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Late |
Delić et al., Microorganisms, doi:10.3390/microorganisms10061118 |
death, ↓9.7%, p=0.67 |
Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial |
Details
RCT mechanically ventilated patients in Croatia, 39 treated with N-acetylcysteine and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-c.. |
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Late treatment study
Late treatment study
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Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial |
Delić et al., Microorganisms, doi:10.3390/microorganisms10061118 |
RCT mechanically ventilated patients in Croatia, 39 treated with N-acetylcysteine and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-caused ventilator-associated pneumonia.
risk of death, 9.7% lower, RR 0.90, p = 0.67, treatment 21 of 39 (53.8%), control 31 of 52 (59.6%), NNT 17.
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Delić et al., 5/28/2022, Randomized Controlled Trial, Croatia, peer-reviewed, 12 authors, study period October 2020 - June 2021.
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Late |
Izquierdo et al., Science Progress, doi:10.1177/00368504221074574 |
death, ↓25.6%, p=0.0007 |
Use of N-Acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19 |
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Retrospective 19,208 COVID+ hospitalized patients in Spain, 2,071 treated with high dose NAC, showing lower mortality with treatment. In multivariable analysis, authors adjust for corticosteroids, but do not adjust for HCQ use which was a.. |
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Late treatment study
Late treatment study
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Use of N-Acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19 |
Izquierdo et al., Science Progress, doi:10.1177/00368504221074574 |
Retrospective 19,208 COVID+ hospitalized patients in Spain, 2,071 treated with high dose NAC, showing lower mortality with treatment. In multivariable analysis, authors adjust for corticosteroids, but do not adjust for HCQ use which was also significantly more common in the NAC group. NAC 600mg every 8 hours.
risk of death, 25.6% lower, RR 0.74, p < 0.001, treatment 136 of 2,071 (6.6%), control 1,935 of 17,137 (11.3%), adjusted, OR converted to RR, multivariable.
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Excluded in after exclusion results of meta analysis:
significant unadjusted confounding possible.
Izquierdo et al., 1/27/2022, retrospective, Spain, peer-reviewed, 7 authors, study period 1 March, 2020 - 24 January, 2021.
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In Vitro |
Goc et al., European Journal of Microbiology and Immunology, doi:10.1556/1886.2021.00022 (In Vitro) |
In Vitro |
Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants |
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In Vitro study testing combinations of plant extracts and micronutrients with several variants of SARS-CoV-2. A combination of vitamin C, N-acetylcysteine, curcumin, quercetin, resveratrol, theaflavin, naringenin, baicalin, and broccoli e.. |
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In Vitro
In Vitro
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Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants |
Goc et al., European Journal of Microbiology and Immunology, doi:10.1556/1886.2021.00022 (In Vitro) |
In Vitro study testing combinations of plant extracts and micronutrients with several variants of SARS-CoV-2. A combination of vitamin C, N-acetylcysteine, curcumin, quercetin, resveratrol, theaflavin, naringenin, baicalin, and broccoli extract showed the highest inhibition of RBD binding, and also decreased RdRp, furin, and cathepsin L activity.
Goc et al., 1/21/2022, peer-reviewed, 5 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Late |
Ramadhan et al., Indonesian Journal of Tropical and Infectious Disease, 9:3 |
death, ↑134.7%, p=0.68 |
The Effects of N-Acetylcysteine as Adjuvant Therapy To Reduce TNF-Α Level And Increase SPO2/FIO2 Ratio In Improving Hypoxemia In COVID-19 Patients |
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Prospective study with 75 NAC patients and 16 control patients, showing no significant difference in mortality. |
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Late treatment study
Late treatment study
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The Effects of N-Acetylcysteine as Adjuvant Therapy To Reduce TNF-Α Level And Increase SPO2/FIO2 Ratio In Improving Hypoxemia In COVID-19 Patients |
Ramadhan et al., Indonesian Journal of Tropical and Infectious Disease, 9:3 |
Prospective study with 75 NAC patients and 16 control patients, showing no significant difference in mortality.
risk of death, 134.7% higher, RR 2.35, p = 0.68, treatment 11 of 75 (14.7%), control 1 of 16 (6.2%), unadjusted.
