Convalescent Plasma as Adjunct Therapy for COVID-19

Convalescent plasma (CP) has been the subject of increasing expectation for treating coronavirus disease 2019 (COVID-19). Reports on CP transfusion have shown promising clinical improvements without serious adverse events. To date, most studies focused on reporting CP treatment in patients with severe COVID-19, but only a few addressed benefits on less severe disease. The vast majority of studies reporting COVID-19 infection and treatment have come from earlier affected countries with established health systems and research infrastructure, while very few are from low- and middle-income countries (LMICs). Nonetheless, CP therapy could be one of the few available options in LMICs where constraints may exist in the access to novel treatments, even once available. Clinical trials conducted in LMICs may differ in many respects from those in high-income countries. This study will evaluate the safety and efficacy of convalescent plasma therapy in hospitalized with moderate and severe COVID-19, to investigate the impacts of the treatment over the course of clinical illness, including non-mortal clinical outcomes.

Sex

All

Minimum age

18 Years

Maximum age

60 Years

INCLUSION CRITERIA:

1. Patients with PCR-confirmed COVID-19
2. Minimal age:18 years
3. Agree to participate in the trial with written informed consent
4. Moderate or Severe COVID-19 at the time of enrollment

   .

   A. Definition of moderate disease (according to Siddiqi et al):

   Moderate COVID-19 is defined as disease with fever, respiratory symptoms (dry cough, chest distress, or shortness of breath after activities), and pulmonary imaging findings, and at least one of the following findings:

   i) Abnormal coagulation parameters:
   * D-dimer \>1 µg/mL (normal \<0.5 µg/mL)
   * Prothrombin time (\>13.6 second) or International normalized ratio (INR) ≥1.8
   * Thrombocyte count \<100x 10\^3/mL

   ii) Increased pro-inflammatory markers:
   * C-reactive protein (CRP) ≥26.9 mg/L
   * Procalcitonin ≥0.5 ng/mL,
   * Lymphocyte count \<1.5x 10\^9/L) or Neutrophil/Lymphocyte ratio (NLR) \>3.3

   iii) Presence of risk factors or comorbidities:
   * Age \>65 years
   * Type 1 Diabetes Mellitus or type 2 Diabetes Mellitus (with any of the following: Fasting blood glucose ≥126 mg/dl, 2-h plasma glucose ≥200 mg/dL, or random plasma glucose ≥200 mg/dL, plus HbA1C \>6.5%)
   * Chronic kidney disease (creatinine \>2.0 mg/dL) or with routine hemodialysis
   * Chronic liver Disease with signs of liver cirrhosis; Child-Turcotte-Pugh (CTP) Class A (score 5-6) or Class B (score 7-9) or higher; or Model for End-Stage Liver Disease (MELD) score \<39
   * Heart failure (New York Health Association \[NYHA\] Class I or II)
   * Bronchial asthma, chronic obstructive pulmonary disease (COPD), or pulmonary tuberculosis
   * Cancer (particularly patients with chemotherapy or immunotherapy)
   * Immunocompromised conditions, including HIV/AIDS, post-organ transplantation, or judged by attending physician (preferable after specialist consultation)
   * Long-term corticosteroid use
   * autoimmune disease
   * Sequential Organ Failure Assessment \[SOFA\] score ≥5.65
   * Body Mass Index (BMI) ≥35 kg/m2

   B. Definition of severe COVID-19 (according to Siddiqi et al):

   Severe Covid-19 is defined as disease with a respiratory rate ≥30 breaths/min, oxygen saturation \<90% or oxygenation index (PaO2/FiO2) ≤300 mmHg, and/or lung infiltrates \>50% within 24-48 h.

   EXCLUSION CRITERIA:
   * Pregnant or lactating woman
   * History of transfusion reaction, blood-group incompatibility, IgA deficiency, or Allergy to Immunoglobulin-containing substances
   * Concurrent participation of clinical trials of COVID-19 treatment
   * Possibility of transfer to other hospital within 72 hours
   * Heart Failure (NYHA Class III or higher) or other diseases with risks of volume overload
   * Permanent organ failure unrelated to COVID-19, including:

     * End-stage liver disease (CTP score \>10 or MELD score \>40)
     * End stage renal disease with creatinine clearance \<30% or in routine dialysis
   * Multiple organ failure (SOFA score ≥11)
   * Concomitant condition or treatment with risks of thrombosis, e.g., cryoglobulinemia, refractory hypertriglyceridemia, or monoclonal gammopathy

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