How Secure was Convalescent Plasma Administration to Non-severe COVID-19 Cases with Lymphopenia?

Abstract

Aim: Many treatment methods have endeavored during the Coronavirus Disease of 2019 (COVID-19) pandemic. Particularly before the vaccines came into use, the medical world gained adequate experience with convalescent plasma (CP) administration, which was ignored after preventive remedies. In this study, we compared the clinical conditions and treatments during the infection with pulmonary fibrosis after recovery. Material and Method: This prospective, cross-sectional study was conducted with COVID-19 patients. The patients were divided into two groups according to the severity of the disease. Sixty of them were reevaluated regarding pulmonary fibrosis via high-resolution computed tomography performed in the 6th month after recovery. Results: A total of 60 patients (mean age=54.05±9.16) participated in this study. Both severe and non-severe groups were equal in the number of patients. There was no difference between the groups in the evaluation of fibrosis scores. However, in those with pulmonary fibrosis, age, CURB-65 scores, and D-dimer levels were found to be higher, whereas hematocrit levels were lower. In lymphopenic patients, almost 95% of those who underwent CP treatment had fibrosis (p=0.013). This fibrosis formation was more prominent in the non-severe group (p=0.028). Comparable fibrosis increation persisted in diabetics. Conclusion: Based on the results, the pulmonary involvement of COVID-19 may form persistent fibrosis after recovery. The accuracy of administering CP treatment in non-severe patients with lymphopenia should be reviewed, as it might increase pulmonary fibrosis.

Keywords

• COVID-19
• Convalescent Plasma
• Lymphopenia
• Post-COVID syndrome
• Pulmonary fibrosis

Lenfopenik Olan Hafif COVID-19 Vakalarında İmmun Plazma Tedavisi Ne Kadar Güvenliydi?

Abstract

Amaç: 2019 Koronavirüs Hastalığı (COVID-19) pandemisi sırasında birçok tedavi yöntemi denenmiştir. Tıp dünyası, hastalık önleyici tedavilerin (özellikle aşıların) kullanıma girmesinden sonra göz ardı edilen immun plazma (İP) uygulamasında yeterli deneyime sahip olmuştur. Bu çalışmada, iyileşme sonrası pulmoner fibrozis ile enfeksiyon sırasındaki klinik süreçleri ve tedavileri karşılaştırdık. Gereç ve Yöntem: Bu prospektif, kesitsel çalışma COVID-19 hastaları ile yapılmıştır. Hastalar hastalık şiddetine göre iki gruba ayrıldı. Bunlardan altmış tanesi, iyileşme sonrası 6. ayda çekilen yüksek çözünürlüklü bilgisayarlı tomografi ile pulmoner fibrozis açısından yeniden değerlendirildi. Bulgular: Bu çalışmaya toplam 60 hasta (ortalama yaş=54.05±9.16) katıldı. Hem şiddetli hem de olmayan gruplarda hasta sayısı eşitti. Fibrozis skorlarının değerlendirilmesinde gruplar arasında fark yoktu. Ancak pulmoner fibrozisi olanlarda yaş, CURB-65 skorları ve D-dimer seviyeleri daha yüksek, hematokrit seviyeleri daha düşük bulundu. Lenfopenik hastalarda, İP tedavisi görenlerin yaklaşık %95'inde fibrozis vardı (p=0.013). Bu fibrozis oluşumu, şiddetli olmayan grupta daha belirgindi (p=0.028). Benzer fibrozis artışı diyabetiklerde sebat etti. Sonuç: Sonuçlara göre, COVID-19'un pulmoner tutulumu iyileşme sonrası kalıcı fibrozis oluşturabilir. Pulmoner fibrozisi artırabileceğinden, lenfopenisi olan hafif vakalarda İP uygulanmasının doğruluğu gözden geçirilmelidir.

Keywords

• COVID-19
• Konvalesan Plazma
• Lenfopeni
• Post-COVID sendrom
• Pulmoner fibroz

References

1. Jiang DH, McCoy RG. Planning for the post-COVID syndrome: how payers can mitigate long-term complications of the pandemic. J Gen Intern Med 2020;35:3036-9.
2. Lewis KL, Helgeson SA, Tatari MM, et al. COVID-19 and the effects on pulmonary function following infection: A retrospective analysis. EClinicalMedicine 2021;39:101079.
3. Das KM, Lee EY, Singh R, et al. Follow-up chest radiographic findings in patients with MERS-CoV after recovery. Indian J Radiol Imaging 2017;27:342-9.
4. Hui DS, Wong KT, Ko FW, et al. The 1-year impact of severe acute respiratory syndrome on pulmonary function, exercise capacity, and quality of life in a cohort of survivors. Chest 2005;128:2247-61.
5. Crisan-Dabija R, Pavel CA, Popa IV, et al "A Chain Only as Strong as Its Weakest Link": An Up-to-Date Literature Review on the Bidirectional Interaction of Pulmonary Fibrosis and COVID-19. J Proteome Res 2020;19:4327-38.
6. COVID-19 Treatment Guidelines [homepage on the Internet]. NIH: [Cited 14 June 2022]. Available from: https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/
7. Tumsatan P, Wongwiwatchai J, Apinives C, et al. Mediastinal Lymphadenopathy in Patients with Systemic Sclerosis. J Med Assoc Thai 2016;99:348-53.
8. Malpani Dhoot N, Goenka U, Ghosh S, et al. Assigning computed tomography involvement score in COVID-19 patients: prognosis prediction and impact on management. BJR Open 2020;2:20200024.

