Treatment options for COVID-19: The

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Journal Pre-proof

Treatment options for COVID-19: the reality and challenges

Shio-Shin Jean, Ping-Ing Lee, Po-Ren Hsueh

PII: S1684-1182(20)30094-3
DOI: https://doi.org/10.1016/j.jmii.2020.03.034
Reference: JMII 1222

To appear in: Journal of Microbiology, Immunology and Infection

Received Date: 30 March 2020

Accepted Date: 31 March 2020

Please cite this article as: Jean S-S, Lee P-I, Hsueh P-R, Treatment options for COVID-19: the
reality and challenges, Journal of Microbiology, Immunology and Infection, https://doi.org/10.1016/
j.jmii.2020.03.034.

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Copyright © 2020, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. All rights
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

7 Medical University, Taipei, Taiwan;

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

11 National Taiwan University College of Medicine, Taipei, Taiwan;

d
12 Department of Laboratory Medicine, National Taiwan University Hospital,

13 National Taiwan University College of Medicine, Taipei, Taiwan;

e
14 Department of Internal Medicine, National Taiwan University Hospital,

15 National Taiwan University College of Medicine, Taipei, Taiwan

16

17 *Corresponding author. Departments of Laboratory Medicine and Internal

18 Medicine, National Taiwan University Hospital, National Taiwan University

19 College of Medicine, No. 7 Chung-Shan South Road, Taipei, 100, Taiwan.

20 E-mail address: hsporen@ntu.edu.tw (P.-R. Hsueh).

21

1
22 Abstract An outbreak related to the severe acute respiratory syndrome

23 coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December

24 2019. An extremely high potential for dissemination resulted in the global

25 coronavirus disease 2019 (COVID-19) pandemic in 2020. Despite the

26 worsening trends of COVID-19, no drugs are validated to have significant

27 efficacy in clinical treatment of COVID-19 patients in large-scale studies.

28 Remdesivir is considered the most promising antiviral agent; it works by

29 inhibiting the activity of RNA-dependent RNA polymerase (RdRp). A

30 large-scale study investigating the clinical efficacy of remdesivir (200 mg on

31 day 1, followed by 100 mg once daily) is on-going. The other excellent

32 anti-influenza RdRp inhibitor favipiravir is also being clinically evaluated for its

33 efficacy in COVID-19 patients. The protease inhibitor lopinavir/ritonavir

34 (LPV/RTV) alone is not shown to provide better antiviral efficacy than standard

35 care. However, the regimen of LPV/RTV plus ribavirin was shown to be

36 effective against SARS-CoV in vitro. Another promising alternative is

37 hydroxychloroquine (200 mg thrice daily) plus azithromycin (500 mg on day 1,

38 followed by 250 mg once daily on day 2-5), which showed excellent clinical

39 efficacy on Chinese COVID-19 patients and anti-SARS-CoV-2 potency in vitro.

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

42 under investigation. Avoiding the prescription of non-steroidal

43 anti-inflammatory drugs, angiotensin converting enzyme inhibitors, or

44 angiotensin II type I receptor blockers is advised for COVID-19 patients.

45

46 KEYWORDS: Severe acute respiratory syndrome coronavirus 2

47 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), remdesivir,

48 hydroxychloroquine, non-steroidal anti-inflammatory drugs, angiotensin

49 converting enzyme inhibitors.

50

3
51 Introduction

52 In December 2019, Wuhan city (the capital city of Hubei province, China)

53 experienced a major outbreak caused by a novel coronavirus. This outbreak

54 was found to be caused by a novel virus, the severe acute respiratory

55 syndrome coronavirus 2 (SARS-CoV-2).1-3 Numerous clinical SARS-Co-2

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

59 infection. It is noteworthy that adults with coronavirus disease 2019 (COVID-19)

60 often present with a profound decrease in both CD4+ and CD8+ T-cell subsets

61 at the early stage of this disease.1,8 Subsequently, patients suffered acute

62 respiratory distress syndrome for about 7-10 days after the onset of COVID-19

63 due to rapid viral replication, a stormy increase of pro-inflammatory cytokines

