Participants will continue to receive standard of care and be closely monitored by ICU team for any change in clinical status, and any adverse events directly related to study intervention will be reported to the study investigator.

Time to treatment failure will be assessed in days and is defined as plasma viscosity > 3.5 cP and/or the participant is offered TPE outside of trial by primary clinical team.

The number of days spent in the ICU after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose ICU stay ended due to death.

The number of days spent hospitalized after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose hospitalization ended due to death.

The number of participants in each study arm discharged to home or to a long-term acute care (LTAC) hospital, versus palliative care or death.

The clinical status of participants was assessed using a single item modified from the World Health Organization (WHO) ordinal clinical severity scale for COVID. The instrument was customized for this study to evaluate thrombotic/bleeding events. In this 12-point ordinal scale, a score of 1 indicates no evidence of infection and the severity of the clinical status increases as the number of necessary interventions increases to the final score of 12, which is death. All patients were included at every timepoint recorded, with "terminal" scores carried over from the measure before for those that expired or fully recovered.

Body temperature will be assessed in degrees Celsius.

Systolic blood pressure will be assessed in millimeters of mercury (mm Hg).

Diastolic blood pressure will be assessed in millimeters of mercury (mm Hg).

Heart rate will be assessed as beats per minute.

Respiratory rate will be assessed as breaths per minute.

The number of days participants are on a ventilator, among participants who were ever on a ventilator after study enrollment.

The oxygen percent delivered with a ventilator that is needed to maintain blood oxygen levels will be compared between study arms.

PEEP during ventilator use is measured in centimeters of water (cmH2O) and is the pressure in the lungs above atmospheric pressure, at the end of an exhalation. Higher PEEP (10 cmH2O or greater) may be associated with improved mortality, compared with PEEP below 10 cmH2O.

Whether or not breathing assistance from vasopressors is needed will be compared between study arms.

Whether or not breathing assistance from an RRT is needed will be compared between study arms.

The Sequential Organ Failure Assessment (SOFA) score is a method of predicting mortality that is based on the degree of dysfunction of six organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). Each organ system is scored between 0 and 4, where 0 indicates normal function and 4 indicates a high degree of dysfunction. Total scores range from 0 to 24. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate.

The PaO2/FiO2 ratio is decreased with hypoxia. A value of less than 200 indicates acute respiratory distress syndrome (ARDS).

Ventilatory ratio will be documented. The formula for the ventilatory is [minute ventilation (ml/min) × PaCO2 (mm Hg)]/(predicted body weight × 100 × 37.5).

The normal range for WBC is 3,400 to 6,600 cells per microliter (cells/mL) of blood. A high WBC occurs when inflammation or infection is present.

Hemoglobin is measured in grams per deciliter (grams/dL). A normal Hb count for males is 13.2 to 16.6 grams/dL and a normal count for females is 11.6 to 15 grams/dL. A patient has anemia when their hemoglobin is low.

A measure of hematocrit is the volume of red blood cells in the total blood volume. Normal hematocrit for males is 40 to 54% and a normal measurement for females is 36 to 48%

A normal platelet is 150,000 to 450,000 platelets per microliter of blood. An excess of platelets in the blood can be caused by inflammation or infection.

MVP is a measurement of platelet size. Platelet size tends to be increased when platelet count is high. Typical platelet volume is 9.4 to 12.3 femtoliters (fL).

The normal range for BUN is 7 to 20 milligrams per deciliter (mg/dL) of blood. A high BUN value indicates that kidneys are not functioning well.

The normal range for creatinine is 0.84 to 1.21 mg/dL of blood. High serum creatinine indicates that kidneys are not functioning well.

For adults, normal values for total bilirubin are around 1.2 mg/dL of blood. High bilirubin indicates that the liver is not functioning well.

The normal range for total protein is 6.0 to 8.3 g/dL of blood. High levels of total protein can occur with inflammation or infection while low levels may indicate kidney or liver problems, or malnutrition.

The normal range for albumin is 3.4 to 5.4 g/dL of blood. High albumin may indicate acute infection while low albumin can indicate malnutrition or liver disease.

A normal value for CRP (with a standard test) is less than 10 milligrams per liter (mg/L) of blood. CRP increases with inflammation, which could be attributed to an infection, chronic inflammatory disease or heart disease.

A normal value for IL-6 is 1.8 picograms per milliliter (pg/mL) or less. IL-6 is increased in patients with infections or chronic inflammation.

Prothrombin time is a measurement of the time it takes (in seconds) for blood to clot. A normal value is 10 to 14 seconds.

