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2000
Volume 7, Issue 2
  • ISSN: 2666-7967
  • E-ISSN: 2666-7975

Abstract

Introduction

Although the COVID-19 pandemic has passed, some patients still experience post-COVID-19 symptoms. It has been reported that COVID-19 symptoms can persist for more than three months after recovery.

Objective

This study aims to analyze biomarkers, severity, and outcome factors associated with post-COVID-19 symptoms.

Methods

This prospective cohort study involves hospitalised COVID-19 patients who were followed for up to 3 months after discharge. Clinical examinations and laboratory tests for MMP-9, TIMP-1, and IL-6 were conducted during hospitalisation and after three months.

Results and Discussion

We enrolled 76 COVID-19 patients, with a mortality rate of 30.26%. Among them, 55 individuals (30.91%) had no residual symptoms, 54.5% had acute COVID-19, 9.09% had ongoing COVID-19, and 5.45% had long-term COVID-19. Symptomatic post-COVID-19 had oxygen demand and respiratory rates higher than no-symptoms groups. Early IL-6, IL-10, MMP-9, and TIMP-1 were lower in symptomatic post-COVID-19 compared to dead and asymptomatic post-COVID-19 groups. IL-6 and MMP-9 decrease, and TIMP-1 increases after cure. IL-6 significantly still increases in post-COVID-19 symptoms compared to no-symptoms (=0.01). Patients more than 50 years old and critically ventilated patients are prone to have symptoms post-COVID-19.

Conclusion

More than half of patients suffer from post-COVID-19 symptoms with various related factors. Even though IL-6 decreases after recovery, IL-6 levels are still higher in symptomatic post-COVID-19 patients.

