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Aging and disease    2021, Vol. 12 Issue (1) : 155-191     DOI: 10.14336/AD.2020.1124
Review |
A Comprehensive Summary of the Knowledge on COVID-19 Treatment
Yu Peng1, Hongxun Tao1, Senthil Kumaran Satyanarayanan1, Kunlin Jin2,*, Huanxing Su1,*
1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
2Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
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Abstract  

Currently, the world is challenged by the coronavirus disease 2019 (COVID-19) pandemic. Epidemiologists and researchers worldwide are invariably trying to understand and combat this precarious new disease. Scrutinizing available drug options and developing potential new drugs are urgent needs to subdue this pandemic. Several intervention strategies are being considered and handled worldwide with limited success, and many drug candidates are yet in the trial phase. Despite these limitations, the development of COVID-19 treatment strategies has been accelerated to improve the clinical outcome of patients with COVID-19, and some countries have efficiently kept it under control. Recently, the use of natural and traditional medicine has also set the trend in coronavirus treatment. This review aimed to discuss the prevailing COVID-19 treatment strategies available globally by examining their efficacy, potential mechanisms, limitations, and challenges in predicting a future potential treatment candidate and bridging them with the effective traditional Chinese medicine (TCM). The findings might enrich the knowledge on traditional alternative medication and its complementary role with Western medicine in managing the COVID-19 epidemic.

Keywords COVID-19      treatment      Chinese Medicine      strategies     
Corresponding Authors: Jin Kunlin,Su Huanxing   
About author:

these authors equally contributed this work.

Just Accepted Date: 06 December 2020   Issue Date: 11 January 2021
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Peng Yu
Tao Hongxun
Satyanarayanan Senthil Kumaran
Jin Kunlin
Su Huanxing
Cite this article:   
Peng Yu,Tao Hongxun,Satyanarayanan Senthil Kumaran, et al. A Comprehensive Summary of the Knowledge on COVID-19 Treatment[J]. Aging and disease, 2021, 12(1): 155-191.
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http://www.aginganddisease.org/EN/10.14336/AD.2020.1124     OR
SARS-CovMERS-CovSARS-Cov-2
GenusBeta-CoVs lineage BBeta-CoVs lineage CBeta-CoVs lineage B
Date/Place first detectedNovember 2002, Guangdong ChinaJune 2012, Jeddah, Saudi ArablaDecember 2020, Wuhan China
Possible nature reservoirBatBatBat
Possible intermediate hostPalm civetsCamelPangolin
Virus transmission1. Respiratory droplets
2. Contact
3. Aerosol [28]
1. Respiratory droplets
2. Contact [29]
1. Respiratory droplets
2. Contact
3. Aerosol [30]
Predominant cellular receptor [31]ACE2DDP4ACE2
Receptor distribution [31]Arterial and venous endothelium; arterial smooth muscle; small intestine, respiratory tract epithelium; alveolar monocytes and macrophagesRespiratory tract epithelium; kidney, small intestine; liver and prostate; activated leukocytesArterial and venous endothelium; arterial smooth muscle; small intestine, respiratory tract epithelium; alveolar monocytes and macrophages
Number of affected countrie and area2927183
Confirmed cases80962494571678
Death cases74485826494
Mortality rate9.19%34.40%4.63%
Severity Rate10-20% [28]--7-21% [17, 18, 32]
Incubation Period4d (2-10d)[33]5.2d (2-14d)[34]5.2d (2-14d)[35]
Epidemic doubling time[36]4.6-14.2906.4
Reproductive number, R0[36, 37]1.4-5.5<12.2-3.6
Ventilation support13-26% [38]85.2% [39]4.2% [32]
ICU admission19-34% [38]53-89% [39]10% [40]
invasive mechanical ventilation17% [31]37% [31]7-9.6% [17, 18]
SymptomFever (99%);
Headache (39%); Myalgia (59%); Cough(58%); Shortness of breath (27%); Sore throat (17%); Nausea/vomiting (15%); Diarrhoea (17%)[31]
Fever (84%);
Headache (19%); Myalgia (98%); Cough(63%); Shortness of breath 35%); Sore throat (13%); Nausea/vomiting (15%); Diarrhoea (20%)[31]
Fever (83%)
Cough (82%) Shortness of breath (31%) Muscle ache (11%) Confusion (9%) Headache (8%) Sore throat (5%) Rthinorrhoea (4%) [18]
PathologyEdematous lung, bronchial epithelial denudation, loss of cilia, squamous metaplasia fibrosis [41].Exudative diffuse alveolar damage with hyaline membranes, pulmonary edema, type II pneumocyte hyperplasia, interstitial pneumonia [41].Inflammation, mucus and fibrosis [18].
CT imaging1. Air-space opacities;
2. ~50% unilateral multifocal or bilateral involvement [31].
1. Ground glass opacities and consolidation;
2. Higher rate of Pleural effusion and pneumothorax [31].
1. Small patches and interstitial changes;
2. Ground glass opacity; 3. Rare Pleural effusion [17].
Clinical characters1. Hypoalbuminemia;
2. Thrombocytopenia;
3. Leukopenia;
4. Lymphopenia.[28, 42]
1. Increase White Blood Cells count;
2. Decrease lymphocytes count;
3. Decrease platelets count; 4. Decrease Red Blood Cells count [43].
1. The total number of peripheral blood leukocytes was normal or decreased;
2. Decreased lymphocyte count; 3. Increased CRP and erythrocyte sedimentation rate [44].
Complication1. Acute kidney injury (AKI) is a significant characteristic of SARS patients [38].1. Acute kidney injury (AKI) is a significant characteristic of MERS patients;
2. Vasopressor therapy was much more common in MERS, (81%)[31].
1. Acute respiratory distress syndrome;
2. RNA aemia, acute cardiac injury;
3. Secondary (super-)infections [41].
Affected organRespiratory tract; kidney; liver [38]Respiratory tract; intestinal tract; genitourinary tract; liver, kidney, neurons; monocyte; T lymphocyte; Cardiovascular [31].Respiratory tract; intestinal tract; liver; kidney [32].
Prognostic factor1. Age
2. Underlying condition
3. Male
4. LDH level
5. Neutrophil count
6. CD4
7. CD8 [38]
1. Age
2. Underlying condition
3. Male [45]
1. Age
2. Underlying condition
3. Male
4. Lymphocyte count
5. Lactic acid
6. IL-6 and CRP [18]
Clinical management-Continuous nasal cannula oxygen is given early (the oxygen concentration is generally 1~3 L/min);
-Given oseltamivir within 48 hours of onset can help reduce the symptoms. -Fever>38.5, or obvious body aches, can use antipyretic analgesics; Those with high fever should be given physical cooling measures; Salicylic acid antipyretic analgesics are forbidden for children. -Cough and expectorants can be given antitussive and expectorant drugs; -With damage to organs such as heart, liver, kidney, etc. should be treated accordingly. -With diarrhea should be paid attention to rehydration and correct water and electrolyte imbalances; -Use of glucocorticoids, the recommended adult dose is equivalent to 80-320 mg/d of methylprednisolone, reduced or stopped when the clinical manifestations have been improved or the chest radiograph shown the absorbed shadows in lung; -Antiviral therapy has not yet found specific drugs; Possible to try protease inhibitors such as lopinavir and ritonavir; -When the diagnosis is unclear, new quinolones or β-lactams combined with macrolides can be used for trial treatment; -The pathogens of secondary infections include gram-negative bacilli, drug-resistant gram-positive cocci, fungi, and Mycobacterium tuberculosis, and appropriate antibacterial drugs should be selected accordingly; -Chinese medicine as an alternative strategy. [46, 47]
For patients with pneumonia or comorbidities:
-With signs of severe respiratory distress, shock or hypoxemia, oxygen therapy should be started immediately. -It is recommended that fluid management in patients is necessary, while provided that there is no sign of shock. -Empirical antibacterial treatment (including antibiotics and antiviral drugs) should be initiated for hospitalized patients with suspected MERS pneumonia; If sepsis is suspected, it should be started within one hour; -Antipyretic/analgesic is recommended to control fever and pain. -Corticosteroids are generally not recommended; however, stress doses can be given when needed. -Patients who are about to develop or have developed respiratory failure should be admitted to the ICU ward. For patients without pneumonia or comorbidities: -Supportive treatment is recommended, including the use of antipyretics and analgesics (such as acetaminophen, ibuprofen) to relieve pain and fever; -Patients should stay hydrated, but should not consume too much fluid, as this may worsen oxygenation [48].