64 as well as chemokine response, and inflammatory cell infiltrates.8,9

65 Nevertheless, contrary to the SARS cases in 2003,10 some SARS-CoV-2

66 infection patients did not have the prodromal symptoms of upper respiratory

67 tract infection (e.g., cough, sore throat, rhinorrhea), viremia-associated

68 laboratory abnormalities (e.g., leukopenia, lymphopenia, anemia, elevation of

69 liver enzymes and lactic dehydrogenase), or initial evidence of diagnostic

4
70 chest roentgenographic abnormalities.6,11 In addition, uncertain seasonality

71 and the incubation period of SARS-CoV-2 infection oscillating between 2 and

72 14 days make it remarkably difficult to achieve early diagnosis and initiate

73 treatment on time.5,9 Previous studies demonstrated that human

74 coronavirus-NL63 (HCoV-NL63) is able to use angiotensin-converting

75 enzyme-2 (ACE2) as a cell receptor in humans.5,12 Although children are

76 considered to be significantly less susceptible to HCoV-NL63 infection and

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

79 of high transmission potential and unpredictability of disease progression.14 In

80 order to contain SARS-CoV-2 spread among community residents, stringent

81 infection control measures were implemented by the Centers for Disease

82 Control (CDC) and Prevention of Taiwan since February, 2020. According to

83 an investigation by To et al. (2020),15 patients with SARS-CoV infection had

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

87 antiviral agents might be beneficial in controlling COVID-19 severity.15

88 However, standard treatment against COVID-19 is presently lacking. Herein,

5
 89 the roles of several drugs including antiviral agents, some antibiotics and

90 anti-inflammatory agents have been reviewed to explore their efficacy in

91 combating the SARS-CoV-2 (data until March 28, 2020).

92

93 RNA-dependent RNA polymerase inhibitors

94 Remdesivir

95 Among several potential drugs tested for efficacy in treatment of SARS-CoV-2

96 infection,16 remdesivir (GS-5734; Gilead Sciences Inc., Foster City, CA, USA)

97 is shown to be the most promising and hopeful anti-viral therapeutic. It works

98 by targeting viral RNA-dependent RNA polymerase (RdRp) while evading

99 proofreading by viral exoribonuclease,17 resulting in premature termination of

100 viral RNA transcription. Unlike other nucleotide analogues, remdesivir is a

101 phosphoramidate prodrug with broad-spectrum activity against many virus

102 families, including Filoviridae, Paramyxoviridae, Pneumoviridae, and

103 Orthocoronavirinae (such as pathogenic SARS-CoV and Middle East

104 respiratory syndrome coronavirus [MERS-CoV]).18,19

105 Information regarding the pharmacokinetics of remdesivir in humans is not

106 available. Nevertheless, valuable data from rhesus monkeys revealed an

107 intravenous 10 mg/kg dose of remdesivir could lead to a remarkably high

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

113 pneumonia on day 7 of hospitalization in January, 2020.4 Phase 3 human trials

114 (ClinicalTrials.gov Identifier: NCT04292899 and NCT04292730, for severe and

115 moderate adult SARS-CoV-2 cases, respectively) have been initiated to

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

119 clinical success in treatment of COVID-19,4,18 uncertainties about adverse

120 effects (e.g., nausea, vomiting, rectal hemorrhage, and hepatic toxicity) and

121 clinical efficacy of remdesivir have been reported recently.22

122 In a mouse model investigating the pathogenesis of SARS-CoV,

123 prophylactic and early therapeutic post-exposure administration of remdesivir

124 were shown to produce a significant reduction in pulmonary viral load (i.e., >2

125 orders of magnitude on day 2-5 post-infection), mitigate disease progression

126 and prominently improve respiration function.18 Furthermore, Brown et al.

