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* [[Remdesivir]] is approved by [[FDA]] on 22 October 2020 for all hospitalized adult and pediatric older than 12 years of age and weighing at least 40 kg (88 pounds).
* [[Remdesivir]] is approved by [[FDA]] on 22 October 2020 for all hospitalized adult and pediatric older than 12 years of age and weighing at least 40 kg (88 pounds).
* [[Remdesivir]] was effective in shortening the time of recovery about 32% and [[survival]] benefit in adult hospitalized [[covid-19]] patients according to '''ACTT-1 trial'''.<ref name="BeigelTomashek2020">{{cite journal|last1=Beigel|first1=John H.|last2=Tomashek|first2=Kay M.|last3=Dodd|first3=Lori E.|last4=Mehta|first4=Aneesh K.|last5=Zingman|first5=Barry S.|last6=Kalil|first6=Andre C.|last7=Hohmann|first7=Elizabeth|last8=Chu|first8=Helen Y.|last9=Luetkemeyer|first9=Annie|last10=Kline|first10=Susan|last11=Lopez de Castilla|first11=Diego|last12=Finberg|first12=Robert W.|last13=Dierberg|first13=Kerry|last14=Tapson|first14=Victor|last15=Hsieh|first15=Lanny|last16=Patterson|first16=Thomas F.|last17=Paredes|first17=Roger|last18=Sweeney|first18=Daniel A.|last19=Short|first19=William R.|last20=Touloumi|first20=Giota|last21=Lye|first21=David Chien|last22=Ohmagari|first22=Norio|last23=Oh|first23=Myoung-don|last24=Ruiz-Palacios|first24=Guillermo M.|last25=Benfield|first25=Thomas|last26=Fätkenheuer|first26=Gerd|last27=Kortepeter|first27=Mark G.|last28=Atmar|first28=Robert L.|last29=Creech|first29=C. Buddy|last30=Lundgren|first30=Jens|last31=Babiker|first31=Abdel G.|last32=Pett|first32=Sarah|last33=Neaton|first33=James D.|last34=Burgess|first34=Timothy H.|last35=Bonnett|first35=Tyler|last36=Green|first36=Michelle|last37=Makowski|first37=Mat|last38=Osinusi|first38=Anu|last39=Nayak|first39=Seema|last40=Lane|first40=H. Clifford|title=Remdesivir for the Treatment of Covid-19 — Final Report|journal=New England Journal of Medicine|year=2020|issn=0028-4793|doi=10.1056/NEJMoa2007764}}</ref>
* [[Remdesivir]] was effective in shortening the time of recovery about 32% and [[survival]] benefit in adult hospitalized [[covid-19]] patients according to '''ACTT-1 trial'''.<ref name="BeigelTomashek2020">{{cite journal|last1=Beigel|first1=John H.|last2=Tomashek|first2=Kay M.|last3=Dodd|first3=Lori E.|last4=Mehta|first4=Aneesh K.|last5=Zingman|first5=Barry S.|last6=Kalil|first6=Andre C.|last7=Hohmann|first7=Elizabeth|last8=Chu|first8=Helen Y.|last9=Luetkemeyer|first9=Annie|last10=Kline|first10=Susan|last11=Lopez de Castilla|first11=Diego|last12=Finberg|first12=Robert W.|last13=Dierberg|first13=Kerry|last14=Tapson|first14=Victor|last15=Hsieh|first15=Lanny|last16=Patterson|first16=Thomas F.|last17=Paredes|first17=Roger|last18=Sweeney|first18=Daniel A.|last19=Short|first19=William R.|last20=Touloumi|first20=Giota|last21=Lye|first21=David Chien|last22=Ohmagari|first22=Norio|last23=Oh|first23=Myoung-don|last24=Ruiz-Palacios|first24=Guillermo M.|last25=Benfield|first25=Thomas|last26=Fätkenheuer|first26=Gerd|last27=Kortepeter|first27=Mark G.|last28=Atmar|first28=Robert L.|last29=Creech|first29=C. Buddy|last30=Lundgren|first30=Jens|last31=Babiker|first31=Abdel G.|last32=Pett|first32=Sarah|last33=Neaton|first33=James D.|last34=Burgess|first34=Timothy H.|last35=Bonnett|first35=Tyler|last36=Green|first36=Michelle|last37=Makowski|first37=Mat|last38=Osinusi|first38=Anu|last39=Nayak|first39=Seema|last40=Lane|first40=H. Clifford|title=Remdesivir for the Treatment of Covid-19 — Final Report|journal=New England Journal of Medicine|year=2020|issn=0028-4793|doi=10.1056/NEJMoa2007764}}</ref>
*In a Phase 3 open label randomized trial, No clinical benefit was observed from the use of [[remdesivir]] in [[patients]] who were admitted to hospital for [[COVID19]],who were [[symptomatic]] for more than 7 days, and required [[oxygen]] support.(doi:10.1016/S1473-3099(21)00485-0)
* The combination of [[Remdesivir]] and [[Baricitinib]] reduced recovery time in hospitalized [[covid-19]] patients  according to '''ACTT-2 trial'''.
* The combination of [[Remdesivir]] and [[Baricitinib]] reduced recovery time in hospitalized [[covid-19]] patients  according to '''ACTT-2 trial'''.
* Safety and efficacy of the  combination of [[Remdesivir]] and [[ interferon b-1a]] is under investigation according to '''ACTT-3 trial'''.
* Safety and efficacy of the  combination of [[Remdesivir]] and [[ interferon b-1a]] is under investigation according to '''ACTT-3 trial'''.