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Excluded in after exclusion results of meta analysis:
excessive unadjusted differences between groups.
Ramadhan et al., 12/27/2021, prospective, Indonesia, peer-reviewed, 6 authors, study period June 2020 - July 2021.
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Late |
Faverio et al., ERJ Open Research, doi:10.1183/23120541.00542-2021 |
death, ↑19.0%, p=0.33 |
Impact of N-acetyl-l-cysteine on SARS-CoV-2 pneumonia and its sequelae: results from a large cohort study |
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Retrospective 1,083 consecutive hospitalized COVID patients in Italy, showing no significant differences with NAC treatment. The number of patients transferred to another facility exceeds the number of deaths, which may significantly affe.. |
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Late treatment study
Late treatment study
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Impact of N-acetyl-l-cysteine on SARS-CoV-2 pneumonia and its sequelae: results from a large cohort study |
Faverio et al., ERJ Open Research, doi:10.1183/23120541.00542-2021 |
Retrospective 1,083 consecutive hospitalized COVID patients in Italy, showing no significant differences with NAC treatment. The number of patients transferred to another facility exceeds the number of deaths, which may significantly affect results.
risk of death, 19.0% higher, RR 1.19, p = 0.33, treatment 91 of 572 (15.9%), control 44 of 329 (13.4%), propensity score weighting.
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risk of ICU admission, 33.8% higher, RR 1.34, p = 0.08, treatment 107 of 572 (18.7%), control 46 of 329 (14.0%), propensity score weighting.
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risk of no hospital discharge, 1.4% lower, RR 0.99, p = 0.94, treatment 180 of 572 (31.5%), control 105 of 329 (31.9%), NNT 224, propensity score weighting.
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Faverio et al., 12/2/2021, retrospective, Italy, peer-reviewed, 10 authors, study period February 2020 - April 2021, trial NCT04424992 (history) (STORM).
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Early |
Ignatova et al., Russian Medical Inquiry, doi:10.32364/2587-6821-2021-5-7-473-478 |
hosp. time, ↓20.3%, p<0.05 |
Therapeutic possibilities of using an expectorant mucolytic agent with antioxidant properties in COVID-19 infection |
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Retrospective 111 patients with moderate COVID-19 pneumonia, 56 treated with NAC, showing shorter hospitalization time with treatment. NAC 1200mg daily intravenous, divided into two doses. |
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Early treatment study
Early treatment study
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Therapeutic possibilities of using an expectorant mucolytic agent with antioxidant properties in COVID-19 infection |
Ignatova et al., Russian Medical Inquiry, doi:10.32364/2587-6821-2021-5-7-473-478 |
Retrospective 111 patients with moderate COVID-19 pneumonia, 56 treated with NAC, showing shorter hospitalization time with treatment. NAC 1200mg daily intravenous, divided into two doses.
hospitalization time, 20.3% lower, relative time 0.80, p < 0.05, treatment 56, control 55.
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Ignatova et al., 11/10/2021, retrospective, Russia, peer-reviewed, median age 49.2, 12 authors, average treatment delay 4.6 days.
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Late |
Avdeev et al., Journal of Infection, doi:10.1016/j.jinf.2021.07.003 |
death, ↓69.4%, p=0.34 |
N-acetylcysteine for the treatment of COVID-19 among hospitalized patients |
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Prospective study of 24 hospitalized COVID-19 patients in Russia treated with NAC, and 22 matched controls, showing significantly improved SpO2/FiO2, and significantly shorter hospitalization with treatment. |
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Late treatment study
Late treatment study
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N-acetylcysteine for the treatment of COVID-19 among hospitalized patients |
Avdeev et al., Journal of Infection, doi:10.1016/j.jinf.2021.07.003 |
Prospective study of 24 hospitalized COVID-19 patients in Russia treated with NAC, and 22 matched controls, showing significantly improved SpO2/FiO2, and significantly shorter hospitalization with treatment.
risk of death, 69.4% lower, RR 0.31, p = 0.34, treatment 1 of 24 (4.2%), control 3 of 22 (13.6%), NNT 11.