-General treatment: strengthen supportive treatment, ensure adequate energy intake; pay attention to water and electrolyte balance, maintain internal environment stability; give effective oxygen therapy measures in time, including nasal cannula, mask oxygen and nasal high flow oxygen therapy; avoid blind or inappropriate use of antibacterial drugs, especially the combined use of broad-spectrum antibacterial drugs.
-Antiviral treatment: drugs with potential antiviral effects (such as α-interferon, ribavirin, chloroquine, and arbidol) should be used early, and recommended to be applied to patients with severe high-risk factors and severely ill tendencies. -Immunotherapy: convalescent plasma from recovered patients, intravenous injection of COVID-19 human immunoglobulin, tocilizumab; -Glucocorticoid treatment can be applied for patients with progressive deterioration of oxygenation indicators, rapid imaging progress, and excessive activation of the body's inflammatory response for a short period of time (equivalent to methylprednisolone 0.5~1mg/kg/day, 3 to 5 days); -For severe and critical cases: On the basis of the above treatment, actively prevent and treat complications, treat basic diseases, prevent secondary infections, and provide organ function support in time; -Chinese medicine as an alternative strategy [49].
Table 1  Pathogenetic, epidemiological and clinical characteristics of SARS-CoV-2, SARS-CoV and MERS-CoV.
TreatmentDrugDrug targetDosageSource
Arbidol + BromhexineArbidolMembrane fusion inhibitorPONCT04273763 (CN)
BromhexineExpectorantPO
Arbidol + IFN-β1αArbidolMembrane fusion inhibitorPO, 200 mg, tid, 14 dNCT04254874 (CN)
IFN-β1αImmunomodulatorINH, 14 d
Chloroquine + IvermectinChloroquineMembrane fusion inhibitor and immunomodulatorPONCT04382846 (EG)
IvermectinImportin (IMP) α/β receptorPO
Chloroquine + Ivermectin + Vitamin DChloroquineMembrane fusion inhibitor and immunomodulatorPO, 500 mg, 4 d, 30 dNCT04399746 (MX)
IvermectinIMP α/β receptorPO, 6 mg, qd, Day 1, 7 and 8
Vitamin DVitaminsPO, 400 UI, bid
Chloroquine + LosartanChloroquineMembrane fusion inhibitor and immunomodulatorPO, 450 mg, bidNCT04428268 (MX)
LosartanAngiotensin II receptor (type AT1) antagonisPO, 25 mg, bid
Chloroquine + ZincChloroquineMembrane fusion inhibitor and immunomodulatorPONCT04447534 (EG)
ZincPO
Hydroxychloroquine + AzithromycinHydroxychloroquine--/ Receptor binding and membrane fusion inhibitorPO, 400 mg, bid, 7 dNCT04321278 (IL)
NCT04322123 (BR) NCT04329832 (US)
AzithromycinTetrcyclinePO, 500 mg, qd
Hydroxychloroquine + Azithromycin + / - tocilizumabHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 800 mg, qdNCT04347031 (RU)
AzithromycinTetrcyclinePO, 250 mg, bid
TocilizumabAnti-IL-6R antibodyIV
Hydroxychloroquine + Azithromycin + Convalescent plasmaHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 400 mg, bid, 5 dNCT04441424 (IQ)
AzithromycinTetrcyclinePO, 500 mg, qd, 5 d
Convalescent plasmaImmunomodulatorIV, 400 mL, 5 d
Hydroxychloroquine + Azithromycin + OseltamivirHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, tid, 5 dNCT04338698 (BR)
NCT04338698 (PK)
AzithromycinTetrcyclinePO, 500 mg, Day 1; 250 mg, Day 2-5
OseltamivirNucleoside analogPO, 75 mg, bid, 5 d
Hydroxychloroquine + Azithromycin + SarilumabHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, tidNCT04341870 (FR)
AzithromycinTetrcyclinePO, 500 mg, Day 1; 250 mg, Day 2-5
SarilumabAnti-IL-6R antibodyIV, 400 mg, Day 1
Hydroxychloroquine + Azithromycin + zincHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 600 mg, Day 1, 200 mg, Day 2-9NCT04528927 (TN)
AzithromycinTetrcyclinePO, 500 mg, Day 1; 250 mg, Day 2-5
ZincPO, 220 mg, 10 d
Hydroxychloroquine + BaricitinibHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, tid, 14 dNCT04373044 (US)
BaricitinibJAK inhibitorPO, 2 mg, qd, 14 d
Hydroxychloroquine + BromhexineHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, tidNCT04273763 (CN)
NCT04340349 (MX)
BromhexineExpectorantPO, 8 mg, tid
Hydroxychloroquine + Camostat mesylateHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 400 mg, bid, 10 dNCT04355052 (IL)
Camostat mesylateTMPRSS2 inhibitorPO, 200 mg, qd, 10 d
Hydroxychloroquine + ClindamycinHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, tid, 7 dNCT04349410 (US)
ClindamycinLincomycin antibioticsIV, 4800 mg
Hydroxychloroquine + Clindamycin + PrimaquineHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, tid, 7 dNCT04349410 (US)
ClindamycinLincomycin antibioticsIV, 4800 mg, 7 d
PrimaquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, qd, 7 d
Hydroxychloroquine + Daclatasvir + SofosbuvirHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 400 mg, bid, 14 dNCT04443725 (EG)
DaclatasvirNucleoside analogPO, 90 mg, qd, 14 d
SofosbuvirNucleoside analogPO, 400 mg, qd, 14 d
Hydroxychloroquine + DoxycyclineHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, tid, 10 dNCT04349410 (US)
DoxycyclineTetrcyclineIV, 100 mg, bid, 10 d
Hydroxychloroquine + FavipiravirHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, bid, 7 dNCT04359615 (IR)
NCT04376814 (IR)
FavipiravirNucleoside analogPO, 1600 mg, Day 1, 600 mg, tid, 7 d
Hydroxychloroquine + IFN-α2βHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPONCT04273763 (CN)
IFN-α2βImmunomodulatorINH
Hydroxychloroquine + ImatinibHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, bidNCT04346147 (ES)
ImatinibTMPRSS2 inhibitorPO, 400 mg, qd
Hydroxychloroquine + Indomethacin +AzithromycinHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, bid, 7dNCT04344457 (US)
IndomethacinNonsteroidal anti-inflammatory drugPO, 50 mg, tid, 14 d
ZithromaxTetrcyclinePO, 500 mg, qd, 3d
Hydroxychloroquine + Lopinavir + Ritonavir + IFN-β1αHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPONCT04350684 (IR)