Revision as of 16:17, 17 September 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand, M.D.[2], Syed Hassan A. Kazmi BSc, MD [3],Sabawoon Mirwais, M.B.B.S, M.D.[4],

Overview

COVID-19 is an inflammatory hypercytokinemia disease. The aim of therapy is prevention of viral replication and controlling the inflammatory process. On February 09, 2021 FDA approved emergency use authorization of monoclonal antibodies including bamlanivimab and etesevimab for mild to moderate covid-19 patients who are high risk for progression of disease ( age > 65years, medical comorbidities).

Antiviral Agents

Remdesivir

  • Significant reduction in viral load in bronchoaleolar lavage
  • Inhibition of SARS-COV-2 replication in nasal and bronchial airway epithelial cells.
  • Remdesivir is approved by FDA on 22 October 2020 for all hospitalized adult and pediatric older than 12 years of age and weighing at least 40 kg (88 pounds).
  • Remdesivir was effective in shortening the time of recovery about 32% and survival benefit in adult hospitalized covid-19 patients according to ACTT-1 trial.[1]
  • In a Phase 3 open label randomized trial, No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID19,who were symptomatic for more than 7 days, and required oxygen support.(doi:10.1016/S1473-3099(21)00485-0)
  • The combination of Remdesivir and Baricitinib reduced recovery time in hospitalized covid-19 patients according to ACTT-2 trial.
  • Safety and efficacy of the combination of Remdesivir and interferon b-1a is under investigation according to ACTT-3 trial.
  • 5-day course of remdesivir in hospitalized patients with moderate Covid-19 had better clinical status compared with standard care at 11 days after starting the treatment.[2]
  • Remdesivir indicates in the treatment of all hospitalized adult and pediatric patients with suspected or laboratory-confirmed COVID-19 , regardless of the severity of disease according to FDA emergency use authorization (EUA) issued on 1 May 2020.
  1. Severe renal impairment (eGFR <30 ml/min)
  2. Severe hepatic dysfunction or alanin transferase (ALT)ᐳ 5-times upper limit

Favipiravir (Avigan)

Atazanavir

Umifenovir (Arbidol)

Hydroxychloroquine and Chloroquine

Clofazimine

Lopinavir-Ritonavir or kalerta

  • Lopinavir-Ritonavir Inhibits the activity of the HIV-1 protease.
  • In the Recovery Trial kaletra was not effective in reducing of mortality, duration of hospitalization or prevention of ventilation.[18]
  • In an open-label randomized controlled trial, the comparison between patients with COVID-19 received either lopinavir-ritonavir 400/100 mg, orally twice daily plus standard of care or standard care alone showed no benefit of administration of lopinavir-ritonavir.[19]
  • Only one study in Korea in the initial phase of outbreak accepted using this combination.[20]
  • Side effects: Diarrhea, nausea, asthenia

Niclosamide and Ivermectin

  • Mechanism of action is the Inhibition of binding of coronavirus onto the cells.[21]

Supportive Agents

Tocilizumab (Actemra)


