Given the current lack of an effective drug or therapy, a clinical trial to better understand the safety and efficacy of therapeutic plasma exchange (TPE) in COVID-19 patients is urgently needed. The goal of this trial is to study the efficacy and safety of TPE therapy in subjects with moderate to severe COVID-19 by determining the morbidity and mortality after TPE therapy.

Inclusion Criteria:

1. Patients with moderate-severe COVID-19 infection including early acute lung injury (ALI)/early acute respiratory distress syndrome (ARDS)
2. Able to provide Informed Consent signed by the subject or by the subject's legal or healthcare proxy.
3. Admitted to the participating facilities as listed above (Larkin South Miami Hospital, Larkin Palm Springs Hospital).
4. Subjects between 18 and 69 years of age.
5. If female, subjects that have a negative result in a quantitative b-HCG blood test if they are within reproductive age.
6. A positive COVID-19 test via nasopharyngeal swab RT-PCR.
7. Agree to not participate in another clinical trial during the study period.

Exclusion Criteria:

1. Under 18 years of age or older than 69 years of age.

2. Severe disease, defined as:

   i. dyspnea ii. respiratory frequency ≥ 30/min iii. blood oxygen saturation ≤ 93% iv. partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 300, and/or v. lung infiltrates > 50% within 24 to 48 hours;

3. Life-threatening disease, defined as:

   i. respiratory failure ii. septic shock, and/or iii. multiple organ dysfunction or failure

4. Unable to provide informed consent or decline to consent.

5. Sequential Organ Failure Assessment (SOFA) score of 12 or above.

6. Hemodynamic instability, sepsis, or other conditions causing inability to tolerate fluid shifts

7. Inability to tolerate central line placement

8. Allergy to FFP or albumin

9. Severe hypocalcemia

10. Patients with heparin allergies should not receive heparin as an anticoagulant during plasmapheresis

11. Patients taking angiotensin-converting enzyme (ACE) inhibitors are advised to stop taking the medication for at least 24 hours before starting plasmapheresis

12. Active or recent bleeding (unless controlled for >48 hours).

13. Thrombocytopenia (≤25,000/L).

14. Advanced cirrhosis with a history of esophageal varices.

15. Chronic kidney disease requiring hemodialysis.

16. Active solid or non-solid malignancy or Lymphoma within the last 2 years.

17. Heart failure (NYHA class III or IV).

18. HIV infection (AIDS criteria), a history of immunodeficiency, or subject is currently receiving immunosuppressive therapy.

19. Women of childbearing age who are pregnant or intend to become pregnant during the study period.

20. Known history of chromosomal or genetic abnormalities.

21. History of hypersensitivity or any kind of adverse reaction to blood products.

22. Contraindication to transfusion of blood products, or refusal due to religious/personal reasons.

23. Any kind of drug or alcohol dependence that would interfere with adherence to the study requirements.

24. Already part of this trial, recruited at a different hospital.