Immunological Characteristics of Unvaccinated Patients with COVID-19 in the Early Pandemic Period
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Immune responses to infectious disease differ according to disease severity. In this study, we investigated the overall laboratory profiles, including antibody titers and cytokine levels in unvaccinated patients with Coronavirus Disease 2019 (COVID-19), according to disease severity at the initial stage during the early pandemic period. Methods: In total, 195 unvaccinated patients with COVID-19, who were hospitalized from February to August 2020 were enrolled in this study. The patients were divided into five severity categories, and their antibody titers and cytokine levels were evaluated by collecting serial blood samples up to the first three months after infection. Results: Older male patients with comorbidities had a higher probability of rapid disease progression. Patients who required intensive care showed significantly lower initial hemoglobin, platelet counts, total protein, and albumin levels, with significantly higher neutrophil-to-lymphocyte ratios, blood urea nitrogen, creatinine, and coagulation, cardiac, and inflammatory markers compared to those in patients who did not require intensive care. At three weeks after infection, the titers of both the anti-receptor binding domain of spike protein and neutralizing antibodies were significantly higher in patients with high disease severity than in patients with low disease severity; a similar trend was observed for IL-6 and TNF-α levels for at least three months from infection onset. Conclusions: Antibody and pro-inflammatory cytokine levels showed a significant difference according to disease severity in the early stage of infection. Therefore, development of drugs targeting these antibodies and cytokines may help alleviate the severity of COVID-19.
Abstract
Background: Immune responses to infectious disease differ according to disease severity. In this study, we investigated the overall laboratory profiles, including antibody titers and cytokine levels in unvaccinated patients with Coronavirus Disease 2019 (COVID-19), according to disease severity at the initial stage during the early pandemic period. Methods: In total, 195 unvaccinated patients with COVID-19, who were hospitalized from February to August 2020 were enrolled in this study. The patients were divided into five severity categories, and their antibody titers and cytokine levels were evaluated by collecting serial blood samples up to the first three months after infection. Results: Older male patients with comorbidities had a higher probability of rapid disease progression. Patients who required intensive care showed significantly lower initial hemoglobin, platelet counts, total protein, and albumin levels, with significantly higher neutrophil-to-lymphocyte ratios, blood urea nitrogen, creatinine, and coagulation, cardiac, and inflammatory markers compared to those in patients who did not require intensive care. At three weeks after infection, the titers of both the anti-receptor binding domain of spike protein and neutralizing antibodies were significantly higher in patients with high disease severity than in patients with low disease severity; a similar trend was observed for IL-6 and TNF-α levels for at least three months from infection onset. Conclusions: Antibody and pro-inflammatory cytokine levels showed a significant difference according to disease severity in the early stage of infection. Therefore, development of drugs targeting these antibodies and cytokines may help alleviate the severity of COVID-19.
참고문헌 (42)
- Rothman KJ, "Causes", Am J Epidemiol, 104, pp.587~592 (1976)
- "Concepts of Disease Occurrence" (2011)[URL]
- Clarke KEN, "Seroprevalence of infection-induced SARS-CoV-2 antibodies-United States, September 2021-February 2022", MMWR Morb Mortal Wkly Rep, 71, pp.606~608 (2022)
- "Coronavirus (COVID-19) Dashboard" (2022)[URL]
- Kim Shin-Woo, "Clinical Characteristics and Outcomes of COVID-19 Cohort Patients in Daegu Metropolitan City Outbreak in 2020", Journal of Korean Medical Science, 36(1), pp.1~15 (2021), 대한의학회[DOI]
- Surme S, "Predictors of intensive care unit admission or mortality in patients with Coronavirus disease 2019 pneumonia in Istanbul, Turkey", Jpn J Infect Dis, 74, pp.458~464 (2021)
- Henry BM, "Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019(COVID-19) : a meta-analysis", Clin Chem Lab Med, 58, pp.1021~1028 (2020)
- Gallo Marin B, "Predictors of COVID-19 severity : a literature review", Rev Med Virol, 31, pp.1~10 (2021)