  1. Hypoxia
  2. Lung infiltration on CXR
  3. High inflammatory markers (CRP>3g/dl, ferritin>400ng/dl
  4. Clinical deterioration
  1. Confirmed bacterial or fungal infection
  2. Platelet count<100000/cc
  3. Neutrophil count<2000/cc
  4. Alanin aminotrasferase or aspartat aminotransferase >5times upper limit normal

Bamlanivimab,Etesevimab

Casirivimab, Imdevimab

Sotrovimab

Corticosteroids

Dexamethasone

  1. Decreased days of intubation
  2. Decreased mortality

Methylprednisolone

  1. Controlled of hypercytokinemia
  2. Anti-inflammatory effect in superimposed infection in COVID-19
  3. Increased blood pressure when it is low
  4. Decreased risk of death in ARDS related COVID-19[34]

Inhaled corticosteroids

Inhaled corticosteroids (budesonide) may improve recovery time and reducing hospital admission or death in high risk covid-19 patients in the community. [35].

Interferon-1

Azithromycin

Vitamin C (Ascorbic Acid)

  1. Maturation of T lymphocytes and NK( natural killer) cells that are involved in the immune response to viral agents.
  2. Inhibition of reactive oxygen species (ROS) production
  3. Remodulation of the cytokine network in systemic inflammatory syndrome.
  • Study in COVID-19 patients in china showed administration of high dose IV,Vitamin C (1500mg per day) in moderate and severe cases was correlated with improvement in oxygenation indexes and recovery.[43]


Convalescent Plasma

Anticoagulation

In COVID-19 hypercoagulable state induces micro-macro-vascular thrombosis.


  • Efficacy of heparin in COVID-19 includes  : 1.anti inflammatory properties,2. prevention of viral attachment via changing in covid 19 spike protein 3.anticoagulation effect. [50]