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2026-01-06

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References

  1. Living guidance for clinical management of COVID-19.2021Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
  2. KhanS. SharmaT. BanerjeeB.D. BranchS. HarrelsonS. Anticipating a post COVID-19 world and the pivotal role of science and technology.Coronaviruses20212327527710.2174/2666796701999201116121451
     [Google Scholar]
  3. DograA. GoyalB. Coronavirus disease (COVID-19): Features, diagnosis, treatments, and impacts.Coronaviruses202341e170423215926Epub ahead of print10.2174/2666796704666230417112151
     [Google Scholar]
  4. SinghV. JainS.K. MishraV. A recent update on SARS-CoV-2 transmission and its variants: Transmission, pathogenic mechanism, and treatment.Coronaviruses202341e02012321232110.2174/2666796704666230102121225
     [Google Scholar]
  5. WangZ. YangB. LiQ. WenL. ZhangR. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China.Clin. Infect. Dis.2020711576977710.1093/cid/ciaa27232176772
     [Google Scholar]
  6. AlibertiS.M. De CaroF. BocciaG. CarusoR. CapunzoM. Dealing with COVID-19: Lessons learned from the Italian experience.Coronaviruses202121272910.2174/2666796701999200908094136
     [Google Scholar]
  7. HarsiniH. AphridasariJ. AdhiputriA. PrasetyoA. SukiyantoH. ListyokoA.S. Interleukin-6 and neutrophil–lymphocyte ratio in predicting outcome of confirmed COVID-19 patients.Jurnal Respirasi20239210811610.20473/jr.v9‑I.2.2023.108‑116
     [Google Scholar]
  8. de GraafM.A. AntoniM.L. ter KuileM.M. Short-term outpatient follow-up of COVID-19 patients: A multidisciplinary approach.EClinicalMedicine20213210073110.1016/j.eclinm.2021.10073133532720
     [Google Scholar]
  9. AiyegbusiO.L. HughesS.E. TurnerG. Symptoms, complications and management of long COVID: A review.J. R. Soc. Med.2021114942844210.1177/0141076821103285034265229
     [Google Scholar]
  10. MińkoA. Turoń-SkrzypińskaA. RyłA. RotterI. The impact of comprehensive rehabilitation on the exercise capacity of patients after COVID-19.Adv. Respir. Med.202391650451510.3390/arm9106003737987299
     [Google Scholar]
  11. HuangC. HuangL. WangY. 6-month consequences of COVID-19 in patients discharged from hospital: A cohort study.Lancet202340110393e21e3310.1016/S0140‑6736(23)00810‑337321233
     [Google Scholar]
  12. PanH. PetoR. Henao-RestrepoA.M. Repurposed antiviral drugs for COVID-19 — Interim WHO solidarity trial results.N. Engl. J. Med.2021384649751110.1056/NEJMoa202318433264556
     [Google Scholar]
  13. SuciY.D. RosyidA.N. WulaaN.L. AlamsyahM. IrmayaniA.K. BachrunT. Guillain-Barré Syndrome and multiple lacunar infarcts in a COVID-19 patient.J. Infect. Dev. Ctries.202317111641164610.3855/jidc.1797538064394
     [Google Scholar]
  14. AccorsiD.X. dos SantosI.A.M. AccorsiJ.X. COVID-19 stress on mental and hair health: A marker for diseases in the post-pandemic era.Coronaviruses202233e080422203322Epub ahead of print10.2174/2666796703666220408120226
     [Google Scholar]
  15. AlkodaymiM.S. OmraniO.A. FawzyN.A. Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: A systematic review and meta-analysis.Clin. Microbiol. Infect.202228565766610.1016/j.cmi.2022.01.01435124265
     [Google Scholar]
  16. Abdel-GawadM. ZaghloulM.S. Abd-elsalamS. Post-COVID-19 syndrome clinical manifestations: A systematic review.Antiinflamm. Antiallergy Agents Med. Chem.202121211512010.2174/187152302166622032811581835346011
     [Google Scholar]
  17. HasanudinH. SukartiniT. MakhfudliM. RosyidA.N. RevitaN.C.T. AiniH.N. The effectiveness of pulmonary rehabilitation on pulmonary function among adults patients of COVID-19 survivors: A systematic review.J Respir2022811510.20473/jr.v8‑I.1.2022.15‑25