NCT04343768 (IR) NCT04350671 (IR)
LopinavirNucleoside analogPO
RitonavirNucleoside analogPO
IFN-β 1aImmunomodulatorIV
Hydroxychloroquine + Lopinavir + RitonavirHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, bidNCT04390152 (CO)
NCT04346147 (ES)
LopinavirNucleoside analogPO, 200 mg, qd
RitonavirNucleoside analogPO, 50 mg, qd
Hydroxychloroquine + Lopinavir + Ritonavir + IFN-β1βHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPONCT04343768 (IR)
LopinavirNucleoside analogPO
RitonavirNucleoside analogPO
IFN-β1βImmunomodulatorPO
Hydroxychloroquine + OseltamivirHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, bid, 5 dNCT04338698 (PK)
NCT04303299 (TH)
OseltamivirNucleoside analogPO, 75 mg, bid, 5 d
Hydroxychloroquine + Sirolimus fHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 600 mg, 10 dNCT04374903 (JO)
SirolimusImmunosuppressantPO, 250 mg, 10 d
Hydroxychloroquine + TofacitinibHydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 200 mg, tid, 14 dNCT04390061(US)
TofacitinibJAK inhibitorPO, 10 mg, bid, 14 d
Azithromycin + AmoxicillinAzithromycinTetrcyclinePO, 500 mg, Day 1; 250 mg, Day 2-5, 2 dNCT04363060 (FR)
Amoxicillin/ClavulanateAntibacterial drugsPO, 250 mg, tid, 2 d
Azithromycin + AtovaquoneAzithromycinTetrcyclinePO, 500 mg, Day 1; 250 mg, Day 2-5NCT04339426 (US)
AtovaquonePO, 750 mg, bid, 10 d
Azithromycin + ClavulanateAzithromycinTetrcyclinePO, 250 mg, tid, 7 dNCT04363060 (FR)
Clavulanate
Azithromycin + DoxycyclineAzithromycinTetrcyclinePO, 500 mg, Day 1; 250 mg, Day 2-5NCT04528927 (TN)
DoxycyclineTetrcyclinePO, 200 mg, qd, 10 d
Azithromycin + Ivermectin + NitazoxanideAzithromycinTetrcyclinePONCT04382846 (EG)
IvermectinIMP α/β receptorPO
NitazoxanideImmunomodulatorPO
Azithromycin + Mefloquine + / - TocilizumabAzithromycinTetrcyclinePO, 250 mg, tid, 7 dNCT04347031 (RU)
MefloquineMembrane fusion inhibitor and immunomodulatorPO, 500 mg, bid, 7 d
TocilizumabAnti-IL-6R antibodyIV
Azithromycin + NitazoxanideAzithromycinTetrcyclinePONCT04382846 (EG)
NitazoxanideImmunomodulatorPO
Azithromycin + OseltamivirAzithromycinTetrcyclinePO, 500 mg, Day 1; 250 mg, Day 2-5NCT04338698 (PK)
OseltamivirNucleoside analogPO, 75 mg, bid
Azythromycin + Ivermectin + DutasterideAzythromycinTetrcyclinePO, 500 mg, qdNCT04446429 (BR)
IvermectinIMP α/β receptorPO, 200 mcg/kg, qd
DutasterideTMPRSS2 inhibitorPO, 0.5 mg
Azythromycin + Ivermectin+ ProxalutamideAzythromycinTetrcyclinePO, 500 mg, qdNCT04446429 (BR)
IvermectinIMP α/β receptorPO, 200 mcg/kg, qd
ProxalutamideTMPRSS2 inhibitorPO, 200 mg
Ivermectin + DoxycyclineIvermectinIMP α/β receptorPO, 200 mcg/kg, qd, 5 dNCT04407130 (BD)
NCT04523831 (BD) NCT04403555 (EG)
DoxycyclineTetrcyclinePO, 200 mg, 5 d
Ivermectin + Dutasteride +IvermectinIMP α/β receptorPO, 200 mcg/kg, qdNCT04446429 (BR)
DutasterideTMPRSS2 inhibitorPO, 0.5 mg
Ivermectin + LosartanIvermectinIMP α/β receptorPO, 12 mg, qd, 15 dNCT04447235 (BR)
LosartanAngiotensin II receptor (type AT1) antagonisPO, 50 mg, qd, 15 d
Ivermectin + NitazoxanideIvermectinIMP α/β receptorPONCT04382846 (EG)
NitazoxanideImmunomodulatorPO
Ivermectin + Nitazoxanide + RibavirinIvermectinIMP α/β receptorPO, 7 dNCT04392427 (EG)
NitazoxanideImmunomodulatorPO, 7 d
RibavirinNucleoside analogPO, 7 d
Ledipasvir + SofosbuvirLedipasvirNucleoside analogPO, 90 mg, qd, 14 dNCT04498936 (EG)
SofosbuvirNucleoside analogPO, 400 mg, qd, 14 d
Daclatasvir + SofusbuvirDaclatasvirNucleoside analogPO, 120 mg, Day 1; 60 mg, Day 2-9NCT04468087 (BR)
NCT04460443 (EG)
SofusbuvirNucleoside analogPO, 800 mg, Day 1; 400 mg, Day 2-9
Danoprevir + RitonavirDanoprevirNucleoside analogPO, 100 mg, bid, 10 dNCT04345276 (CN)
NCT04291729 (CN)
RitonavirNucleoside analogPO, 100 mg, bid
Darunavir + CobicistatDarunavirViral RNA-dependent RNA polymerase inhibitor/ CYP3A protein inhitorPO, 800 mg, qd, 5 dNCT04252274 (CN)
NCT04425382 (QA)
CobicistatProtease inhibitorPO, 150 mg, qd, 5 d
Darunavir + Ritonavir + Favipiravir+ HydroxychloroquineDarunavirNucleoside analogPO, 400 mg, tidNCT04303299 (TH)
RitonavirNucleoside analogPO, 200 mg, qd
FavipiravirNucleoside analogPO, 2400 mg, qd
HydroxychloroquineMembrane fusion inhibitor and immunomodulatorPO, 800 mg, qd
Darunavir + Ritonavir + Oseltamivir + HydroxychloroquineDarunavirNucleoside analogPO, 400 mg, tidNCT04303299 (TH)
RitonavirNucleoside analogPO, 200 mg, qd
OseltamivirNucleoside analogPO, 300 mg, qd
HydroxychloroquineMembrane fusion inhibitor and immunomodulator8 PO, 00 mg, qd
Darunavir + Ritonavir + OseltamivirDarunavirNucleoside analogPO, 400 mg, tidNCT04303299 (TH)
RitonavirNucleoside analogPO, 200 mg, qd
OseltamivirNucleoside analogPO, 300 mg, qd
Emtricitabine + TenofovirEmtricitabineProtease inhibitorPO, 300 mg, qd, 8 dNCT04519125 (CO)
TenofovirNucleoside analogPO, 200 mg, qd
Emtricitabine + Tenofovir AlafenamideEmtricitabineProtease inhibitorPO, 200 mg, qdNCT04405271 (AR)
Tenofovir alafenamideNucleoside analogPO, 25 mg, qd
Favipiravir + MaravirocFavipiravirNucleoside analogPO, 200 mg, qd, 10 dNCT04475991 (MX)
MaravirocChemokine receptor antagonistPO, 300 mg, qd, 10 d
Favipiravir + TocilizumabFavipiravirNucleoside analogPO, 1600 mg, Day 1, 600 mg, tid, 6 dNCT04310228 (CN)
TocilizumabAnti-IL-6R antibodyIV, 4-8 mg/kg, 7 d
Oseltamivir + ASC09FOseltamivirRdRP inhibitorPO, 75 mg, qd, 14 dNCT04261270 (CN)
ASC09FCYP3A4 inhibitorPO, 400 mg, bid, 14 d
Oseltamivir + Mesenchymal stem cellsOseltamivirNucleoside analogPO, 4 wNCT04371601 (CN)
Mesenchymal stem cellsMSC therapyIV, 1 ×10^6 cell/kg/w, 4 w
Oseltamivir + RitonavirOseltamivirViral RNA-dependent RNA/ Booster of other protease polymerase inhibitorPO, 75 mg, qd, 7 dNCT04315896 (MX)
NCT04318444 (US) NCT04328285 (FR)
RitonavirNucleoside analogPO, 300 mg, bid, 7 d
