Outcomes in COVID-19 N-acetylcysteine studies
0
0.5
1
1.5+
ALL STUDIES
MORTALITY
VENTILATION
ICU ADMISSION
HOSPITALIZATION
RECOVERY
CASES
RANDOMIZED CONTROLLED TRIALS
RCT MORTALITY
PEER-REVIEWED
After Exclusions
ALL STUDIES
All
Prophylaxis
Early
Late
N-acetylcysteine for COVID-19
C19EARLY.COM/NA AUG 2022
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Altay (DB RCT)
80%
0.20 [0.01-4.85]
hosp.
0/229
1/76
CT1
Improvement, RR [CI]
Treatment
Control
Ignatova
20%
0.80 [0.64-1.00]
hosp. time
56 (n)
55 (n)
Tau2 = 0.00, I2 = 0.0%, p = 0.043
Early treatment
21%
0.79 [0.63-0.99]
0/285
1/131
21% improvement
de Alencar (DB RCT)
-3%
1.03 [0.41-2.27]
death
9/67
9/68
Improvement, RR [CI]
Treatment
Control
Gaynitdinova (RCT)
15%
0.85 [0.77-0.93]
hosp. time
24 (n)
22 (n)
Pellegrini
52%
0.48 [0.33-0.70]
death
138 (n)
726 (n)
Pourhoseingholi
11%
0.89 [0.68-1.18]
death
65/309
274/2,159
Taher (DB RCT)
18%
0.82 [0.43-1.58]
death
12/47
14/45
Assimakopoulos
97%
0.03 [0.00-0.30]
death
2/42
12/40
Avdeev
69%
0.31 [0.03-2.72]
death
1/24
3/22
Faverio (PSW)
-19%
1.19 [0.85-1.66]
death
91/572
44/329
Ramadhan
-135%
2.35 [0.33-16.9]
death
11/75
1/16
Izquierdo
26%
0.74 [0.63-0.88]
death
136/2,071
1,935/17,137
Delić (RCT)
10%
0.90 [0.63-1.30]
death
21/39
31/52
Intubated patients
Tau2 = 0.06, I2 = 73.5%, p = 0.019
Late treatment
22%
0.78 [0.63-0.96]
348/3,408
2,323/20,616
22% improvement
Huh
26%
0.74 [0.68-0.80]
cases
population-based cohort
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Prophylaxis
26%
0.74 [0.68-0.80]
26% improvement
All studies
22%
0.78 [0.68-0.90]
348/3,693
2,324/20,747
22% improvement
14 N-acetylcysteine COVID-19 studies
c19early.com/na Aug 2022
Tau2 = 0.03, I2 = 69.3%, p = 0.00056
Effect extraction pre-specified (most serious outcome)
1 CT: study uses combined treatment
Favors N-acetylcysteine
Favors control
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Altay (DB RCT)
80%
0.20 [0.01-4.85]
hosp.