Ibuprofen

References

  1. ↑ Beigel, John H.; Tomashek, Kay M.; Dodd, Lori E.; Mehta, Aneesh K.; Zingman, Barry S.; Kalil, Andre C.; Hohmann, Elizabeth; Chu, Helen Y.; Luetkemeyer, Annie; Kline, Susan; Lopez de Castilla, Diego; Finberg, Robert W.; Dierberg, Kerry; Tapson, Victor; Hsieh, Lanny; Patterson, Thomas F.; Paredes, Roger; Sweeney, Daniel A.; Short, William R.; Touloumi, Giota; Lye, David Chien; Ohmagari, Norio; Oh, Myoung-don; Ruiz-Palacios, Guillermo M.; Benfield, Thomas; Fätkenheuer, Gerd; Kortepeter, Mark G.; Atmar, Robert L.; Creech, C. Buddy; Lundgren, Jens; Babiker, Abdel G.; Pett, Sarah; Neaton, James D.; Burgess, Timothy H.; Bonnett, Tyler; Green, Michelle; Makowski, Mat; Osinusi, Anu; Nayak, Seema; Lane, H. Clifford (2020). "Remdesivir for the Treatment of Covid-19 — Final Report". New England Journal of Medicine. doi:10.1056/NEJMoa2007764. ISSN 0028-4793.
  2. ↑ Spinner, Christoph D.; Gottlieb, Robert L.; Criner, Gerard J.; Arribas López, José Ramón; Cattelan, Anna Maria; Soriano Viladomiu, Alex; Ogbuagu, Onyema; Malhotra, Prashant; Mullane, Kathleen M.; Castagna, Antonella; Chai, Louis Yi Ann; Roestenberg, Meta; Tsang, Owen Tak Yin; Bernasconi, Enos; Le Turnier, Paul; Chang, Shan-Chwen; SenGupta, Devi; Hyland, Robert H.; Osinusi, Anu O.; Cao, Huyen; Blair, Christiana; Wang, Hongyuan; Gaggar, Anuj; Brainard, Diana M.; McPhail, Mark J.; Bhagani, Sanjay; Ahn, Mi Young; Sanyal, Arun J.; Huhn, Gregory; Marty, Francisco M. (2020). "Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19". JAMA. 324 (11): 1048. doi:10.1001/jama.2020.16349. ISSN 0098-7484.
  3. ↑ Furuta Y, Komeno T, Nakamura T (2017). "Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase". Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. 93 (7): 449–463. doi:10.2183/pjab.93.027. PMC 5713175. PMID 28769016.
  4. ↑ De Clercq E (November 2019). "New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections". Chem Asian J. 14 (22): 3962–3968. doi:10.1002/asia.201900841. PMC 7159701 Check |pmc= value (help). PMID 31389664.
  5. ↑ Joshi, Shashank; Parkar, Jalil; Ansari, Abdul; Vora, Agam; Talwar, Deepak; Tiwaskar, Mangesh; Patil, Saiprasad; Barkate, Hanmant (2021). "Role of favipiravir in the treatment of COVID-19". International Journal of Infectious Diseases. 102: 501–508. doi:10.1016/j.ijid.2020.10.069. ISSN 1201-9712.
  6. ↑ Dabbous HM, Abd-Elsalam S, El-Sayed MH, Sherief AF, Ebeid F, El Ghafar M, Soliman S, Elbahnasawy M, Badawi R, Tageldin MA (March 2021). "Efficacy of favipiravir in COVID-19 treatment: a multi-center randomized study". Arch Virol. 166 (3): 949–954. doi:10.1007/s00705-021-04956-9. PMC 7829645 Check |pmc= value (help). PMID 33492523 Check |pmid= value (help). Vancouver style error: initials (help)
  7. ↑ 7.0 7.1 Chen, Chang; Zhang, Yi; Huang, Jianying; Yin, Ping; Cheng, Zhenshun; Wu, Jianyuan; Chen, Song; Zhang, Yongxi; Chen, Bo; Lu, Mengxin; Luo, Yongwen; Ju, Lingao; Zhang, Jingyi; Wang, Xinghuan (2020). doi:10.1101/2020.03.17.20037432. Missing or empty |title= (help)
  8. ↑ . doi:10.1101/2020.04.04.020925doi: bioRxiv preprint Check |doi= value (help). Missing or empty |title= (help)
  9. ↑ Rahmani H, Davoudi-Monfared E, Nourian A, Nabiee M, Sadeghi S, Khalili H, Abbasian L, Ghiasvand F, Seifi A, Hasannezhad M, Ghaderkhani S, Mohammadi M, Yekaninejad MS (December 2020). "Comparing outcomes of hospitalized patients with moderate and severe COVID-19 following treatment with hydroxychloroquine plus atazanavir/ritonavir". Daru. 28 (2): 625–634. doi:10.1007/s40199-020-00369-2. PMC 7453126 Check |pmc= value (help). PMID 32857301 Check |pmid= value (help).