- Dispinseri S, "Neutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival", Nat Commun, 12, pp.2670~ (2021)
- Maeda T, "Early anti-SARS-CoV-2 immunoglobulin G response may be associated with disease severity in patients with COVID-19", Jpn J Infect Dis, 74, pp.560~562 (2021)
- Kwon JS, "Factors of severity in patients with COVID-19 : cytokine", chemokine concentrations, viral load, and antibody responses, 2020, pp.103, 2412~2418
- Costela-Ruiz VJ, "SARS-CoV-2 infection : the role of cytokines in COVID-19 disease", Cytokine Growth Factor Rev, 54, pp.62~75 (2020)
- Shah VK, "Overview of immune response during SARS-CoV-2 infection : lessons from the past", Front Immunol, 11, pp.1949~ (2020)
- Brodin P, "Human immune system variation", Nat Rev Immunol, 17, pp.21~29 (2017)
- Marshall JS, "An introduction to immunology and immunopathology", Allergy Asthma Clin Immunol, 14(Suppl 2), pp.49~ (2018)
- Cooper NR, "The role of antibody and complement in the control of viral infections", J Invest Dermatol, 83, pp.121s~127s (1984)
- Brady LJ, "Antibody-mediated immunomodulation : a strategy to improve host responses against microbial antigens", Infect Immun, 73, pp.671~678 (2005)
- Jalkanen P, "COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants", Nat Commun, 12, pp.3991~ (2021)
- Doria-Rose N, "Antibody persistence through 6 months after the second dose of mRNA-1273 vaccine for Covid-19", N Engl J Med, 384, pp.2259~2261 (2021)
- Kim Namhee, "Positivity of SARS-CoV-2 Antibodies among Korean Healthy Healthcare Workers 1 and 2 Weeks after Second Dose of Pfizer-BioNTech Vaccination", Journal of Korean Medical Science, 36(21), pp.1~6 (2021), 대한의학회[DOI]
- Yang L, "COVID-19 antibody therapeutics tracker : a global online database of antibody therapeutics for the prevention and treatment of COVID-19", Antib Ther, 3, pp.205~212 (2020)
- Deb P, "An update to monoclonal antibody as therapeutic option against COVID-19", Biosaf Health, 3, pp.87~91 (2021)
- Zheng J, "Characterization of SARS-CoV-2-specific humoral immunity and its potential applications and therapeutic prospects", Cell Mol Immunol, 19, pp.150~157 (2022)
- Dinarello CA, "Historical insights into cytokines", Eur J Immunol, 37(Suppl 1), pp.S34~S45 (2007)
- Zhang J-M, "Cytokines, inflammation, and pain", Int Anesthesiol Clin, 45, pp.27~37 (2007)
- Beltra JC, "Cytokines and persistent viral infections", Cytokine, 82, pp.4~15 (2016)
- Ragab D, "The COVID-19 cytokine storm; what we know so far", Front Immunol, 11, pp.1146~ (2020)
- Del Valle DM, "An inflammatory cytokine signature predicts COVID-19 severity and survival", Nat Med, 26, pp.1636~1643 (2020)
- "Clinical Spectrum of SARS-CoV-2 Infection" (2022)[URL]
- Gandhi RT, "Mild or moderate Covid-19", N Engl J Med, 383, pp.1757~1766 (2020)
- Korea Disease Control and Prevention Agency, "Coronavirus (COVID-19) guideline, Republic of Korea (local government)" (2022), Central Disaster Management Headquarters and Central Disease Control Headquarters
- "Underlying medical conditions associated with higher risk for severe COVID-19: Information for healthcare professionals"[URL]
- Sanyaolu A, "Comorbidity and its impact on patients with COVID-19", SN Compr Clin Med, 2, pp.1069~1076 (2020)
- Basheer M, "The cytokine storm in COVID-19 : the strongest link to morbidity and mortality in the current epidemic", COVID, 2, pp.540~552 (2022)
- Niedźwiedzka-Rystwej P, "Immune signature of COVID-19 : In-depth reasons and consequences of the cytokine storm", Int J Mol Sci, 23, pp.4545~ (2022)
- Jing X, "Association between inflammatory cytokines and anti-SARS-CoV-2 antibodies in hospitalized patients with COVID-19", Immun Ageing, 19, pp.12~ (2022)
- Schultheiß C, "The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19", Cell Rep Med, 3, pp.100663~ (2022)
- Ling L, "Longitudinal cytokine profile in patients with mild to critical COVID-19", Front Immunol, 12, pp.763292~ (2021)
- Do TND, "SARS-CoV-2 virion infectivity and cytokine production in primary human airway epithelial cells", Viruses, 14, pp.951~ (2022)
- Nyberg T, "Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron(B. 1. 1. 529)and delta(B. 1. 617. 2)variants in England : a cohort study", Lancet, 399, pp.1303~1312 (2022)
- Servellita V, "Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants", Cell, 185, pp.1539~1548 (2022)
- Korea Disease Control and Prevention Agency, "July 2021 status and characteristics of the COVID-19 variant virus outbreak in the Republic of Korea", Public Health Wkly Rep, 14, pp.3388~3396 (2021)
