chang ◽  
Junwen Wang ◽  
Yongfeng Hu ◽  
...  
Keyword(s):  
Disease Severity ◽  
Neutralizing Antibodies ◽  
Late Onset ◽  
Geometric Mean ◽  
Humoral Response ◽  
Spike Protein ◽  
Appearance Time ◽  
Global Pandemic ◽  
Antibody Titers

AbstractCoronavirus Disease 2019 (COVID-19) has caused a global pandemic. Here we profiled the humoral response against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by measuring immunoglobulin (Ig) A, IgM, and IgG against nucleocapsid and spike proteins, along with IgM and IgG antibodies against receptor-binding domain (RBD) of the spike protein and total neutralizing antibodies (NAbs). We tested 279 plasma samples collected from 176 COVID-19 patients who presented and enrolled at different stages of their disease. Plasma dilutions were optimized and based on the data, a single dilution of plasma was used. The mean absorbance at 450 nm was measured for Ig levels and NAbs were measured using geometric mean titers. We demonstrate that 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 disease severity. The appearance time and titers of NAbs showed a significant positive correlation to the antibodies against spike protein. Our results suggest the 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.

scholarly journals Asymptomatic and symptomatic SARS-CoV-2 infections elicit polyfunctional antibodies

2020 ◽  
Author(s):  
Jérémy Dufloo ◽  
Ludivine Grzelak ◽  
Isabelle Staropoli ◽  
Yoann Madec ◽  
Laura Tondeur ◽  
...  
Keyword(s):  
Disease Severity ◽  
Humoral Response ◽  
List Type ◽  
Antiviral Activities ◽  
Infected Cells ◽  
Asymptomatic Individuals ◽  
Antibody Levels ◽  
Kinetics Of ◽  
Complement Deposition

AbstractA large proportion of SARS-CoV-2 infected individuals remains asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyzed antibody functions in 52 asymptomatic infected individuals, 119 mild and 21 hospitalized COVID-19 patients. We measured anti-Spike antibody levels with the S-Flow assay and mapped SARS-CoV-2 Spike- and N-targeted regions by Luminex. Neutralization, complement deposition and Antibody-Dependent Cellular Cytotoxicity (ADCC) were evaluated using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC and trigger complement deposition. Antibody levels and activities are slightly lower in asymptomatic individuals. The different functions of the antibodies are correlated, independently of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction, with minor variations. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells.-Sera from convalescent COVID-19 patients activate the complement and kill infected cells by ADCC.-Asymptomatic and symptomatic SARS-CoV-2-infected individuals harbor polyfunctional antibodies.-Antibody levels and functions are slightly lower in asymptomatic individuals-The different antiviral activities of anti-Spike antibodies are correlated regardless of disease severity.-Functions of anti-Spike antibodies have similar kinetics of induction and contraction.

scholarly journals Longitudinal analysis of the humoral response to SARS-CoV-2 spike RBD in convalescent plasma donors

2020 ◽  
Author(s):  
Josée Perreault ◽  
Tony Tremblay ◽  
Marie-Josée Fournier ◽  
Mathieu Drouin ◽  
Guillaume Beaudoin-Bussières ◽  
...  
Keyword(s):  
Longitudinal Analysis ◽  
Plasma Cells ◽  
De Novo ◽  
Disease Onset ◽  
Humoral Response ◽  
Spike Protein ◽  
Strongly Correlated ◽  
Receptor Binding Domain ◽  
Specific Antibodies ◽  
Plasma Collection

ABSTRACTHéma-Québec, the blood supplier in the Province of Quebec, Canada, collects and tests convalescent plasma used in a clinical trial to determine the clinical efficacy of this product for the treatment of hospitalized COVID-19 patients. So far, we have collected 1159 plasma units from 282 COVID-19 convalescent donors. The presence of antibodies to the receptor binding domain (RBD) of SARS-CoV-2 spike protein in convalescent donors was established at the first donation. Seropositive donors were asked to donate additional plasma units every six days. Until now, 15 donors have donated at least four times and, in some cases, up to nine times. This allowed us to perform a longitudinal analysis of the persistence of SARS-CoV-2 RBD-specific antibodies in these repeat donors, with the first donation occurring 33-77 days after symptoms onset and donations up to 71-114 days after symptoms onset thereafter. In all donors, the level of antibodies remained relatively stable up to about 76 days after symptoms onset but then started to decrease more rapidly to reach, in some convalescent donors, a seronegative status within 100-110 days after symptoms onset. The decline in anti-RBD antibodies was not related to the number of donations but strongly correlated with the numbers of days after symptoms onset (r = 0.821). This suggests that de novo secretion of SARS-CoV-2 RBD antibodies by short-lived plasma cells stopped about 2-3 months after disease onset, an observation that has important implications for convalescent plasma collection and seroprevalence studies undertaken several months after the peak of infection.

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

2021 ◽  
Vol 11 (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.

PHYSICO-CHEMICAL ASPECTS OF YAMUNA RIVER AT GOKUL BARRAGE, MATHURA (UP) INDIA

2017 ◽  
Vol 23 (2) ◽  
Author(s):  
AJAY KUMAR RAJAWAT ◽  
PRAVEEN KUMAR
Keyword(s):  
Water Samples ◽  
Suspended Solids ◽  
Total Dissolved Solids ◽  
Tolerance Limit ◽  
Chemical Condition ◽  
Yamuna River ◽  
Dissolved Solids ◽  
Time Period ◽  
Physico Chemical ◽  
Almost All

An attempt has been made to study the Physico-chemical condition of water of Yamuna River at Gokul Barrage, Mathura, (UP). The time period of study was July 2015 to June 2016. Three water samples were selected from different sites in each month for study. The parameters studied were Temperature, Turbidity, pH, DO, BOD, COD, Total Dissolved Solids and Suspended Solids. Almost all the parameters were found above the tolerance limit.

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