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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 15  |  Issue : 1  |  Page : 149-152

A review of convalescent plasma therapy an immediately available therapeutic option for COVID-19 in light of the available data


1 Department of Surgery, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed University), Wardha, Maharashtra, India
2 Department of Radiodiagnosis, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed University), Wardha, Maharashtra, India

Date of Submission25-Mar-2020
Date of Decision10-Apr-2020
Date of Acceptance15-Apr-2020
Date of Web Publication13-Oct-2020

Correspondence Address:
Dr. Meenakshi Yeola
Department of Surgery, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed University), Sawangi (Meghe), Wardha - 442 107, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdmimsu.jdmimsu_149_20

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  Abstract 


After being first recognized in December 2019, the latest public health threat emanating from the infection of coronavirus has taken many lives encompassing whole geographical locations. The virus named novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new infection to which humans were never exposed. There is no research, no vaccine, no drugs, and no specific treatment. This has allowed this virus to disseminate and infect the millions of people worldwide with daily increasing count. In the absence of specific treatment, and based on past experiences of SARS, Middle East respiratory syndrome and Ebola outbreaks, convalescent plasma (CP) has shown promising results in the saving lives of infected patients. There are a lot many patients who have recovered from novel coronavirus infection, and they may prove to be the source of the CP therapy, which employs passive immunity of body to neutralize the virus and improve the outcomes in infected patients. Literature search was done using the PubMed and Google Scholar search engines, searching terms “COVID-19”, “SARS-CoV-2,” “2019-Ncov,” “Corona,” “Convalescent,” “Serum,” “Plasma” “Treatment” titles, abstracts, and keywords. The data were reviewed, analyzed, and presented.

Keywords: Convalescent plasma, coronavirus, COVID-19, passive immunity, treatment


How to cite this article:
Singh AK, Yeola M, Singh N. A review of convalescent plasma therapy an immediately available therapeutic option for COVID-19 in light of the available data. J Datta Meghe Inst Med Sci Univ 2020;15:149-52

How to cite this URL:
Singh AK, Yeola M, Singh N. A review of convalescent plasma therapy an immediately available therapeutic option for COVID-19 in light of the available data. J Datta Meghe Inst Med Sci Univ [serial online] 2020 [cited 2020 Oct 31];15:149-52. Available from: http://www.journaldmims.com/text.asp?2020/15/1/149/297969




  Introduction Top


Since its first appearance in Wuhan province of China on December 12, 2019, the World Health Organization (WHO) named severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) virus is causing pneumonia like illness associated with acute respiratory distress syndrome.[1] The WHO initially declared the outbreak as a Public Health Emergency of International Concern on January 30, 2020. As the virus spread rapidly across the globe, the WHO declared it a pandemic on March 11, 2020.[2] As per the WHO, there were 1,812,734 active cases worldwide, 113,675 deaths worldwide in 213 effected countries on April 13, 2020. As per the Government of India data, there were 8988 active cases, 339 deaths, and 1035 cured patients till April 13, 2020 and Maharashtra state is most effected having 1985 active cases.[3]

Currently, there are no specific antiviral treatment directed against novel coronavirus, some drugs such as remdesivir, lopinavir, and ritonavir are under the evaluation for safety and efficacy.[2] The role of chloroquine and hydroxychloroquine is under the clinical trial.[4] In the absence of specific antiviral treatment and vaccines, there is the urgent need to look to other therapies which may be effective for the treatment of severely ill COVID-19 patients. Convalescent plasma (CP) therapy has been used successfully for more than a century for the prevention and treatment of many infectious diseases. In the past two decades when world faced and successfully came out of SARS, Middle East respiratory syndrome (MERS) and H1N1 pandemics with use of CP, has given a ray of hope to cope with COVID-19 pandemic.[5],[6],[7]


  Methodolgy Top


Literature search was done using PubMed and Google Scholar search engines, searching terms “COVID-19,” “SARS-CoV-2,” “2019-nCOV,” “Corona,” “Convalescent,” “Serum,” “Plasma” “Treatment” titles, abstracts, and keywords. Afterward, clinical trials, clinical reports, case reports, and suggestions for potential medications, especially the role of convalescent therapy against COVID-19, were briefiy reviewed.


