|
Antimalarial
|
| Chen J et al. 1313 Chen J, Liu D, Liu L, Liu P, Xu Q, Xia L, Ling Y, Huang D, Song S, Zhang D, Qian Z, Li T, Shen Y, Lu H. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19). J Zhejiang Univ (Med Sci) 2020; 49(2):215-219. (2020) |
A:hydroxychloroquine (HCQ) 400 milligrams (mg) per day for 5 days (n=15) |
B: placebo (n=15) |
Time to clinical improvement |
Median of days |
A: 1 (0-3) versus B: 1 (0-2) |
| Detection of viral load by reverse transcription followed by polymerase chain reaction (RT-PCR) |
% of negative |
After 7 days: 86.7 versus 93.3
After 14 days: 100 |
| Radiological progression |
% patients who improved |
A: 33,0 versus B: 46,7 |
| Adverse events |
Number of events |
A: 4 (2 diarrheas, 1 worsening of the clinical picture with discontinuation of treatment, 1 transient increase in aspartate) versus B: 3 (1 increase in serum creatinine, 1 anemia, 1 transient increase in aspartate aminotransferase) |
| Chen Z et al. 1414 Chen Z, Hu J, Zhang Z, Jiang S, Han S, Yan D, Zhuang R, Hu B, Zhang Z. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv 2020 [preprint]. (2020) |
A: HCQ (400 mg/day 5 days (n=31) |
B: standard treatment (oxygen therapy, antiviral agents, antibacterials and immunoglobulin, with or without corticosteroids) (n=31) |
Time to clinical improvement |
Mean days for normalizing body temperature
Mean days for improving cough |
A: 2.2 (standard deviation 0.4) versus B: 3.2, p=0.0008
A: 2 days (SD 0.2) versus
B: 3.1 days, p=0.0016 |
| Radiological progression by computed tomography (CT) |
% of pneumonia improvement |
A: 80.6 versus B: 54.8, p=0.0476, Chi-square test |
| Adverse events |
Number of events |
A: 2 (1 skin rash, 1 headache) |
| Borba et al. 1515 Borba MGS, Val FFA, Sampaio VS, Alexandre MAA, Melo AGC, Brito M, Mourão MPG, Brito-Sousa JD, Baía-da-Silva D, Guerra MVF, Hajjar LA, Pinto RC, Balieiro AAS, Pacheco AGF, Santos Jr JDO, Naveca FG, Xavier MS, Siqueira AM, Schwarzbold A, Croda J, Nogueira ML, Romero GAS, Bassat Q, Fontes CJ, Albuquerque BC, Daniel-Ribeiro CT, Monteiro WM, Lacerda MVG, CloroCovid-19 Team. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection. A Randomized Clinical Trial. JAMA 2020; 3(4):e208857. (2020) |
A: high-dose chloroquine (CQ): 600mg/day for 10 days or total dose of 12 g (n=41)
B: low-dose CQ: 450 mg for 5 days, twice a day only on the first day, or total dose of 2.7g (n=40) |
No comparator |
Mortality in 28 days |
Mortality rate |
A: 13.5%; 95% Confidence Interval 95% CI: 6.9-23.0 |
| Adverse events |
% of patients who presented QT interval > 500ms |
A: 11.1 versus B: 18.9 |
| Tang et al. 1616 Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, Wu Y, Xiao W, Liu S, Chen E, Chen W, Wang X, Yang J, Lin J, Zhao Q, Yan Y, Xie Z, Li D, Yang Y, Liu L, Qu J, Ning G, Shi G, Xie Q. Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial. medRxiv 2020 [preprint]. (2020) |
A: HCQ (200 mg/day for three days followed by 800 mg/day for 2 weeks for patients with mild symptoms and 3 weeks for severe symptoms (n=75) |
B: standard treatment (standard care for COVID-19, according to the Chinese National Guide)
(n=75) |
Detection of viral load by RT-PCR |
% of negative |
A: 85,4 versus B: 81,3, p=0,341 |
| Time to negative viral load (RT-PCR) |
Median days
Relative Risk (RR) |
A: 8 days versus B:7 days
0.846; 95% CI 0.58-1.23, p=0.341 |
| Clinical improvement |
|
A: 19 days versus B: 21 days, p=0.96
A: 59.9; 95% CI 45.0-75.3 versus B: 66.6; 95% CI 39.5-90.9 |
