Treatment Options For Covid 19 The Reality and Challenges Shio Shin Jean Full Chapter PDF
Treatment Options For Covid 19 The Reality and Challenges Shio Shin Jean Full Chapter PDF
Treatment Options For Covid 19 The Reality and Challenges Shio Shin Jean Full Chapter PDF
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Please cite this article as: Jean S-S, Lee P-I, Hsueh P-R, Treatment options for COVID-19: the
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reserved.
1 Treatment options for COVID-19: the reality
2 and challenges
3
4 Shio-Shin Jeana,b, Ping-Ing Leec, Po-Ren Hsuehd,e*
5
a
6 Department of Emergency, School of Medicine, College of Medicine, Taipei
b
8 Department of Emergency Medicine, Department of Emergency and Critical
9 Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;
c
10 Department of Pediatrics, National Taiwan University Children’s Hospital and
d
12 Department of Laboratory Medicine, National Taiwan University Hospital,
e
14 Department of Internal Medicine, National Taiwan University Hospital,
16
21
1
22 Abstract An outbreak related to the severe acute respiratory syndrome
32 anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its
34 (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard
38 followed by 250 mg once daily on day 2-5), which showed excellent clinical
40 The roles of teicoplanin (which inhibits the viral genome exposure in cytoplasm)
2
41 and monoclonal and polyclonal antibodies in the treatment of SARS-CoV-2 are
45
50
3
51 Introduction
52 In December 2019, Wuhan city (the capital city of Hubei province, China)
56 cases have been reported and were distributed among more than half of the
57 countries of the world during a less than 6-month period (data till March 28,
58 2020).4-7 The lower respiratory tract is the primary target of the SARS-CoV-2
60 often present with a profound decrease in both CD4+ and CD8+ T-cell subsets
62 respiratory distress syndrome for about 7-10 days after the onset of COVID-19
66 infection patients did not have the prodromal symptoms of upper respiratory
4
70 chest roentgenographic abnormalities.6,11 In addition, uncertain seasonality
77 have milder disease severity than adults,1,5,8,13 the SARS-CoV-2 infection has
78 become a public health menace to people around the world presently because
84 the highest viral load (measured from posterior oropharyngeal saliva samples)
85 close to when they presented. To et al. concluded that since viral load had
86 already peaked around the time of hospital admissions, early use of potent
5
89 the roles of several drugs including antiviral agents, some antibiotics and
92
94 Remdesivir
96 infection,16 remdesivir (GS-5734; Gilead Sciences Inc., Foster City, CA, USA)
6
108 intracellular concentration (>10 μM) of active triphosphate form in peripheral
109 blood mononuclear cells for at least 24 h,20 supporting its clinical potential in
110 the treatment of human SARS-CoV-2 infection. Additionally, data on the safety
111 of remdesivir in humans are available online.21 The first COVID-19 patient in
112 the USA was successfully treated with remdesivir for the progression of
116 evaluate its efficacy in patients with SARS-CoV-2 infection since March, 2020.
117 Patients received 200 mg on day 1, followed by 100 mg once daily from day 2.
118 Despite its encouragingly high in vitro potency against SARS-CoV-2 and the
120 effects (e.g., nausea, vomiting, rectal hemorrhage, and hepatic toxicity) and
124 were shown to produce a significant reduction in pulmonary viral load (i.e., >2
7
127 observed that remdesivir displayed half-maximum effective concentrations
128 (EC50s) of 0.069 μM for SARS-CoV, and 0.074 μM for MERS-CoV in tissue
129 culture models.23 In addition, tissue culture experiments also revealed that
130 many highly divergent CoV including the endemic human CoVs (HCoV-OC43,
131 HCoV-229E) and zoonotic CoV are effectively inhibited by remdesivir within
132 the submicromolar EC50s.23,24 Of note, the similar efficacy of prophylactic and
138 this resistance also impaired the fitness of the tested CoVs and is actually
140
141 Favipiravir
142 The other RdRp inhibitor favipiravir (Fujifilm Toyama Chemical Co. Ltd, Tokyo,
144 and C viruses.26 After being converted into an active phosphoribosylated form,
8
