scholarly journals SARS-CoV-2 Antibody responses do not predict COVID-19 disease severity

2020 ◽  
Author(s):  
William S. Phipps ◽  
Jeffrey A. SoRelle ◽  
Quan-Zhen Li ◽  
Lenin Mahimainathan ◽  
Ellen Araj ◽  
...  
Keyword(s):  
Disease Severity ◽  
Symptom Onset ◽  
Severe Disease ◽  
Cross Reactivity ◽  
Reactivity Index ◽  
Disease Course ◽  
Igg Antibodies ◽  
Previous Diagnosis ◽  
Healthy Donors ◽  
Antibody Levels

Background: Initial reports indicate adequate performance of some serological-based SARS-CoV-2 assays. However, additional studies are required to facilitate interpretation of results, including how antibody levels impact immunity and disease course. Methods: In this study, a total of 968 subjects were tested for IgG antibodies reactive to SARS-CoV-2. We confirmed analytic specificity using 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for PCR-based respiratory viral panel. One-hundred seventy-three cases of confirmed or suspected SARS-CoV-2 were tested for IgG. A subgroup of 37 SARS-CoV-2 PCR-positive cases was tested for nucleocapsid-specific IgM antibody using an in-house developed microarray method. Antibody levels were compared between disease severity groups. Results: All specificity specimens were negative for SARS-CoV-2 IgG antibodies (0/656, 0%). Cross reactivity was not detected in specimens with antinuclear antibodies and rheumatoid factor, or cases with previous diagnosis of viral infection including human coronavirus. Positive agreement of IgG with PCR was 83% of samples confirmed to be more than 14 days from symptom onset, with less than 100% sensitivity attributable to a case with severe immunosuppression. Virus-specific IgM was positive in a higher proportion of cases less than 3 days from symptom onset. No association was observed between mild and severe disease course with respect to IgG and IgM levels. Conclusions: The studied SARS-CoV-2 IgG assay had 100% specificity and no adverse cross-reactivity. Index values of IgG and IgM antibodies did not predict disease severity in our patient population.

scholarly journals SARS-CoV-2 Antibody Responses Do Not Predict COVID-19 Disease Severity

2020 ◽  
Vol 154 (4) ◽  
pp. 459-465 ◽  
Author(s):  
William S Phipps ◽  
Jeffrey A SoRelle ◽  
Quan-Zhen Li ◽  
Lenin Mahimainathan ◽  
Ellen Araj ◽  
...  
Keyword(s):  
Disease Severity ◽  
Symptom Onset ◽  
Severe Disease ◽  
Cross Reactivity ◽  
Disease Course ◽  
Igg Antibodies ◽  
Igm Antibodies ◽  
Healthy Donors ◽  
Polymerase Chain ◽  
Antibody Levels

Abstract Objectives Initial reports indicate adequate performance of some serology-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assays. However, additional studies are required to facilitate interpretation of results, including how antibody levels impact immunity and disease course. Methods A total of 967 subjects were tested for IgG antibodies reactive to SARS-CoV-2, including 172 suspected cases of SARS-CoV-2, 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for polymerase chain reaction (PCR)–based respiratory viral panel. A subgroup of SARS-CoV-2 PCR-positive cases was tested for IgM antibodies by proteome array method. Results All specificity and cross-reactivity specimens were negative for SARS-CoV-2 IgG antibodies (0/795, 0%). Positive agreement of IgG with PCR was 83% of samples confirmed to be more than 14 days from symptom onset, with less than 100% sensitivity attributable to a case with severe immunosuppression. Virus-specific IgM was positive in a higher proportion of cases less than 3 days from symptom onset. No association was observed between mild and severe disease course with respect to IgG and IgM levels. Conclusions The studied SARS-CoV-2 IgG assay had 100% specificity and no adverse cross-reactivity. Measures of IgG and IgM antibodies did not predict disease severity in our patient population.

scholarly journals Association between incubation period and clinical characteristics of patients with COVID-19

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095683
Author(s):  
Yeyu Cai ◽  
Jiayi Liu ◽  
Haitao Yang ◽  
Mian Wang ◽  
Qingping Guo ◽  
...  
Keyword(s):  
Incubation Period ◽  
Disease Severity ◽  
Symptom Onset ◽  
Clinical Characteristics ◽  
Characteristic Curve ◽  
Severe Disease ◽  
Receiver Operator Characteristic Curve ◽  
Hunan Province ◽  
Laboratory Findings ◽  
Incubation Periods