  Discussion Top


The Virus

The coronavirus is a Ribovirus from family Coronoviradae, having single-stranded RNA. It has the diameter of 80–120 nm.[8] Before this novel coronavirus, six corona viruses were known to cause disease in humans, SARS-Cov-2 is the seventh member of coronavirus family with ability to infect human beings. Four viruses 229E, OC43, NL63, and HKU1 are relatively common and have been found to cause common cold in healthy individuals. SARS-CoV and MERS-CoV are two other viruses of zoonotic origin, that have been linked to severe respiratory illnesses.[9]

Zhou et al.[10] and Ji et al.[11] have reported probable source of origin of SARS-CoV-2 are bats as they are the natural hosts of this virus and pangolins and snakes are considered to be the intermediate host, however, Zhang et al.[12] found no host relationship with snakes. At present SARS-CoV-2-infected patients are the main source of transmission of virus.[10] Transmission from effected and close contacts are the most common path of transmission for novel coronavirus. Research has shown aerosol might be the way of transmission; however, virus has been consistently isolated from gastrointestinal tract, saliva, tears, stools, and urine. Based on the data available, gastrointestinal tract might also be the route of transmission. Virus was found to be viable in aerosol for 3 h, on copper for 4 h, up to 24 h on cardboard, up to 2–3 days on plastic and steel.[13] Data on incubation period of novel coronavirus are limited; however, the analysis of different studies has put it variably from 5 days to 6.4 days with a range from 2 to 14 days.[14] Fever has been found to be most common symptom found in 83%–99% cases, followed by cough (59%–82%), fatigue (44%–70%), anorexia (40%–84%), shortness of breath (31%–40%), sputum production (28%–33%), myalgia (11%–35%), whereas diarrhoea and vomiting have also been reported in significantly lesser cases.[15]

Reverse-transcriptase polymerase chain reaction (PCR) which detects RNA of SARS-CoV-2 is the standard diagnostic test for COVID-19. Nasopharynx sample yield is better in detection of SARS-CoV-2 RNA in comparison to throat samples; however, lower respiratory tract samples are expected to yield better than upper respiratory tract samples. Newly developed rapid disposable tests for antigen detection of COVID-19 are still to be evaluated for test performance and clinical utility hence are currently not recommended for clinical diagnosis. Currently, molecular PCR testing of respiratory tract samples is recommended diagnostic and confirmatory test for COVID-19.[15],[16]


  Treatment Options for Covid-19 Top


Currently, there are no drugs or other potential therapy to prevent or treat COVID 19. Current clinical management includes supportive care, infection control, supplemental oxygen, and mechanical ventilation when needed.[17] There are more than 300 active clinical trials underway; however, there is no clinical trial data supporting any prophylactic therapy.[18]

Chloroquine and hydroxychloroquine

Chloroquine and hydroxychloroquine have long been used as antimalarial and in the treatment of systemic lupus erythematosus and rheumatoid arthritis. Both these drugs appear to block the virus entry into the cells by inhibition of glycosylation of host receptors, proteolytic processing, and endosomal acidification.[18] A recent trial by Gautret et al.[19] in 36 patients (20 in hydroxychloroquine group and 16 in control group) showed improved virologic clearance with hydroxychloroquine, 200 mg, per orally every 8 h as compared to the control group who received standard supportive care. The author also reported higher virologic clearance by the addition of azithromycin to hydroxychloroquine group; however, concerns are being raised due to arrhythmogenic effects of these drugs.[20]

Remdesivir

Remdesivir was first used clinically in the treatment of Ebola.[18] Remdesivir is an intravenous antiviral drug under trial with broad antiviral activity that works by inhibiting viral replication through premature termination of RNA transcription. Remdesivir has shown in vitro activity against SARS-CoV-2.[17] In a study by Grein et al.[21] on 61 severely ill COVID-19 patients, clinical improvement was seen in 68% patients.

Immunomodulator agents

Monoclonal antibodies directed against the cytokines which spike as the result of inflammatory cytokine storm in COVID-19 patients is being investigated.