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

133 therapeutic remdesivir treatment (24 h prior to inoculation, and 12 h

134 post-inoculation, respectively) was also seen in the context of a non-human

135 primate (rhesus macaque) model of MERS-CoV infection.25 Although two

136 amino acid substitutions (F476L, V553L) in the non-structural protein 12

137 polymerase were demonstrated to confer low-level resistance to remdesivir,

138 this resistance also impaired the fitness of the tested CoVs and is actually

139 difficult to select.17

140

141 Favipiravir

142 The other RdRp inhibitor favipiravir (Fujifilm Toyama Chemical Co. Ltd, Tokyo,

143 Japan) is known to be active in vitro against oseltamivir-resistant influenza A, B,

144 and C viruses.26 After being converted into an active phosphoribosylated form,

145 favipiravir is easily recognized as a substrate of viral RNA polymerase in many

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

153 efficacy of favipiravir plus interferon-α (ChiCTR2000029600) and favipiravir

154 plus baloxavir marboxil (ChiCTR2000029544).

155

156 Ribavirin

157 Ribavirin (Bausch Health Companies Inc., Bridgewater, NJ, USA) is a

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

161 SARS-CoV was estimated to be at a concentration of 50 μg/mL.29 However, it

162 has the undesirable adverse effect of reducing hemoglobin, which is harmful

163 for patients in respiratory distress.19

164

9
165 Interferons

166 Treatment with interferon β (IFNb)-1b (Bayer Pharmaceutical Co., Leverkusen,

167 Germany), an immunomodulatory agent, was shown to result in clinical

168 improvement among MERS-CoV-infected common marmosets, but the

169 benefits of IFNb-1b for SARS patients remains uncertain.29,30

170

171 Protease inhibitors

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

178 controversial, despite a good effect in mitigating disease progression in

179 MERS-CoV-infected marmosets.29 Of note, Sheahan et al. (2020) compared

180 the efficacy of prophylactic remdesivir (25 mg/kg twice a day, administered 1

181 day prior to infection) as well as therapeutic remdesivir with that of

182 LPV/ritonavir (RTV, used to prolong the LPV’s half-life)-IFNb combination

183 therapy in a humanized transgenic mouse MERS-CoV infection model. They

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

186 of pathologic change in lung tissue.31 In addition to gastrointestinal adverse

187 effects (nausea, vomiting, and diarrhea) induced by LPV/RTV, it is noteworthy

188 that LPV/RTV treatment alone (400/100 mg administered orally twice daily for

189 14 days; Chinese Clinical Trial Register number, ChiCTR2000029308) failed to

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

194 Despite discouraging results, it is intriguing that a slightly lower number of

195 deaths was observed in the group receiving LPV/RTV in the late stage of

196 SARS-CoV-2 infection compared with the standard-care group. Moreover,

197 Baden and Ruben (2020) and Sheahan et al. (2020) suggested that the

198 LPV/RTV concentration necessary to inhibit pulmonary SARS-CoV-2

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

201 (200/50 mg twice a day) among hospitalized patients with SARS-CoV-2

202 infections in 2020 (ChiCTR2000029308). The role of darunavir (Janssen

11
203 Pharmaceutica, Beerse, Belgium), also a promising PI against SARS-CoV-2 in

204 vitro, needs to be further evaluated.34 Ribavirin in combination with interferon-α

205 2b was shown to be active against MERS-CoV in a rhesus macaque model.35

206 Additionally, the regimen of LPV/RTV plus ribavirin was shown to be effective

207 against SARS-CoV in patients and in tissue culture.36

208

209 Chloroquine, hydroxychloroquine, and azithromycin

210 Chloroquine is active against malaria as well as autoimmune diseases (such

211 as rheumatoid arthritis [RA], lupus erythematosus). It was recently reported as

212 a potential broad-spectrum antiviral drug for treatment of viruses such as

213 influenza H5N1 in an animal model.37 Chloroquine was shown to increase

214 endosomal pH, which prevents virus/cell fusion. It also interferes with the

215 glycosylation of cellular receptors of SARS-CoV.38,39 Although the in vitro data

216 of chloroquine is promising (EC90 of 6.90 μM, using Vero E6 cells infected by

217 SARS-CoV-2), an extensive prescription of chloroquine in clinical treatment of

218 SARS-CoV-2 is a completely off-label use. It is not recommended in light of

219 safety concerns (adverse effects on the hematologic, hepatic and renal

220 systems, QTc prolongation with ventricular dysrhythmia) and will likely result in