Purpose To investigate associations between the clinical characteristics and incubation periods of patients infected with coronavirus disease 2019 (COVID-19) in Wuhan, China. Methods Complete clinical and epidemiological data from 149 patients with COVID-19 at a hospital in Hunan Province, China, were collected and retrospectively analyzed. Results Analysis of the distribution and receiver operator characteristic curve of incubation periods showed that 7 days was the optimal cut-off value to assess differences in disease severity between groups. Patients with shorter (≤7 days) incubation periods (n = 79) had more severe disease, longer durations of hospitalization, longer times from symptom onset to discharge, more abnormal laboratory findings, and more severe radiological findings than patients with longer (>7 days) incubation periods. Regression and correlation analyses also showed that a shorter incubation period was associated with longer times from symptom onset to discharge. Conclusion The associations between the incubation periods and clinical characteristics of COVID-19 patients suggest that the incubation period may be a useful marker of disease severity and prognosis.

scholarly journals Long-Term Course of Humoral and Cellular Immune Responses in Outpatients After SARS-CoV-2 Infection

2021 ◽  
Vol 9 ◽  
Author(s):  
Julia Schiffner ◽  
Insa Backhaus ◽  
Jens Rimmele ◽  
Sören Schulz ◽  
Till Möhlenkamp ◽  
...  
Keyword(s):  
Immune Responses ◽  
Peripheral Blood ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Disease Course ◽  
Igg Antibodies ◽  
Igg Antibody ◽  
Moderate Disease ◽  
Ifn Γ ◽  
Antibody Levels

Characterization of the naturally acquired B and T cell immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important for the development of public health and vaccination strategies to manage the burden of COVID-19 disease. We conducted a prospective, cross-sectional analysis in COVID-19 recovered patients at various time points over a 10-month period in order to investigate how circulating antibody levels and interferon-gamma (IFN-γ) release by peripheral blood cells change over time following natural infection. From March 2020 till January 2021, we enrolled 412 adults mostly with mild or moderate disease course. At each study visit, subjects donated peripheral blood for testing of anti-SARS-CoV-2 IgG antibodies and IFN-γ release after SARS-CoV-2 S-protein stimulation. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies were positive in 316 of 412 (76.7%) and borderline in 31 of 412 (7.5%) patients. Our confirmation assay for the presence of neutralizing antibodies was positive in 215 of 412 (52.2%) and borderline in 88 of 412 (21.4%) patients. Likewise, in 274 of 412 (66.5%) positive IFN-γ release and IgG antibodies were detected. With respect to time after infection, both IgG antibody levels and IFN-γ concentrations decreased by about half within 300 days. Statistically, production of IgG and IFN-γ were closely associated, but on an individual basis, we observed patients with high-antibody titres but low IFN-γ levels and vice versa. Our data suggest that immunological reaction is acquired in most individuals after natural infection with SARS-CoV-2 and is sustained in the majority of patients for at least 10 months after infection after a mild or moderate disease course. Since, so far, no robust marker for protection against COVID-19 exists, we recommend utilizing both, IgG and IFN-γ release for an individual assessment of the immunity status.

scholarly journals Dynamic Alterations of Anti-S-Protein Igg Subclasses and of Th1/Th2 Responses are Hallmarks of Acute Severe COVID-19 Disease

2021 ◽  
Author(s):  
Yun Shan Goh ◽  
Siew-Wai Fong ◽  
Siti Naqiah Amrun ◽  
Cheryl Lee ◽  
Pei Xiang Hor ◽  
...  
Keyword(s):  
Disease Severity ◽  
Severe Disease ◽  
Th2 Response ◽  
S Protein ◽  
Th1 Response ◽  
Humoral Immune ◽  
Mild Disease ◽  
Humoral Immune Responses ◽  
Disease Spectrum ◽  
Antibody Levels