Monoclonal antibodies directed against key inflammatory cytokines or other aspects of the innate immune response represent another potential class of adjunctive therapies for COVID-19. The rationale for their use is that the underlying pathophysiology of significant organ damage in the lungs and other organs is caused by an amplified immune response and cytokine release or cytokine storm. Monoclonal antibodies such as tocilizumab directed against interleukin 6 has shown clinical improvements in patients of COVID-19.[18]

Convalescent serum

After infection by a pathogen like novel coronavirus, human body's immune system produces antibodies directed against the pathogen. These antibodies formed in response to antigen reach out, identify and mark the pathogen. White blood cells attach to the identified antigen, neutralize it, and the body gets rid of infection. The therapy harvests the antibody from a person who has recovered from the disease and ingested into a diseased person. Body immune system with the help of antibody mounts a robust attack on the virus.[22] In diseases caused by viruses, the antibodies present in convalescent serum block the entry of virus into uninfected cells, promote antibody directed cell-mediated cytotoxicity by natural-killer cells which clear the viruses.[23] In wake of large-scale epidemics CP has gained significant attention. CP is the currently preferred therapeutic tool for various reasons such as large volumes collected per person, frequent donations if necessary and absence of impact on donor's haemoglobin. The donor recruitment from areas where epidemic has broken can offer added tool in boosting artificially acquired passive immunity against the pathogen causing epidemic.[24] Although efficacy and safety of CP have not been fully proven yet, the empiric treatment could be a valid option in the treatment or prophylaxis of several infectious diseases. CP therapy both in association with other drugs and preventive measures may be the only therapy when a specific treatment is not available.[24]

Historically, a retrospective meta-analysis of studies during the 1918 influenza H1N1 pandemic showed CP obtained from recovered patients was used to successfully treat acutely ill patient and mortality was less in those who received the CP.[25],[26] CP was successfully used to treat patients with argentine haemorrhagic fever caused by Junin virus. The patients treated with CP had significantly reduced mortality as compared to patients treated with conventional therapy.[27] In a retrospective study by Soo et al.,[28] CP therapy was found to be more effective in reducing mortality and hospital stay than high doses of methylprednisolone therapy in severe SARS patients. Hung et al.[7] in a prospective study showed that relative risk of death in patients treated with CP was significantly lower than the other patients of 2009–2010 H1N1 pandemic treated only with standard care. A small nonrandomized study in Sierra Leone during 2013 West African Ebola epidemic revealed significantly longer survival for those treated with convalescent serum relative to those who received supportive standard treatment.[29]

In a recent study from China by Shen et al.,[30] CP was used to treat critically ill patients of COVID-19 which was marked by improvement in their clinical status. However, small sample size of five patients without randomization is limitations of study. In another study by Duan et al.[2] on ten critically ill patients from China, one dose of 200 mL CP obtained from recently recovered donor was transfused in addition to maximal supportive care and antiviral therapy. This study concluded that CP therapy was tolerated well by patients and could potentially improve clinical outcomes by neutralizing viremia in severe COVID-19 patients.

With US Food and Drug Administration (FDA)[31] and ICMR[32] issuing guidelines for trials of CP, the stage has been set for clinical trials and use of CP as therapeutics to contain this COVID-19 pandemic. After regulatory approvals John Hopkins University, Baltimore[33] in United States of America and Sree Chitra Tirunal Institute for Medical Sciences and Technology[22] in India have paced trials of CP therapy for COVID-19 and recommendations may soon be available.


  Conclusion Top


Current COVID-19 pandemic caused by a novel corona virus has turned focus onto possible use of CP in treatment of infectious diseases because of unavailability of drugs, vaccines or any other specific treatment. In such cases CP therapy is the only therapeutic strategy available. Since COVID-19 infection has spread rapidly, the available treatment options are limited. Various drugs like hydroxychloroquine, remdesivir have been used to treat patients with variable positive results on patient outcome, however there is no standardisation. Although there are very few studies with very limited patients on which convalescent serum therapy has been used with positive patient outcome, the recent approval by ICMR and FDA/Centers for Disease Control and Prevention for use of convalescent serum in treatment of seriously ill patients holds potential in these gloomy times. With large number of patients recovering from COVID-19 infection, availability of serum should not be a constraint. Convalescent serum therapy has been a proven effective therapy for more than a century now holds promise in containing this pandemic till definitive antiviral drugs or vaccines are safely tested and made available.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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