221 a major shortage of anti-malarial armamentaria.40

12
222 Hydroxychloroquine is also proposed to control the cytokine storm that

223 occurs in critically ill late phase SARS-CoV-2 infected patients.41

224 Hydroxychloroquine is significantly more potent than chloroquine in vitro (EC50

225 values: 0.72 and 5.47 μM, respectively) and has lower potential for drug-drug

226 interactions than chloroquine. Pharmacokinetic models demonstrate that

227 hydroxychloroquine sulfate is significant superior (5 days in advance) to

228 chloroquine phosphate in inhibiting SARS-CoV-2 in vitro.41 The Taiwan CDC

229 declared hydroxychloroquine as an important anti-SARS-CoV-2 agent on 26

230 March, 2020. Of note, patients with retinopathy, deficiency of

231 glucose-6-phosphatase, QTc prolongation in electrocardiograms, history of

232 allergy to hydroxychloroquine or who are pregnant or breastfeeding are

233 contraindicated for receiving hydroxychloroquine therapy.42

234 Azithromycin (Pfizer Inc., Manhattan, New York City, NY, USA) was shown

235 to be active in vitro against Ebola viruses.43 Furthermore, azithromycin is

236 thought to have good potential in preventing severe respiratory tract infections

237 among pre-school children when it is administrated to patients suffering viral

238 infection.44 According to one recent study, azithromycin (500 mg on day 1,

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

242 hydroxychloroquine concentration was 0.46±0.20 µg/mL. The good clinical

243 outcome among these COVID-19 patients was thought to be due to the

244 excellent efficiency of virus elimination after administration of this combination

245 therapy.42 Consequently, the regimen of hydroxychloroquine in combination

246 with azithromycin might be a promising alternative to remdesivir in the

247 treatment of patients with SARS-CoV-2 infection in the future. Nevertheless,

248 the possibility of complicated QTc prolongation should be concerned.

249

250 Teicoplanin and other glycopeptides

251 The other antibiotics worth mentioning in this review are glycopeptides.

252 Teicoplanin (Sanofi Pharmaceuticals, Paris, France) was demonstrated to

253 potently prevent the entry of Ebola envelope pseudotyped viruses into the

254 cytoplasm, and also has an inhibitory effect on transcription- as well as

255 replication-competent virus-like particles in the low micromolar range (IC50,

256 330 nM).45 Moreover, teicoplanin is able to block the MERS and SARS

257 envelope pseudotyped viruses as well.45 Mechanistic investigations revealed

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)

264 as novel inhibitors of cathepsin L-dependent viruses.

265 A brief summary of the mechanism of action and targets of potential

266 antimicrobial agents against SARS-CoV-2 is shown in Table 1.

267

268 Monoclonal or polyclonal antibodies and other therapies

269 Monoclonal or polyclonal antibodies have been suggested as prophylactic and

270 therapeutic tools (targeting hemagglutinin binding) against some viral

271 infections, such as influenza.48 Current efforts in developing monoclonal and

272 polyclonal antibodies against coronaviruses mainly target MERS-CoV.18 For

273 example, a human polyclonal antibody SAB-301 (50 mg/kg) that was

274 generated in transchromosomic cattle was observed to be well tolerated and

275 safe in healthy participants of a phase 1 clinical trial.49 However, Cockrell et al.

276 (2016) observed that immune-based therapy with human monoclonal

277 antibodies only provided protection against early stage disease caused by

278 MERS-CoV in mouse models.19,50

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

283 transmembrane serine protease TMPRSS2 was suggested to be an important

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

287 the enzymatic activity of TMPRSS2.52 Additionally, the cysteine PI K11777

288 showed promising potency in inhibiting MERS-CoV and SARS-CoV replication

289 within the submicromolar range.53

290 Use of stem cells against COVID-19 has been under evaluation in China

291 recently. Additionally, tocilizumab (Roche Pharmaceuticals, Basel, Switzerland)

