Potential Efficacy of Convalescent Plasma to Treat Severe COVID-19 and Patients at High Risk of Developing Severe COVID-19
Condition: Convalescent Plasma for COVID 19
MeSH terms: COVID-19
Study type: Interventional
Phase: Phase 2

Summary: 
      Coronavirus disease (COVID-19) pandemic has started to affect Saudi Arabia and is expected to
      cause a lot of morbidities and many patients, especially the elderly, will require intensive
      care unit (ICU) support to survive as its lethality increases with the increasing age.
      Development of a vaccine by pharmaceutical companies like Roche and antibody concentrates
      from convalescent patients' plasma by Takeda will take 10-12 months to complete, and we
      speculate that it will be overwhelmingly expensive and limited in supply. We are presenting
      this urgent proposal to use the convalescent plasma to save the lives of severely affected
      COVID-19 patients. Most of the logistic support is already available in MOH Saudi Arabia, and
      it will be a cheap and quick technique based on the time-tested principles of passive
      immunization which is supported by the most recent data from China. We are proposing to test
      the therapeutic potential of convalescent plasma (from patients who have fully recovered from
      COVID-19) in treating patients with serious COVID-19 disease or those who are at risk of
      developing a serious disease based on their comorbidities profile. Convalescent plasma could
      provide our first-line defense for people with Covid-19, especially those who are older and
      at a much higher risk for complications. Amid the COVID-19 pandemic, with no available
      vaccine or proven antiviral drug, antibodies from recovering patients could provide a
      "stopgap" measure to help in controlling the pandemic effects on health and economy.

      We plan to recruit at least 40 consenting donors and patients. Non-consenting patients will
      serve as controls.
    

Detailed description: 
      Coronaviruses (CoV) are a large family of RNA viruses that cause illnesses ranging from the
      common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and
      Severe Acute Respiratory Syndrome (SARS-CoV).1,2 The new strain of coronavirus identified in
      December 2019 in Wuhan city, Hubei province of China, was called 2019 novel coronavirus
      (2019- nCoV) and has been named by the International Committee on Taxonomy of Viruses (ICTV)
      as Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). The ICTV have determined
      that SARS-CoV-2 is the same species as SARS-CoV but a different strain. The World Health
      Organization (WHO) has named the disease associated with SARS-CoV-2 infections as "COVID-19".

      Clinical features of SARS-CoV-2 infection typically include respiratory symptoms, fever,
      cough, shortness of breath and breathing difficulties. In more severe cases, the infection
      can cause pneumonia, severe acute respiratory distress syndrome (ARDS), kidney failure and
      even death. It is not easy to differentiate between non-SARS-CoV-2 seasonal influenza and
      other respiratory viruses including the locally reported MERS-CoV and H1N1 influenza viruses.
      SARS-CoV-2 has a higher transmission rate (TR) with an approximate fatality rate of 3%.
      Although most of the younger patients recover after milder disease, but COVID-19 is most
      aggressive in the elderly population with worst pneumonia and death rates may reach 14.8%.4
      Final diagnosis of SARS-CoV-2 infection depends on viral detection (and if possible,
      exclusion of other viruses e.g. by Respiratory Viral Panel). Laboratory detection of the
      SARS-CoV2 is based on detection of viral RNA by real-time reverse transcription-polymerase
      chain reaction (rRT-PCR) with confirmation by nucleic acid sequencing when necessary.1-5 For
      example, GeneFinder™ COVID-19 Plus RealAmp Kit is the One-Step Reverse Transcription
      Real-Time PCR Kit designed to detect the Novel Coronavirus (COVID-19) qualitatively through
      Reverse Transcription reaction and Real-Time Polymerase Chain Reaction. We will use this or
      equivalent method to confirm the diagnosis and will repeat the rRT-PCR to make sure it has
      become negative in a recovered patient. As of now, no vaccine or antiviral drug coming soon,
      antibodies from recovering patients could provide a "stop-gap" measure to help in controlling
      the pandemic. The concept of using convalescent plasma is not new. It has been tried in
      limited numbers of patients during more-recent viral crises, including the 2003 SARS (severe
      acute respiratory syndrome) epidemic, the 2009 "swine flu" epidemic, and the 2012 outbreak of
      MERS (Middle East respiratory syndrome).6 Convalescent plasma treatment reduced mortality in
      patients with severe pandemic influenza A (H1N1) 2009 Virus Infection.7 Patients with a
      resolved viral infection will develop a polyclonal antibody immune response to different
      viral antigens of 2019-nCoV. Some of these polyclonal antibodies will likely neutralize the
      virus and prevent new rounds of infection, and the patients with resolved infection should
      produce 2019-nCoV antibodies in high titer. Patients with resolved cases of 2019-nCoV can
      simply donate plasma, and then this plasma can be transfused into infected patients.8 Given
      that plasma donation is well established, and the transfusion of plasma is also routine
      medical care, this proposal does not need any new science or medical approvals in order to be
      put into place. Indeed, the same rationale was used in the treatment of several Ebola
      patients with convalescent serum during the outbreak in 2014-2015.9 Since the emergence of
      this SARS-CoV-2 infection in Wuhan, China, in December 2019, it has rapidly spread across
      China and more than 188 other countries and territories. According to the WHO, as of March
      27, 2020, there have been 540,832 confirmed cases worldwide and 24,294 deaths. SARS-CoV-2 has
      structural similarity to SARS-CoV that caused SARS and MERS-CoV.3 In the Kingdom of Saudi
      Arabia, there are 1012 confirmed cases reported till now, with 3 deaths (on March 26, 2020).

      The Saudi government's prompt actions to slow down the spread of SARS-CoV-2 seem to be
      effective. However, CDC Estimates 40-70% of the US population will be infected with
      SARS-CoV-2. Even with curtailment measures, judging from past pandemics, approximately 40% of
      human beings will be exposed to COVID-19 over the next 2-3 years. Most of these infected
      people will recover and almost all of them will be immune. Vigilance and readiness are needed
      to teach the masses about preventive measures because older people and those with
      comorbidities will be the sickest. Contemporaneously, therapeutic measures are highly needed
      from the medical community to treat COVID-19 patients.
    

Intervention name(s): convalescent plasma from recovered COVID 19 donor
Intervention type(s): Other
Intervention description(s): After obtaining informed consent, Eligible Patients who have severe COVID-19 and have not recovered yet will be infused with the donated convalescent plasma (10-15 ml/kg body weight of recipient)19 at least once & if possible, daily, for up to 5 sessions.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: experimental arm receiving convalescent plasma and parallel arm is control.
Masking: None (Open Label)
Primary purpose: Treatment