Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score

ABSTRACT Effective methods for predicting COVID-19 disease trajectories are urgently needed. Here, enzyme-linked immunosorbent assay (ELISA) and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the intensive care unit (ICU), requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within 6 days post-symptom onset and sometimes within 1 day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patient’s comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 likelihood ratio (96.7% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention. IMPORTANCE The COVID-19 pandemic has resulted in over two million deaths worldwide. Despite efforts to fight the virus, the disease continues to overwhelm hospitals with severely ill patients. Diagnosis of COVID-19 is readily accomplished through a multitude of reliable testing platforms; however, prognostic prediction remains elusive. To this end, we identified a short epitope from the SARS-CoV-2 nucleocapsid protein and also a disease risk factor score based upon comorbidities and age. The presence of antibodies specifically binding to this epitope plus a score cutoff can predict severe COVID-19 outcomes with 96.7% specificity.

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Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score

10.1101/2020.10.15.341743 ◽

2020 ◽

Author(s):

Sanjana Sen ◽

Emily C. Sanders ◽

Kristin N. Gabriel ◽

Brian M. Miller ◽

Hariny M. Isoda ◽

...

Keyword(s):

Risk Factor ◽

Factor Score ◽

Disease Risk ◽

Severe Disease ◽

Disease Risk Factor ◽

Disease States ◽

Wide Range ◽

Risk Patients ◽

New Type ◽

Risk Factor Score

AbstractEffective methods for predicting COVID-19 disease trajectories are urgently needed. Here, ELISA and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide-range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the ICU, requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within six days post-symptom onset and sometimes within one day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patient’s comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 Likelihood Ratio (96.72% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention.

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Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

BMC Infectious Diseases ◽

10.1186/s12879-021-05992-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

M. Flook ◽

C. Jackson ◽

E. Vasileiou ◽

C. R. Simpson ◽

M. D. Muckian ◽

...

Keyword(s):

Public Health ◽

Risk Factors ◽

Systematic Review ◽

At Risk ◽

Risk Factor ◽

Disease Severity ◽

Severe Disease ◽

Public Health Response ◽

Wide Range ◽

Multivariable Analyses

Abstract Background Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. Registration This review was registered on PROSPERO as CRD42020177714.

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Prevalence and outcome of young stroke patients with middle cerebral artery stenosis

BMC Neurology ◽

10.1186/s12883-021-02125-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wenjuan Xu ◽

Xiaoyu Zhang ◽

Huan Chen ◽

Zhangning Zhao ◽

Meijia Zhu

Keyword(s):

Risk Factors ◽

Logistic Regression ◽

Risk Factor ◽

Factor Score ◽

Unfavorable Outcome ◽

Stroke Patients ◽

Young Stroke ◽

Stroke In Young Adults ◽

Risk Factor Score ◽

Stroke In Young

Abstract Background Etiologies of acute ischemic stroke in young adults are heterogeneous. Middle cerebral artery (MCA) stenosis is a common finding in Asians which may be an important cause of stroke in young adults. However, studies of stroke in young Asian populations are rare. Our study was to investigate the prevalence and outcome of young stroke patients with MCA stenosis in Chinese populations. Methods Young patients with MCA territory infarction between January 2013 and September 2018 were retrospectively recruited. Subjects were defined as stenosis group (MCA stenosis ≥50%) and no-stenosis group (MCA stenosis<50% or no stenosis) by their MCA stenosis. For patients in stenosis group, they were categorized as uni-MCA stenosis subgroup and multiple stenosis subgroup. Demographic data, risk factors, imaging feature and complications were compared between groups. Prevalence of MCA stenosis and risk factor score (score ≥ 2 or 3) in different age groups were investigated. Modified Rankin Scale (mRS) was used for evaluating functional outcome at discharge (unfavorable outcome: 3–6). Binary logistic regression was performed to determine independent risk factors of unfavorable outcome. Results Two hundred forty-nine young stroke patients were included in our study and 110 (44.2%) patients were defined as stenosis group. 55 (50%) patients were categorized as uni-MCA stenosis subgroup and 55 (50%) were multiple stenosis subgroup. The most common traditional vascular risk factors included hypertension, hyperlipemia, smoking, hyperhomocysteinemia and alcohol consumption. Prevalence of risk factor score ≥ 2 or 3 increased with age, but not incidence of MCA stenosis. By TOAST classification, the most common etiologies were large-artery atherosclerosis (41.0%) and small vessel disease (33.7%). Compared with no-stenosis group, patients in stenosis group were more likely to have large territorial infarct, develop complications and have unfavorable outcome. No significant difference was found between patients in uni-MCA stenosis and multiple stenosis subgroups except history of stroke/TIA, risk factor score ≥ 3 and silent infarct. By logistic regression, hypertension (OR = 3.561; 95%CI, 1.494 to 8.492; p = 0.004), NIHSS scores at admission (OR = 1.438; 95%CI, 1.276 to 1.620; p = 0,000) and infarct size (p = 0.015) independently predicted unfavorable outcome. Conclusions Forty-four point two percent young Chinese adults with MCA territory infarction had MCA stenosis. Prevalence of MCA stenosis did not increase with age. Patients with MCA stenosis had worse clinical outcome, however, only hypertension, NIHSS scores at admission and infarct size were independent predictors.

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