292 is a monoclonal antibody that is used in the treatment of RA exacerbation. It

293 was designed to inhibit the binding of interleukin-6 to its receptors, thus

294 alleviating cytokine release syndrome. Currently, it is also being investigated

295 for treatment of COVID-19.54

296

297 Convalescent plasma

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

306 convalescent plasma with a SARS-CoV-2–specific antibody (binding titer

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

310 and methylprednisolone were also administered. Following plasma

311 transfusions, improvements in clinical condition were observed, including

312 normalization of body temperature within 3 days (in 4/5 patients), decrease in

313 Sequential Organ Failure Assessment score, rise in PaO2/FiO2, resolution of

314 ARDS (4 patients at 12 days after transfusion), a success of weaning from

315 mechanical ventilation (3 patients within 2 weeks of treatment), and decline 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

320 that use of convalescent plasma transfusion is beneficial among patients

321 infected with SARS-CoV-2, even though the sample number in this study is

322 small.56

323

324 Herbal medications

325 Based on the historical records and anecdotal evidence of SARS and H1N1

326 pdm09 prevention, Chinese herbal drugs were also considered as an

327 alternative approach for prevention of COVID-19 in high-risk populations.

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

331 commonly used herbal medicines were Astragali Radix (Huangqi),

332 Glycyrrhizae Radix Et Rhizoma (Gancao), Saposhnikoviae Radix (Fangfeng),

333 Atractylodis Macrocephalae Rhizoma (Baizhu), Lonicerae Japonicae Flos and

334 Fructus forsythia (Lianqiao). However, rigorous clinical trials on large

335 populations should be conducted to confirm the potential preventive effect of

18
336 Chinese medicine.57,58

337

338 Antimicrobial agents for potential co-infection

339 The prevalence of co-infection varied among COVID-19 patients, ranging from

340 0% to 50% among non-survivors. Reported co-pathogens included bacteria,

341 such as Mycoplasma pneumoniae, Candida species, and viruses (influenza,

342 rhinovirus, coronavirus, and HIV). Influenza A virus was the commonest

343 co-infective virus.59 Co-administration of anti-influenza agents and

344 anti-bacterial agents in patients with COVID-19 pneumonia was common.59

345 Consequently, a cautious prescription of effective antibiotic(s) covering

346 Staphylococcus aureus (including methicillin-resistant S. aureus),

347 multidrug-resistant Streptococcus pneumoniae, Klebsiella pneumoniae, and

348 Pseudomonas aeruginosa as well as Acinetobacter baumannii species for

349 patients undergoing long hospitalization (> 6 days) is advised.60,61

350

351 Other considerations and precautions regarding concomitant

352 medication

353 Based on the research of Yang et al. (2020),62 the most distinctive

354 comorbidities among the non-survivors of COVID-19 in intensive care units

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

357 inhibitors or angiotensin II type I receptor blockers (ARB). As mentioned

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

360 kidney.64 Consequently, careful administration of an ACE inhibitor or ARB for

361 patients with SARS-CoV infection in the absence of ARDS is advised.

362 Additionally, despite conflicting advice from the US Food and Drug

363 Administration,65 the use of non-steroidal anti-inflammatory drugs (NSAIDs),

364 such as ibuprofen, was thought to be likely to result in an induction of

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

367 than NSAIDs.67 Of note, according to a study by Wu et al. (2020), treatment of

368 COVID-19 patients with methylprednisolone was shown to decrease the

369 case-fatality risk (HR, 0.38; 95% CI, 0.20-0.72).68 However, the administered

370 dose of methylprednisolone is not specified in that investigation. Despite a lack

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

373 (e.g., intravenous hydrocortisone 200 mg per day, as a “shock-reversal”

20
374 strategy).68

375 Moreover, a recent report by Tang et al. (2020) demonstrated that

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

379 patients with sepsis-induced coagulopathy scores ≥4 (40.0% vs. 64.2%,

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

387 homeostasis, allowing patients to recover on their own.71,72

388

389 Conclusions

390 In summary, we are facing a terrible virus with greater infectivity than the

391 SARS-CoV pandemic of 2003. There is presently no vaccine or documented

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

395 addition, favipiravir and combination therapy with hydroxychloroquine plus

396 azithromycin appear to be acceptable alternatives for treatment of COVID-19

397 patients. For patients with SARS-CoV-2 infection, ACE inhibitor and ARB need

398 to be prescribed with caution. Compared with NSAIDs, acetaminophen might

399 be a safer agent for treating fever in COVID-19 patients. Finally, low-dose

400 steroid (hydrocortisone) might be prescribed for treatment of refractory shock

401 in patients with COVID-19.