| Adverse events |
% de patients |
Any adverse event - A: 30.0 versus B:8.8. p-value: 0.001
Most frequent adverse event (diarrhea): A: 10 versus B:0
Severe adverse event A:2.6 versus B: 0 |
| Mahévas et al. 1717 Mahévas M, Tran V, Roumier M, Chabrol A, Paule R, Guillaud C, Gallien S, Lepeule R, Szwebel TA, Lescure X, Schlemmer F, Matignon M, Khellaf M, Crickx E, Terrier B, Morbieu C, Legendre P, Dang J, Schoindre Y, Pawlotski JM, Michel M, Perrodeau E, Carlier N, Roche N, De Lastours V, Mouthon L, Audureau E, Ravaud P, Godeau B, Costedoat N. No evidence of clinical efficacy of hydroxychloroquine in patients hospitalised for COVID-19 infection and requiring oxygen: results of a study using routinely collected data to emulate a target trial. medRxiv 2020 [preprint]. (2020) |
A: HCQ (600 mg/day started in the first 48h of hospitalization)
(n=84)
B: HCQ + azithromycin (AZT)
(n=17)
C: No exposure to HCQ (n=97) |
No comparator |
Transfer to Intensive Care Unit (ICU) |
% of hospitalization
RR |
A: 20,2 versus B: 22,1
0,91 (0,48-1,81) |
| Mortality by all causes |
% of deaths
RR |
A: 2,8 versus B: 4,6
R0,61; IC 95%: 0,13-2,90 |
| Progression to severe acute respiratory syndrome (SARS) |
% of patients RR |
A: 9.5 These patients had to discontinue HCQ
RR=1.15; 95% CI: 0.66-2.01 |
| Magagnoli et al. 1818 Magagnoli J, Narendran S, Pereira F, Cummings T, Hardin JW, Sutton SS, Ambati J. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. Med 2020; 1:1-4. (2020) |
A: HCQ (n=97)
B: HCQ + AZT (n=113)
Without HCQ (n=158) |
No comparator |
Mortality |
% of deaths Adjusted RR |
A: 27.8 versus B: 22.1 versus C:11.4
A: 2.61; 95% CI 1.10-6.17. P=0.03 versus B: 1.14; 95% CI 0.56-2.32. P=0.72 |
| Need for mechanical ventilation |
% of patients Adjusted RR |
A: 13.3 versus B: 6.9 versus C:14.1
A: 1.43; 95% CI 0.53 - 3.79. P=0.48 versus B: 0.43; 95% CI 0.16 -1.12; P=0.09 |
| Gautret et al. 1919 Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Vieira VE, Dupont HT, Honoré S, Colson P, Chabrière E, La Scola B, Rolain JM, Brouqui P, Raoult D. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020; 105949. (2020) |
A: HCQ (600 mg/day for 10 days) (n=20)
B: HCQ (600mg/day for 10 days) + AZT (500 mg/day for 4 days) (n=6)
C: Standard treatment (n=16) |
No comparator |
Detection of viral load by RT-PCR |
% of negative |
After 6 days- A: 70.0 versus B: 12.5
Post-hoc analysis: A: 100.0 versus B: 57.1 versus C: 12.5. p<0.001 |
| Chorin et al. 2222 Chorin E, Dai M, Shulman E, Wadhwani L, Cohen RB, Barbhaiya C, Aizer A, Holmes D, Bernstein S, Soinelli M, Park DS, Chinitz L, Jankelosn L. The QT Interval in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine/Azithromycin. medRxiv 2020 [preprint]. (2020) |
A: HCQ+AZT (n=84) |
No comparator |
Adverse events |
% of patients with alteration in the prolongation of the QT interval |
>400ms: 30
> 500 ms: 11 |
| Gautret et al. 2121 Gautret P, Lagier J-C, Parola P, Hoang VT, Meddeb L, Sevestre J, Mailhe M, Doudier B, Aubry C, Amrane S, Seng P, Hocquart M, Eldin C, Finance J, Vieira VE, Tissot-Dupont HT, Honoré S, Stein A, Million M, Colson P, La Scola B, Veit V, Jacquier A, Deharo JC, Drancourt M, Fournier PE, Rolain JM, Brouqui P, Raoult D. Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study. Travel Med Infect Dis 2020; 34:101663. (2020) |
A: HCQ (200mg/day for 10 days) + AZT (500mg/day for 1 day, then 250 mg/day for 4 days) |
No comparator |
Negative viral load by RT-PCR |
% of negative |