     [Google Scholar]
  18. YeQ. WangB. MaoJ. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19.J. Infect.202080660761310.1016/j.jinf.2020.03.03732283152
     [Google Scholar]
  19. MukherjeeM.D. KumarA. SolankiP.R. Recent advances in understanding SARS-CoV-2 infection and updates on potential diagnostic and therapeutics for COVID-19.Coronaviruses202234e020322201607Epub ahead of print10.2174/2666796703666220302143102
     [Google Scholar]
  20. Di GennaroF. PizzolD. MarottaC. Coronavirus diseases (COVID-19) current status and future perspectives: A narrative review.Int. J. Environ. Res. Public Health20201782690Epub ahead of print10.3390/ijerph1708269032295188
     [Google Scholar]
  21. LingeswaranM. GoyalT. GhoshR. Inflammation, immunity and immunogenetics in COVID-19: A narrative review.Indian J. Clin. Biochem.202035326027310.1007/s12291‑020‑00897‑332641873
     [Google Scholar]
  22. PurwatiB Budiono  RachmanBE A randomized, double-blind, multicenter clinical study comparing the efficacy and safety of a drug combination of lopinavir/ritonavir-azithromycin, lopinavir/ritonavir-doxycycline, and azithromycin-hydroxychloroquine for patients diagnosed with mild to moderate COVID-19 infections.Biochem. Res. Int.2021202111210.1155/2021/668592133628506
     [Google Scholar]
  23. PurwatiMA MiatmokoA Nasronudin  An in vitro study of dual drug combinations of anti-viral agents, antibiotics, and/or hydroxychloroquine against the SARS-CoV-2 virus isolated from hospitalized patients in Surabaya, Indonesia.PLoS One2021166e025230210.1371/journal.pone.025230234143818
     [Google Scholar]
  24. Purwati MiatmokoA. The potency of hematopoietic stem cells (hscs) and natural killer (nk) cells as a therapeutic of SARS-CoV-2 Indonesia isolates infection by viral inactivation (in vitro Study).Syst. Rev. Pharm.20201110.31838/srp.2020.5.112
     [Google Scholar]
  25. MagroG. SARS-CoV-2 and COVID-19: Is interleukin-6 (IL-6) the ‘culprit lesion’ of ARDS onset? What is there besides tocilizumab? SGP130Fc.Cytokine X20202210002910.1016/j.cytox.2020.10002932421092
     [Google Scholar]
  26. TanakaT. NarazakiM. KishimotoT. IL-6 in inflammation, immunity, and disease.Cold Spring Harb. Perspect. Biol.2014610a016295a510.1101/cshperspect.a01629525190079
     [Google Scholar]
  27. OjoA.S. BalogunS.A. WilliamsO.T. OjoO.S. Pulmonary fibrosis in COVID-19 survivors: Predictive factors and risk reduction strategies.Pulm. Med.2020202011010.1155/2020/617596432850151
     [Google Scholar]
  28. SimeP.J. O’ReillyK.M.A. Fibrosis of the lung and other tissues: New concepts in pathogenesis and treatment.Clin. Immunol.200199330831910.1006/clim.2001.500811358425
     [Google Scholar]
  29. GillS. ParksW. Metalloproteinases and their inhibitors: Regulators of wound healing.Int. J. Biochem. Cell Biol.2008406-71334134710.1016/j.biocel.2007.10.02418083622
     [Google Scholar]
  30. IzuharaY. TakahashiS. NangakuM. Inhibition of plasminogen activator inhibitor-1: Its mechanism and effectiveness on coagulation and fibrosis.Arterioscler. Thromb. Vasc. Biol.200828467267710.1161/ATVBAHA.107.15747918239154
     [Google Scholar]
  31. RazzaqueM.S. TaguchiT. Pulmonary fibrosis: Cellular and molecular events.Pathol. Int.200353313314510.1046/j.1440‑1827.2003.01446.x12608894
     [Google Scholar]
  32. DiambraL. RastmaneshR. COVID-19 mortality and the cytokine storm: An added value for APOE genotyping.Coronaviruses202236e05122221159810.2174/2666796704666221205152504
     [Google Scholar]
  33. MondalS. AdhikariN. BanerjeeS. AminS.A. JhaT. Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview.Eur. J. Med. Chem.202019411226010.1016/j.ejmech.2020.11226032224379