402

403 Statement of interests

404 The authors declare that they have no conflicts of interest.

405 Funding

406 No external funding.

407

22
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666

36
667 Table 1 Mechanisms of action and targets of potential treatment agents for SARS-CoV-2 infections

Mechanism of action and targets Drugs

Inhibition of the RNA-dependent RNA polymerase Remdesivir
Favipiravir
Ribavirin
Inhibition of spike protein on SARS-CoV-2 (non-endosomal pathway) TMPRSS2 inhibitor (camostat mesylate)
Inhibition of endosomal acidification (early endosomal pathway) Chloroquine, hydroxychloroquine
(azithromycin is reported to greatly enhance the
anti-SARS-CoV-2 activity of hydroxychloroquine)
Inhibition of viral exocytosis Interferon-α 2a
Interferon-β 1b
Inhibition of papain-like protease and 3C-like protease Lopinavir/ritonavir
Inhibition of cathepsin L and cathepsin B in host cells (late endosomal Teicoplanin (other glycopeptides including dalbavancin,
pathway) oritavancin, and telavancin)
Enhancement of the anti-SARS-CoV-2 activity of hydroxychloroquine Azithromycin
668

37
Another random document with
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 CHAPTER I
THE RISE OF THE 17TH LIGHT DRAGOONS, 1759