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risk of mechanical ventilation, 77.1% lower, RR 0.23, p = 0.18, treatment 1 of 24 (4.2%), control 4 of 22 (18.2%), NNT 7.1.
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risk of ICU admission, 77.1% lower, RR 0.23, p = 0.18, treatment 1 of 24 (4.2%), control 4 of 22 (18.2%), NNT 7.1.
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hospitalization time, 15.4% lower, relative time 0.85, p = 0.01, treatment 24, control 22.
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Avdeev et al., 7/9/2021, retrospective, Russia, peer-reviewed, 4 authors, study period 12 April, 2020 - 20 June, 2020, average treatment delay 7.2 days.
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Late |
Assimakopoulos et al., Infectious Diseases, doi:10.1080/23744235.2021.1945675 |
death, ↓97.1%, p=0.006 |
N-acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: a two-center retrospective cohort study |
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Retrospective 42 hospitalized PCR+ COVID-19 pneumonia patients treated with NAC, and a matched control group of 40 patients, showing significantly lower severe respiratory failure and significantly lower mortality with treatment. NAC 600 .. |
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Late treatment study
Late treatment study
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N-acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: a two-center retrospective cohort study |
Assimakopoulos et al., Infectious Diseases, doi:10.1080/23744235.2021.1945675 |
Retrospective 42 hospitalized PCR+ COVID-19 pneumonia patients treated with NAC, and a matched control group of 40 patients, showing significantly lower severe respiratory failure and significantly lower mortality with treatment. NAC 600 mg bid orally for 14 days.
risk of death, 97.1% lower, RR 0.03, p = 0.006, treatment 2 of 42 (4.8%), control 12 of 40 (30.0%), NNT 4.0, OR converted to RR.
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Assimakopoulos et al., 6/29/2021, retrospective, Greece, peer-reviewed, 9 authors, study period 1 February, 2021 - 30 April, 2021.
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Early |
Altay et al., Advanced Science, doi:10.1002/advs.202101222 |
hosp., ↓80.1%, p=0.25 |
Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19 |
Details
RCT 304 low-risk outpatients, 229 treated with N-acetylcysteine, l-carnitine tartrate, nicotinamide riboside chloride, and serine, showing significantly faster recovery with treatment. Plasma levels of proteins and metabolites associated .. |
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Early treatment study
Early treatment study
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Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19 |
Altay et al., Advanced Science, doi:10.1002/advs.202101222 |
RCT 304 low-risk outpatients, 229 treated with N-acetylcysteine, l-carnitine tartrate, nicotinamide riboside chloride, and serine, showing significantly faster recovery with treatment. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism were significantly improved in treated patients.
risk of hospitalization, 80.1% lower, RR 0.20, p = 0.25, treatment 0 of 229 (0.0%), control 1 of 76 (1.3%), NNT 76, relative risk is not 0 because of continuity correction due to zero events.
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risk of no recovery, 82.7% lower, RR 0.17, p < 0.001, treatment 229, control 75, multivariate Cox regression.
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Altay et al., 6/28/2021, Double Blind Randomized Controlled Trial, placebo-controlled, Turkey, peer-reviewed, 18 authors, this trial uses multiple treatments in the treatment arm (combined with l-carnitine tartrate, nicotinamide riboside chloride, serine) - results of individual treatments may vary.