     [Google Scholar]
  34. FooS.S. CambouM.C. MokT. The systemic inflammatory landscape of COVID-19 in pregnancy: Extensive serum proteomic profiling of mother-infant dyads with in utero SARS-CoV-2.Cell Rep. Med.202121110045310.1016/j.xcrm.2021.10045334723226
     [Google Scholar]
  35. HabeebS. ChuganiM. Impact of novel coronavirus (COVID-19) on pregnant women: A review.Coronaviruses202234e03012218801110.2174/2666796701999201116123457
     [Google Scholar]
  36. SignoroniA. SavardiM. BeniniS. BS-Net: Learning COVID-19 pneumonia severity on a large chest X-ray dataset.Med. Image Anal.20217110204610.1016/j.media.2021.10204633862337
     [Google Scholar]
  37. GreenhalghT. KnightM. A’CourtC. BuxtonM. HusainL. Management of post-acute COVID-19 in primary care.BMJ2020370m302610.1136/bmj.m302632784198
     [Google Scholar]
  38. RosyidA.N. PuspitasariA.D. SoebaktiE. Chest X-Ray using brixia and fractional inspiratory oxygen as severity and mortality predictor of COVID-19.ICMHI 2023: 2023 the 7th International Conference on Medical and Health Informatics.182-7.May 12 - 14, 2023; Kyoto, Japan. 2023; pp: 182-187.10.1145/3608298.3608332
     [Google Scholar]
  39. GiannitrapaniL. MirarchiL. AmodeoS. Can baseline IL-6 levels predict long COVID in subjects hospitalized for SARS-CoV-2 disease?Int. J. Mol. Sci.2023242173110.3390/ijms2402173136675242
     [Google Scholar]
  40. DavisH.E. McCorkellL. VogelJ.M. TopolE.J. Long COVID: major findings, mechanisms and recommendations.Nat. Rev. Microbiol.202321313314610.1038/s41579‑022‑00846‑236639608
     [Google Scholar]
  41. ChungT. MastalerzM.H. MorrowA.K. Long COVID: Long-term effects of COVID-19.2022Available from: https://www.hopkinsmedicine.org/health/conditions-anddiseases/coronavirus/covid-long-haulers-long-term-effects-of-covid19
  42. AstinR. BanerjeeA. BakerM.R. Long COVID: Mechanisms, risk factors and recovery.Exp. Physiol.20231081122710.1113/EP09080236412084
     [Google Scholar]
  43. SherifZA GomezCR ConnorsTJ HenrichTJ ReevesWB Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC).eLife202312e8600210.7554/eLife.8600236947108
     [Google Scholar]
  44. KimS. LeeH. LeeJ. Short- and long-term neuropsychiatric outcomes in long COVID in South Korea and Japan.Nat. Hum. Behav.2024881530154410.1038/s41562‑024‑01895‑838918517
     [Google Scholar]
  45. KimM.S. LeeH. LeeS.W. Long-term autoimmune inflammatory rheumatic outcomes of COVID-19.Ann. Intern. Med.2024177329130210.7326/M23‑183138437702
     [Google Scholar]
  46. COVID-19: Clinical presentation and diagnosis of adults with persistent symptoms following acute illness (“long COVID”).2024Available from: https://www.uptodate.com/contents/covid-19-clinical-presentation-and-diagnosis-of-adults-with-persistent-symptoms-following-acute-illness-long-covid
  47. SchultheißC. WillscherE. PascholdL. The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19.Cell Rep. Med.20223610066310.1016/j.xcrm.2022.10066335732153
     [Google Scholar]
  48. Wisnu WardanaV.A. RosyidA.N. Inflammatory mechanism and clinical implication of asthma in COVID-19.Clin. Med. Insights Circ. Respir. Pulm. Med.20211510.1177/1179548421104271134594145
     [Google Scholar]
  49. BellanM. ApostoloD. AlbèA. Determinants of long COVID among adults hospitalized for SARS-CoV-2 infection: A prospective cohort study.Front. Immunol.202213103822710.3389/fimmu.2022.103822736601115
     [Google Scholar]
  50. SmithP. ProesmansK. Van CauterenD. Post COVID-19 condition and its physical, mental and social implications: Protocol of a 2-year longitudinal cohort study in the Belgian adult population.Arch. Public Health202280115110.1186/s13690‑022‑00906‑235659364
