The Inflammatory environment in patients with COVID-19
Systematic review
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Abstract
The SARS-CoV-2 virus is the main cause of the pandemic viral pneumonia known as COVID-19. Some studies suggest that, in this disease, lymphopenia is the most common sign of infection, as well as increased CRP and IL-6 caused by a cytokine storm directed at the lungs. Therefore, the hypothesis of the study is to make a systematic revision of scientific studies linked to the immunological phenomenon known as COVID-19.
Objectives: The main aim is to study the cytokine storm of COVID-19, as well as to determine the role of IL-6 and T-lymphocytes.
Methods: A search strategy was made through the PICOS questions, based on the PRISMA method. The MeSH terms were looked up on PubMed, Google Scholar and SciELO (2019-2021). The level of quality was sought according to the ranking of Scimago institutions, and the H index of the journals was assessed.
Results: 43 articles were included, and clinic, diagnosis, treatment, and pathogenesis were compared. A decrease in TCD4 / CD8 lymphocytes was shown in patients with severe disease, as well as an increase in IL-6 and CRP.
Conclusions: The immunological phenomenon known as COVID-19 is characterized by lymphopenia and an increase in IL-6 amongst critically ill patients. Monitoring those parameters could help to understand the progression of the COVID-19 disease.
References
Coomes EA, Haghbayan H. Interleukin-6 in Covid-19: A systematic review and meta-analysis. Rev Med Virol. 2020;(May):1–9. ?
Bordallo B, Bellas M, Cortez AF, Vieira M, Pinheiro M. Severe COVID-19: what have we learned with the immunopathogenesis? Adv Rheumatol (London, England). 2020;60(1):50.
Pedersen SF, Ho YC. SARS-CoV-2: A storm is raging. Journal of Clinical Investigation. 2020. ?
I am M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID- 19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol. 2020;39(7):2085–94. ?
Jamilloux Y, Henry T, Belot A, Viel S, Fauter M, El Jammal T, et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev [Internet]. 2020;19(7):102567. Available from: https://doi.org/10.1016/j.autrev.2020.102567 ?
Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620–9. ?
Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of Immune Response in Patients with COVID-19 in Wuhan, China. SSRN Electron J. 2020; ?
Sekine T, Perez-Potti A, Rivera-Ballesteros O, Strålin K, Gorin J-B, Olsson A, et al. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell. 2020; ?
Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L. SARS- CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev [Internet]. 2020;54(May):62–75. Available from: https://doi.org/10.1016/j.cytogfr.2020.06.001 ?
Yang J, Zheng Y, Gou X, Pu K, Chen Z. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2. Int J Infect Dis. 2020;94(April):91–5. ?
Zheng Z, Peng F, Xu B, Zhao J, Liu H, Peng J, et al. Risk factors of critical & mortal COVID- 19 cases: A systematic literature review and meta-analysis. J Infect [Internet]. 2020;81(2):e16–25. Available from: https://doi.org/10.1016/j.jinf.2020.04.021 ?
Hu Y, Sun J, Dai Z, Deng H, Li X, Huang Q, et al. Prevalence and severity of corona virus disease 2019 (COVID-19): A systematic review and meta-analysis. J Clin Virol [Internet]. 2020;127:104371. Available from: https://doi.org/10.1016/j.jcv.2020.104371 ?
Medeiros Figueiredo A, Daponte-Codina A, Moreira Marculino Figueiredo DC, Toledo Vianna RP, Costa de Lima K, Gil-García E. Factors associated with the incidence and mortality from COVID-19 in the autonomous communities of Spain. Gac Sanit [Internet]. 2020;(xx). Available from: https://doi.org/10.1016/j.gaceta.2020.05.004 ?
Weiskopf D, Immunol S, Weiskopf D, Schmitz KS, Raadsen MP, Grifoni A, et al. Phenotype and kinetics t cell in covid19+ARDS. 2020;2071:1–15. Inflammatory environment in patients with COVID-19: Systematic Review
Wang J, Jiang M, Chen X, Montaner LJ. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts. J Leukoc Biol. 2020;108(1):17–41. ?
Sekine T, Perez-Potti A, Rivera-Ballesteros O, Strålin K, Gorin J-B, Olsson A, et al. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell. 2020;158–68. ?