0/229
1/76
CT1
Improvement, RR [CI]
Treatment
Control
Ignatova
20%
0.80 [0.64-1.00]
hosp. time
56 (n)
55 (n)
Tau2 = 0.00, I2 = 0.0%, p = 0.043
Early treatment
21%
0.79 [0.63-0.99]
0/285
1/131
21% improvement
de Alencar (DB RCT)
-3%
1.03 [0.41-2.27]
death
9/67
9/68
Improvement, RR [CI]
Treatment
Control
Gaynitdinova (RCT)
15%
0.85 [0.77-0.93]
hosp. time
24 (n)
22 (n)
Pellegrini
52%
0.48 [0.33-0.70]
death
138 (n)
726 (n)
Pourhoseingholi
11%
0.89 [0.68-1.18]
death
65/309
274/2,159
Taher (DB RCT)
18%
0.82 [0.43-1.58]
death
12/47
14/45
Assimakopoulos
97%
0.03 [0.00-0.30]
death
2/42
12/40
Avdeev
69%
0.31 [0.03-2.72]
death
1/24
3/22
Faverio (PSW)
-19%
1.19 [0.85-1.66]
death
91/572
44/329
Delić (RCT)
10%
0.90 [0.63-1.30]
death
21/39
31/52
Intubated patients
Tau2 = 0.10, I2 = 77.2%, p = 0.039
Late treatment
25%
0.75 [0.58-0.99]
201/1,262
387/3,463
25% improvement
Huh
26%
0.74 [0.68-0.80]
cases
population-based cohort
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Prophylaxis
26%
0.74 [0.68-0.80]
26% improvement
All studies
22%
0.78 [0.67-0.92]
201/1,547
388/3,594
22% improvement
12 N-acetylcysteine COVID-19 studies after exclusions
c19early.com/na Aug 2022
Tau2 = 0.04, I2 = 73.0%, p = 0.0025
Effect extraction pre-specified (most serious outcome)
1 CT: study uses combined treatment
Favors N-acetylcysteine
Favors control
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
de Alencar (DB RCT)
-3%
1.03 [0.41-2.27]
9/67
9/68
Improvement, RR [CI]
Treatment
Control
Pellegrini
52%
0.48 [0.33-0.70]
138 (n)
726 (n)
Pourhoseingholi
11%
0.89 [0.68-1.18]
65/309
274/2,159
Taher (DB RCT)
18%
0.82 [0.43-1.58]
12/47
14/45
Assimakopoulos
97%
0.03 [0.00-0.30]
2/42
12/40
Avdeev
69%
0.31 [0.03-2.72]
1/24
3/22
Faverio (PSW)
-19%
1.19 [0.85-1.66]
91/572
44/329
Ramadhan
-135%
2.35 [0.33-16.9]
11/75
1/16
Izquierdo
26%
0.74 [0.63-0.88]
136/2,071
1,935/17,137
Delić (RCT)
10%
0.90 [0.63-1.30]
21/39
31/52
Intubated patients
Tau2 = 0.12, I2 = 75.6%, p = 0.044
Late treatment
26%
0.74 [0.55-0.99]
348/3,384
2,323/20,594
26% improvement
All studies
26%
0.74 [0.55-0.99]
348/3,384
2,323/20,594
26% improvement
10 N-acetylcysteine COVID-19 mortality results
c19early.com/na Aug 2022
Tau2 = 0.12, I2 = 75.6%, p = 0.044
Favors N-acetylcysteine
Favors control
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
de Alencar (DB RCT)
-16%
1.16 [0.59-2.01]
16/67
14/68
Improvement, RR [CI]
Treatment
Control
Taher (DB RCT)
14%
0.86 [0.53-1.40]
18/47
20/45
Avdeev
77%
0.23 [0.03-1.90]
1/24
4/22
Tau2 = 0.02, I2 = 10.9%, p = 0.7
Late treatment
8%
0.92 [0.60-1.40]
35/138
38/135
8% improvement
All studies
8%
0.92 [0.60-1.40]
35/138
38/135
8% improvement
3 N-acetylcysteine COVID-19 mechanical ventilation results
c19early.com/na Aug 2022
Tau2 = 0.02, I2 = 10.9%, p = 0.7
Favors N-acetylcysteine
Favors control
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
de Alencar (DB RCT)
9%
0.91 [0.59-1.28]
29/67
32/68
Improvement, RR [CI]
Treatment
Control
Taher (DB RCT)
20%
0.80 [0.44-1.47]
47 (n)
45 (n)
Avdeev
77%
0.23 [0.03-1.90]
1/24
4/22
Faverio (PSW)
-34%
1.34 [0.97-1.84]
107/572
46/329
Tau2 = 0.05, I2 = 45.5%, p = 0.99
Late treatment
0%
1.00 [0.70-1.42]
137/710
82/464
0% improvement
All studies
0%
1.00 [0.70-1.42]
137/710
82/464
0% improvement
4 N-acetylcysteine COVID-19 ICU results
c19early.com/na Aug 2022
Tau2 = 0.05, I2 = 45.5%, p = 0.99
Favors N-acetylcysteine
Favors control
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Altay (DB RCT)
80%
0.20 [0.01-4.85]
hosp.