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Late |
Taher et al., Pharmacological Reports, doi:10.1007/s43440-021-00296-2 |
death, ↓17.9%, p=0.65 |
A pilot study on intravenous N-Acetylcysteine treatment in patients with mild-to-moderate COVID19-associated acute respiratory distress syndrome |
Details
RCT 92 hospitalized patients, 47 treated with NAC, showing non-significant improvements in outcomes. IRCT20120215009014N355. NAC 40mg/kg/day intravenous for 3 days. |
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Late treatment study
Late treatment study
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A pilot study on intravenous N-Acetylcysteine treatment in patients with mild-to-moderate COVID19-associated acute respiratory distress syndrome |
Taher et al., Pharmacological Reports, doi:10.1007/s43440-021-00296-2 |
RCT 92 hospitalized patients, 47 treated with NAC, showing non-significant improvements in outcomes. IRCT20120215009014N355. NAC 40mg/kg/day intravenous for 3 days.
risk of death, 17.9% lower, RR 0.82, p = 0.65, treatment 12 of 47 (25.5%), control 14 of 45 (31.1%), NNT 18.
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risk of mechanical ventilation, 13.8% lower, RR 0.86, p = 0.67, treatment 18 of 47 (38.3%), control 20 of 45 (44.4%), NNT 16.
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ICU time, 20.0% lower, relative time 0.80, p = 0.48, treatment 47, control 45.
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hospitalization time, 33.3% lower, relative time 0.67, p = 0.31, treatment 47, control 45.
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risk of no recovery, 14.5% lower, RR 0.85, p = 0.41, treatment 25 of 47 (53.2%), control 28 of 45 (62.2%), NNT 11.
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Taher et al., 6/10/2021, Double Blind Randomized Controlled Trial, Iran, peer-reviewed, 6 authors, average treatment delay 7.0 days.
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Late |
Pourhoseingholi et al., Research Square, doi:10.21203/rs.3.rs-365321/v2 (Preprint) |
death, ↓11.0%, p=0.43 |
Case Characteristics, Clinical Data, And Outcomes of Hospitalized COVID-19 Patients In Qom Province, Iran: A Prospective Cohort Study |
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Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing no significant difference with NAC treatment. IR.MUQ.REC.1399.013. |
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Late treatment study
Late treatment study
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Case Characteristics, Clinical Data, And Outcomes of Hospitalized COVID-19 Patients In Qom Province, Iran: A Prospective Cohort Study |
Pourhoseingholi et al., Research Square, doi:10.21203/rs.3.rs-365321/v2 (Preprint) |
Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing no significant difference with NAC treatment. IR.MUQ.REC.1399.013.
risk of death, 11.0% lower, HR 0.89, p = 0.43, treatment 65 of 309 (21.0%), control 274 of 2,159 (12.7%), adjusted, multivariable, Cox proportional hazards.
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Pourhoseingholi et al., 5/26/2021, prospective, Iran, preprint, mean age 57.9, 11 authors, study period 2 February, 2020 - 20 July, 2020, average treatment delay 7.4 days.
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Late |
Pellegrini et al., Gastroenterology, doi:10.1016/S0016-5085(21)02756-6 |
death, ↓51.7%, p=0.0001 |
A Retrospective Analysis of Outcomes Amongst COVID-19 Infected Patients with Acute Hepatitis Receiving N-Acetylcysteine Therapy in a Safety Net Hospital |
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Retrospective 864 hospitalized late stage COVID-19 patients in the USA, 138 receiving NAC treatment for acute hepatitis, showing lower mortality with treatment. Results are adjusted for confounders, however details are not provided. |
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Late treatment study
Late treatment study
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A Retrospective Analysis of Outcomes Amongst COVID-19 Infected Patients with Acute Hepatitis Receiving N-Acetylcysteine Therapy in a Safety Net Hospital |
Pellegrini et al., Gastroenterology, doi:10.1016/S0016-5085(21)02756-6 |
Retrospective 864 hospitalized late stage COVID-19 patients in the USA, 138 receiving NAC treatment for acute hepatitis, showing lower mortality with treatment. Results are adjusted for confounders, however details are not provided.
risk of death, 51.7% lower, OR 0.48, p < 0.001, treatment 138, control 726, adjusted, multivariable, RR approximated with OR.
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Pellegrini et al., 5/23/2021, retrospective, USA, peer-reviewed, 10 authors, study period March 2020 - May 2020.