Abstract PurposeCOVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), has a wide disease spectrum ranging from asymptomatic to severe. While it is widely accepted that specific humoral immune responses are critical in controlling the infection, the relationship between the humoral immune response and disease severity is currently unclear.MethodsUsing a flow cytometry-based assay to detect specific antibodies against full length S protein, we compared the antibody levels between patients from different severity groups. We also analysed the cytokine profiles of patients from different severity groups by multiplex microbead-based immunoassay.ResultsWe found an association between specific IgM, IgA and IgG against the spike protein and disease severity. By comparing the ratio of Th1 IgG1 and IgG3 to Th2 IgG2 and IgG4, we observed that all severity groups exhibited a ratio that was skewed towards a stronger Th1 response over Th2 response. In addition to the strong Th1 response, patients with severe disease also developed a Th2 response, as exemplified by the smaller ratio of IgG1 and IgG3 over IgG2 and IgG4 and the smaller Th1/Th2 cytokine ratios, compared to patients with mild disease severity. ConclusionThe results suggest that acute severity or disease resolution is associated with a specific immunological phenotype. A smaller skew towards a Th1 response over Th2 response, during infection, may contribute to disease progression, while a greater skew towards a Th1 response over Th2 response may contribute to a better disease outcome. This may suggest potential therapeutic approaches to COVID-19 disease management.

scholarly journals Retiform Purpura in the Setting of COVID-19: A Harbinger of Underlying Coagulopathy and Severe Disease Course

2021 ◽  
Vol 5 (4) ◽  
pp. 434-436
Author(s):  
Gabrielle Brody ◽  
Michael O. Nguyen ◽  
Delila Pouldar Foulad ◽  
Nathan W. Rojek
Keyword(s):  
Current Literature ◽  
Symptom Onset ◽  
Severe Disease ◽  
Outpatient Setting ◽  
Clinical Deterioration ◽  
Cutaneous Manifestation ◽  
Disease Course ◽  
Clinical Challenge ◽  
Retiform Purpura

While the majority of COVID-19 cases are mild and can be managed in the outpatient setting, more severe cases have proven to be a clinical challenge. While some cases demonstrate a more slow and indolent decline, others seem to deteriorate rapidly with little forewarning. The current literature has connected Retiform Purpura as a cutaneous manifestation associated with severe COVID-19 infections, however timing of cutaneous presentation and severe clinical COVID-19 symptoms has not been well described. Here we report a case of a 58-year-old female who developed Retiform Purpura nearly a week prior to the development of any significant COVID-19 symptoms. This case demonstrates that Retiform Purpura is not only associated with severe COVID-19 disease, but can present prior to symptom onset and should be seen as a harbinger for impending clinical deterioration.

scholarly journals Course and Survival of COVID-19 Patients with Comorbidities in Relation to the Trace Element Status at Hospital Admission

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3304
Author(s):  
Gijs Du Du Laing ◽  
Mirko Petrovic ◽  
Carl Lachat ◽  
Marthe De De Boevre ◽  
Georg J. Klingenberg ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Trace Element ◽  
Disease Severity ◽  
Clinical Care ◽  
Severe Disease ◽  
Therapeutic Interventions ◽  
Zn Deficiency ◽  
Disease Course ◽  
Entire Study ◽  
Risk Of Cancer

Selenium (Se) and zinc (Zn) are essential trace elements needed for appropriate immune system responses, cell signalling and anti-viral defence. A cross-sectional observational study was conducted at two hospitals in Ghent, Belgium, to investigate whether Se and/or Zn deficiency upon hospital admission correlates to disease severity and mortality risk in COVID-19 patients with or without co-morbidities. Trace element concentrations along with additional biomarkers were determined in serum or plasma and associated to disease severity and outcome. An insufficient Se and/or Zn status upon hospital admission was associated with a higher mortality rate and a more severe disease course in the entire study group, especially in the senior population. In comparison to healthy European adults, the patients displayed strongly depressed total Se (mean ± SD: 59.2 ± 20.6 vs. 84.4 ± 23.4 µg L−1) and SELENOP (mean ± SD: 2.2 ± 1.9 vs. 4.3 ± 1.0 mg L−1) concentrations at hospital admission. Particularly strong associations were observed for death risk of cancer, diabetes and chronic cardiac disease patients with low Se status, and of diabetes and obese patients with Zn deficiency. A composite biomarker based on serum or plasma Se, SELENOP and Zn at hospital admission proved to be a reliable tool to predict severe COVID-19 course and death, or mild disease course. We conclude that trace element assessment at hospital admission may contribute to a better stratification of patients with COVID-19 and other similar infectious diseases, support clinical care, therapeutic interventions and adjuvant supplementation needs, and may prove of particular relevance for patients with relevant comorbidities.