A: 83 on day 7 and 93 on day 8 |
| Length of hospital stay |
Median of days |
A: 4.6 |
| Adverse events |
% of events |
A: 2.5 nausea and vomiting. 5 diarrheas. 1.2 blurry vision |
| Molina et al. 2020 Molina JM, Delaugerre C, Le Goff J, Mela-Lima B, Ponscarme D, Goldwirt L, Castro N. No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection. Med Mal Infect 2020; 50(4):384. (2020) |
A: HCQ (600 mg/day for 10 days)
+ AZT (500 mg/day on day 1 and 250 mg/day on days 2 to 5) |
No comparator |
Mortality |
Number of deaths |
A: 1 |
| Positive viral load by RT-PCR |
% of positivity |
80.0; 95% CI: 49-94 |
|
Antivirals and Antiretrovirals
|
| Li et al. 2323 Li Y, Xie Z, Lin W, Cai W, Wen C, Guan Y, Mo X, Wang J, Wang Y, Peng P, Chen X, Hong W, Xiao G, Liu J, Zhang L, Hu F, Li F, Li F, Zhang F, Deng X, Li L. An exploratory randomized, controlled study on the efficacy and safety of lopinavir/ritonavir or arbidol treating adult patients hospitalized with mild/moderate COVID-19 (ELACOI). medRxiv 2020 [preprint]. (2020) |
A: Lopinavir (200 mg), by Ritonavir (50 mg) (administered orally, twice a day, 500 mg, each time for 7-14 days) (n=34)
B: Arbidol (100 mg) (administered orally, 200 mg three times a day for 7-14 days) (n=35) |
C: Without antiviral therapy (n=17) |
Negative viral load by RT-PCR |
% of negative |
After 7 days:
A: 35.3% versus B: 37.1% versus C: 41.2%. p=0.966
After 14 days:
A: 85.3% versus B: 91.4% versus C: 76.5%. p=0.352 |
| Adverse events |
Number of patients |
A:12 (9 diarrheas. 1 elevation of alanine aminotransferase. 2 loss of appetite) versus B: 5 (3 diarrheas. 2 nauseas) |
| Young et al. 2525 Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, Ng OT, Marimuthu K, Ang LW, Mak TM, Lau SK, Anderson DE, Chan KS, Tan TY, Ng TY, Cui L, Said Z, Kurupatham L, Chen MIC, Chan M, Vasoo S, Wang LF, Tan BH, Lin RTP, Lee VJM, Leo YS, Lye DC, Singapore 2019 Novel Coronavirus Outbreak Research Team. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA 2020; 323(15):1488-1494. (2020) |
A: Lopinavir/ritonavir(n=5) |
B: Without Lopinavir/Ritonavir |
Clinical improvement |
Body temperature normalization in days |
A: 3 versus B: 3 |
| Time of use of supplemental oxygen therapy |
A: -3 days |
| Need for invasive mechanical ventilation |
A: 2 |
| Adverse events |
Number of events |
A: 4 (Nausea, vomit, diarrhea, hepatic alterations) |
| Cao et al. 2424 Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med 2020; 382:1787-1799. (2020) |
A: Lopinavir-Ritonavir 400 mg and 100 mg, administered orally, twice a day associated with standard treatment por 14 days (n=99) |
B: standard treatment (n=100) |
Time to clinical improvement |
Length of stay in the Intensive Care Unit (number of days) |
A: 6 versus 11 |
| Mortality |
Mortality rate |
19.2. 95% CI 17.3% to 5.7% |
| Adverse events |
Number of events |
A: 19 (Gastrointestinal, including nausea, vomit and diarrhea)
B: 32 (Respiratory failure. Acute kidney injury and secondary infection) |
|
Immunomodulators
|
| Zhou et al. 2626 Zhou Q, Wei XS, Xiang X, Wang X, Wang ZH, Chen V, Shannon CP, Tebbutt SJ, Kollmann TR, Fish EN. Interferon-a2b treatment for COVID-19. medRxiv 2020 [preprint]. (2020) |
A: IFN-α2b nebulized (5mU, bid) n=7
B: INF + Arbidol (tablet - 200 mg, tid) n=46
C: Arbidol n=24 |
No comparator |
Viral clearance |
Median (interquartile range) |
A: 8.0 (5.5-15.5) versus B: 6.5 (3.0-10.0) versus C: 10.0 (4.5-19.5) |
|
Anticoagulant
|
