Zhicheng Zhang1,2, Guo Ai3, Liping Chen1, Shunfang Liu4, Chen Gong4, Xiaodong Zhu5, Chunli Zhang6, Hua Qin1, Junhui Hu7, Jinjin Huang8. 1. Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, USA. 3. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 4. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 5. Department of Oncology, Huang Gang Central Hospital, Huanggang, China. 6. Department of Endocrinology, Huang Gang Central Hospital, Huanggang, China. 7. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, USA. junhuihu@mednet.ucla.edu. 8. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. zczhang@tjh.tjmu.edu.cn.
Abstract
BACKGROUND: COVID-19 has spread widely worldwide, causing millions of deaths. We aim to explore the association of immunological features with COVID-19 severity. METHODS: We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature. RESULTS: A total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of immune cells including CD3+ T cell (× 106, MD, - 413.87; 95%CI, - 611.39 to - 216.34), CD4+ T cell (× 106, MD, - 203.56; 95%CI, - 277.94 to - 129.18), CD8+ T cell (× 106, MD, - 128.88; 95%CI, - 163.97 to - 93.79), B cell (× 106/L; MD, - 23.87; 95%CI, - 43.97 to - 3.78) and NK cell (× 106/L; MD, - 57.12; 95%CI, - 81.18 to - 33.06), and significantly higher levels of cytokines including TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of chemokines as MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant difference was found in other indicators such as Treg cell (× 106, MD, - 0.13; 95%CI, - 1.40 to 1.14), CD4+/CD8+ ratio (MD, 0.26; 95%CI, - 0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, - 0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, - 0.49 to 0.60), IL-4 (pg/ml; MD, - 0.03; 95%CI, - 0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, - 0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, - 2.88 to 4.75). CONCLUSION: Our meta-analysis revealed significantly lower levels of immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells), higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases in comparison to mild cases of COVID-19. Measurement of immunological features could help assess disease severity for effective triage of COVID-19 patients.
BACKGROUND:COVID-19 has spread widely worldwide, causing millions of deaths. We aim to explore the association of immunological features with COVID-19 severity. METHODS: We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature. RESULTS: A total of 21 studies with 2033 COVID-19patients were included. Compared with mild cases, severe cases showed significantly lower levels of immune cells including CD3+ T cell (× 106, MD, - 413.87; 95%CI, - 611.39 to - 216.34), CD4+ T cell (× 106, MD, - 203.56; 95%CI, - 277.94 to - 129.18), CD8+ T cell (× 106, MD, - 128.88; 95%CI, - 163.97 to - 93.79), B cell (× 106/L; MD, - 23.87; 95%CI, - 43.97 to - 3.78) and NK cell (× 106/L; MD, - 57.12; 95%CI, - 81.18 to - 33.06), and significantly higher levels of cytokines including TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of chemokines as MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant difference was found in other indicators such as Treg cell (× 106, MD, - 0.13; 95%CI, - 1.40 to 1.14), CD4+/CD8+ ratio (MD, 0.26; 95%CI, - 0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, - 0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, - 0.49 to 0.60), IL-4 (pg/ml; MD, - 0.03; 95%CI, - 0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, - 0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, - 2.88 to 4.75). CONCLUSION: Our meta-analysis revealed significantly lower levels of immune cells (CD3+ T, CD4+ T, CD8+ T, B and NK cells), higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases in comparison to mild cases of COVID-19. Measurement of immunological features could help assess disease severity for effective triage of COVID-19patients.
Authors: Meredith C Rogers; Kristina D Lamens; Nazly Shafagati; Monika Johnson; Tim D Oury; Sebastian Joyce; John V Williams Journal: J Immunol Date: 2018-07-11 Impact factor: 5.422
Authors: Sophie Hue; Asma Beldi-Ferchiou; Inés Bendib; Mathieu Surenaud; Slim Fourati; Thomas Frapard; Simon Rivoal; Keyvan Razazi; Guillaume Carteaux; Marie-Héléne Delfau-Larue; Armand Mekontso-Dessap; Etienne Audureau; Nicolas de Prost Journal: Am J Respir Crit Care Med Date: 2020-12-01 Impact factor: 21.405
Authors: Jose Manuel Quesada-Gomez; José Lopez-Miranda; Marta Entrenas-Castillo; Antonio Casado-Díaz; Xavier Nogues Y Solans; José Luis Mansur; Roger Bouillon Journal: Nutrients Date: 2022-06-29 Impact factor: 6.706
Authors: Alyssa C Fears; Brandon J Beddingfield; Nicole R Chirichella; Nadia Slisarenko; Stephanie Z Killeen; Rachel K Redmann; Kelly Goff; Skye Spencer; Breanna Picou; Nadia Golden; Cecily C Midkiff; Duane J Bush; Luis M Branco; Matthew L Boisen; Hongmei Gao; David C Montefiori; Robert V Blair; Lara A Doyle-Meyers; Kasi Russell-Lodrigue; Nicholas J Maness; Chad J Roy Journal: PLoS Pathog Date: 2022-07-05 Impact factor: 7.464
Authors: Amal F Alshammary; Jawaher M Alsughayyir; Khalid K Alharbi; Abdulrahman M Al-Sulaiman; Haifa F Alshammary; Heba F Alshammary Journal: Front Med (Lausanne) Date: 2022-04-28
Authors: Lise Lund Berven; Joel Selvakumar; Lise Havdal; Tonje Stiansen-Sonerud; Gunnar Einvik; Truls Michael Leegaard; Trygve Tjade; Annika E Michelsen; Tom Eirik Mollnes; Vegard Bruun Bratholm Wyller Journal: Front Immunol Date: 2022-02-09 Impact factor: 7.561
Authors: Anita Pirabe; Stefan Heber; Waltraud C Schrottmaier; Anna Schmuckenschlager; Sonja Treiber; David Pereyra; Jonas Santol; Erich Pawelka; Marianna Traugott; Christian Schörgenhofer; Tamara Seitz; Mario Karolyi; Bernd Jilma; Ulrike Resch; Alexander Zoufaly; Alice Assinger Journal: Cells Date: 2021-11-30 Impact factor: 6.600