Lopinavir + RitonavirLopinavirAnti-retroviral of the protease inhibitor/booster of other protease inhibitorsPO, 400 mg, bid, 5 dGuidelines (version 7) for treatment of COVID-19
NCT04328285 (FR) NCT04328012 (US)
RitonavirNucleoside analogPO, 100 mg, bid, 5 d
Lopinavir + Ritonavir + ArbidolLopinavirAnti-retroviral of the protease inhibitor/booster of other protease inhibitorsPO, 400 mg, bid, 5-21 dNCT04350671 (IR)
NCT04403100 (BR) NCT04376814 (IR)
RitonavirNucleoside analogPO, 100 mg, bid, 5-21 d
ArbidolMembrane fusion inhibitor and immunomodulator/Anti-retroviral of the protease inhibitor/booster of other proteasePO, 200 mg, tid, 5-21 d
Lopinavir + Ritonavir + AtorvastatinLopinavirAnti-retroviral of the protease inhibitor/booster of other protease inhibitorsPO, 200 mg, qd, 10 dNCT04466241 (FR)
RitonavirNucleoside analogPO, 50 mg, qd, 10 d
AtorvastatinStatin medicationPO, 20 mg, qd, 10 d
Lopinavir + Ritonavir + FavipiravirLopinavirAnti-retroviral of the protease inhibitor/booster of other protease inhibitorsPO, 400 mg, bid, 7 dNCT04499677 (GB)
NCT04303299 (TH)
RitonavirNucleoside analogPO, 100 mg, bid, 7 d
FavipiravirNucleoside analogPO, 1800 mg, bid, Day 1; 400 mg, 4 times, 7 d
Lopinavir + Ritonavir + IFN-β1αLopinavirAnti-retroviral of the protease inhibitor/booster of other protease inhibitorsPO, 200 mg, qdNCT04315948 (FR)
NCT04276688 (CN)
RitonavirNucleoside analogPO, 50 mg, qd
IFN-β1αImmunomodulatorINH, 44 μg/ 0.5 mL
Lopinavir + Ritonavir + OseltamivirLopinavirAnti-retroviral of the protease inhibitor/booster of other protease inhibitorsPO, 800 mg, qdNCT04303299 (TH)
RitonavirNucleoside analogPO, 200 mg, qd
OseltamivirNucleoside analogPO, 300 mg, qd
Lopinavir + Ritonavir + TelmisartanLopinavirAnti-retroviral of the protease inhibitor/booster of other protease inhibitorsPO, 200 mg, qd, 10 dNCT04466241 (FR)
RitonavirNucleoside analogPO, 50 mg, qd, 10 d
TelmisartanAngiotensin II receptor (type AT1) antagonisPO, 40 mg, qd, 10 d
Lopinavir + Ritonavir +Ribavirin + IFN-β1αLopinavirAnti-retroviral of the protease inhibitor/booster of other protease inhibitorsPO, 400 mg, bid, 14 dNCT04276688 (CN)
NCT04343768 (IR)
RitonavirNucleoside analogPO, 100 mg, bid, 14 d
RibavirinNucleoside analogPO, 400 mg, bid, 14 d
IFN-β1αImmunomodulatorSC, 0.25 mg
Remdesivir + ApremilastRemdesivirNucleoside analogPO, 200 mg, qd, Day 1; 100 mg, qd, Day 2-9NCT04488081 (US)
ApremilastAntiemeticPO, 30 mg, bid, 9 d
Remdesivir + CenicrivirocRemdesivirNucleoside analogPO, 200 mg, qd, Day 1; 100 mg, qd, Day 2-9NCT04488081 (US)
CenicrivirocCCR5 inhibitorPO, 150 mg, bid, 28 d
Remdesivir + BaricitinibRemdesivirNucleoside analogPO, 200 mg, qd, Day 1; 100 mg, qd, Day 2-9NCT04401579 (US)
BaricitinibJAK inhibitorPO, 4 mg, qd, 14 d
Remdesivir + IcatibantRemdesivirNucleoside analogPO, 200 mg, qd, Day 1; 100 mg, qd, Day 2-9NCT04488081 (US)
IcatibantPeptide-based hormoneSC, 30 mg, 9 d
Remdesivir + IFN-β1αRemdesivirNucleoside analogPO, 200 mg, qd, Day 1; 100 mg, qd, Day 2-9NCT04492475 (US)
IFN-β1αImmunomodulatorSC, 44 μg/ 0.5 mL
Remdesivir + MerimepodibRemdesivirNucleoside analogPO, 200 mg, qd, Day 1; 100 mg, qd, Day 2-9NCT04410354 (US)
MerimepodibInosine monophosphate dehydrogenase (IMPDH) inhibitorIV, 400 mg, tid, 10 d
Remdesivir + NA-831RemdesivirNucleoside analogPO, 1 mg/kgNCT04480333 (US)
NA-831Endogenous small moleculeINH, 0.2 mg/kg
Remdesivir + RazuprotafibRemdesivirNucleoside analogPO, 200 mg, qd, Day 1; 100 mg, qd, Day 2-9NCT04488081 (US)
RazuprotafibVE-PTP inhibitorSC, 10 mg, tid, 7d
Remdesivir + TocilizumabRemdesivirNucleoside analogPO, 10 dNCT04409262 (US)
TocilizumabAnti-IL-6R antibodyIV, 10 d
Ribavirin + SofosbuvirRibavirinNucleoside analogPONCT04460443 (EG)
SofosbuvirNucleoside analogPO
Ritonavir + ASC09RitonavirNucleoside analogPO, 100 mg, bid, 14 dNCT04261907 (CN)
ASC09Protease inhibitorsPO, 300 mg, bid, 14 d
Ritonavir + Ganovo + IFN-NebulizationRitonavirNucleoside analogPO, 100 mg, bid, 14 dNCT04291729 (CN)
DanoprevirNucleoside analogPO, 100 mg, bid, 14 d
IFN-NebulizationImmunomodulatorINH, 50 μg, bid, 14 d
IFN-α1β + Thymosin α1IFN-α1βImmunomodulatorISIN, 2-3 drops, 4 timesNCT04320238 (CN)
Thymosin α1ImmunomodulatorSC, 1 time per week
IFN-β1β + clofazimineIFN-β1βImmunomodulatorSC or IV, 16 million UI, 3 dNCT04465695 (CN)
ClofazimineNucleoside analogPO, 100 mg, bid
Adalimumab + TocilizumabAdalimumabHumanized monoclonal antibody against the TNF-alphaAdalimumab: SC, 40 mg, every 2 wekks;
Tocilizumab: IV, 8 mg/kg, 6 times in 4 weeks
ChiCTR2000030580
TocilizumabAnti-IL-6R antibodyIV
C486-SC or IV
REGN10933 + REGN10987REGN10933Anti-Spike (S) SARS-CoV-2 antibodySC or IVNCT04426695 (US)
NCT04519437 (US) NCT04452318 (US)
REGN10987
Tocilizumab + DexamethasoneTocilizumabAnti-IL-6R antibodyIV, 8 mg/kg, Day 1 and 3NCT04476979 (GF)
DexamethasoneCorticosteroidsIV, 10 mg for 5 d, 2.5 mg for 4 d
Tocilizumab + MethylprednisoloneTocilizumabAnti-IL-6R antibodyIV, 8 mg/kg, Day 1 and 3NCT04377503 (ES)
MethylprednisoloneCorticosteroidsIV, 1.5 mg/kg/d, 21 d
Tocilizumab + PembrolizumabTocilizumabAnti-IL-6R antibodyIV, 8 mg/kgNCT04335305 (ES)
PembrolizumabPD-1 antibodyIV, 200 mg
Toremifene + MelatoninToremifeneHormonePO, 60 mg, qdNCT04531748 (US)
MelatoninHormonePO, 40 mg, morning; 60 mg, evening
Anakinra + RuxolitinibAnakinraIL antagonistsIV, 300 mg/d, 5 dNCT04366232 (FR)
RuxolitinibJAK inhibitorPO, 5 mg, bid, 14-28 d
Anakinra + SiltuximabAnakinraIL antagonistsSC, 100 mg, qdNCT04330638 (BE)
SiltuximabAnti-IL-6R antibodyIV, 11 mg/kg
Anakinra + TocilizumabAnakinraIL antagonistsSC, 100 mg, qdNCT04330638 (BE)
TocilizumabAnti-IL-6R antibodyIV, 8 mg/kg
Colchicine + EdoxabanColchicineNLRP Inflammasome inhibitorPO, 0.5 mg, qdNCT04516941 (CH)
EdoxabanThrombolytic medicationPO, 60 mg, qd
Colchicine + MethylprednisoloneColchicineNLRP Inflammasome inhibitorPO, 0.5 mg, qd, 14 dNCT04492358 (ES)