     [Google Scholar]
  51. TsampasianV. ElghazalyH. ChattopadhyayR. Risk factors associated with post−COVID-19 condition.JAMA Intern. Med.2023183656658010.1001/jamainternmed.2023.075036951832
     [Google Scholar]
  52. KhidirM. SiswantoS. RasenaH.A. Comparison of forced expiratory flow (FEF) 25-75% between post-COVID-19 patients with different severity at Universitas Gadjah Mada Academic Hospital.Jurnal Respirasi2024101232910.20473/jr.v10‑I.1.2024.23‑29
     [Google Scholar]
  53. BergantiniL. d’AlessandroM. GangiS. Predictive role of cytokine and adipokine panel in hospitalized COVID-19 patients: Evaluation of disease severity, survival and lung sequelae.Int. J. Mol. Sci.202324161299410.3390/ijms24161299437629176
     [Google Scholar]
  54. Setyo NugrohoG.M. MarhanaI.A. KusumastutiE.H. Interleukin-6 (IL-6) expression of lung tissue in COVID-19 patient severity through core biopsy post mortem.Ann. Med. Surg. (Lond.)20228210464810.1016/j.amsu.2022.10464836157132
     [Google Scholar]
  55. KusumastutiE.H. WiratamaP.A. ArianiG. Differences in interleukin-6 and interleukin-17 expression in COVID-19 post-mortem lung tissue biopsy compared with nonCOVID-19.Pharmacogn. J.2023146s88789210.5530/pj.2022.14.184
     [Google Scholar]
  56. LuQ. ZhuZ. TanC. Changes of serum IL‐10, IL‐1β, IL‐6, MCP‐1, TNF‐α, IP‐10 and IL‐4 in COVID‐19 patients.Int. J. Clin. Pract.2021759e1446210.1111/ijcp.1446234107113
     [Google Scholar]
  57. LaiY.J. LiuS.H. ManachevakulS. LeeT.A. KuoC.T. BelloD. Biomarkers in long COVID-19: A systematic review.Front. Med. (Lausanne)202310108598810.3389/fmed.2023.108598836744129
     [Google Scholar]
  58. YinJ.X. AgbanaY.L. SunZ.S. Increased interleukin-6 is associated with long COVID-19: A systematic review and meta-analysis.Infect. Dis. Poverty20231214310.1186/s40249‑023‑01086‑z37095536
     [Google Scholar]
  59. NugrohoC.W. SuryantoroS.D. YuliasihY. Optimal use of tocilizumab for severe and critical COVID-19: A systematic review and meta-analysis.F1000 Res.2021107310.12688/f1000research.45046.133763201
     [Google Scholar]
  60. CarliniV. NoonanD.M. AbdalalemE. The multifaceted nature of IL-10: regulation, role in immunological homeostasis and its relevance to cancer, COVID-19 and post-COVID conditions.Front. Immunol.202314116106710.3389/fimmu.2023.116106737359549
     [Google Scholar]
  61. HuangJ.J. WangC.W. LiuY. Role of the extracellular matrix in COVID-19.World J. Clin. Cases2023111738310.12998/wjcc.v11.i1.7336687194
     [Google Scholar]
  62. HuangH. Matrix metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: Recent advances.Sensors (Basel)20181810324910.3390/s1810324930262739
     [Google Scholar]
  63. AgrawalN. ChougaleS.D. JedgeP. IyerS. DsouzaJ. Brixia chest X-ray scoring system in critically ill patients with COVID-19 pneumonia for determining outcomes.J. Clin. Diagn. Res.20211581510.7860/JCDR/2021/48844.15197
     [Google Scholar]
  64. RosyidA.N. PuspitasariA.D. SensusiatiA.D. NugrahaJ. AminM. Interleukin-6 and interleukin-10 as a predictor of mortality in elderly with COVID-19.Ann. Afr. Med.202423457557910.4103/aam.aam_1_2439138918
     [Google Scholar]
  65. HanH. MaQ. LiC. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors.Emerg. Microbes Infect.2020911123113010.1080/22221751.2020.177012932475230
     [Google Scholar]
  66. AlbiniA. CalabroneL. CarliniV. Preliminary evidence for IL-10-induced ACE2 mRNA expression in lung-derived and endothelial cells: Implications for SARS-CoV-2 ARDS pathogenesis.Front. Immunol.20211271813610.3389/fimmu.2021.71813634646263
     [Google Scholar]