Meftahi GH, Jangravi Z, Sahraei H, Bahari Z. The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of "inflame- aging." Inflamm Res [Internet]. 2020;69(9):825–39. Available from: https://doi.org/10.1007/s00011-020-01372-8
Wan S, Li M, Ye Z, Yang C, Cai Q, Duan S, et al. CT Manifestations and Clinical Characteristics of 1115 Patients with Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-analysis [Internet]. Vol. 27, Academic Radiology. Elsevier Inc.; 2020. 910– 921 p. Available from: https://doi.org/10.1016/j.acra.2020.04.033 ?
Nile SH, Nile A, Qiu J, Li L, Jia X, Kai G. COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine Growth Factor Rev. 2020;53:66–70. ?
Cheung KS, Hung IFN, Chan PPY, Lung KC, Tso E, Liu R, et al. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis. Gastroenterology [Internet]. 2020;159(1):81–95. Available from: https://doi.org/10.1053/j.gastro.2020.03.065 ?
Suresh Kumar VC, Mukherjee S, Harne PS, Subedi A, Ganapathy MK, Patthipati VS, et al. Novelty in the gut: A systematic review and meta-analysis of the gastrointestinal manifestations of COVID-19. BMJ Open Gastroenterol. 2020;7(1). ?
Yee J, Kim W, Han JM, Yoon HY, Lee N, Lee KE, et al. Clinical manifestations and perinatal outcomes of pregnant women with COVID-19: a systematic review and meta-analysis. Sci Rep [Internet]. 2020;10(1):1–7. Available from: https://doi.org/10.1038s41598-020-75096-4 ?
Moutchia J, Pokharel P, Kerri A, McGaw K, Uchai S, Nji M, et al. Clinical laboratory parameters associated with severe or critical novel coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. PLoS One [Internet]. 2020;15(10 October):1–25. Available from: http://dx.doi.org/10.1371/journal.pone.0239802 ?
Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Front Immunol. 2020;11(June):1–4. ?
Copaescu A, Smibert O, Gibson A, Phillips EJ, Trubiano JA. The role of IL-6 and other mediators in the cytokine storm associated with SARS-CoV-2 infection. J Allergy Clin Immunol [Internet]. 2020;146(3):518-534.e1. Available from: https://doi.org/10.1016/j.jaci.2020.07.001 ?
Mangalmurti N, Hunter CA. Cytokine Storms: Understanding COVID-19. Immunity [Internet]. 2020;53(1):19–25. Available from: https://doi.org/10.1016/j.immuni.2020.06.017 ?
Sun X, Wang T, Cai D, Hu Z, Chen J, Liao H, et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. Cytokine Growth Factor Rev [Internet]. 2020;53(March):38–42. Available from: https://doi.org/10.1016/j.cytogfr.2020.04.002 ?
Tufan A, Avano?lu Güler A, Matucci-Cerinic M. Covid-19, immune system response, hyperinflammation and repurposinantirheumatic drugs. Turkish J Med Sci. 2020;50(SI- 1):620–32. ?
Mahmudpour M, Roozbeh J, Keshavarz M, Farrokhi S, Nabipour I. COVID-19 cytokine storm: The anger of inflammation. Cytokine. 2020;133(April). ?
Ulhaq ZS, Soraya GV. Interleukin-6 as a potential biomarker of COVID-19 progression. Med Mal Infect [Internet]. 2020;50(4):382–3. Available from: https://doi.org/10.1016/j.medmal.2020.04.002
Mojtabavi H, Saghazadeh A, Rezaei N. Interleukin-6 and severe COVID-19: a systematic review and meta-analysis. Eur Cytokine Netw. 2020;31(2):44–9. ?
Li X, Pan X, Li Y, An N, Xing Y, Yang F, et al. Cardiac injury associated with severe disease or ICU admission and death in hospitalized patients with COVID-19: A meta-analysis and systematic review. Crit Care. 2020;24(1):1–16. ?
Tang Y, Liu J, Zhang D, Xu Z, Ji J, Wen C. Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies. Front Immunol. 2020;11(July):1–13. ?
Grifoni A, Weiskopf D, Ramirez SI, Mateus J, Dan JM, Moderbacher CR, et al. Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell. 2020; ?
Wang C, Xie J, Zhao L, Fei X, Zhang H, Tan Y, et al. Alveolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. EBioMedicine [Internet]. 2020;57:102833. Available from: https://doi.org/10.1016/j.ebiom.2020.102833 ?
Hu B, Huang S, Yin L. The cytokine storm and COVID?19. J Med Virol. 2020;2:0–2. ?
