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“Convalescent Plasma” a valuable trial with COVID_19, Is it safe?

Sever acute respiratory syndrome corona virus_2 (SARS_cov_2), the cause of novel corona virus (COVID_19) as named by World Health Organization (WHO). It emerged in december 2019 in Wuhan, China, and then developed into a “pandemic” as it spread rapidly worldwide.
In 21 July 2020, globally; there are (14,562,550) laboratory confirmed infected cases, (607,781) confirmed death in (205) countries, areas or territories with mrtality rate of (0.04%)[1].
The effects of COVID_19 ranges from asymptomatic patients _most of cases_ to severe acute respiratory syndrome (SARS) patients _who represent the main deaths_.
Until now, there is no effectively approved antiviral agents or specific vaccines to prevent the COVID 19 infection. The scientists estimated months to years will take to become there is vaccine to sale while some drugs like remdesivir and lopinavir/ritonavir still under investigations to determined it’s safety and efficacy [2,3].
Since a specific vaccine and effective medicines are unavailable, an urgent need to search about another therapeutic options for COVID_19 treatment specially among clinically compromised patients.
Convalescent plasma (CP) or Hyperimmune_Intravenous Immunoglobins (H_IVIG), a passive immmunotherapy has been used to prevent and treat of many viral infections in the early 20th century [4].
CP has been proved successfully used in several viral infections such as Middle East Respiratiry Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), Influenza (H1N1) and even in Chikungunya, Ebola, and Zika virus infections [4, 5, 6,7]
The SARS_Cov_2 specific IgG antibodies passively transferred by transfusing plasma reduce viral load by binding to epitopes of external surface of viral particles, thus blocking the entry of virus into cells and viral replication, they called Neutralizing Antibodies (NAbs) [5].
CP transfusion showed evidence of reduction in the use of critical resources and shorten length of hospital stay.
Recently, the US Food and Drug Administration (FDA) has approved the use of CP from recovered pts. to treat seriously ill COVID_19 infected individuals [6]
A significantly better outcomes was obtained with implementation of Three key points: (1) earlier transfusion _before day 14_ (2) high levels of Neutralizing Antibodies in CP and (3) appropriate plasma volume.
Clinically, in several studies the routine laboratory criteria showed that lymphocytopenia (important index for prognosis in COVID_19) tended to increase in counts.
As well as observed a tendency of decrement of parameters indicative of inflammation and/or liver dysfunction as stared before CP transfusion. These including C_reactive protein (CRP), alanine and aspartate aminotransferases indicating improvement of immunological and hepatic function [4, 8,9]

Also an increase in SPo2 levels, ameasurement which could indicate recovering lung function [4].
To date, there are approximately 9million patients who recovered from COVID_19. They could represent an important resources of CP or H_IVIG.
In other hand, due to lack of full knowledge about virus biology, plasma collected locally may better reflect the circulating virus in population.
The Donors criteria for donation of CP were summarize: (1) normality of body temperature for more than 3d (2)resolution of respiratory tract symptoms (3) confirmation of resolution of infection by two consecutively negative results of sputum SARS_Cov_2 by RT_PCR assay (one day sampling interval) (4) written informed consent was obtained from each patients (5) all donors tested negative for other respiratory virus, syphilis, HIV and Hepatitis B and C viruses[4,10].
ABO compatible plasma units collected by aphresis, with volume at least 200_600ml (without anticoagulant) based on procedures and regulatory limits. The initial dose of 200ml followed by one or two additional dose of 200ml according to disease severity and tolerance of infusions. In many jurisdictions the interval between CP donation of 600ml or more should not be less than 7 day and that between whole blood donation should be at least 8 weeks [10].
CP therapy it self has important transfusions reactions and complications. For examples: (1)Transfusion_Related Acute Lung Injury (TRALI) (2)increase risk of same_day thrombotic events[5] (3)circulatory overload or anaphylaxis[6, 7] (4)antibody_dependent enhancement of entry ADE [7]
Now, to avoid TRALI preference should be given to use CP of male donors or female donors who have never pregnant including abortions. This measure lower the possibility of presence in plasma of the antibodies to HLA or granulocyte antigens that cause TRALI which occur after 6 hours of transfusion and can be severe[10,11]
It is worth to noting that, CP was administered when antiviral drugs and corticosteroids were taken. In other word these three elements may be combined to give a synergic therapeutic effect.
CP therapy is not enough to win the battle we must need also suppress viral replications and prepare for cytokines storm that occur during treatments.

References:

1.       Coronavirus disease 2019 (COVID-19) situation report_183. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports .

2.       H. Lu, Drug treatment options for the 2019-new coronavirus (2019-nCoV). Bioscience trends 14(1), (Jan. 2020), DOI: 10.5582/bst.2020.01020

3.       M. Wang et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Research 30(3):1-3, (Feb.2020), https://doi.org/10.1038/s41422-020-0282-0 .

4.       K. Duan et al., Effectiveness of convalescent plasma therapy in severe COVID_19 patients. p.1_2(7), PNAS April 28, 2020 117 (17) 9490-9496; first published April 6, 2020,  https://doi.org/10.1073/pnas.2004168117 .

5.       T. Adriana, M. Marco, Immunoglobulins or convalescent plasma to tackle COVID-19: buying time to save lives _ current situation and perspectives.  April. 2020, DOI: https://doi.org/10.4414/smw.2020.20264

6.       Langhi Junior DM, et al., COVID-19 convalescent plasma transfusion. Hematol Transfus Cell Ther. 2020,  https://doi.org/10.1016/j.htct8.2020.04.003 .

7.       J_H. Yoo, Convalescent Plasma Therapy for Corona Virus Disease 2019: a Long Way to Go but Worth Trying, Apr.2020, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152529/ .

8.       K. Sridevi et al., Convalescent Plasma Therapy for Prophylaxis and Treatment of COVID-19: A Systematic Research of Facts and Files, A Narrative Review. Vol.8 No.2:314, 2020, www.imedpub.com, DOI: 10.36648/2386-5180.8.2.314 .

9.       C. Shen et al., Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020;323(16):1582-1589, doi:10.1001/jama.2020.4783

10.    J. Epstein, T. Burnouf, Points to consider in the preparation and transfusionof COVID-19 convalescent plasma. Apr.2020, https://doi.org/10.1111/vox.12939 .

11.    P. Toy. Update on Transfusion-Related Acute Lung Injury. Clinical Advances in Hematology & Oncology: 2019; 17(7): 378-381.

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University nurse Rajwan Talib Abdullah

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