MethylprednisoloneCorticosteroidsPO, 60 mg, qd, 3d
Colchicine + RosuvastatinColchicineNLRP Inflammasome inhibitorPO, 0.6 mg, qd, 3 dNCT04472611 (US)
RosuvastatinHMG-CoA reductase inhibitorsPO, 40 mg, qd, 3 d
Dexamethasone + Placenta-Derived MMSCsDexamethasoneCorticosteroidsIVNCT04461925 (UA)
Placenta-Derived MMSCsMSC therapyIV, 1 ×10^6 cell/kg, Day 1, 4 and 7
Diltiazem + NiclosamideDiltiazemCalcium-channel blockerPO, 500 mg × 4 times, 10 dNCT04372082 (FR)
Niclosamide-PO, 60 mg, tid, 10 d
Dipyridamole + AspirinDipyridamoleThrombolytic medicationPO, 200 mg, qd, 14 dNCT04410328 (US)
AspirinThrombolytic medicationPO, 25 mg, qd, 14 d
Enoxaparin + MethylprednisoloneEnoxaparinThrombolytic medicationSC, 4000-6000 UINCT04528888 (IT)
MethylprednisoloneCorticosteroidsIV, 0.5 mg/kg
Heparin + MethylprednisoloneHeparinThrombolytic medicationIV, 18 UI/kg/hNCT04485429 (BR)
NCT04528888 (IT)
MethylprednisoloneCorticosteroidsIV, 0.5 mg/kg
Heparin + Umbilical Cord Mesenchymal Stem CellsHeparinThrombolytic medicationIVNCT04355728 (US)
Umbilical Cord Mesenchymal Stem CellsMSC therapyIV, 100 ×10^6 cell
Levamisole + IsoprinosineLevamisole-PO, 50 mg, tid, 14 dNCT04383717 (EG)
NCT04360122 (EG)
Isoprinosine-PO, 1 g, 4 times
Metenkefalin + TridecactideMetenkefalinOpioid delta receptor agonistsIV, 5 mgNCT04374032 (YU)
TridecactideTh1 cell modulatorsIV, 1 mg
Nitazoxanide + atazanavir+ ritonavirNitazoxanideImmunomodulatorPO, 1000 mg, bidNCT04459286 (NG)
AtazanavirNucleoside analogPO, 300 mg, qd
RitonavirNucleoside analogPO, 100 mg, qd
Paracetamol + ChAdOx1 nCoV-19ParacetamolNon-steroidal anti-inflammatory drugsPO,NCT04324606 (GB)
ChAdOx1 nCoV-19VaccineIV, 5 ×10^10 vp
Paracetamol + MenACWYParacetamolNon-steroidal anti-inflammatory drugsIVNCT04324606 (GB)
MenACWYVaccineIV
Ruxolitinib + SimvastatinRuxolitinibJAK inhibitorPO, 5 mg, bid, 14 dNCT04348695 (ES)
SimvastatinStatin medicationPO, 40 mg, qd, 14 d
SnPP Protoporphyrin + Sunlight exposureSnPP ProtoporphyrinPhotodynamic therapyIV, 5, 7 and 9 mg, 14 dNCT04371822 (EG)
Sunlight exposure1 h, 14 d
Sulfonatoporphyrin(TPPS) + Sunlight exposureSulfonatoporphyrin(TPPS)Photodynamic therapyIV, 5 mg, 14 dNCT04371822 (EG)
Sunlight exposure1 h, 14 d
Tacrolimus + MethylprednisoloneTacrolimusImmunosuppressantPO, 8-10 ng/mL blood levelNCT04341038 (ES)
MethylprednisoloneCorticosteroidsPO, 120 mg, 3 d
Tirofiban + Clopidogrel + Acetylsalicylic acid + FondaparinuxTirofibanThrombolytic medicationIV, 0.15 μg/kg/minNCT04368377
ClopidogrelThrombolytic medicationPO, initial dose of 300 mg, then 75 mg/d
Acetylsalicylic acidThrombolytic medicationIV, initial dose of 75 mg, then 30 mg/d
FondaparinuxThrombolytic medicationIV, 2.5 mg
Table 2  Combined use of different treatments in COVID19.
Figure 1.  The development of COVID19. Viral infection: TMPRSS2 cleaves the S protein of SARS-CoV-2; The RBD on the S1 subunit binds to ACE2 on the cell surface. Following entry into the cell, viral RNA is released and combined with RdRp to synthesize a full-length negative-strand RNA as an RNA replication template. After translation, structural proteins are localized to the inner membrane of Golgi for assembly. Cytokine storm syndrome: The immune system is over-activated, followed by the overproduction of multiple inflammatory factors. Multiple immune cells are recruited. As a result, healthy cells are damaged by overactive immune response. Acute respiratory distress syndrome: In the exudative phase, macrophages are activated and release pro-inflammatory mediators, which leads to the aggregation of neutrophils and monocytes. Activated neutrophils induce further damage. The injury leads to loss of barrier function and fluid accumulation in the interstitium and alveoli. In the proliferative period, the tissue homeostasis is recovered.
Clinical stageSyndromeSymptomFormulaRef.
Observation periodFatigue with gastrointestinal discomfortHuoxiang Zhengqi (HXZQ) capsule (pill, liquid or oral solution)[102, 238]
Fatigue with feverJinhua Qinggan granules;
Lianhua Qingwen capsule (or granules); Shufeng Jiedu capsule (or granules); Fang Feng Tong Sheng pill (or granules)
[102, 238]
Treatment periodMild casesCold-damp invading the lungAversion to cold with fever or no fever, muscle aches or headaches, dry throat with cough, tiredness and fatigue, stuffy feeling in chest and stomach, or vomiting, loose stools, light or red tongue, white and greasy fur, tight, wiry or moisten pulse
i
Rhizoma Atractylodes 15g, dried Pericarpium Citri Reticulatae 10g, Cortex Magnoliae Officinalis 10g, Chinese Patchouli 10g, Fructus Amomi 6g, raw Herba Ephedrae 6g, Rhizoma et Radix Notopterygii 10g, Rhizoma Zingiberis Recens 10g, Semen Arecae 10g[238]
Raw Herba Ephedrae 6g, Gypsum Fibrosum 15g, Semen Armeniacae Amarum 9g, Rhizoma et Radix Notopterygii 15g, Semen Lepidii 15g, Rhizoma Cyrtomii 9g, earthworm Pheretima 15g, Radix Cynanchi Paniculati 15g, Chinese Patchouli 15g, Herba Eupatorii 9g, Rhizome Atratylodes 15g, Poria Cocos 45g, raw white Atractylodes Rhizome 30g, charred triplet (charred malt, charred hawthorn, charred medicated leaven) 9g for each, Cortex Magnoliae Officinalis 15g, charred Semen Arecae 9g, roasted Fructus Amomi 9g, Rhizoma Zingiberis Recens 15g[102]
Damp-heat obstructing the lungLow or no fever, slight aversion to cold, fatigue, heavy head and body feeling, muscular soreness, dry cough with less sputum, sore throat, dry mouth without desire of drinking, or accompanied by stuffy feeling in chest and stomach, no sweat or sweating is not smooth, with a disgusted and dull expression, laxness or loose stools, reddish tongue with thick and greasy or light yellow fur, rolling, rapid or moisten pulseSemen Arecae 10g, Fructus Amomi 10g, Cortex Magnoliae Officinalis 10g, Rhizoma Anemarrhenae 10g, Radix Scutellariae 10g, Radix Bupleuri 10g, Radix Paeoniae Rubra 10g, Fructus Forsythiae 15g, Herba Artemisiae Annuae 10g (decocted later), Rhizoma Atractylodes 10g, Folium Isatidis 10g, raw Radix Glycyrrhizae 5g[102]