| Negri et al. 2727 Negri EM, Piloto B, Morinaga LK, Jardim CVP, Lamy SAED, Ferreira MA, D'Amico EA, Deheinzelin D. Heparin therapy improving hypoxia in COVID-19 patients - a case series. medRxiv 2020 [preprint]. (2020) |
A: Heparin 1 mg/kg every 24hs |
No comparator |
Oxygenation index |
PaO2/FiO2 ratio (standard deviation) |
A: 325 (80). p=0.013 |
| Length of hospital stay |
Mean (standard deviation) |
A: 7.3 days (4.0) |
| Length of mechanic ventilation |
Mean (standard deviation) |
A: 10.3 days (1.5) |
| Shi C et al. 2828 Shi C, Wang C, Wang H, Yang C, Cai F, Zeng F, Cheng F, Liu Y, Zhou T, Deng B, Vlodavsky I, Li J, Zhang Y. The potential of low molecular weight heparin to mitigate cytokine storm in severe COVID-19 patients: a retrospective clinical study. medRxiv 2020 [preprint]. (2020) |
A: Heparin (n=21) |
Without heparin (n=21) |
Length of hospital stay
Viral clearance |
Mean days (Interquartile range)
Mean days (Interquartile range); p-value |
A: - 29 days (7.0-42.0) versus B: 27 days (24.0- 31.0)
A:20;(11 -31) versus B:19;(12 - 30) P=0.46 |
| Coagulation parameters |
Levels of D-dimer; standard deviation; p-value |
A:(0.90±0.44.170 1.00±1.06. p=0.368) versus B:(3.75±4.04. 0.90±0.44. p=0.001) |
| C-reactive protein levels |
Levels of CRP; standard deviation; p-value |
B:22.62±23.79. -20.23±33.91. p=0.660 |
| Inflammatory cytokine levels (IL6) |
Levels of cytokines; standard deviation; p-value |
A:47.47±58.86. 198 15.76±25.71. p=0.006) versus
B: -32.46±65.97.200 14.96±151.09. p=0031 |
| Lymphocyte levels |
Lymphocyte levels; standard deviation; p-value |
A: 18.84±8.24. 29.94±7.92. p=0.00048 versus
B:11.10±9.50. 3.08±9.66. p=0.011 |
|
Corticoids
|
| Arabi et al. 2929 Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Almekhlafi GA, Hussein MA, Jose J, Pinto R, Al-Omari A, Kharaba A, Almotairi A, Al Khatib K, Alraddadi B, Shalhoub S, Abdulmomen A, Qushmaq I, Mady A, Solaiman O, Al-Aithan AM, Al-Raddadi R, Ragab A, Balkhy HH, Harthy A, Deeb AM, Mutairi HA, Al-Dawood A, Merson L, Hayden FG, Fowler RA, Saudi Critical Care Trial Group. Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. Am J RespirCrit Care Med 2018; 197(6):757-767. (2018) |
A: Corticosteroids (n=151) |
B: Without corticosteroids (n=158) |
Mortality |
Mortality rate |
A: 74.2%
B: 57.6%
P= 0.002 |
| Need for invasive mechanical ventilation |
% of days |
A: 93.4 versus B: 76.6 |
| Wang et al. 3030 Wang Y, Jiang W, He Q, Wang C, Wang B, Zhou P, Dong N, Tong Q. Early, low-dose and short-term application of corticosteroid treatment in patients with severe COVID-19 pneumonia: single-center experience from Wuhan, China. medRxiv 2020 [preprint]. (2020) |
A: Methylprednisolone, 1mg/(kg) for 5 to 7 days (n=26) |
Without Methylprednisolone |
Improvement of symptoms |
Mean days and standard deviation |
Body temperature normalization
A: 2.06 (0.28) versus B: 5.29 (0.70). p=0.010
Need for higher supplemental oxygen therapy in the group without Methylprednisolone
A: 8.2 (7.0) versus B: 13.5 (10.3) p<0.001 |
| Lu et al. 3131 Lu X, Chen T, Wang Y, Wang J, Zhang B, Li Y, Yan F. Adjuvant corticosteroid therapy for critically ill patients with COVID-19. medRxiv 2020 [preprint]. (2020) |
A: Corticosteroids (n=31)
Corticosteroids n=151 (hydrocortisone: 100-800mg/d) 8 (4-12) days (Methylprednisolone, dexamethasone and hydrocortisone) + oseltamivir, arbidol, lopinavir / ritonavir, ganciclovir, interferon-α) |
B: without corticosteroids (n=31)
Without corticosteroids n= 93 + oseltamivir, arbidol, lopinavir / ritonavir, ganciclovir, interferon-α) |