146 RNA viruses.27 The recommended dose of favipiravir against influenza virus is
147 1600 mg administered orally twice daily on day 1, then 600 mg orally twice
148 daily on day 2-5, and 600 mg once on day 6. Recently, preliminary results of
149 clinical studies have shown favipiravir to have promising potency in treatment
150 of Chinese patients with SARS-CoV-2 infection.28 Favipiravir was approved for
151 the treatment of COVID-19 in China in March, 2020. In addition, patients with
152 COVID-19 infection are being recruited for randomized trials to evaluate the
155
156 Ribavirin
158 guanosine analogue antiviral drug that has been used to treat several viral
159 infections, including hepatitis C virus, respiratory syncytial virus (RSV), and
160 some viral hemorrhagic fevers. The in vitro antiviral activity of ribavirin against
162 has the undesirable adverse effect of reducing hemoglobin, which is harmful
164
9
165 Interferons
170
172 Lopinavir/ritonavir
173 Protease inhibitors (PIs) are important agents in the contemporary treatment of
174 patients with chronic human immunodeficiency virus (HIV) infection. In the
175 Orthocoronavirinae family, the targets of PIs are papain-like protease and
176 3C-like protease.30 The antiviral activity of lopinavir (LPV; Abbott Laboratories,
177 Lake Bluff, Illinois, US) against MERS-CoV in a tissue culture model is
180 the efficacy of prophylactic remdesivir (25 mg/kg twice a day, administered 1
10
184 observed the efficacy of remdesivir was superior to that of LPV/RTV-IFNb
185 against MERS-CoV in terms of viral load reduction and improvement in extent
188 that LPV/RTV treatment alone (400/100 mg administered orally twice daily for
190 provide benefits compared to standard care alone. Median time to clinical
191 improvement in both cases was 16 days (hazard ratio [HR], 1.31; 95%
192 confidence interval [CI], 0.95 to 1.85; P=0.09) and there was no difference in
193 the reduction of viral RNA loading for severe SARS-CoV-2 patients.32
195 deaths was observed in the group receiving LPV/RTV in the late stage of
197 Baden and Ruben (2020) and Sheahan et al. (2020) suggested that the
199 replication might be higher than the serum level.31,33 A randomized, controlled
200 open-label trial was launched in China to evaluate the efficacy of LPV/RTV
11
203 Pharmaceutica, Beerse, Belgium), also a promising PI against SARS-CoV-2 in
206 Additionally, the regimen of LPV/RTV plus ribavirin was shown to be effective
208
214 endosomal pH, which prevents virus/cell fusion. It also interferes with the
216 of chloroquine is promising (EC90 of 6.90 μM, using Vero E6 cells infected by
219 safety concerns (adverse effects on the hematologic, hepatic and renal
220 systems, QTc prolongation with ventricular dysrhythmia) and will likely result in
12
222 Hydroxychloroquine is also proposed to control the cytokine storm that
225 values: 0.72 and 5.47 μM, respectively) and has lower potential for drug-drug
234 Azithromycin (Pfizer Inc., Manhattan, New York City, NY, USA) was shown
236 thought to have good potential in preventing severe respiratory tract infections
239 followed by 250 mg per day on day 2-5) was shown to significantly reinforce
240 the efficacy of hydroxychloroquine (200 mg three times per day for 10 days) in
13
241 the treatment of 20 patients with severe COVID-19. Mean serum
243 outcome among these COVID-19 patients was thought to be due to the
249
251 The other antibiotics worth mentioning in this review are glycopeptides.
253 potently prevent the entry of Ebola envelope pseudotyped viruses into the
256 330 nM).45 Moreover, teicoplanin is able to block the MERS and SARS
258 that teicoplanin specifically inhibits the activities of host cell’s cathepsin L and
259 cathepsin B, which are responsible for cleaving the viral glycoprotein allowing
14
260 exposure of the receptor-binding domain of its core genome and subsequent
261 release into the cytoplasm of host cells.46,47 Thus, teicoplanin blocks Ebola
262 virus entry in the late endosomal pathway. These studies indicate the potential
263 role of teicoplanin and its derivatives (dalbavancin, oritavancin, and telavancin)
267
273 example, a human polyclonal antibody SAB-301 (50 mg/kg) that was
275 safe in healthy participants of a phase 1 clinical trial.49 However, Cockrell et al.