  10. ↑ Pécheur EI, Borisevich V, Halfmann P, Morrey JD, Smee DF, Prichard M, Mire CE, Kawaoka Y, Geisbert TW, Polyak SJ (January 2016). "The Synthetic Antiviral Drug Arbidol Inhibits Globally Prevalent Pathogenic Viruses". J. Virol. 90 (6): 3086–92. doi:10.1128/JVI.02077-15. PMC 4810626. PMID 26739045.
  11. ↑ Villalaín J (July 2010). "Membranotropic effects of arbidol, a broad anti-viral molecule, on phospholipid model membranes". J Phys Chem B. 114 (25): 8544–54. doi:10.1021/jp102619w. PMID 20527735.
  12. ↑ Deng L, Li C, Zeng Q, Liu X, Li X, Zhang H, Hong Z, Xia J (July 2020). "Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study". J. Infect. 81 (1): e1–e5. doi:10.1016/j.jinf.2020.03.002. PMC 7156152 Check |pmc= value (help). PMID 32171872 Check |pmid= value (help).
  13. ↑ Huang, Dong; Yu, He; Wang, Ting; Yang, Huan; Yao, Rong; Liang, Zongan (2020). "Efficacy and safety of umifenovir for coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis". Journal of Medical Virology. 93 (1): 481–490. doi:10.1002/jmv.26256. ISSN 0146-6615.
  14. ↑ Skipper, Caleb P.; Pastick, Katelyn A.; Engen, Nicole W.; Bangdiwala, Ananta S.; Abassi, Mahsa; Lofgren, Sarah M.; Williams, Darlisha A.; Okafor, Elizabeth C.; Pullen, Matthew F.; Nicol, Melanie R.; Nascene, Alanna A.; Hullsiek, Kathy H.; Cheng, Matthew P.; Luke, Darlette; Lother, Sylvain A.; MacKenzie, Lauren J.; Drobot, Glen; Kelly, Lauren E.; Schwartz, Ilan S.; Zarychanski, Ryan; McDonald, Emily G.; Lee, Todd C.; Rajasingham, Radha; Boulware, David R. (2020). "Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19". Annals of Internal Medicine. doi:10.7326/M20-4207. ISSN 0003-4819.
  15. ↑ Rajasingham, Radha; Bangdiwala, Ananta S; Nicol, Melanie R; Skipper, Caleb P; Pastick, Katelyn A; Axelrod, Margaret L; Pullen, Matthew F; Nascene, Alanna A; Williams, Darlisha A; Engen, Nicole W; Okafor, Elizabeth C; Rini, Brian I; Mayer, Ingrid A; McDonald, Emily G; Lee, Todd C; Li, Peter; MacKenzie, Lauren J; Balko, Justin M; Dunlop, Stephen J; Hullsiek, Katherine H; Boulware, David R; Lofgren, Sarah M (2020). doi:10.1101/2020.09.18.20197327. Missing or empty |title= (help)
  16. ↑ Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ (2014). "Chloroquine is a zinc ionophore". PLoS ONE. 9 (10): e109180. doi:10.1371/journal.pone.0109180. PMC 4182877. PMID 25271834.
  17. ↑ Yuan, Shuofeng; Yin, Xin; Meng, Xiangzhi; Chan, Jasper Fuk-Woo; Ye, Zi-Wei; Riva, Laura; Pache, Lars; Chan, Chris Chun-Yiu; Lai, Pok-Man; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Lee, Andrew Chak-Yiu; Matsunaga, Naoko; Pu, Yuan; Yuen, Chun-Kit; Cao, Jianli; Liang, Ronghui; Tang, Kaiming; Sheng, Li; Du, Yushen; Xu, Wan; Lau, Chit-Ying; Sit, Ko-Yung; Au, Wing-Kuk; Wang, Runming; Zhang, Yu-Yuan; Tang, Yan-Dong; Clausen, Thomas Mandel; Pihl, Jessica; Oh, Juntaek; Sze, Kong-Hung; Zhang, Anna Jinxia; Chu, Hin; Kok, Kin-Hang; Wang, Dong; Cai, Xue-Hui; Esko, Jeffrey D.; Hung, Ivan Fan-Ngai; Li, Ronald Adolphus; Chen, Honglin; Sun, Hongzhe; Jin, Dong-Yan; Sun, Ren; Chanda, Sumit K.; Yuen, Kwok-Yung (2021). "Clofazimine broadly inhibits coronaviruses including SARS-CoV-2". Nature. doi:10.1038/s41586-021-03431-4. ISSN 0028-0836.
  18. ↑ Horby, Peter W; Mafham, Marion; Bell, Jennifer L; Linsell, Louise; Staplin, Natalie; Emberson, Jonathan; Palfreeman, Adrian; Raw, Jason; Elmahi, Einas; Prudon, Benjamin; Green, Christopher; Carley, Simon; Chadwick, David; Davies, Matthew; Wise, Matthew P; Baillie, J Kenneth; Chappell, Lucy C; Faust, Saul N; Jaki, Thomas; Jefferey, Katie; Lim, Wei Shen; Montgomery, Alan; Rowan, Kathryn; Juszczak, Edmund; Haynes, Richard; Landray, Martin J (2020). "Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial". The Lancet. 396 (10259): 1345–1352. doi:10.1016/S0140-6736(20)32013-4. ISSN 0140-6736.