Mortality in 28 days |
Mortality rate
OR;95% CI; p-value |
A: 39% versus B: 16%. P=0.09
OR : 1.05; (-1.92-2.01); p-value = > 0.3 |
| Auyeung et al. 3232 Auyeung TW, Lee JS, Lai WK, Choi CH, Lee HK, Lee JS, Li PC, Lok KH, Ng YY, Wong WM, Yeung YM. The use of corticosteroid as treatment in SARS was associated with adverse outcomes: A retrospective cohort study. J Infect 2005; 51(2):98-102. (2005) |
Corticoesteroids |
Without corticosteroids |
Mortality em 28 days |
Odds Ratio |
20.7 (1.3 - 338) - for admission in ICU* or death |
|
Combined therapies
|
| Morra et al. 3434 Morra ME, Van Thanh L, Kamel MG, Ghazy AA, Altibi AMA, Dat LM, Thy TNX, Vuong NL, Mostafa MR, Ahmed SI, Elabd SS, Fathima S, Vu TLH, Omrani AS, Memish ZA, Hirayama K, Huy NT. Clinical outcomes of current medical approaches for Middle East respiratory syndrome: A systematic review and meta-analysis. Rev Med Virol 2018; 28(3):e1977. (2018) |
A: INF alpha-2a, alpha-2b or beta-1a + ribavirin (n= 68) |
B: Support measure (n=48) |
Mortality em 28 days |
Mortality rate |
71% (61.8% - 79.5%)
*Survival. Days (95% CI)
A: 21.3 (14.1-28.5)
B: 21.4 (12.4-30.4) |
| Need for invasive mechanical ventilation |
% |
A: 76.0 versus B: 90.0 |
| Adverse events |
Number of events |
A: 3 (Elevation of pancreatic enzymes. Hemolysis.) |
| Al-Tawfiq e Memish 6161 Al-Tawfiq JA, Memish ZA. Update on therapeutic options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Expert Rev Anti Infect Ther 2017; 15(3):269-275. (2017) |
A: ribavirin + IFN alfa2a
B: ribavirin + IFN beta1a |
Several comparators |
Mortality in 28 days |
Mortality rate |
A: 85%
B: 64% |
| Momattin et al. 6262 Momattin H, Mohammed K, Zumla A, Memish ZA, Al-Tawfiq JA. Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV)--possible lessons from a systematic review of SARS-CoV therapy. Int J Infect Dis 2013; 17(10):e792-e798. (2013) |
Ribavirin, lopinavir/ritonavir, convalescent plasma, INF alpha, corticosteroids |
Several comparators |
Mortality in 28 days |
Mortality rate |
4% (Lopinavir/ritonavir) From 6.5% to 12.7% (ribavirin) 12.5% (convalescent plasma) 23.8% (corticosteroid) 7.7% (corticosteroids) 0% (INFalpha-1) |
| ICU admission rate |
% |
% a 20% (ribavirin)
23.1% (corticosteroids)
11.1% (INF alpha) |
| Chiou et al. 3535 Chiou HE, Liu CL, Buttrey MJ, Kuo HP, Liu HW, Kuo HT, Lu YT. Adverse effects of ribavirin and outcome in severe acute respiratory syndrome: Experience in two medical centers. Chest 2005; 128(1):263-272. (2005) |
Oral ribavirin oral associated with Methylprednisolone, followed by oral prednisolone, Pulse methylprednisolone, oxygen therapy by nasal cannula, non-respiratory mask or mechanical ventilation (n=44) |
Treatment without ribavirin (n=7) |
Mortality in 28 days |
Mortality rate |
A: 29%
B: 13% |
| Absorption of infiltrations in the chest image |
% |
A: 71 versus B: 67. p=0.05) |
| Level of hemoglobin (% of reduction) |
% |
A: 73 versus B: 14. p=0.006 |
| Lau et al. 6363 Lau AC, So LK, Miu FP, Yung RW, Poon E, Cheung TM, Yam LY. Outcome of coronavirus-associated severe acute respiratory syndrome using a standard treatment protocol. Respirology 2004; 9(2):173-183. (2004) |
Intravenous ribavirin (3,3 mg/kg of body weight)
Corticosteroids (Methylprednisolone 0,3 mg/kg for 10 days, oral prednisolone at 1 mg/kg (n=71) + |
No comparator |
Mortality in 28 days |
Mortality rate |
3.4% |
| Time to clinical stabilization |
Mean |
8 days |