  67. SmailS.W. BabaeiE. AminK. AbdulahadW.H. Serum IL-23, IL-10, and TNF-α predict in-hospital mortality in COVID-19 patients.Front. Immunol.202314114584010.3389/fimmu.2023.114584037283736
     [Google Scholar]
  68. RajamanickamA. NathellaP.K. SelvarajN. Characterization of IL-10 family of cytokines in acute and convalescent COVID-19 individuals.J. Interferon Cytokine Res.2023431046947710.1089/jir.2023.007537708007
     [Google Scholar]
  69. AltableM. Neuroinfl ammation links COVID-19 and fragile X syndrome: Role of MMP-9, IGF-1, IL-10, metformin, statins and curcumin.Qeios202110.32388/KO4C77
     [Google Scholar]
  70. Aktug DemirN. Yilmaz KirikS. SumerS. An evaluation of matrix metalloproteinase-9 (Mmp-9) and tissue inhibitor metalloproteinase-1 (Timp-1) serum levels and the Mmp-9/Timp-1 Ratio in Covid-19 patients.Afr. Health Sci.2023231374310.4314/ahs.v23i1.537545954
     [Google Scholar]
  71. WafaI.A. PratamaN.R. BudiD.S. The efficacy and safety of monoclonal antibody treatments against COVID-19: A systematic review and meta-analysis of randomized clinical trials.medRxiv202110.1101/2021.06.04.21258343
     [Google Scholar]
  72. BrusaS. TerraccianoD. BruzzeseD. Circulating tissue inhibitor of metalloproteinases 1 (TIMP-1) at COVID-19 onset predicts severity status.Front. Med. (Lausanne)20229103428810.3389/fmed.2022.103428836523781
     [Google Scholar]
  73. VisuddhoV. SubagjoA. SetyoningrumR.A. RosyidA.N. Survival analysis and outcome prediction of COVID-19 patients: A retrospective observational study from tertiary referral hospital in Indonesia.Trop. Biomed.202239223924610.47665/tb.39.2.01335838097
     [Google Scholar]
  74. WitartoA.P. WitartoB.S. PutraA.J.E. PramuditoS.L. RosyidA.N. Serum krebs von den lungen-6 for predicting the severity of COVID-19 lung injury: A systematic review and meta-analysis.Iran. Biomed. J.202125638138910.52547/ibj.25.6.38134641641
     [Google Scholar]
  75. Nasronudin, Rosyid AN, Rachman BE. Bronchial asthma, hypertension and COVID-19: A case report.Malays J Med Res202117Sup.l 4167169
     [Google Scholar]
  76. AsmarawatiT.P. SuryantoroS.D. RosyidA.N. Predictive value of Sequential Organ Failure Assessment (SOFA), quick Sequential Organ Failure Assessment (qSOFA), Acute Physiology and Chronic Health Evaluation (APACHE II), and New Early Warning Signs (NEWS-2) scores estimate mortality of COVID-19 patient.Indian J. Crit. Care Med.20222610.5005/jp‑journals‑10071‑2417035656039
     [Google Scholar]
  77. WitartoA.P. RosyidA.N. WitartoB.S. PramuditoS.L. PutraA.J.E. An in-depth investigation of serum Krebs von den Lungen-6 and other biomarkers in COVID-19 severity and mortality.Monaldi Arch. Chest Dis.20242610.4081/monaldi.2024.284839077858
     [Google Scholar]
  78. Nasr El-DinA. AtaK.A.E.S.A. Abdel-GawadA.R. FahmyN.F. Impact of high serum levels of MMP-7, MMP-9, TGF-β and PDGF macrophage activation markers on severity of COVID-19 in obese-diabetic patients.Infect. Drug Resist.2021144015402510.2147/IDR.S32900434611417
     [Google Scholar]
  79. D’Avila-MesquitaC. CoutoA.E.S. CamposL.C.B. MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients.Biomed. Pharmacother.202114211206710.1016/j.biopha.2021.11206734449310
     [Google Scholar]
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Revealing the Unseen: Post COVID-19 Biomarkers, Severity, and Outcome Mysteries
Coronaviruses 7, E26667975330646 (2026); https://doi.org/10.2174/0126667975330646241021085300
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  • Article Type:     Research Article
Keyword(s): biomarkers; IL-10; IL-6; MMP-9; outcome; Post COVID-19; severity; TIMP-1

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