0/229
1/76
CT1
Improvement, RR [CI]
Treatment
Control
Ignatova
20%
0.80 [0.64-1.00]
hosp. time
56 (n)
55 (n)
Tau2 = 0.00, I2 = 0.0%, p = 0.043
Early treatment
21%
0.79 [0.63-0.99]
0/285
1/131
21% improvement
de Alencar (DB RCT)
-10%
1.10 [0.37-3.23]
hosp. time
67 (n)
68 (n)
Improvement, RR [CI]
Treatment
Control
Gaynitdinova (RCT)
15%
0.85 [0.77-0.93]
hosp. time
24 (n)
22 (n)
Taher (DB RCT)
33%
0.67 [0.31-1.45]
hosp. time
47 (n)
45 (n)
Avdeev
15%
0.85 [0.75-0.96]
hosp. time
24 (n)
22 (n)
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Late treatment
15%
0.85 [0.78-0.91]
0/162
0/157
15% improvement
All studies
16%
0.84 [0.78-0.90]
0/447
1/288
16% improvement
6 N-acetylcysteine COVID-19 hospitalization results
c19early.com/na Aug 2022
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
1 CT: study uses combined treatment
Favors N-acetylcysteine
Favors control
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Altay (DB RCT)
80%
0.20 [0.01-4.85]
hosp.
0/229
1/76
CT1
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.33
Early treatment
80%
0.20 [0.01-4.85]
0/229
1/76
80% improvement
de Alencar (DB RCT)
-3%
1.03 [0.41-2.27]
death
9/67
9/68
Improvement, RR [CI]
Treatment
Control
Pellegrini
52%
0.48 [0.33-0.70]
death
138 (n)
726 (n)
Pourhoseingholi
11%
0.89 [0.68-1.18]
death
65/309
274/2,159
Taher (DB RCT)
18%
0.82 [0.43-1.58]
death
12/47
14/45
Assimakopoulos
97%
0.03 [0.00-0.30]
death
2/42
12/40
Avdeev
69%
0.31 [0.03-2.72]
death
1/24
3/22
Faverio (PSW)
-19%
1.19 [0.85-1.66]
death
91/572
44/329
Ramadhan
-135%
2.35 [0.33-16.9]
death
11/75
1/16
Izquierdo
26%
0.74 [0.63-0.88]
death
136/2,071
1,935/17,137
Delić (RCT)
10%
0.90 [0.63-1.30]
death
21/39
31/52
Intubated patients
Tau2 = 0.12, I2 = 75.6%, p = 0.044
Late treatment
26%
0.74 [0.55-0.99]
348/3,384
2,323/20,594
26% improvement
All studies
27%
0.73 [0.55-0.98]
348/3,613
2,324/20,670
27% improvement
11 N-acetylcysteine COVID-19 serious outcomes
c19early.com/na Aug 2022
Tau2 = 0.12, I2 = 73.4%, p = 0.036
Effect extraction pre-specified (most serious outcome)
1 CT: study uses combined treatment
Favors N-acetylcysteine
Favors control
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Altay (DB RCT)
83%
0.17 [0.13-0.24]
no recov.
229 (n)
75 (n)
CT1
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Early treatment
83%
0.17 [0.13-0.24]
0/229
0/75
83% improvement
Gaynitdinova (RCT)
51%
0.49 [0.32-0.75]
Ct imp.
24 (n)
22 (n)
Improvement, RR [CI]
Treatment
Control
Taher (DB RCT)
15%
0.85 [0.60-1.22]
no recov.
25/47
28/45
Faverio (PSW)
1%
0.99 [0.81-1.20]
no disch.