Sun P, Qie S, Liu Z, Ren J, Li K, Xi J. Clinical characteristics of hospitalized patients with Inflammatory environment in patients with COVID-19: Systematic Review
SARS-CoV-2 infection: A single arm meta-analysis. J Med Virol. 2020;92(6):612–7.
Xie Y, Wang Z, Liao H, Marley G, Wu D, Tang W. Epidemiologic, clinical, and laboratory findings of the COVID-19 in the current pandemic: Systematic review and meta-analysis. BMC Infect Dis. 2020;20(1):1–12. ?
Dhama K, Patel SK, Pathak M, Yatoo MI, Tiwari R, Malik YS, et al. An update on SARS- ?CoV-2/COVID-19 with particular reference to its clinical pathology, pathogenesis, immunopathology and mitigation strategies. Travel Med Infect Dis [Internet]. 2020;37:101755. Available from: https://doi.org/10.1016/j.tmaid.2020.101755 ?
Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R, Costa F, et al. COVID-19 diagnosis and management: a comprehensive review. J Intern Med. 2020;288(2):192–206. ?
Hasani H, Mardi S, Shakerian S, Taherzadeh-Ghahfarokhi N, Mardi P. The Novel Coronavirus Disease (COVID-19): A PRISMA Systematic Review and Meta-Analysis of Clinical and Paraclinical Characteristics. Biomed Res Int. 2020;2020:3149020. ?
Bao J, Li C, Zhang K, Kang H, Chen W, Gu B. Comparative analysis of laboratory indexes of severe and non-severe patients infected with COVID-19. Clin Chim Acta [Internet]. 2020;509:180–94. Available from: https://doi.org/10.1016/j.cca.2020.06.009 ?
Akbari H, Tabrizi R, Lankarani KB, Aria H, Vakili S, Asadian F, et al. The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis [Internet]. Vol. 258, Life Sciences. Elsevier Inc; 2020. 118167 p. Available from: https://doi.org/10.1016/j.lfs.2020.118167 ?
Ghahramani S, Tabrizi R, Lankarani KB, Kashani SMA, Rezaei S, Zeidi N, et al. Laboratory features of severe vs. non-severe COVID-19 patients in Asian populations: A systematic review and meta-analysis. Eur J Med Res [Internet]. 2020;25(1):1–10. Available from: https://doi.org/10.1186/s40001-020-00432-3 ?
Li Y, Yao L, Li J, Chen L, Song Y, Cai Z, et al. Stability issues of RT-PCR testing of SARS- CoV-2 for hospitalized patients clinically diagnosed with COVID-19. J Med Virol. 2020;92(7):903–8. ?
Ye Q, Wang B, Mao J. The pathogenesis and treatment of the 'Cytokine Storm'' in COVID-19.' J Infect [Internet]. 2020;80(6):607–13. Available from: https://doi.org/10.1016/j.jinf.2020.03.037
McGonagle D, Sharif K, O'Regan A, Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev [Internet]. 2020;19(6):102537. Available from:
https://doi.org/10.1016/j.autrev.2020.102537
Chakraborty C, Sharma AR, Bhattacharya M, Sharma G, Lee SS, Agoramoorthy G. COVID- 19: Consider IL-6 receptor antagonist for the therapy of cytokine storm syndrome in SARS- CoV-2 infected patients. J Med Virol. 2020;92(11):2260–2. ?
Aminjafari A, Ghasemi S. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19 . The COVID-19 resource centre is hosted on Elsevier Connect , the company's public news and information . 2020;(January). ?
Liu B, Li M, Zhou Z, Guan X, Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J Autoimmun [Internet]. 2020;111(March):102452. Available from: https://doi.org/10.1016/j.jaut.2020.102452 ?
Zhang X, Zhang Y, Qiao W, Zhang J, Qi Z. Baricitinib, a drug with potential effect to prevent SARS-COV-2 from entering target cells and control cytokine storm induced by COVID-19. Int Immunopharmacol [Internet]. 2020;86(299):106749. Available from: https://doi.org/10.1016/j.intimp.2020.106749
Available treatments subject to special conditions of access for the management of respiratory infection by SARS-CoV-2 General considerations. ?
Sariol A, Perlman S. Lessons for COVID-19 Immunity from Other Coronavirus Infections. Immunity [Internet]. 2020;53(2):248–63. Available from: https://doi.org/10.1016/j.immuni.2020.07.005 ?