An INR of around 1.1 is considered normal. Lower INR can means that blood is clotting faster than desired while higher INR indicates that blood is clotting slower than normal.

The aPTT test is a measurement of blood clotting time. Normal values for aPTT are around 30 to 40 seconds. Higher aPTT values can indicate a bleeding risk.

The anti-factor Xa assay measures plasma heparin and is useful with monitoring anticoagulation therapy. Interpretation of the resulting values depends on the anticoagulation medication used as well as the dosing schedule and indication. Patients not taking heparin should have an anti-Xa value of 0 units per milliliter (U/mL).

Fibrinogen is a protein that helps with the formation of blood clots. For adults, the normal range of fibrinogen is 200 to 400 mg/dL. Fibrinogen can be increased in patients with liver, kidney, or inflammatory diseases. The risk of developing a thromboembolism is increased with chronically high levels of fibrinogen.

The D-dimer blood test is a method of screening for deep vein thrombosis or pulmonary embolism. A normal D-dimer value is less than 0.50 micrograms per milliliter (mcg/mL) of blood. High levels of D-dimer can occur when a patient has a major blood clot, infection, or liver disease.

Total of all reporting groups

The primary safety endpoint is assessed as the cumulative incidence of adverse events directly associated with TPE during the study period as determined by clinical judgment of ICU team providing direct patient care and the study PI.

This analysis includes participants in the TPE study arm.

The number of participants dying from any cause is reported as a cumulative measures of mortality.

The number of bleeding and thromboembolic complications will be compared between study arms. This endpoint is a composite outcome including any acute bleeding requiring transfusion support, venous thrombosis (deep vein thrombosis or pulmonary embolism), arterial clots (myocardial infarction, stroke, limb ischemia), renal replacement therapy or catheter line related clots. The values reported are cumulative.

Time to treatment failure will be assessed in days and is defined as plasma viscosity > 3.5 cP and/or the participant is offered TPE outside of trial by primary clinical team.

This analysis includes participants experiencing treatment failure.

The number of days spent in the ICU after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose ICU stay ended due to death.

The number of days spent hospitalized after study enrollment is presented here. All patients are included in calculating the reported mean, including those whose hospitalization ended due to death.

The number of participants in each study arm discharged to home or to a long-term acute care (LTAC) hospital, versus palliative care or death.

The clinical status of participants was assessed using a single item modified from the World Health Organization (WHO) ordinal clinical severity scale for COVID. The instrument was customized for this study to evaluate thrombotic/bleeding events. In this 12-point ordinal scale, a score of 1 indicates no evidence of infection and the severity of the clinical status increases as the number of necessary interventions increases to the final score of 12, which is death. All patients were included at every timepoint recorded, with "terminal" scores carried over from the measure before for those that expired or fully recovered.

Body temperature will be assessed in degrees Celsius.

Body temperature was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Systolic blood pressure will be assessed in millimeters of mercury (mm Hg).

Blood pressure was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Diastolic blood pressure will be assessed in millimeters of mercury (mm Hg).

Blood pressure was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Heart rate will be assessed as beats per minute.

Heart rate was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Respiratory rate will be assessed as breaths per minute.

Respiratory rate was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

The number of days participants are on a ventilator, among participants who were ever on a ventilator after study enrollment.

This analysis includes participants who were on a ventilator; two participants in the TPE arm were never on a ventilator.

The oxygen percent delivered with a ventilator that is needed to maintain blood oxygen levels will be compared between study arms.

FiO2 was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

PEEP during ventilator use is measured in centimeters of water (cmH2O) and is the pressure in the lungs above atmospheric pressure, at the end of an exhalation. Higher PEEP (10 cmH2O or greater) may be associated with improved mortality, compared with PEEP below 10 cmH2O.

This analysis includes participants who were assessed for PEEP at the indicated time point.

Whether or not breathing assistance from vasopressors is needed will be compared between study arms.

Vasopressor requirements were not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

Whether or not breathing assistance from an RRT is needed will be compared between study arms.

Need for treatment from an RRT was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

The Sequential Organ Failure Assessment (SOFA) score is a method of predicting mortality that is based on the degree of dysfunction of six organ systems (respiratory, nervous, cardiovascular, liver, coagulation, and kidneys). Each organ system is scored between 0 and 4, where 0 indicates normal function and 4 indicates a high degree of dysfunction. Total scores range from 0 to 24. A score of 0-6 is associated with a mortality rate of less than 10% while a score between 16 and 24 is associated with a greater than 90% mortality rate.

