Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19

Table 1 Principles of coronavirus disease 2019 management according to disease severity and presence of comorbidities

Severity	No comorbidities present	Comorbidities present
Mild	Conservative at home	Steroids,or/and plasma therapy
Moderate	Conservative at home	Steroids, or/and plasma therapy
Severe	Hospitalized: Treatment focused on the complication	Intravenous fluid, oxygen, corticosteroids

Table 2 Details of clinical trial

	Arm	Intervention/Treatment
NCT04455243	Experimental: Intervention group	Drug N-acetylcysteine is given as 150 mg/kg q 12 h PO or IV every 12 h for 14 d diluted in 200 mL diluent (D5 % NS)
	Placebo comparator: Control group	Matching drug placebo is administered in the same schedule and volume as N-acetylcysteine
NCT04374461	Experimental: Arm A. (1) Transfer out of the critical care unit; (2) Extubation; (3) Toxicity; and (4) Death	Drug NAC. Others: Peripheral blood dosages are given in both groups as mentioned above
	Experimental: Arm B. (1) Discharge from the hospital; (2) Admission to a critical care unit; (3) Intubation; (4) Toxicity; and (5) Death	Drug NAC. Others: Peripheral blood dosage details as mentioned above
NCT04419025	Active Comparator: NAC Patients receiving N-acetylcysteine	Drug: N-acetylcysteine. In-patient: (1) Oral formulation 600 mg capsules of NAC q4 h until discharge; and (2) 1200 mg PO BID × 1-wk post-discharge Outpatient :2400 mg PO × 1 then 1200 mg PO BID × 2 wk
	No Intervention: Control patients not receiving N-acetylcysteine
NCT04458298	Experimental: Cohort A: OP-101 2 mg/kg. Participants will receive a single intravenous (IV) infusion of OP-101 2 milligram per kilogram (mg/kg) on Day 1	Drug: OP-101 will be administered as an IV infusion
	Experimental: Cohort B: OP-101 4 mg/kg. Participants will receive a single IV infusion of OP-101 4 mg/kg on Day 1	Drug: OP-101 will be administered as an IV infusion
	Experimental: Cohort C: OP-101 8 mg/kg Participants will receive a single IV infusion of OP-101 8 mg/kg on Day 1	Drug: OP-101 will be administered as an IV infusion
	Placebo Comparator: Cohort D: Placebo Participants will receive a single IV infusion of matching placebo on Day 1	Drug: Placebo. Matching placebo infusion will be administered intravenously

PO: Peros; NAC: N-acetylcysteine; NAC: N-acetylcysteine; BID: Bisindie; PO: Peros.

Table 3 Summary of ongoing clinical trials of N-acetyl cysteine and corona virus disease 2019

Nct	Drug or other interventions	Diseases	Location (State, Country)	Status (Recruiting or completed)	Results (Yes or not available)	Phase
NCT04455243	N-acetyl cysteine vs placebo	COVID 19	Riyadh, Saudi Arabia	Not yet recruiting	Pending	3
NCT04374461	N-acetyl cysteine vs peripheral blood	COVID 19	New York, United States	Trial began May 2020	Pending, expected May 2022	2
NCT04419025	N-acetyl cysteine	COVID 19 SARS COV 2, SARS associated Coronavirus disease, Oxidative stress	Massachusetts, United States	Trial began September 2020	Pending, expected May 2021	4
NCT04458298	OP-101 (Dendrimer N-Acetylcysteine) Placebo	COVID 19	California, United States	Trial began July 2020	Pending, expected February 2021	2

COVID 19: Corona virus disease 2019; SARS COV 2: Severe acute respiratory syndrome coronavirus 2.