| Adverse events |
% of events |
Hyperglycemia (58%). Pneumothorax (13%). Psychiatric manifestations (7%). Pneumonia associated with mechanical ventilation (2%) |
| Chen X et al. 6464 Chen X, Zhang Y, Zhu B, Zeng J, Hong W, He X, Chen J, Zheng H, Qiu S, Deng Y, Chan J, Wang J. Associations of clinical characteristics and antiviral drugs with viral RNA clearance in patients with COVID-19 in Guangzhou, China: a retrospective cohort study. medRxiv 2020 [preprint]. (2020) |
ICU care
Oxygen therapy
Mechanical ventilation
Antibiotics
Ribavirin
Chloroquine
Corticosteroid
Immunoglobulin
Oseltamivir lopinavir/ritonavir
Arbidol
(n = 185;viral clearance ≤14 days) |
ICU care
Oxygen therapy
Mechanical ventilation
Antibiotics
Ribavirin
Chloroquine
Corticosteroid
Immunoglobulin
Oseltamivir lopinavir/ritonavir, arbidol
(n = 95 viral clearance >14 days) |
Hospital discharge with cure |
Number of cases |
A:183 versus B:91 |
| Hospital stay |
Number of cases |
A:0 versus B:3 |
| Death |
Number of cases |
A:1 versus B:0 |
| Hospital stay in days |
Number of days; IQR; p-value |
A:17(12-23) versus B:21 (15 -28) |
| Hospital admission time to viral Clearance in days |
p-value=<0.000 |
A: 5 (3 -8) versus B:14 (9 -19)
p-value = <0.0001 |
| Bian et al. 3333 Bian H, Zheng Z, Wei D, Zhang Z, Kang W, Hao C, Dong K, Kang W, Xia J, Miao J, Xie R, Wang B, Sun X, Yang X, Lin P, Geng J, Wang K, Cui H, Zhang K, Chen X, Tang H, Du H, Yao N, Liu S, Liu L, Zhang Z, Gao Z, Nan G, Wang Q, Lian J, Chen Z, Zhu P. Meplazumab treats COVID-19 pneumonia: an controlled add-on clinical trial open-labelled, concurrent. medRxiv 2020 [preprint]. (2020) |
Meplazumab (10 mg on the 1st, 2nd and 5th day via intravenous infusion within 60 to 90 minutes) + Lopinavir/ritonavir
Interferon α-2b
Glucocorticoid
Antibiotic (n=17) |
Lopinavir/ritonavir
Interferon α-2b
Glucocorticoid
Antibiotic (n=11) |
Hospital discharge
(28th day) |
Number of cases; p-value |
A:16 versus B:9 P=0.006. |
| Improving chest X-rays (7th, 14th and 21st day post-treatment) |
P-value |
p=0.010; 0.006;0.037 |
| Viral clearance |
Median of days; IQR |
A:3(1.5 - 4.5) versus A:0.37 (0.155 - 0.833); p-value 0.014 |
| Increased C-reactive protein concentration in 28 days |
HR; P-value |
A:14; p-value = <0.05 |
| Elevation of ALT and AST |
Number of cases; p-value |
A:2
B:2 |
| Shi Q et al. 6565 Shi Q, Zhao K, Yu J, Jiang F, Feng J, Zhao K, Zhang X, Chen X, Hu P, Hong Y, Li M, Liu F, Chen C, Wang W. Clinical characteristics of 101 COVID-19 nonsurvivors in Wuhan, China: a retrospective study. medRxiv 2020 [preprint]. (2020) |
Antiviral
Antibiotics
Glucocorticoid
Immunoglobulin
High-flow oxygen inhalation
Non-invasive mechanical ventilation
Invasive mechanical ventilation
Continuous renal replacement therapy
(n=101) |
No comparator |
Mortality up to 3 days |
Number of cases |
48 |
| Mortality after 3 days |
Number of cases |
53 |
| Jiang et al. 6666 Jiang X, Tao J, Wu H, Wang Y, Zhao W, Zhou M, Huang J, You Q, Meng H, Zhu F, Zhang X, Qian M, Qiu Y. Clinical features and management of severe COVID-19: A retrospective study in Wuxi, Jiangsu Province, China. medRxiv 2020 [preprint]. (2020) |
Antiviral:
Interferon α
Lopinavir/ritonavir
Arbidol
Chloroquine
Antibiotic
Antifungal
Corticosteroid
Immunoglobulin
Timosine
Probiotics
Low molecular weight heparin
High-flow oxygen cannula
Mechanical ventilation
Transfusion of convalescent plasma
Extracorporeal membrane oxygenation
Lung transplant (n=47; non-severe cases) |
Antiviral:
Interferon α
Lopinavir/ritonavir
Arbidol
Chloroquine
Antibiotic
Antifungal
Corticosteroid
Immunoglobulin
Timosine
Probiotics
Low molecular weight heparin High-flow oxygen cannula
Mechanical ventilation
Transfusion of convalescent plasma
Extracorporeal membrane oxygenation
Lung transplant (n=8; severe cases) |
Liver damage |
Number of cases; p-value |
A:12 (25.5%) versus B:4 (50%) P=0.0323 |
| Acute respiratory syndrome |
Number of cases; p-value |
A:2 (4.3%) versus B:2 (25%) p-value= 0.073 |
| Respiratory arrest |
Number of cases; p-value |
A:2(4,3%) versus B:8 (100%) P valor=<0,00 |
| Secondary infection |
Number of cases; p-value |
A:2(4.3%) versus B:8 (100%) p-value=<0.00 |
| Acute kidney injury |
Number of cases; p-value |
A:2(4.3%) versus B:2(25%)
p-value = 0.176
A:1(2.1%) versus B:2 (25%)
p-value = 0.073 |
| Hu et al. 6767 Hu L, Chen S, Fu Y, Gao Z, Long H, Ren H, Zuo Y, Li H, Wang J, Xv Q, Yu W, Liu J, Shao C, Hao J, Wang C, Ma Y, Wang Z, Yanagihara R, Wang J, Deng Y. Risk Factors Associated with Clinical Outcomes in 323 COVID-19 Patients in Wuhan, China. medRxiv 2020 [preprint]. (2020) |
Antiviral:
Oseltamivir
Ganciclovir
Arbidol
Kaletra
Interferon -α
Antibiotics: moxifloxacin
Corticosteroid/Glucocorticoid
Continuous renal replacement
Alternative therapy:
Non-invasive ventilation
Invasive ventilation
(n=260; favorable clinical outcome) |
Antiviral:
Oseltamivir
Ganciclovir
Arbidol
Kaletra
Interferon -α
Antibiotics: moxifloxacin
Corticosteroid/Glucocorticoid
Continuous renal replacement
Alternative therapy:
Non-invasive ventilation
Invasive ventilation
(n=63; unfavorable clinical outcome) |
Shock |
Number of events; p-value |
A:8 versus B:35 p-value = <0.001 |
| Acute cardiac injury |
Number of events; p-value |
A:3 versus B:21 p-value = <0.001 |
| Arrhythmia |
Number of events; p-value |
A:51 versus B:47 p-value = <0.001 |
| Acute respiratory syndrome grave |
Number of events; p-value |
A:56 versus B:44 p-value = <0.001 |
| Acute kidney injury |
Number of events; p-value |
A:3 versus B:14 p-value = <0.001 |
| Acute lung injury |
Number of events; p-value |
A:56 versus B:44 p-value = <0.001 |
| Septic shock |
Number of events; p-value |
A:0 versus B:19 p-value = <0.001 |
| Secondary infection |
Number of events; p-value |
A:0 versus B:9 p-value = <0.001 |
| Duan et al. 6868 Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, Zhou M, Chen L, Meng S, Hu Y, Peng C, Yuan M, Huang J, Wang Z, Yu J, Gao X, Wang D, Yu X, Li L, Zhang J, Wu X, Li B, Yu Y, Chen W, Peng Y, Hu Y, Lin L, Liu X, Huang S, Zhou Z, Zhang L, Wang Y, Zhang Z, Deng K, Xia Z, Gong Q, Zhang W, Zheng X, Liu Y, Yang H, Zhou D, Yu D, Hou J, Shi Z, Chen S, Chen Z, Zhang X, Yang X. The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study. medRxiv 2020 [preprint]. (2020) |
Convalescent plasma 200Ml + Ribavirin 0,5g, Arbidol 0,2g, Remdesivir 0,2g, Interferon-α 500MIU, Oseltamivir, Peramivir
(n=10) |
Ribavirin, Arbidol, Remdesivir
Interferon-α,
Cefoperazone
Moxifloxacin
Methylprednisolone
(N=10)
** Control group results were not shown in the studies |
Titer of neutralizing antibodies after treatment with PC |
Titers; Number of cases |
A:1:640;10 |
| Clinical improvement of symptoms; fever, cough, shortness of breath, chest pain |
Mean days |
A:3 |
| Improvement of symptoms of chest X-rays |
Mean days |
A:7 |
| Viral clearance |
Number of cases |
A:10 |
| Adverse effects red spots on the face |
Number of cases |
A:2 |