  19. ↑ Cao, Bin; Wang, Yeming; Wen, Danning; Liu, Wen; Wang, Jingli; Fan, Guohui; Ruan, Lianguo; Song, Bin; Cai, Yanping; Wei, Ming; Li, Xingwang; Xia, Jiaan; Chen, Nanshan; Xiang, Jie; Yu, Ting; Bai, Tao; Xie, Xuelei; Zhang, Li; Li, Caihong; Yuan, Ye; Chen, Hua; Li, Huadong; Huang, Hanping; Tu, Shengjing; Gong, Fengyun; Liu, Ying; Wei, Yuan; Dong, Chongya; Zhou, Fei; Gu, Xiaoying; Xu, Jiuyang; Liu, Zhibo; Zhang, Yi; Li, Hui; Shang, Lianhan; Wang, Ke; Li, Kunxia; Zhou, Xia; Dong, Xuan; Qu, Zhaohui; Lu, Sixia; Hu, Xujuan; Ruan, Shunan; Luo, Shanshan; Wu, Jing; Peng, Lu; Cheng, Fang; Pan, Lihong; Zou, Jun; Jia, Chunmin; Wang, Juan; Liu, Xia; Wang, Shuzhen; Wu, Xudong; Ge, Qin; He, Jing; Zhan, Haiyan; Qiu, Fang; Guo, Li; Huang, Chaolin; Jaki, Thomas; Hayden, Frederick G.; Horby, Peter W.; Zhang, Dingyu; Wang, Chen (2020). "A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19". New England Journal of Medicine. 382 (19): 1787–1799. doi:10.1056/NEJMoa2001282. ISSN 0028-4793.
  20. ↑ Lim J, Jeon S, Shin HY, Kim MJ, Seong YM, Lee WJ, Choe KW, Kang YM, Lee B, Park SJ (February 2020). "Case of the Index Patient Who Caused Tertiary Transmission of COVID-19 Infection in Korea: the Application of Lopinavir/Ritonavir for the Treatment of COVID-19 Infected Pneumonia Monitored by Quantitative RT-PCR". J. Korean Med. Sci. 35 (6): e79. doi:10.3346/jkms.2020.35.e79. PMC 7025910 Check |pmc= value (help). PMID 32056407 Check |pmid= value (help).
  21. ↑ Wu CJ, Jan JT, Chen CM, Hsieh HP, Hwang DR, Liu HW, Liu CY, Huang HW, Chen SC, Hong CF, Lin RK, Chao YS, Hsu JT (July 2004). "Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide". Antimicrob. Agents Chemother. 48 (7): 2693–6. doi:10.1128/AAC.48.7.2693-2696.2004. PMC 434198. PMID 15215127.
  22. ↑ 22.0 22.1 Gassen NC, Niemeyer D, Muth D, Corman VM, Martinelli S, Gassen A, Hafner K, Papies J, Mösbauer K, Zellner A, Zannas AS, Herrmann A, Holsboer F, Brack-Werner R, Boshart M, Müller-Myhsok B, Drosten C, Müller MA, Rein T (December 2019). "SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection". Nat Commun. 10 (1): 5770. doi:10.1038/s41467-019-13659-4. PMC 6920372 Check |pmc= value (help). PMID 31852899.
  23. ↑ Caly, Leon; Druce, Julian D.; Catton, Mike G.; Jans, David A.; Wagstaff, Kylie M. (2020). "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro". Antiviral Research. 178: 104787. doi:10.1016/j.antiviral.2020.104787. ISSN 0166-3542.
  24. ↑ Fu B, Xu X, Wei H (April 2020). "Why tocilizumab could be an effective treatment for severe COVID-19?". J Transl Med. 18 (1): 164. doi:10.1186/s12967-020-02339-3. PMC 7154566 Check |pmc= value (help). PMID 32290839 Check |pmid= value (help).
  25. ↑ Salama, Carlos; Han, Jian; Yau, Linda; Reiss, William G.; Kramer, Benjamin; Neidhart, Jeffrey D.; Criner, Gerard J.; Kaplan-Lewis, Emma; Baden, Rachel; Pandit, Lavannya; Cameron, Miriam L.; Garcia-Diaz, Julia; Chávez, Victoria; Mekebeb-Reuter, Martha; Lima de Menezes, Ferdinando; Shah, Reena; González-Lara, Maria F.; Assman, Beverly; Freedman, Jamie; Mohan, Shalini V. (2021). "Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia". New England Journal of Medicine. 384 (1): 20–30. doi:10.1056/NEJMoa2030340. ISSN 0028-4793.
