Retrospective Cohort Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Infect Dis. Sep 29, 2022; 12(2): 50-60
Published online Sep 29, 2022. doi: 10.5495/wjcid.v12.i2.50
Clinical significance of anti-nucleocapsid-IgG sero-positivity in SARS-CoV-2 infection in hospitalized patients in North Dakota
Bakir Dzananovic, Mark Williamson, Casmiar Nwaigwe, Chittaranjan Routray
Bakir Dzananovic, Department of Medicine, Idaho College of Osteopathic Medicine, Meridian, ID 83642, United States
Mark Williamson, Department of Biostatistics, Epidemiology and Research Design Core, University of North Dakota, Grand Forks, ND 58202, United States
Casmiar Nwaigwe, Department of Internal Medicine, University of North Dakota School of Medicine and Health Sciences, Minot, ND 58701, United States
Chittaranjan Routray, Family Medicine, University of North Dakota School of Medicine and Health Sciences, Minot, ND 58701, United States
Chittaranjan Routray, Department of Internal Medicine, Trinity Health, Minot, ND 58701, United States
Author contributions: Routray C was the principal investigator and designed the study; Nwaigwe C was the co-investigator, participating in study design and revision of manuscript for intellectual content; Dzananovic B helped with data acquisition, analysis and initial manuscript writing; Williamson M performed the biostatistical analysis and interpretation of the data.
Supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award, No. U54GM128729.
Institutional review board statement: Institutional review board statement: This study was reviewed and approved by the Trinity Hospital, Institutional Review Board Committee.
Informed consent statement: Obtaining informed consent was waived by the IRB committee since this was a retrospective cohort study.
Conflict-of-interest statement: There are no conflict of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE statement- checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Chittaranjan Routray, MD, Clinical Assistant Professor (Honorary), Family Medicine, University of North Dakota School of Medicine and Health Sciences, Minot, ND 58701, United States.
Received: June 18, 2022
Peer-review started: June 18, 2022
First decision: July 14, 2022
Revised: August 2, 2022
Accepted: September 21, 2022
Article in press: September 21, 2022
Published online: September 29, 2022

During the peak of the coronavirus diseases 2019 (COVID-19) pandemic, clinicians actively studied the utility of various epidemiologic-clinical parameters to determine the prognosis for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Serum IgG antibody level, D-Dimer, C-reactive protein and neutrophil to lymphocyte ratio, etc. were studied to assess their association with the clinical course in hospitalized patients and predict who may be at increased risk for poor clinical outcome. However, the influence of SARS-CoV-2-anti-nucleocapsid-IgG antibody (IgG-N) sero-positivity on the clinical outcome of patients with COVID-19 is largely unknown.


To study the influence of SARS-CoV-2 anti-nucleocapsid-IgG seropositivity on clinical course and diseases severity in hospitalized COVID-19 patients.


We conducted a retrospective study of adults admitted to a tertiary care community hospital in North Dakota with COVID-19. Included patients had severe COVID-19 disease or worse and so required supplemental oxygen on admission. They were serologically tested for SARS-CoV-2-anti-nuceocapsid-IgG (IgG-N). The IgG-N positive group were 26 patients and the IgG-N negative group had 33 patients. The groups received similar treatment for COVID-19 as approved by our healthcare system from Day 1 of admission until discharge or death. Measurable parameters for monitoring the patients’ clinical course included the following: Length of hospitalization (LOS), use of high flow nasal canula (HFNC), use of noninvasive bilevel positive pressure ventilation (BiPAP), admission into the intensive care unit, need for mechanical ventilation (VENT); and the patient outcome/discharge or death. Other variables included were age, gender and body-mass-index, and duration of symptoms before presentation. For each variable, the outcome was modeled as a function of SARS-CoV-2-IgG-N status (positive or negative) using a generalized linear model. For LOS-days, a negative binomial distribution was used as it had a better fit than a Poisson or Gaussian distribution as evidenced by a Pearson chi-square/df value closer to 1.0. All other outcomes utilized a binary logistic regression model.


After a thorough examination of patient data, it was found that admission rates to the Intensive Care Unit, as well as the usage of BiPAP, HFNC and VENT support, in conjunction with patient outcomes, were not significantly different across IgG-N status. However, the LOS variable when assessed by IgG-N status was found to be significant (t value = 2.16, P value = 0.0349). IgG-N negative patients had higher than average LOS in comparison to IgG-N positive patients (15.12 vs 9.35 d). Even when removing the extreme value (an LOS of 158 d), IgG-N negative patients still had slightly higher than average stays (10.66 vs 9.35 d) but the relationship was no longer significant. For patient outcome/death, only age (numerical) was a significant predictor (F value = 4.66, P value = 0.0352). No other variables for any of the outcomes were significant predictors of clinical course or disease severity.


Our study demonstrated that IgG-N seroconversion had no significant association with clinical outcomes in hospitalized COVID-19 patients.

Keywords: COVID-19, SARS-CoV-2 IgG-N, Anti-nucleocapsid IgG, Cytokines

Core Tip: We intended to study an immunologic marker to predict the need for advanced oxygen supplement system and clinical outcome in order to support our hospital crisis management system during the peak of the pandemic. Our study demonstrated that presence of anti-nucleocapsid-IgG (IgG-N) against severe acute respiratory syndrome coronavirus 2 infection had no impact on the clinical outcome or disease severity in hospitalized coronavirus disease 2019 (COVID-19) patients. We did not find a correlation of statistical significance to use IgG-N as a biomarker to predict clinical outcome in COVID-19 patients admitted to a community hospital in North Dakota.