| Chen H et al. 6969 Chen H, Zhang Z, Wang L, Huang Z, Gong F, Li X, Chen Y, Wu JJ. First Clinical Study Using HCV Protease Inhibitor Danoprevir to Treat Naive and Experienced COVID-19 Patients. medRxiv 2020 [preprint]. (2020) |
Danoprevir 100 mg twice a day + Ritonavir 100 mg twice a day with or without nebulization of Interferon 5 uM, 4 to 12 days (n=9, who had already received antivirals) |
Danoprevir
Ritonavir
Nebulization with
Interferon (n=2, diagnosed recently and not having received antivirals) |
Hospital discharge |
Number of cases; number of days |
A:9;4 to 12 versus A:2;4 to 12 |
| Normal body temperature for at least 3 days |
Number of cases; number of days |
A:9;4 to 12 versus A:2;4 to 12 |
| Significant recovery from respiratory symptoms |
Number of cases; number of days |
A:9;4 to 12 versus A:2;4 to 12 |
| Improved chest images |
Number of cases; number of days |
A:9;4 to12 versus A:2;4 to 12 |
| Two consecutive negative RT-PCR tests |
Number of cases; number of days |
A:9;4 to 12 versus A:2;4 to 12 |
| Length of hospital stay |
Median of days; number of days |
A:20 (7-22) versus B: 9.7 |
| Tsui et al. 7070 Tsui PT, Kwok ML, Yuen H, Lai ST. Severe acute respiratory syndrome: Clinical outcome and prognostic correlates. Emerg Infect Dis 2003; 9(9):1064-1069. (2003) |
Antibiotics (levofloxacin, amoxicillin/clavulanate) + combination of ribavirin and steroids (n=323) |
No comparator |
Mortality |
Mortality rate |
7.9% (5-10.8%) |
Without lopinavir/Ritonavir
Corticosteroid
Antibiotics
Oxygen therapy with nasal cannula
Non-invasive mechanical ventilation
Invasive mechanical ventilation (n=42) |
Need for invasive mechanical ventilation |
% |
13% |
| Yan et al. 3636 Yan D, Liu XY, Zhu YN, Huang L, Dan BT, Zhang GJ, Gao YH. Factors associated with prolonged viral shedding and impact of Lopinavir/Ritonavir treatment in patients with SARS-CoV-2 infection. medRxiv 2020 [preprint]. (2020) |
Lopinavir/Ritonavir (400 mg and 100 mg, orally, twice a day) + Corticosteroid
Antibiotics
Oxygen therapy com nasal cannula
Non-invasive mechanical ventilation
Invasive mechanical ventilation (n=78) |
|
Without lopinavir/Ritonavir
Corticosteroid
Antibiotics
Oxygen therapy with nasal cannula
Non-invasive mechanical ventilation
Invasive mechanical ventilation (n=42) |
Days of treatment
Median of days; IQR |
A:22 (18-29) versus B:28.5 (19.5 - 38) |
Viral clearance
Median of days; IQR |
A:22 (18-29) versus B:28.5 (19.5 - 38) |
Hospital stay
Median of days; IQR |
A:23 (19-27) versus B:18.5 (13 -22.5) |
| Habib et al. 7171 Habib AMG, Ali MAE, Zouaoui BR, Taha MAH, Mohammed BS, Saquib N. Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. BMC Infect Dis 2019; 19(1):870. (2019) |
A: Ribavirin + Interferon (IFN) (n=63) |
No comparator |
Mortality |
Mortality rate |
A: 22.9% |
| Ho et al. 7272 Ho JC, Wu AY, Lam B, Ooi GC, Khong PL, Ho PL, Chan-Yeung M, Zhong NS, Ko C, Lam WK, Tsang KW. Pentaglobin in steroid-resistant severe acute respiratory syndrome. Int J Tuberc Lung Dis 2004; 8(10):1173-1179. (2004) |
Post-treatment pentaglobin with corticosteroids and ribavirin |
No comparator |
Absorption of infiltrations in the chest image
Improvement between days 1, 5 and 7 |
Median and IQR |
5 liters (L); 8-12 L (day 1) 7.5L; 5-9.5 L (day 5)
6L; 2.5-8 L (day 7) |
| Need for oxygen |
Median and IQR |
Improvement between days 1, 6 and 7
2.5 L/min*; 2-4 L/min (day 1)
1 L/min; 0-2.8 L/min (day 6)
0.5 L/min; 0-2.8 L/min (day 7) |
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