This analysis includes participants who had a SOFA score assessment at the indicated time point.

The PaO2/FiO2 ratio is decreased with hypoxia. A value of less than 200 indicates acute respiratory distress syndrome (ARDS).

This analysis includes participants with available arterial blood gas (ABG) values.

Ventilatory ratio will be documented. The formula for the ventilatory is [minute ventilation (ml/min) × PaCO2 (mm Hg)]/(predicted body weight × 100 × 37.5).

Information for calculating the ventilatory ratio was not collected in an effort to reduce redundancy and workload for clinicians as more relevant/direct measures were already being collected.

The normal range for WBC is 3,400 to 6,600 cells per microliter (cells/mL) of blood. A high WBC occurs when inflammation or infection is present.

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

Hemoglobin is measured in grams per deciliter (grams/dL). A normal Hb count for males is 13.2 to 16.6 grams/dL and a normal count for females is 11.6 to 15 grams/dL. A patient has anemia when their hemoglobin is low.

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

A measure of hematocrit is the volume of red blood cells in the total blood volume. Normal hematocrit for males is 40 to 54% and a normal measurement for females is 36 to 48%

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

A normal platelet is 150,000 to 450,000 platelets per microliter of blood. An excess of platelets in the blood can be caused by inflammation or infection.

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

MVP is a measurement of platelet size. Platelet size tends to be increased when platelet count is high. Typical platelet volume is 9.4 to 12.3 femtoliters (fL).

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

The normal range for BUN is 7 to 20 milligrams per deciliter (mg/dL) of blood. A high BUN value indicates that kidneys are not functioning well.

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

The normal range for creatinine is 0.84 to 1.21 mg/dL of blood. High serum creatinine indicates that kidneys are not functioning well.

This analysis includes participants who had creatinine assessed at the indicated time point.

For adults, normal values for total bilirubin are around 1.2 mg/dL of blood. High bilirubin indicates that the liver is not functioning well.

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

The normal range for total protein is 6.0 to 8.3 g/dL of blood. High levels of total protein can occur with inflammation or infection while low levels may indicate kidney or liver problems, or malnutrition.

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

The normal range for albumin is 3.4 to 5.4 g/dL of blood. High albumin may indicate acute infection while low albumin can indicate malnutrition or liver disease.

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

A normal value for CRP (with a standard test) is less than 10 milligrams per liter (mg/L) of blood. CRP increases with inflammation, which could be attributed to an infection, chronic inflammatory disease or heart disease.

This analysis includes participants who had CRP assessed at the indicated time point.

A normal value for IL-6 is 1.8 picograms per milliliter (pg/mL) or less. IL-6 is increased in patients with infections or chronic inflammation.

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

Prothrombin time is a measurement of the time it takes (in seconds) for blood to clot. A normal value is 10 to 14 seconds.

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

An INR of around 1.1 is considered normal. Lower INR can means that blood is clotting faster than desired while higher INR indicates that blood is clotting slower than normal.

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

The aPTT test is a measurement of blood clotting time. Normal values for aPTT are around 30 to 40 seconds. Higher aPTT values can indicate a bleeding risk.

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

The anti-factor Xa assay measures plasma heparin and is useful with monitoring anticoagulation therapy. Interpretation of the resulting values depends on the anticoagulation medication used as well as the dosing schedule and indication. Patients not taking heparin should have an anti-Xa value of 0 units per milliliter (U/mL).

Information for this outcome was not collected for any participants. Limited laboratory data was available for clinical parameters ordered by the patients' healthcare providers as part of routine clinical care and later abstracted by study team members by chart review. This analyte was not abstracted by the study team for any patient given realization that too few points were available for analysis to generate meaningful data for interpretation.

Fibrinogen is a protein that helps with the formation of blood clots. For adults, the normal range of fibrinogen is 200 to 400 mg/dL. Fibrinogen can be increased in patients with liver, kidney, or inflammatory diseases. The risk of developing a thromboembolism is increased with chronically high levels of fibrinogen.

This analysis includes participants who had fibrinogen assessed at the indicated time point.

The D-dimer blood test is a method of screening for deep vein thrombosis or pulmonary embolism. A normal D-dimer value is less than 0.50 micrograms per milliliter (mcg/mL) of blood. High levels of D-dimer can occur when a patient has a major blood clot, infection, or liver disease.

This analysis includes participants who had D-dimer at the indicated time point.

Participants with COVID-19-associated elevated plasma viscosity randomized to receive standard of care treatment.