Ozamiz-Etxebarria N, Dosil-Santamaria M, Picaza-Gorrochategui M, Idoiaga-Mondragon N. Stress, anxiety, and depression levels in the initial stage of the COVID-19 outbreak in a population sample in the northern Spain. Cad Saude Publica.2020;36(4):19. ?
Linares-Espinós E, Hernández V, Domínguez-Escrig JL, Fernández-Pello S, Hevia V, Mayor J, et al. Methodology of a systematic review. Actas Urol Esp [Internet]. 2018;42(8):499–506. Available from: https://doi.org/10.1016/j.acuro.2018.01.010 ?
Urrutia G, Bonfill X. PRISMA_Spanish.pdf [Internet]. Vol. 135, Clinical Medicine. 2010. p. 507–11. Available from: http://es.cochrane.org/sites/es.cochrane.org/files/public/uploads/PRISMA_Spanish.pdf
Genomewide Association Study of Severe Covid-19 with Respiratory Failure. N Engl J Med. Inflammatory environment in patients with COVID-19: Systematic Review 2020;383(16):1522–34.
Li L quan, Huang T, Wang Y qing, Wang Z ping, Liang Y, Huang T bi, et al. COVID-19 ?patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis. J Med Virol. 2020;92(6):577–83. ?
Zhu J, Zhong Z, Ji P, Li H, Li B, Pang J, et al. Clinicopathological characteristics of 8697 patients with COVID-19 in China: A meta-analysis. Fam Med Community Heal. 2020;8( 2):1–11. ?
Hansrivijit P, Qian C, Boonpheng B, Thongprayoon C, Vallabhajosyula S, Cheungpasitporn W, et al. Incidence of acute kidney injury and its association with mortality in patients with COVID-19: A meta-analysis. J Investig Med. 2020;68(7):1261–70. ?
Aggarwal G, Cheruiyot I, Aggarwal S, Wong J, Lippi G, Lavie CJ, et al. Association of ?Cardiovascular Disease With Coronavirus Disease 2019 (COVID-19) Severity: A Meta- Analysis. Curr Probl Cardiol [Internet]. 2020;45(8):100617. Available from: https://doi.org/10.1016/j.cpcardiol.2020.100617 ?
Krittanawong C, Virk HUH, Narasimhan B, Wang Z, Narasimhan H, Zhang HJ, et al. Coronavirus disease 2019 (COVID-19) and cardiovascular risk: A meta-analysis. Prog Cardiovasc Dis [Internet]. 2020;63(4):527–8. Available from: https://doi.org/10.1016/j.pcad.2020.05.001 ?
Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020;109(5):531–8. ?
Walker C, Deb S, Ling H, Wang Z. Assessing the Elevation of Cardiac Biomarkers and the Severity of COVID-19 Infection: A Meta-analysis. J Pharm Pharm Sci. 2020;23(4):396–405. ?
Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis. Prog Cardiovasc Dis [Internet]. 2020;63(3):390–1. Available from: https://doi.org/10.1016/j.pcad.2020.03.001 ?
Kumar A, Arora A, Sharma P, Anikhindi SA, Bansal N, Singla V, et al. Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis. Diabetes Metab Syndr Clin Res Rev [Internet]. 2020;14(4):535–45. Available from: https://doi.org/10.1016/j.dsx.2020.04.044
Mantovani A, Byrne CD, Zheng MH, Targher G. Diabetes as a risk factor for greater COVID- 19 severity and in-hospital death: A meta-analysis of observational studies. Nutr Metab Cardiovasc Dis [Internet]. 2020;30(8):1236–48. https://doi.org/10.1016 j.numecd.2020.05.014
Di Minno A, Ambrosino P, Calcaterra I, Di Minno MND. COVID-19 and Venous ?Thromboembolism: A Meta-analysis of Literature Studies. Semin Thromb Hemost. ?2020;46(7):763–71. ?
Ren X, Huang W, Pan H, Huang T, Wang X, Ma Y. Mental Health During the Covid-19 ?Outbreak in China: a Meta-Analysis. Psychiatr Q. 2020;91(4):1033–45. ?
Assaker R, Colas AE, Julien-Marsollier F, Bruneau B, Marsac L, Greff B, et al. Presenting symptoms of COVID-19 in children: a meta-analysis of published studies. Br J Anaesth. 2020;125(3):e330–2. ?
Zhang L, Peres TG, Silva MVF, Camargos P. What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases. Pediatr Pulmonol. 2020;55(8):2115–27. ?