180/572
105/329
Tau2 = 0.08, I2 = 76.7%, p = 0.18
Late treatment
23%
0.77 [0.53-1.13]
205/643
133/396
23% improvement
All studies
48%
0.52 [0.23-1.18]
205/872
133/471
48% improvement
4 N-acetylcysteine COVID-19 recovery results
c19early.com/na Aug 2022
Tau2 = 0.68, I2 = 96.5%, p = 0.12
1 CT: study uses combined treatment
Favors N-acetylcysteine
Favors control
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Huh
26%
0.74 [0.68-0.80]
cases
population-based cohort
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Prophylaxis
26%
0.74 [0.68-0.80]
26% improvement
All studies
26%
0.74 [0.68-0.80]
26% improvement
1 N-acetylcysteine COVID-19 case result
c19early.com/na Aug 2022
Tau2 = 0.00, I2 = 0.0%, p < 0.0001
Favors N-acetylcysteine
Favors control
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Altay (DB RCT)
80%
0.20 [0.01-4.85]
hosp.
0/229
1/76
CT1
Improvement, RR [CI]
Treatment
Control
Tau2 = 0.00, I2 = 0.0%, p = 0.33
Early treatment
80%
0.20 [0.01-4.85]
0/229
1/76
80% improvement
de Alencar (DB RCT)
-3%
1.03 [0.41-2.27]
death
9/67
9/68
Improvement, RR [CI]
Treatment
Control
Gaynitdinova (RCT)
15%
0.85 [0.77-0.93]
hosp. time
24 (n)
22 (n)
Taher (DB RCT)
18%
0.82 [0.43-1.58]
death
12/47
14/45
Delić (RCT)
10%
0.90 [0.63-1.30]
death
21/39
31/52
Intubated patients
Tau2 = 0.00, I2 = 0.0%, p = 0.00084
Late treatment
15%
0.85 [0.77-0.94]
42/177
54/187
15% improvement
All studies
15%
0.85 [0.77-0.93]
42/406
55/263
15% improvement
5 N-acetylcysteine COVID-19 Randomized Controlled Trials
c19early.com/na Aug 2022
Tau2 = 0.00, I2 = 0.0%, p = 0.00076
Effect extraction pre-specified (most serious outcome)
1 CT: study uses combined treatment
Favors N-acetylcysteine
Favors control
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
de Alencar (DB RCT)
-3%
1.03 [0.41-2.27]
9/67
9/68
Improvement, RR [CI]
Treatment
Control
Taher (DB RCT)
18%
0.82 [0.43-1.58]
12/47
14/45
Delić (RCT)
10%
0.90 [0.63-1.30]
21/39
31/52
Intubated patients
Tau2 = 0.00, I2 = 0.0%, p = 0.5
Late treatment
10%
0.90 [0.67-1.21]
42/153
54/165
10% improvement
All studies
10%
0.90 [0.67-1.21]
42/153
54/165
10% improvement
3 N-acetylcysteine COVID-19 RCT mortality results
c19early.com/na Aug 2022
Tau2 = 0.00, I2 = 0.0%, p = 0.5
Favors N-acetylcysteine
Favors control
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Altay (DB RCT)
80%
0.20 [0.01-4.85]
hosp.
0/229
1/76
CT1
Improvement, RR [CI]
Treatment
Control
Ignatova
20%
0.80 [0.64-1.00]
hosp. time
56 (n)
55 (n)
Tau2 = 0.00, I2 = 0.0%, p = 0.043
Early treatment
21%
0.79 [0.63-0.99]
0/285
1/131
21% improvement
de Alencar (DB RCT)
-3%
1.03 [0.41-2.27]
death
9/67
9/68
Improvement, RR [CI]
Treatment
Control
Gaynitdinova (RCT)
15%
0.85 [0.77-0.93]
hosp. time
24 (n)
22 (n)
Pellegrini
52%
0.48 [0.33-0.70]
death
138 (n)
726 (n)
Taher (DB RCT)
18%
0.82 [0.43-1.58]
death
12/47
14/45
Assimakopoulos
97%
0.03 [0.00-0.30]
death
2/42
12/40
Avdeev
69%
0.31 [0.03-2.72]
death
1/24
3/22
Faverio (PSW)
-19%
1.19 [0.85-1.66]
death
91/572
44/329
Ramadhan
-135%
2.35 [0.33-16.9]
death
11/75
1/16
Izquierdo
26%
0.74 [0.63-0.88]
death
136/2,071
1,935/17,137
Delić (RCT)
10%
0.90 [0.63-1.30]
death
21/39
31/52
Intubated patients
Tau2 = 0.08, I2 = 75.9%, p = 0.023
Late treatment
25%
0.75 [0.59-0.96]
283/3,099
2,049/18,457
25% improvement
All studies
24%
0.76 [0.62-0.94]
283/3,384
2,050/18,588
24% improvement
12 N-acetylcysteine COVID-19 peer reviewed trials
c19early.com/na Aug 2022
Tau2 = 0.06, I2 = 71.1%, p = 0.0095
Effect extraction pre-specified (most serious outcome)
1 CT: study uses combined treatment
Favors N-acetylcysteine
Favors control
0
0.25
0.5
0.75
1
1.25
1.5
1.75
2+
Altay (DB RCT)
80%
0.20 [0.01-4.85]
hosp.