277 antibodies only provided protection against early stage disease caused by
15
279 Numerous in vitro studies have shown that the spike protein of SARS-CoV
280 is important in mediating viral entry into target cells. Furthermore, the cleavage
281 and subsequent activation of the SARS-CoV spike protein by a protease of the
282 host cell is absolutely essential for infectious viral entry.51 Type II
284 host protease that cleaves and activates the SARS-CoV spike protein in cell
285 cultures, and was thus explored as a potential antiviral agent.18 In the past
286 decade, the serine protease inhibitor camostat mesylate was shown to inhibit
290 Use of stem cells against COVID-19 has been under evaluation in China
293 was designed to inhibit the binding of interleukin-6 to its receptors, thus
296
16
298 Convalescent plasma has also been used as a last resort to improve the
299 survival rate of patients with various viral infections, such as SARS, H5N1 avian
300 influenza, pandemic 2009 influenza A H1N1 (H1N1 pdm09), and severe Ebola
301 virus infection.55,56 One possible explanation for the efficacy of convalescent
302 plasma therapy is that the immunoglobulin antibodies in the plasma of patients
303 recovering from viral infection might suppress viremia. Shen et al. (2020)
304 reported on five critically ill patients with laboratory-confirmed COVID-19 and
305 acute respiratory distress syndrome (ARDS) who received transfusion with
307 >1:1000 and neutralization titer >40). The convalescent plasma was obtained
308 from 5 patients who recovered from COVID-19 and it was administered to the
309 five enrolled patients between 10 and 22 days after admission. Antiviral agents
312 normalization of body temperature within 3 days (in 4/5 patients), decrease in
316 viral loads (became negative within 12 days) and increase in SARS-CoV-2–
17
317 specific ELISA and neutralizing antibody titers. Of the 5 patients, 3 were
318 discharged from the hospital (lengths of stay: 53, 51, and 55 days), while 2
319 were in stable condition at 37 days after transfusions.56 The authors concluded
321 infected with SARS-CoV-2, even though the sample number in this study is
322 small.56
323
325 Based on the historical records and anecdotal evidence of SARS and H1N1
328 However, clinical evidence for these treatments in the prevention of this
329 emerging viral infection is lacking.57,58 During the COVID-19 outbreak in China,
330 some traditional Chinese medicine was widely used, and the six most
18
336 Chinese medicine.57,58
337
339 The prevalence of co-infection varied among COVID-19 patients, ranging from
342 rhinovirus, coronavirus, and HIV). Influenza A virus was the commonest
350
352 medication
353 Based on the research of Yang et al. (2020),62 the most distinctive
19
355 were cerebrovascular disease and diabetes. Similar findings were also
356 observed by Guan et al. (2020);63 these patients were usually treated with ACE
358 above,5,12 SARS-CoV-2 and SARS-CoV can bind to their target cells through
359 ACE2 receptors expressed by the epithelial cells of lung, intestine and
362 Additionally, despite conflicting advice from the US Food and Drug
365 increased ACE2 receptors.66 For critically ill adults with COVID-19 who
366 develop fever, acetaminophen might be a better choice for temperature control
369 case-fatality risk (HR, 0.38; 95% CI, 0.20-0.72).68 However, the administered
371 of supporting evidence, some critical care experts advocate the use of
372 low-dose corticosteroid therapy in adults with COVID-19 and refractory shock
20
374 strategy).68
376 anticoagulant therapy with heparin (mainly with low molecular weight heparin)
377 was associated with better prognosis in severe COVID-19 patients. The
378 28-day mortality of heparin users was lower than that of non-users among
380 P=0.029), or D-dimer > 6-fold the upper limit of normal (32.8% vs. 52.4%,
381 P=0.017).69
382 Finally, high ACE2 activity is associated with reduced severity of ARDS
383 among patients with lower respiratory tract infection caused by RSV.70 Fedson
384 et al. (2016, 2020) observed that statins target the host response to infection
385 (endothelial dysfunction) rather than the virus itself, and suggested that
386 combination therapy with ARB and statins might accelerate a return to
388
389 Conclusions
390 In summary, we are facing a terrible virus with greater infectivity than the
392 specific anti-SARS-CoV-2 drug regimen to treat critically ill patients. Most of
21
393 the potential drugs for treatment of COVID-19 are being investigated for safety
394 and efficacy against SARS-CoV-2. Remdesivir is the most promising agent. In
397 patients. For patients with SARS-CoV-2 infection, ACE inhibitor and ARB need
399 be a safer agent for treating fever in COVID-19 patients. Finally, low-dose
402
405 Funding
407
22
408 References
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35
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660 71. Fedson DS. Treating the host response to emerging virus diseases:
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666
36
667 Table 1 Mechanisms of action and targets of potential treatment agents for SARS-CoV-2 infections
37
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CHAPTER I
THE RISE OF THE 17TH LIGHT DRAGOONS, 1759
Captains.
Franklin Kirby 4th Nov.
Samuel Birch 5th „
Martin Basil 6th „
Edward Lascelles 7th „
John Burton 7th „
Samuel Townshend 8th „
Lieutenants.
Thomas Lee 4th Nov.
William Green 5th „
Joseph Hall 6th „
Henry Wallop 7th „
Henry Cope 7th „
Yelverton Peyton 8th „
Cornets.
Robert Archdall 4th Nov.
Henry Bishop 5th „
Joseph Stopford 6th „
Henry Crofton 7th „
Joseph Moxham 7th „
Daniel Brown 8th „
Adjutant.—Richard Westbury.
Surgeon.—John Francis.
CHAPTER II
THE MAKING OF THE 17TH LIGHT DRAGOONS
Nor was even this all, for we find (though without mention of their
price) that a pair of checked sleeves for every man, and a powder
bag with two puffs for every two men had likewise to be supplied
from the same slender pittance.
Turning next from the man himself to his horse, his arms, and
accoutrements, we discover yet further charges against his purse,
thus—
Horse-picker and turnscrew £0 0 2
Worm and oil-bottle 0 0 3½
Goatskin holster tops 0 1 6
Curry-comb and brush 0 2 3
Mane comb and sponge 0 0 8
Horse-cloth 0 4 9
Snaffle watering bridle 0 2 0
£0 11 7½