Wang B, Li R, Lu Z, Huang Y. Does comorbidity increase the risk of patients with COVID-19. ?Aging (Albany NY). 2020;12(7):6049–57. ?
Sterne JAC, Murthy S, Diaz J V., Slutsky AS, Villar J, Angus DC, et al. Association between Administration of Systemic Corticosteroids and Mortality among Critically Ill Patients with COVID-19: A Meta-analysis. JAMA - J Am Med Assoc. 2020;324(13):1330–41. ?
Pirola CJ, Sookoian S. Estimation of Renin-Angiotensin-Aldosterone-System (RAAS)- Inhibitor effect on COVID-19 outcome: A Meta-analysis. J Infect [Internet]. 2020;81(2):276– 81. Available from: https://doi.org/10.1016/j.jinf.2020.05.052 ?
Kow CS, Hasan SS. Meta-analysis of Effect of Statins in Patients with COVID-19. Am J ?Cardiol [Internet]. 2020;134:153–5. Available from: ?https://doi.org/10.1016/j.amjcard.2020.08.004 ?
Yokoyama Y, Briasoulis A, Takagi H, Kuno T. Effect of remdesivir on patients with COVID- 19: A network meta-analysis of randomized control trials. Res Virus [Internet]. ?2020;288(July):198137. Available from: https://doi.org/10.1016/j.virusres.2020.198137 ?
Wu J, Zhou X, Tan Y, Wang L, Li T, Li Z, et al. Phase 1 trial for treatment of COVID-19 ?patients with pulmonary fibrosis using hESC-IMRCs. Cell Prolif. 2020;53(12):1–3. ?
Ramiro S, Mostard RLM, Magro-Checa C, Van Dongen CMP, Dormans T, Buijs J, et al. Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: Results of the CHIC study. Ann Rheum Dis. 2020;79(9):1143–51. ?
Sekhavati E, Jafari F, SeyedAlinaghi SA, Jamalimoghadamsiahkali S, Sadr S, Tabarestani M, et al. Safety and effectiveness of azithromycin in patients with COVID-19: An open-label randomised trial. Int J Antimicrob Agents. 2020;56(4). ?
Dastan F, Saffaei A, Haseli S, Marjani M, Moniri A, Abtahian Z, et al. Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial. Int Immunopharmacol [Internet]. 2020;88(June):106869. Available from: https://doi.org/10.1016/j.intimp.2020.106869 ?
Castro R, Luz PM, Wakimoto MD, Veloso VG, Grinsztejn B, Perazzo H. COVID-19: a meta- analysis of diagnostic test accuracy of commercial assays registered in Brazil. Brazilian J Infect Dis [Internet]. 2020;24(2):180–7. Available from: https://doi.org/10.1016/j.bjid.2020.04.003 ?
Elshazli RM, Toraih EA, Elgaml A, El-Mowafy M, El-Mesery M, Amin MN, et al. Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients. PLoS One [Internet]. 2020;15(8 August):1–20. Available from: http://dx.doi.org/10.1371/journal.pone.0238160 ?
Soraya GV, Ulhaq ZS. Crucial laboratory parameters in COVID-19 diagnosis and prognosis: An updated meta-analysis. Med Clin (Barc) [Internet]. 2020;155(4):143–51. Available from: https://doi.org/10.1016/j.medcli.2020.05.017 ?
Zhu J, Zhong Z, Li H, Ji P, Pang J, Li B, et al. CT imaging features of 4121 patients with COVID-19: A meta-analysis. J Med Virol. 2020;92(7):891–902. ?
Zhang P, Shi L, Xu J, Wang Y, Yang H. Elevated interleukin-6 and adverse outcomes in COVID-19 patients: a meta-analysis based on adjusted effect estimates. Immunogenetics [Internet]. 2020;72(8):431–7. Available from: https://doi.org/10.1007/s00251-020-01179-1 ?
Zeng F, Huang Y, Guo Y, Yin M, Chen X, Xiao L, et al. Association of inflammatory markers with the severity of COVID-19: A meta-analysis. Int J Infect Dis [Internet]. 2020;96:467–74. Available from: https://doi.org/10.1016/j.ijid.2020.05.055 ?
Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta [Internet]. 2020;506(March):145–8. Available from: https://doi.org/10.1016/j.cca.2020.03.022 ?