0/229
1/76
CT1
Improvement, RR [CI]
Treatment
Control
Altay (DB RCT)
83%
0.17 [0.13-0.24]
no recov.
229 (n)
75 (n)
CT1
Ignatova
20%
0.80 [0.64-1.00]
hosp. time
56 (n)
55 (n)
de Alencar (DB RCT)
-3%
1.03 [0.41-2.27]
death
9/67
9/68
de Alencar (DB RCT)
-16%
1.16 [0.59-2.01]
ventilation
16/67
14/68
de Alencar (DB RCT)
9%
0.91 [0.59-1.28]
ICU
29/67
32/68
de Alencar (DB RCT)
-12%
1.12 [0.77-1.65]
ICU
67 (n)
68 (n)
de Alencar (DB RCT)
-10%
1.10 [0.37-3.23]
hosp. time
67 (n)
68 (n)
Gaynitdinova (RCT)
15%
0.85 [0.77-0.93]
hosp. time
24 (n)
22 (n)
Gaynitdinova (RCT)
51%
0.49 [0.32-0.75]
Ct imp.
24 (n)
22 (n)
Pellegrini
52%
0.48 [0.33-0.70]
death
138 (n)
726 (n)
Pourhoseingholi
11%
0.89 [0.68-1.18]
death
65/309
274/2,159
Taher (DB RCT)
18%
0.82 [0.43-1.58]
death
12/47
14/45
Taher (DB RCT)
14%
0.86 [0.53-1.40]
ventilation
18/47
20/45
Taher (DB RCT)
20%
0.80 [0.44-1.47]
ICU
47 (n)
45 (n)
Taher (DB RCT)
33%
0.67 [0.31-1.45]
hosp. time
47 (n)
45 (n)
Taher (DB RCT)
15%
0.85 [0.60-1.22]
no recov.
25/47
28/45
Assimakopoulos
97%
0.03 [0.00-0.30]
death
2/42
12/40
Avdeev
69%
0.31 [0.03-2.72]
death
1/24
3/22
Avdeev
77%
0.23 [0.03-1.90]
ventilation
1/24
4/22
Avdeev
77%
0.23 [0.03-1.90]
ICU
1/24
4/22
Avdeev
15%
0.85 [0.75-0.96]
hosp. time
24 (n)
22 (n)
Faverio (PSW)
-19%
1.19 [0.85-1.66]
death
91/572
44/329
Faverio (PSW)
-34%
1.34 [0.97-1.84]
ICU
107/572
46/329
Faverio (PSW)
1%
0.99 [0.81-1.20]
no disch.
180/572
105/329
Ramadhan
-135%
2.35 [0.33-16.9]
death
11/75
1/16
Izquierdo
26%
0.74 [0.63-0.88]
death
136/2,071
1,935/17,137
Delić (RCT)
10%
0.90 [0.63-1.30]
death
21/39
31/52
Intubated patients
Huh
26%
0.74 [0.68-0.80]
cases
population-based cohort
N-acetylcysteine COVID-19 outcomes
c19early.com/na Aug 2022
1 CT: study uses combined treatment
Favors N-acetylcysteine
Favors control
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