  26. ↑ Stone, John H.; Frigault, Matthew J.; Serling-Boyd, Naomi J.; Fernandes, Ana D.; Harvey, Liam; Foulkes, Andrea S.; Horick, Nora K.; Healy, Brian C.; Shah, Ruta; Bensaci, Ana Maria; Woolley, Ann E.; Nikiforow, Sarah; Lin, Nina; Sagar, Manish; Schrager, Harry; Huckins, David S.; Axelrod, Matthew; Pincus, Michael D.; Fleisher, Jorge; Sacks, Chana A.; Dougan, Michael; North, Crystal M.; Halvorsen, Yuan-Di; Thurber, Tara K.; Dagher, Zeina; Scherer, Allison; Wallwork, Rachel S.; Kim, Arthur Y.; Schoenfeld, Sara; Sen, Pritha; Neilan, Tomas G.; Perugino, Cory A.; Unizony, Sebastian H.; Collier, Deborah S.; Matza, Mark A.; Yinh, Janeth M.; Bowman, Kathryn A.; Meyerowitz, Eric; Zafar, Amna; Drobni, Zsofia D.; Bolster, Marcy B.; Kohler, Minna; D’Silva, Kristin M.; Dau, Jonathan; Lockwood, Megan M.; Cubbison, Caroline; Weber, Brittany N.; Mansour, Michael K. (2020). "Efficacy of Tocilizumab in Patients Hospitalized with Covid-19". New England Journal of Medicine. doi:10.1056/NEJMoa2028836. ISSN 0028-4793.
  27. ↑ Xu X, Han M, Li T, Sun W, Wang D, Fu B, Zhou Y, Zheng X, Yang Y, Li X, Zhang X, Pan A, Wei H (May 2020). "Effective treatment of severe COVID-19 patients with tocilizumab". Proc. Natl. Acad. Sci. U.S.A. 117 (20): 10970–10975. doi:10.1073/pnas.2005615117. PMC 7245089 Check |pmc= value (help). PMID 32350134 Check |pmid= value (help).
  28. ↑ Kewan, Tariq; Covut, Fahrettin; Al–Jaghbeer, Mohammed J.; Rose, Lori; Gopalakrishna, K.V.; Akbik, Bassel (2020). "Tocilizumab for treatment of patients with severe COVID–19: A retrospective cohort study". EClinicalMedicine: 100418. doi:10.1016/j.eclinm.2020.100418. ISSN 2589-5370.
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  35. ↑ Yu L-M et al. Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): A randomised, controlled, open-label, adaptive platform trial. Lancet 2021 Aug 10; [e-pub]. https://doi.org/10.1016/S0140-6736(21)01744-X
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  42. ↑ van Gorkom G, Klein Wolterink R, Van Elssen C, Wieten L, Germeraad W, Bos G (March 2018). "Influence of Vitamin C on Lymphocytes: An Overview". Antioxidants (Basel). 7 (3). doi:10.3390/antiox7030041. PMC 5874527. PMID 29534432. Vancouver style error: initials (help)
  43. ↑ Cheng RZ (March 2020). "Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)?". Med Drug Discov. 5: 100028. doi:10.1016/j.medidd.2020.100028. PMC 7167497 Check |pmc= value (help). PMID 32328576 Check |pmid= value (help).
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  46. ↑ 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, Xu 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 (April 2020). "Effectiveness of convalescent plasma therapy in severe COVID-19 patients". Proc. Natl. Acad. Sci. U.S.A. 117 (17): 9490–9496. doi:10.1073/pnas.2004168117. PMC 7196837 Check |pmc= value (help). PMID 32253318 Check |pmid= value (help).
  47. ↑ Tang N, Li D, Wang X, Sun Z (April 2020). "Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia". J. Thromb. Haemost. 18 (4): 844–847. doi:10.1111/jth.14768. PMC 7166509 Check |pmc= value (help). PMID 32073213 Check |pmid= value (help).
  48. ↑ Nadkarni GN, Lala A, Bagiella E, Chang HL, Moreno P, Pujadas E; et al. (2020). "Anticoagulation, Mortality, Bleeding and Pathology Among Patients Hospitalized with COVID-19: A Single Health System Study". J Am Coll Cardiol. doi:10.1016/j.jacc.2020.08.041. PMC 7449655 Check |pmc= value (help). PMID 32860872 Check |pmid= value (help).
  49. ↑ Lemos ACB, do Espírito Santo DA, Salvetti MC, Gilio RN, Agra LB, Pazin-Filho A; et al. (2020). "Therapeutic versus prophylactic anticoagulation for severe COVID-19: A randomized phase II clinical trial (HESACOVID)". Thromb Res. 196: 359–366. doi:10.1016/j.thromres.2020.09.026. PMC 7503069 Check |pmc= value (help). PMID 32977137 Check |pmid= value (help).
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