Giannakoulis VG, Papoutsi E, Siempos II. Effect of Cancer on Clinical Outcomes of Patients With COVID-19: A Meta-Analysis of Patient Data. JCO Glob Oncol. 2020;(6):799–808. ?
Ou M, Zhu J, Ji P, Li H, Zhong Z, Li B, et al. Risk Factors of Severe Cases with COVID-19: A Meta-Analysis. Epidemiol Infect. 2020;
Huang I, Pranata R, Lim MA, Oehadian A, Alisjahbana B.C-reactive protein, procalcitonin, D- dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis. Ther Adv Respir Dis. 2020;14:1–14. ?
Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID- 19): A meta-analysis. Clin Chim Acta [Internet]. 2020;505(March):190–1. Available from: https://doi.org/10.1016/j.cca.2020.03.004 ?
Henry BM, Benoit SW, de Oliveira MHS, Hsieh WC, Benoit J, Ballout RA, et al. Laboratory abnormalities in children with mild and severe coronavirus disease 2019 (COVID-19): A pooled analysis and review. Clin Biochem [Internet]. 2020;81(May):1–8. Available from: https://doi.org/10.1016/j.clinbiochem.2020.05.012 ?
Huang W, Berube J, McNamara M, Saksena S, Hartman M, Arshad T, et al. Lymphocyte Subset Counts in COVID-19 Patients: A Meta-Analysis. Cytom Part A. 2020;97(8):772–6. ?
Sattler A, Angermair S, Stockmann H, Heim KM, Khadzhynov D, Treskatsch S, et al. SARS– CoV-2–specific T cell responses and correlations with COVID-19 patient predisposition. J Clin Invest. 2020;130(12):6477–89. ?
Oja AE, Saris A, Ghandour CA, Kragten NAM, Hogema BM, Nossent EJ, et al. Divergent SARS-CoV-2-specific T- and B-cell responses in severe but not mild COVID-19 patients. Eur J Immunol. 2020; ?
Gong F, Dai Y, Zheng T, Cheng L, Zhao D, Wang H, et al. Peripheral CD4+ T cell subsets and antibody response in COVID-19 convalescent individuals. J Clin Invest. 2020;130(12):6588– 99. ?
Mazzoni A, Maggi L, Capone M, Spinicci M, Salvati L, Colao MG, et al. Cell?mediated and humoral adaptive immune responses to SARS?CoV?2 are lower in asymptomatic than symptomatic COVID?19 patients. European Journal of Immunology. 2020. ?
Payen D, Cravat M, Maadadi H, Didelot C, Prosic L, Dupuis C, et al. A Longitudinal Study of Immune Cells in Severe COVID-19 Patients. Front Immunol. 2020;11(October):1–12. ?
Lagunas-Rangel FA, Chávez-Valencia V. High IL-6/IFN-? ratio could be associated with severe disease in COVID-19 patients. J Med Virol. 2020;92(10):1789–90. ?
Jiang N, Li Z, Yang B, Jin M, Sun Y, He Y, et al. Peripheral Inflammatory Cytokines and Lymphocyte Subset Features of Deceased COVID-19 Patients. Biomed Res Int. 2021;2021. ?
Zheng M, Wang X, Guo H, Fan Y, Song Z, Lu Z, et al. The Cytokine Profiles and Immune Response Are Increased in COVID-19 Patients with Type 2 Diabetes Mellitus. J Diabetes Res. 2021;2021.?
Rostad BS, Shah JH, Rostad CA, Jaggi P, Richer EJ, Linam LE, et al. Chest radiograph features of multisystem inflammatory syndrome in children (MIS-C) compared to pediatric COVID-19. Pediatr Radiol. 2021;51(2):231–8.?
Ferrara F, Vitiello A. The advantages of drug treatment with statins in patients with SARS- CoV-2 infection. Wien Klin Wochenschr. 2021;?
Aomar-Millán IF, Salvatierra J, Torres-Parejo Ú, Nuñez-Nuñez M, Hernández-Quero J, Anguita-Santos F. Glucocorticoids alone versus tocilizumab alone or glucocorticoids plus tocilizumab in patients with severe SARS-CoV-2 pneumonia and mild inflammation. Med Clin (Barc). 2021;(xx):4–7.
Attia YA, El-Saadony MT, Swelum AA, Qattan SYA, Al-qurashi AD, Asiry KA, et al. COVID-19: pathogenesis, advances in treatment and vaccine development and environmental impact—an updated review. Environ Sci Pollut Res. 2021;2020.