Chinese Patchouli 10g (decocted later), Cortex Magnoliae Officinalis 10g, Rhizoma Pinellinae Praeparata 10g, Poria Cocos 15g, Radix Bupleuri 15g, Radix Scutellariae 10g, Radix Codonopsis 10g, Semen Armeniacae Amarum 10g, Semen Coicis 20g, Agar 10g, Rhizoma Alismatis 10g, Fructus Amomi Rotundu 10g (decocted later), Semen Sojae Preparatum 10g, Medulla Tetrapanacis 10g, Rhizoma Zingiberis Recens 5g, Fructus Jujubae 5gg[243]
Moderate casesToxic damp depressing the lungLow to medium fever, which is obvious in the afternoon, slight aversion to cold, dry cough with less sputum, dry and sore throat, light tongue with yellow greasy fur, rolling and rapid pulseFolium Isatidis 15g, Radix Scrophulariae 20g, Radix Bupleuri 15g, Radix Scutellariae 15g, Rhizoma Pinellinae Praeparata 10g, Fructus Arctii 10g, Fructus Forsythiae 10g, Herba Taraxaci 20g, Rhizoma Cyrtomii 10g, Herba Schizonepetae 10g, raw Radix Glycyrrhizae 10g, Radix Isatidis 10g, Poria Cocos 15g, Semen Armeniacae Amarum 12g[238]
Raw Herba Ephedrae 6g, Semen Armeniacae Amarae 15g, Gypsum Fibrosum 30g, raw Semen Coicis 30g, Rhizoma Atractylodes 10g, Chinese Patchouli 15g, Herba Artemisiae Annuae 12g, Rhizoma Polygontum Cuspidatum 20g, Herba Verbenae 30g, dried Rhizoma Phragmitis 30g, Semen Lepidii 15g, Exocarpium Citri Grandis 15g, raw Radix Glycyrrhizae 10g[102]
Cold-damp obstructing the lungHidden low fever, dry cough with less sputum, tiredness and fatigue, stuffy feeling in chest and stomach, or vomiting, and loose stools, pale or light red tongue with white or greasy fur, moisten pulseRhizoma Atractylodes 15g, dried Pericarpium Citri Reticulatae 10g, Cortex Magnoliae Officinalis 10g, Chinese Patchouli 10g, Fructus Amomi 6g, raw Ephedrae 6g, Rhizoma et Radix Notopterygii 10g, Rhizoma Zingiberis Recens 10g, Semen Arecae 10g[102]
Toxic damp accumulated in interior, involving lung and spleenLow fever, which is obvious in the afternoon, dry cough with less sputum, dry and sore throat, stuffy feeling in chest and stomach, vomiting and anorexia, laxness and fatigue, pale tongue with greasy fur, rolling and rapid pulseFolium Isatidis 15g, Radix Scrophulariae 20g, Radix Bupleuri 15g, Radix Scutellariae 15g, Rhizoma Pinellinae Praeparata 10g, Fructus Arctii 10g, Fructus Forsythiae 10g, Herba Taraxaci 20g, Rhizoma Cyrtomii 10g, Herba Schizonepetae 10g, raw Radix Glycyrrhizae 10g, Poria Cocos 15g, Semen Armeniacae Amarum12g, Radix Angelica Dahurica 10g, Chinese Patchouli 10g, Herba Eupatorii 10g[238]
Toxic damp obstructing the spleenMental depression, fatigue, weakness, anorexia, loose stools, borborygmus, abdominal fullness, chest tightness and shortness of breath, pale tongue with greasy fur, soft and moisten pulseChinese Patchouli 15g, Radix Angelica Dahurica 10g, Folium Perillae 6g, Poria Cocos 30g, Rhizoma Pinelliae processed by ginger juice 12g, Rhizoma Atractylodes 10g, white Atractylodes Rhizome 15g, dried Pericarpium Citri Reticulatae 10g, Cortex Magnoliae Officinalis 10g, Radix Glycyrrhiza Preparata 6g, Fructus Amomi Rotundu 10g, Radix Platycodonis 10g[238]
Evil heat obstructing the lungFever or high fever, cough, yellow or thick phlegm, fatigue, headache, muscular stiffness, dry and bitter mouth, anxiety, red urinary and constipation, red tongue with yellow or greasy fur, rolling and rapid pulseFried Herba Ephedrae 8g, Semen Armeniacae Amarum 10g, Gypsum Fibrosum 30g, Radix Glycyrrhizae 10g, Semen Arecae 10g, Cortex Magnoliae Officinalis 10g, Fructus Amomi 10g, Rhizoma Anemarrhenae 10g, Radix Paeoniae Alba 10g, Radix Scutellariae 15g[243]
Severe casesToxic plague blocking the lungChest tightness, shortness of breath, coughing and panting, extreme fatigue, asthmatic, cough with less sputum or hemoptysis or yellow sputum, thirsty and irritable, high fever does not retreat, bloating and constipation, dark red tongue with yellow greasy fur, slippery or heavy pulseSemen Armeniacae Amarum 10g, Gypsum Fibrosum 30g, Pericarpium Trichosanthis or Semen Trichosanthis 30g, raw Radix et Rhizoma Rhei 6g (decocted later), fried Herba Ephedrae 6g, Semen Lepidii 10g, Semen Persicae 10g, Fructus Amomi 6g, Semen Arecae 10g, Rhizoma Atractylodes 10g[238]
Semen Armeniacae Amarum 15g, Gypsum Fibrosum 30g (chopped), Fructus Trichosanthis 30g, Fructus Aurantii Immaturus 15g, raw Radix et Rhizoma Rhei 15g (decocted later), raw Herba Ephedrae 6~10g, Semen Lepidii 30g, Semen Persicae 10g, Radix Paeoniae Rubra 15g, raw Radix Glycyrrhizae 6g, Rhizoma Phragmitis 30g[238]
Raw Herba Ephedrae 6g, Semen Armeniacae Amarum 9g, Gypsum Fibrosum 15g, Radix Glycyrrhizae 3g, Chinese Patchouli 10g (decocted later), Cortex Magnoliae Officinalis 10g, Rhizoma Atractylodes 15g, Fructus Amomi 10g, Rhizoma Pinellinae Praeparata 9g, Poria Cocos 15g, raw Radix et Rhizoma Rhei 5g (decocted later), raw Radix Astragali 10g, Semen Lepidii 10g, Radix Paeoniae Rubra 10g[102]
Fever, cough, thick yellow phlegm, chest tightness, wheezing, thirst, stinking tone, bloating and constipation, dark red tongue with thick and yellow fur, slippery or tight pulseRaw Herba Ephedrae 8g, Semen Armeniacae Amarum 12g, Gypsum Fibrosum 30g, raw Radix et Rhizoma Rhei 10g, Semen Trichosanthis 30g, Semen Persicae 10g, Radix Paeoniae Rubra 15g, Semen Lepidii 20g, Rhizoma Coptidis 3g, Radix Scutellariae 10g, Cortex Mori 10g, Rhizoma Paridis 10g, Cortex Moutan 15g, Radix Curcumae 15g, Rhizoma Acori Graminei 15g, raw Radix Rehmanniae 15g, Radix Scrophulariae 15g[243]
Hidden fever, disturbed hidrosis, panting, dry coughing or bucking, or with sore throat, stuffy feeling in chest and stomach, dry mouth,