Elevated soluble MUC1 levels and decreased anti-MUC1 antibody levels in patients with multiple myeloma

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3147-3153 ◽  
Author(s):  
Steven P. Treon ◽  
Peter Maimonis ◽  
Deborah Bua ◽  
Gloria Young ◽  
Noopur Raje ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Burden ◽  
Plasma Cells ◽  
Residual Disease ◽  
Tumor Burden ◽  
Igg Antibodies ◽  
Healthy Donors ◽  
Antibody Levels ◽  
Minimal Residual ◽  
Active Disease

Abstract Soluble MUC1 (sMUC1) levels are elevated in many MUC1+cancers. We and others have shown that MUC1 is expressed on multiple myeloma (MM) plasma cells and B cells. In this study, we measured sMUC1 levels in bone marrow (BM) plasma from 71 MM patients and 21 healthy donors (HDs), and in peripheral blood (PB) plasma from 42 MM patients and 13 HDs using an immunoassay that detects the CA27.29 epitope of MUC1. sMUC1 levels were found to be significantly greater (mean 31.76 U/mL, range 5.69 to 142.48 U/mL) in MM patient BM plasma versus HD BM plasma (mean 9.68 U/mL, range 0.65 to 39.83 U/mL) (P < .001). Importantly, BM plasma sMUC1 levels were related to tumor burden because sMUC1 levels were significantly higher for MM patients with active disease (34.62 U/mL, range 5.69 to 142.48 U/mL) versus MM patients with minimal residual disease (16.16 U/mL, range 5.7 to 56.68 U/mL) (P = .0026). sMUC1 levels were also elevated in the PB plasma of MM patients (32.79 U/mL, range 4.15 to 148.84 U/mL) versus HDs (18.47 U/mL, range 8.84 to 42.49) (P = .0052). Lastly, circulating immunglobulin M (IgM) and IgG antibodies to MUC1 were measured in 114 MM patients and 31 HDs, because natural antibodies to MUC1 have been detected in patients with other MUC1-bearing malignancies. These studies demonstrated lower levels of circulating IgM (P < .001) and IgG (P = .078) antibodies to MUC1 in MM patients compared with HDs. Our data therefore show that in MM patients, sMUC1 levels are elevated and correlate with disease burden, whereas anti-MUC1 antibody levels are decreased.

scholarly journals Dynamic change and clinical relevance of post-infectious SARS-CoV-2 antibody responses

2021 ◽  
Author(s):  
P W G Mallon ◽  
W Tinago ◽  
A Garcia Leon ◽  
K McCann ◽  
G Kenny ◽  
...  
Keyword(s):  
Disease Severity ◽  
Symptom Onset ◽  
Post Infection ◽  
Dynamic Change ◽  
Severe Disease ◽  
Additive Models ◽  
Antibody Responses ◽  
Rapid Decline ◽  
Relative Differences ◽  
Post Infectious

Abstract Background Although reports suggest that most individuals with COVID-19 develop detectable antibodies post infection, the kinetics, durability, and relative differences between IgM and IgG responses beyond the first few weeks after symptom onset remain poorly understood. Methods Within a large, well-phenotyped, diverse, prospective cohort of subjects with and without SARS-CoV-2 PCR-confirmed infection and historical controls derived from cohorts with high prevalence of viral coinfections and samples taken during prior flu seasons, we measured SARS-CoV-2 serological responses (both IgG and IgM) using commercially available assays. We calculated sensitivity and specificity, relationship with disease severity and mapped the kinetics of antibody responses over time using generalised additive models. Results We analysed 1,001 samples from 752 subjects, 327 with confirmed SARS-CoV-2 (29.7% with severe disease) spanning a period of 90 days from symptom onset. Sensitivity was lower (44.1-47.1%) early (<10 days) after symptom onset but increased to >80% after 10 days. IgM positivity increased earlier than IgG-targeted assays but positivity peaked between day 32 and 38 post onset of symptoms and declined thereafter, a dynamic that was confirmed when antibody levels were analysed, with more rapid decline observed with IgM. Early (<10 days) IgM but not IgG levels were significantly higher in those who subsequently developed severe disease (signal / cut-off 4.20 (0.75-17.93) versus 1.07 (0.21-5.46), P=0.048). Conclusions This study suggests that post-infectious antibody responses in those with confirmed COVID-19 begin to decline relatively early post infection and suggests a potential role for higher IgM levels early in infection predicting subsequent disease severity

scholarly journals An Original ELISA-Based Multiplex Method for the Simultaneous Detection of 5 SARS-CoV-2 IgG Antibodies Directed against Different Antigens