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Submit Corrections or Comments
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Late |
Gaynitdinova et al., Pulmonologiya, doi:10.18093/0869-0189-2021-31-1-21-29 |
hosp. time, ↓15.4%, p<0.001 |
N-acetylcysteine as a part of complex treatment of moderate COVID-associated pneumonia |
Details
RCT 46 hospitalized patients with moderate COVID-19 pneumonia, 24 treated wth N-acetylcysteine, showing significantly shorter hospitalization with treatment. NAC 1,200 – 1,500mg/day intravenously. |
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Late treatment study
Late treatment study
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N-acetylcysteine as a part of complex treatment of moderate COVID-associated pneumonia |
Gaynitdinova et al., Pulmonologiya, doi:10.18093/0869-0189-2021-31-1-21-29 |
RCT 46 hospitalized patients with moderate COVID-19 pneumonia, 24 treated wth N-acetylcysteine, showing significantly shorter hospitalization with treatment. NAC 1,200 – 1,500mg/day intravenously.
hospitalization time, 15.4% lower, relative time 0.85, p < 0.001, treatment 24, control 22.
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relative improvement in lung Ct, 50.7% better, RR 0.49, p < 0.001, treatment 24, control 22.
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Gaynitdinova et al., 2/19/2021, Randomized Controlled Trial, Russia, peer-reviewed, 6 authors, average treatment delay 7.0 days.
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Submit Corrections or Comments
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Late |
de Alencar et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa1443 |
death, ↑2.6%, p=0.94 |
Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19) |
Details
RCT 135 severe stage patients in Brazil, showing no significant differences. NAC 21g (~300mg/kg) for 20 hours. U1111-1250-356 . |
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Late treatment study
Late treatment study
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Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19) |
de Alencar et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa1443 |
RCT 135 severe stage patients in Brazil, showing no significant differences. NAC 21g (~300mg/kg) for 20 hours. U1111-1250-356 [ensaiosclinicos.gov.br].
risk of death, 2.6% higher, RR 1.03, p = 0.94, treatment 9 of 67 (13.4%), control 9 of 68 (13.2%), OR converted to RR.
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risk of mechanical ventilation, 16.0% higher, RR 1.16, p = 0.64, treatment 16 of 67 (23.9%), control 14 of 68 (20.6%), OR converted to RR.
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risk of ICU admission, 8.5% lower, RR 0.91, p = 0.65, treatment 29 of 67 (43.3%), control 32 of 68 (47.1%), NNT 26, OR converted to RR.
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ICU time, 12.5% higher, relative time 1.12, p = 0.56, treatment 67, control 68.
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hospitalization time, 10.0% higher, relative time 1.10, p = 0.87, treatment 67, control 68.
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de Alencar et al., 9/23/2020, Double Blind Randomized Controlled Trial, placebo-controlled, Brazil, peer-reviewed, median age 59.0, 65 authors, average treatment delay 7.0 days.
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PrEPPEP |
Huh et al., medRxiv, doi:10.1101/2020.05.04.20089904 (Preprint) |
cases, ↓26.2%, p<0.0001 |
Association of previous medications with the risk of COVID-19: a nationwide claims-based study from South Korea |
Details
Retrospective database analysis of 65,149 in South Korea, showing significantly lower cases with existing N-acetylcysteine treatment. The journal version of this paper does not present the N-acetylcysteine results. |
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Prophylaxis study
Prophylaxis study
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Association of previous medications with the risk of COVID-19: a nationwide claims-based study from South Korea |
Huh et al., medRxiv, doi:10.1101/2020.05.04.20089904 (Preprint) |
Retrospective database analysis of 65,149 in South Korea, showing significantly lower cases with existing N-acetylcysteine treatment. The journal version of this paper does not present the N-acetylcysteine results.
risk of case, 26.2% lower, RR 0.74, p < 0.001, treatment 710 of 13,788 (5.1%), control 4,462 of 51,361 (8.7%), adjusted, OR converted to RR, multivariable.
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Huh et al., 5/4/2020, retrospective, database analysis, South Korea, preprint, 10 authors.
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