bitter or sticky in the mouth, sticky stools, dark red tongue with yellow and greasy fur, slippery pulse
Raw Herba Ephedrae 8g, Semen Armeniacae Amarum 12g, Gypsum Fibrosum 30g, raw Radix Glycyrrhizae 10g, Talcum powder 30g, Herba Artemisiae Scopariae 20g, Radix Scutellariae 15g, Fructus Amomi Rotundu 10g (decocted later), Chinese Patchouli 15g, Rhizoma Pinellinae Praeparata 15g, Rhizoma Atractylodes 15g, Semen Lepidii 20g, Fructus Forsythiae 15g, Bombyx Batryticatus 5g, Periostracum Cicadae 5g, Rhizoma Curcumae Longae 10g, raw Radix et Rhizoma Rhei 5g, Rhizoma Paridis 10g, Cortex Moutan 15g, Radix Paeoniae Rubra 15g, Radix Curcumae 15g, Rhizoma Acori Graminei 15g, raw Radix Rehmanniae 15g, Radix Scrophulariae 15g[243]
raw Herba Ephedrae 8g, Semen Armeniacae Amarum 12g, Gypsum Fibrosum 30g, raw Radix Glycyrrhizae 10g, Talcum powder 30g, Herba Artemisiae Scopariae 20g, Radix Scutellariae 15g, Fructus Amomi Rotundu 10g (decocted later), Chinese Patchouli 15g, Rhizoma Pinellinae Praeparata 15g, Rhizoma Atractylodes 15g, Semen Lepidii 20g, Fructus Forsythiae 15g, Bombyx Batryticatus 5g, Periostracum Cicadae 5g, Rhizoma Curcumae Longae 10g, raw Radix et Rhizoma Rhei 5g, Rhizoma Paridis 10g, Cortex Moutan 15g, Radix Paeoniae Rubra 15g, Radix Curcumae 15g, Rhizoma Acori Graminei 15g, raw Radix Rehmanniae 15g, Radix Scrophulariae 15g[243]
Blazing heat in qi and ying fenHot and thirsty, panting, dizzy delirium, blurred vision with macula, hematemesis and epistaxis, convulsions in the limbs, crimson tongue with little or no fur, deep, thin and rapid pulse, or floating and rapid pulseGypsum Fibrosum 30~60g (decocted first), Rhizoma Anemarrhenae 30g, Radix Rehmanniae Preparata 30~60g, Cornu Bubali 30g (decocted first), Radix Paeoniae Rubra 30g, Radix Scrophulariae 30g, Fructus Forsythiae 15g, Cortex Moutan 15g, Rhizoma Coptidis 6g, Folium Phyllostachys 12g, Semen Lepidii 15g, raw Radix Glycyrrhizae 6g[102]
Critical casesInner blocking causing collapseDyspnea, asthmatic, or assisted ventilation needed, with dizziness and irritability, sweating, cold limbs, dark purple tongue with thick, greasy or dry fur, large floating and weak pulseRadix Ginseng 15g, Radix Aconiti Lateralis Preparata 10g (decocted first), Fructus Corni 15g; with Suhexiang pill or Angong Niuhuang pill; high fever plus Zixue powder; severe breathing plus Semen Lepidii and Herba Ephedrae[238]
Radix Panacis Quinquefolii 15g, Radix Aconiti Lateralis Preparata 10g, Fructus Corni 30g, crude Os Draconis 30g, Concha Ostreae 30g, Magnetitum 30g; with Angong Niuhuang pill[238]
Radix Ginseng 15g, Radix Aconiti Lateralis Preparata 10g (decocted first), Fructus Corni 15g; with Suhexiang pill or Angong Niuhuang pill[102]
High fever and irritability, cough and shortness of breath, the nose wings incite, phlegm in the throat, holding breath in embarrassment, intermittent voice, spots of rash, or even dizzy coma, sweating, cold limbs, dark purple lips, dark red tongue with yellow and greasy fur, deep, thin and delicate pulseRadix Ginseng Rubra 10g, Radix Aconiti Lateralis Preparata 10g (decocted first), Fructus Corni 30g, Radix Ophiopogonis 20g, Radix Notoginseng 10g[243]
Recovery periodQi deficiency of lung and spleenShortness of breath, fatigue, anorexia, vomiting, fullness, weak and loose stools, pale fat tongue with white and greasy fur.Rhizoma Pinellinae Praeparata 9g, dried Pericarpium Citri Reticulatae 10g, Radix Codonopsis 15g, Radix Astragali Preparata 30g, Poria Cocos 15g, Chinese Patchouli 10g, Fructus Amomi 6g (decocted later)[102, 238]
Dried Radix Ginseng 10g (boiled separately), fried Rhizoma Atractylodis Macrocephalae 15g, Poria Cocos 15g, Semen Lablab Album 30g, Fructus Amomi 6g (chopped, decocted later), Semen Nelumbinis 30g, Radix Glycyrrhiza Preparata 6g, Radix Platycodonis 10g, Rhizoma Dioscoreae 15g, Semen Coicis 30g, fried Fructus Hordei Germinatus 30g, medicated leaven 10g[243]
Deficiency of both qi and yinShortness of breath, fatigue, coughing, less phlegm, low or no fever, thirst, anorexia, dry and dark tongue with dry and white fur, thin and weak pulseRadix Adenophorae 10g, Radix Glehniae 10g, Radix Ophiopogonis 6g, Fructus Schisandrae 10g, Gypsum Fibrosum 15g, Herba Lophatheri 10g, Folium Mori 6g, Rhizoma Phragmitis 15g, Radix Trichosanthis 15g, Poria Cocos 10g, Radix Salviae Miltiorrhizae 15g, Semen Persicae 10g, Radix Glycyrrhizae 6g[102, 238]
Buzhong Yiqi pill;
Shengmai drink; Xiangsha Liujunzi pill; Shen Ling Baizhu powder
[238]
Radix Panacis Quinquefolii 20g, Herba Dendrobii 10g, Radix Ophiopogonis 10g, Rhizoma Anemarrhenae 10g, Herba Lophatheri 10g, Rhizoma Coptidis 3g, Radix Glycyrrhizae 6g, Poria Cocos 15g, Rhizoma Pinellinae Praeparata 10g, Exocarpium Citri Rubrum 10g, dried Pericarpium Citri Reticulatae 10g, fried Fructus Hordei Germinatus 30g[243]
PreventionHigh-risk groupRadix Astragali 15g, fried Rhizoma Atractylodes 10g, Radix Sileris 10g, Flos Lonicerae 10g, Rhizoma Dryopteris Crassirhizomatis 10g, dried Pericarpium Citri Reticulatae 10g, Semen Lablab Album 15g, Poria Cocos 10g[238]
Raw Radix Astragali 10g, fried white Atractylodes Rhizome 10g, Radix Sileris 6g, Flos Lonicerae 10g, Herba Eupatorii 10g, dried Pericarpium Citri Reticulatae 10g, Chinese Patchouli 10g, Poria Cocos 10g, raw Radix Glycyrrhizae 6g[238]
Healthy groupRoasted Rhizoma Atractylodes 3g, Flos Lonicerae 3g, dried Pericarpium Citri Reticulatae 3g, Rhizoma Phragmitis 6g, Folium Mori 3g, Folium Perillae 3g, raw Radix Astragali 6g[238]
Radix Codonopsis 20g, Folium Perillae 10g, Herba Schizonepetae 10g, Radix Sileris 10g[243]
Rhizoma Zingiberis Recens 10g, Fructus Jujubae 15g, Radix Sileris 10g[243]
Table 3  Prescription for COVID-19 recommended by Chinese medicine.