2020 ◽  
Vol 9 (11) ◽  
pp. 3752
Author(s):  
Constant Gillot ◽  
Jonathan Douxfils ◽  
Julie Cadrobbi ◽  
Kim Laffineur ◽  
Jean-Michel Dogné ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Clinical Performance ◽  
Severe Disease ◽  
Simultaneous Detection ◽  
Hospitalized Patients ◽  
Igg Antibodies ◽  
Specificity And Sensitivity ◽  
Significant Difference ◽  
Antibody Titers

Strategies to detect SARS-CoV-2 are increasingly being developed. Among them, serological methods have been developed. Nevertheless, although these may present an interesting clinical performance, they are often directed against only one antigen. This study aims at evaluating the clinical performance of an innovative multiplex immunoassay (i.e., CoViDiag assay) detecting simultaneously the presence of antibodies directed against N, S1, S2, RBD and NTD antigens. Sensitivity was evaluated in 135 samples obtained from 94 rRT-PCR confirmed coronavirus disease 2019 (COVID-19) patients. Non-SARS-CoV-2 sera (n = 132) collected before the COVID-19 pandemic with potential cross-reactions to the SARS-CoV-2 immunoassay were included in the specificity analysis. The antibody signature was also studied in hospitalized and non-hospitalized patients. The specificity of the CoViDiag assay was excellent for all antibodies (99.2 to 100%) using adapted cut-offs. None of the false positive samples were positive for more than one antibody. The sensitivity obtained from samples collected 14 days since symptom onset varied from 92.0 to 100.0% depending on the antibody considered. Among samples collected more than 14 days after symptom onset, 12.8, 66.3, 3.5, 9.3, 5.8 and 2.3% were positive for 5, 4, 3, 2, 1 or 0 antibodies, respectively. A trend toward higher antibody titers was observed in hospitalized patient in the early days since symptom onset. However, no significant difference was observed compared to non-hospitalized patients after 14 days since symptom onset. The clinical performance of the CoViDiag 5 IgG assay is sufficient to recommend its use for the detection and the characterization of the antibody signature following SARS-CoV-2 infection. The combination of several antigens in the same test improves the overall specificity and sensitivity of the test. Further research is needed to investigate whether this strategy may be of interest to identify severe disease outcome in patients with SARS-CoV-2 infection.

scholarly journals Dynamic change and clinical relevance of post-infectious SARS-CoV-2 antibody responses

2021 ◽  
Author(s):  
PWG Mallon ◽  
W Tinago ◽  
A Garcia Leon ◽  
K McCann ◽  
G Kenny ◽  
...  
Keyword(s):  
Disease Severity ◽  
Symptom Onset ◽  
Post Infection ◽  
Dynamic Change ◽  
Severe Disease ◽  
Additive Models ◽  
Antibody Responses ◽  
Rapid Decline ◽  
Relative Differences ◽  
Post Infectious

AbstractBackgroundAlthough reports suggest that most individuals with COVID-19 develop detectable antibodies post infection, the kinetics, durability, and relative differences between IgM and IgG responses beyond the first few weeks after symptom onset remain poorly understood.MethodsWithin a large, well-phenotyped, diverse, prospective cohort of subjects with and without SARS-CoV-2 PCR-confirmed infection and historical controls derived from cohorts with high prevalence of viral coinfections and samples taken during prior flu seasons, we measured SARS-CoV-2 serological responses (both IgG and IgM) using commercially available assays. We calculated sensitivity and specificity, relationship with disease severity and mapped the kinetics of antibody responses over time using generalised additive models.ResultsWe analysed 1,001 samples from 752 subjects, 327 with confirmed SARS-CoV-2 (29.7% with severe disease) spanning a period of 90 days from symptom onset. Sensitivity was lower (44.1-47.1%) early (<10 days) after symptom onset but increased to >80% after 10 days. IgM positivity increased earlier than IgG-targeted assays but positivity peaked between day 32 and 38 post onset of symptoms and declined thereafter, a dynamic that was confirmed when antibody levels were analysed, with more rapid decline observed with IgM. Early (<10 days) IgM but not IgG levels were significantly higher in those who subsequently developed severe disease (signal / cut-off 4.20 (0.75-17.93) versus 1.07 (0.21-5.46), P=0.048).ConclusionsThis study suggests that post-infectious antibody responses in those with confirmed COVID-19 begin to decline relatively early post infection and suggests a potential role for higher IgM levels early in infection predicting subsequent disease severity.

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