9. Nguyen Y, Corre F, Honsel V, et al. Applicability of the CURB-65 pneumonia severity score for outpatient treatment of COVID-19. J Infect 2020;81:e96-e8.
10. Approach to the adult with lymphocytosis or lymphocytopenia [homepage on the Internet]. USA: [Cited 14 June 2022]. Available from: https://www.uptodate.com/contents/approach-to-the-adult-with-lymphocytosis-or-lymphocytopenia?search=lymphopenia/;
11. Mohamed Khosroshahi L, Rezaei N. Dysregulation of the immune response in coronavirus disease 2019. Cell Biol Int 2021;45:702-7.
12. Tan L, Wang Q, Zhang D, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct Target Ther 2020;5:33.
13. Gattinoni L, Gattarello S, Steinberg I, et al. COVID-19 pneumonia: pathophysiology and management. Eur Respir Rev 2021;30.
14. Yu M, Liu Y, Xu D, et al. Prediction of the Development of Pulmonary Fibrosis Using Serial Thin-Section CT and Clinical Features in Patients Discharged after Treatment for COVID-19 Pneumonia. Korean J Radiol 2020;21:746-55.
15. Huang Y, Tan C, Wu J, et al. Impact of coronavirus disease 2019 on pulmonary function in early convalescence phase. Respir Res 2020;21:163.
16. Hama Amin BJ, Kakamad FH, Ahmed GS, et al. Post COVID-19 pulmonary fibrosis; a meta-analysis study. Ann Med Surg (Lond) 2022;77:103590.
17. Margaria JP, Moretta L, Alves-Filho JC, et al. PI3K Signaling in Mechanisms and Treatments of Pulmonary Fibrosis Following Sepsis and Acute Lung Injury. Biomedicines 2022;10.
18. Xiang M, Jing H, Wang C, et al. Persistent Lung Injury and Prothrombotic State in Long COVID. Front Immunol 2022;13:862522.
19. Phua J, Weng L, Ling L, et al. Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations. Lancet Respir Med 2020;8:506-17.
20. Anti-SARS-CoV-2 Antibody Products. [homepage on the Internet]. NIH: [Cited 14 June 2022]. Available from: https://www.covid19treatmentguidelines.nih.gov/therapies/anti-sars-cov-2-antibody-products/;
21. Akay Cizmecioglu H, Goktepe MH, Demircioglu S, et al. Efficacy of convalescent plasma therapy in severe COVID-19 patients. Transfus Apher Sci 2021;60:103158.
22. Rojas M, Rodriguez Y, Monsalve DM, et al. Convalescent plasma in Covid-19: Possible mechanisms of action. Autoimmun Rev 2020;19:102554.
23. Nezlin R. Dynamic Aspects of the Immunoglobulin Structure. Immunol Invest 2019;48:771-80.
24. van Erp EA, Luytjes W, Ferwerda G, et al. Fc-Mediated Antibody Effector Functions During Respiratory Syncytial Virus Infection and Disease. Front Immunol 2019;10:548.
25. Moss P. The T cell immune response against SARS-CoV-2. Nat Immunol 2022;23:186-93.
26. Taeschler P, Adamo S, Deng Y, et al. T-cell recovery and evidence of persistent immune activation 12 months after severe COVID-19. Allergy 2022.
27. Valdebenito S, Bessis S, Annane D, et al. COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases. Front Immunol 2021;12:735922.
28. Lu X, Cui Z, Pan F, et al. Glycemic status affects the severity of coronavirus disease 2019 in patients with diabetes mellitus: an observational study of CT radiological manifestations using an artificial intelligence algorithm. Acta Diabetol 2021;58:575-86.
29. Mohammadi A, Balan I, Yadav S, et al. Post-COVID-19 Pulmonary Fibrosis. Cureus 2022;14:e22770.
30. van Dam LF, Kroft LJM, van der Wal LI, et al. Clinical and computed tomography characteristics of COVID-19 associated acute pulmonary embolism: A different phenotype of thrombotic disease? Thromb Res 2020;193:86-9.
31. Loo J, Spittle DA, Newnham M. COVID-19, immunothrombosis and venous thromboembolism: biological mechanisms. Thorax 2021;76:412-20.
32. Gangadharan S, Parker S, Ahmed FW. Chest radiological finding of COVID-19 in patients with and without diabetes mellitus: Differences in imaging finding. World J Radiol 2022;14:13-8.
33. Bhandari S, Rankawat G, Singh A, Gupta V, Kakkar S. Impact of glycemic control in diabetes mellitus on management of COVID-19 infection. Int J Diabetes Dev Ctries 2020:1-6.