TreatmentAdministration and DosageOutcome MeasuresSource
Lianhua QingwenPO, 4 capsules, tid, 7 dVirological clearanceNCT04433013 (SG)
Xiyanping injectionIV, 10-20 mL, qd, Combination medication, 14 dClinical recovery timeNCT04275388 (CN)
NCT04295551 (CN)
Huaier keliPO, 20 g, 14 dMortalityNCT04291053 (CN)
T89 (Danshen Diwan)PO, 30 pills, bidImprove oxygen saturationNCT04285190 (CN)
Fuzheng Huayu TabletPO, 1.6 g, tidEvaluation of Pulmonary fibrosis Improvement.NCT04279197 (CN)
Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) and Traditional Chinese Medicines (TCMs) granulesPO, 20 g, bid, 14 dThe incidence rate of ARDS developmentNCT04251871 (CN)
Chinese Herbal MedicinePOPatient reported main complaintNCT04380870 (US)
ReginmunePO, 1000 mg, tid, 10 dTime to clinical improvementNCT04494204 (IN)
Licorice extractPO, 250 mg standardized extract, 10 dIncreased number of recovery from COVID19NCT04487964 (EG)
Iota-CarrageenanISIN, 4 times, 21 dChange in SARS-CoV-2 antibody titersNCT04521322 (AR)
çaí palm berry extractPO, 520 mg, tid, 30 d7-point ordinal symptom scaleNCT04404218 (CA)
P2Et (Caesalpinia spinosa extract)PO, 250 mg, bid, 14 dProportion of patients who reduce the time in the hospitalNCT04410510 (CO)
Nigella sativaPO, 500 mg, Black seed oilProportion of patients who are clinically recoveredNCT04401202 (SA)
Nigella Sativa / Black CuminPO, 80 mg/kg/d, 14 dTime needed to turn positive COVID-19 PCR to negativeNCT04472585 (PK)
NCT04347382
Natural HoneyPO, 30 mL, bid, 14 dTime needed to turn positive COVID-19 PCR to negativeNCT04323345 (EG)
NCT04347382 (PK)
Antioxidation TherapyTwo proprietary formulations composed of reduced glutathione, N-acetylcysteine, supero×ide dismutase, and bovine lactoferrin and immunoglobulins. PO, 28 dTime to clinical improvementNCT04466657 (NG)
AromatherapyINH, 15 minChange from baseline in state anxiety on the State portion of the State Trait Anxiety Scale (STAI-S) at 15 minutesNCT04495842 (US)
AyurvedaPOTime to achieve afebrileNCT04395976 (GB)
NCT04345549 (GB) NCT04351542
Ayurvedic KadhaPO, 30 dPreventionNCT04387643 (IN)
Natural HoneyPO, 1 g/kg/d, 14 dRate of recoveryNCT04323345 (EG)
NCT04347382 (PK)
QuadraMune(TM)PO, 2 pills, 84 dPreventionNCT04421391 (US)
ResveratrolPO, 15 dLength of stay in hospitalNCT04400890 (US)
TetrandrinePO, 60 mg, qd, 7 dSurvival rateNCT04308317 (CN)
QuercetinPO, 500 mg, 90 dPrevalence of COVID-19NCT04377789 (TR)
SilymarinPO, 140 mg, tid, 7-28 dTime to clinical improvementNCT04394208 (EG)
EscinPO, 40 mg, tid, 12 dMortalityNCT04322344 (IT)
Pyronaridine-ArtesunatePO, Pyronaridine 180mg/ Artesunate 60mg, 7 dVirological clearanceNCT04475107 (KR)
Artemisinin / ArtesunatePO, 100 mg, 5 dLength of stay in hospitalNCT04387240 (SA)
ArtemiCPOTime to clinical improvementNCT04382040 (IL)
FisetinPO, 20 mg/kg/dSerious adverse events and change in oxygenation statusNCT04476953 (US)
LEAF-4L6715IV, initial dose of 5 mg, 2.5 mg, qdImprove oxygenation statusNCT04378920 (FR)
LEAF-4L7520IV, 0.25 mg/kg per 3hImprove oxygenation statusNCT04378920 (FR)
ManremycPO, 1×10^5 heat-inactivated Mycobacterium s. 14 dDocumented cumulative incidence of SARS-CoV-2 infectionNCT04452773 (ES)
GlycinePO, 0.5 g/kgMortalityNCT04443673 (US)
EPA-FFAPO, 1 g, bidRate of treatment failureNCT04335032 (CH)
omega3-FAPO, 300 mg, 60 dInflammatory factor levelsNCT04483271 (JO)
VitaminsAZINC forme etvitalité®, 2 tablets, PO, 9 dOccurrence of hospitalization and mortalityNCT04356495 (FR)
Vitamin DPO, 1000-500000 UI, 30 dMortalityNCT04334005 (ES)
NCT04335084 (US) NCT04344041 (FR)
Vitamin D3PO, 2000-100000 UI, 10-30 dSeverity, mortality and inflammatory factor levelsNCT04351490 (FR)
NCT04395768 (AU) NCT04400890 (US)
Vitamin CIV, 10-12 g or 50-60 mg/kg, 9 dMortality and dependency on mechanical ventilation, renal replacement, or vasopressorsNCT03680274 (CN)
NCT04323514 (IT) NCT04328961 (US)
PO, 500-1000 mgSymptom SeverityNCT04354428 (US)
NCT04530539 (US)
Vitamin C +Vitamin D +zincPOPreventionNCT04335084 (US)
NCT04334512 (US)
Vitamin C + Folic AcidVC: PO, 500 mg, 9 d
Folic acid: PO, 400 mcg, 9 d
Incidence of hospitalization or mortality and change in upper respiratory viral sheddingNCT04354428 (US)
Vitamin BSuper B-Comple×, bid, PO, 42 dPreventionNCT04343248 (US)
Vitamin B12Adjuvant therapy: PO, 14 dSymptoms, length of hospital stay and mortalityNCT04395768 (AU)
Vitamin B3IV, 20000 UI, 3 dChange in SARS-CoV-2 antibody titersNCT04482673 (US)
Zinc gluconatePO, 15-20 mg, bid, 60 dSurvival rate in asymptomatic subjects at inclusionNCT04351490 (FR)
NCT04447534 (EG) NCT04472585 (PK)
L-citrullinePO, 7 dSOFA score for organ failures on D7 or last known SOFA score if the patient has died or been resuscitatedNCT04404426 (FR)
Nutritional support systemDiet based on the Basal Energy E×penditure plus the stress factor using the Harris Benedict equation.Oxygen saturationNCT04507867 (MX)
SivoMixxComposition of SivoMi××: Streptococcus thermophilus DSM322245, Bifidobacterium lactis DSM 32246, Bifidobacterium lactis DSM 32247, Lactobacillus acidophilus DSM 32241, Lactobacillus helveticus DSM 32242, Lactobacillus paracasei DSM 32243, Lactobacillus plantarum DSM 32244, Lactobacillus brevis DSM 27961 (NB: DSM n°... : bacterial strain identification code), 21 dDelta of time of disappearance of acute diarrheaNCT04368351 (IT)
Omnibiotic AADBacterial strains in Omni-Biotic® 10 AAD are Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Enterococcus faecium W54, Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus plantarum W1, Lactobacillus plantarum W62, Lactobacillus rhamnosus W71 and Lactobacillus salivarius W24 which are embedded in a matri× containing maize starch, maltode×trin, inulin, potassium chloride, hydrolysed rice protein, magnesium sulphate, fructooligosaccharide (FOS), enzymes (amylases), vanilla flavour and manganese sulphate, 30 dDelta of time of disappearance of acute diarrheaNCT04420676 (AT)
MRx-4DP0004Lyophilised formulation of a proprietary strain of bacteria: 4 × 10^9 to 4 ×10^10 colony forming units, PO, 14 dChange in mean clinical status score in each treatment armNCT04363372 (GB)
ProbioticPO, 1×10^9 cfu of the probiotic, 30 dCases with discharge to ICUNCT04390477 (ES)
NCT04517422
bacTRL-SpikeSingle dose of bacTRL-Spike, equivalent to 1-3 billion colony forming units (cfu) of Bifidiobacterium longum; POGenetically modified probiotic bacteria colonize the gut, bind directly to intestinal epithelial cells and constitutively replicate, secrete and deliver plasmid DNA molecules encoding antigenic transgenes and neutralizing nanobodies.NCT04334980 (US, CA)
Previfenon®PO, 250 mg, tidImprove symptomsNCT04446065 (AU)
Table 4  Commercial Chinese medicine preparations and herb supplement in treatment of COVID19.
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