The British Cavalry Soldier and the British

Cavalry Regiment, such as we now know them, 1645.
may be said to date from 1645, that being the year
in which the Parliamentary Army, then engaged in fighting against
King Charles the First, was finally remodelled. At the outbreak of the
war the Parliamentary cavalry was organised in seventy-five troops
of horse and five of dragoons: the Captain of the 67th troop of horse
was Oliver Cromwell. In the winter of 1642–43 Captain Cromwell
was promoted to be Colonel, and entrusted with the task of raising a
regiment of horse. This duty he fulfilled after a fashion peculiarly his
own. Hitherto the Parliamentary horse had been little better than a lot
of half-trained yeomen: Colonel Cromwell took the trouble to make
his men into disciplined cavalry soldiers. Moreover, he raised not one
regiment, but two, which soon made a mark by their superior
discipline and efficiency, and finally at the battle of Marston Moor
defeated the hitherto invincible cavalry of the Royalists. After that
battle Prince Rupert, the Royalist cavalry leader, gave Colonel
Cromwell the nickname of Ironside; the name was passed on to his
regiments, which grew to be known no longer as Cromwell’s, but as
Ironside’s.
In 1645, when the army was remodelled, these two famous
regiments were taken as the pattern for the English cavalry; and
having been blent into one, appear at the head of the list as Sir
Thomas Fairfax’s Regiment of Horse. Fairfax was General-in-Chief,
and his appointment to the colonelcy was of course a compliment to
the regiment. Besides Fairfax’s there were ten other regiments of
horse, each consisting of six troops of 100 men apiece, including
three corporals and two trumpeters. As the field-officers in those
days had each a troop of his own, the full establishment of the
regiments was 1 colonel, 1 major, 4 captains, 6 lieutenants, 6
cornets, 6 quartermasters. Such was the origin of the British Cavalry
Regiment.
 The troopers, like every other man in this remodelled army, wore
scarlet coats faced with their Colonel’s colours—blue in the case of
Fairfax. They were equipped with an iron cuirass and an iron helmet,
armed with a brace of pistols and a long straight sword, and
mounted on horses mostly under fifteen hands in height. For drill in
the field they were formed in five ranks, with six feet (one horse’s
length in those days), both of interval and distance, between ranks
and files, so that the whole troop could take ground to flanks or rear
by the simple words, “To your right (or left) turn;” “To your right (or
left) about turn.” Thus, as a rule, every horse turned on his own
ground, and the troop was rarely wheeled entire: if the latter course
were necessary, ranks and files were closed up till the men stood
knee to knee, and the horses nose to croup. This formation
deservedly bore the name of “close order.” For increasing the front
the order was, “To the right (or left) double your ranks,” which
brought the men of the second and fourth ranks into the intervals of
the first and third, leaving the fifth rank untouched. To diminish the
front the order was: “To the right (or left) double your files,” which
doubled the depth of the files from five to ten in the same way as
infantry files are now doubled at the word, “Form fours.”
The principal weapons of the cavalry soldiers were his firearms,
generally pistols, but sometimes a carbine. The lance, which had
formerly been the favourite weapon, at Crecy for instance, was
utterly out of fashion in Cromwell’s time, and never employed when
any other arm was procurable. Firearms were the rage of the day,
and governed the whole system of cavalry attack. Thus in action the
front rank fired its two pistols, and filed away to load again in the
rear, while the second and third ranks came up and did likewise. If
the word were given to charge, the men advanced to the charge
pistol in hand, fired, threw it in the enemy’s face, and then fell in with
the sword. But though there was a very elaborate exercise for
carbine and pistol, there was no such thing as sword exercise.
Moreover, though the whole system of drill was difficult, and
required perfection of training in horse and man, yet there was no
such thing as a regular riding-school. If a troop horse was a kicker a
bell was placed on his crupper to warn men to keep clear of his
heels. If he were a jibber the following were the instructions given for
his cure:—
“If your horse be resty so as he cannot be put forwards then let
one take a cat tied by the tail to a long pole, and when he [the horse]
goes backward, thrust the cat within his tail where she may claw him,
and forget not to threaten your horse with a terrible noise. Or
otherwise, take a hedgehog and tie him strait by one of his feet to
the horse’s tail, so that he [the hedgehog] may squeal and prick
him.”
For the rest, certain peculiarities should be noted which
distinguish cavalry from infantry. In the first place, though every troop
and every company had a standard of its own, such standard was
called in the cavalry a Cornet, and in the infantry an Ensign, and
gave in each case its name to the junior subaltern whose duty it was
to carry it. In the second place there were no sergeants in old days
except in the infantry, the non-commissioned officers of cavalry being
corporals only. In the third place, the use of a wind instrument for
making signals was confined to the cavalry, which used the trumpet;
the infantry as yet had no bugle, but only the drum. There were
originally but six trumpet-calls, all known by foreign names; of which
names one (Butte sella or Boute selle) still survives in the corrupted
form, “Boots and saddles.”
How then have these minor distinctions which formerly separated
cavalry from infantry so utterly disappeared? Through what channel
did the two branches of the service contrive to meet? The answer is,
through the dragoons. Dragoons were originally mounted infantry
pure and simple. Those of the Army of 1645 were organised in ten
companies, each 100 men strong. They were armed like infantry and
drilled like infantry; they followed an ensign and not a cornet; they
obeyed, not a trumpet, but a drum. True, they were mounted, but on
inferior horses, and for the object of swifter mobility only; for they
always fought on foot, dismounting nine men out of ten for action,
and linking the horses by the rude process of throwing each animal’s
bridle over the head of the horse standing next to it in the ranks.
Such were the two branches of the mounted service in the first
British Army.
 A century passes, and we find Great Britain
again torn by internal strife in the shape of the 1745.
Scotch rebellion. Glancing at the list of the British
cavalry regiments at this period we find them still divided into horse
and dragoons; but the dragoons are in decided preponderance, and
both branches unmistakably “heavy.” A patriotic Englishman, the
Duke of Kingston, observing this latter failing, raised a regiment of
Light Horse (the first ever seen in England) at his own expense, in
imitation of the Hussars of foreign countries. Thus the Civil War of
1745 called into existence the only arm of the military service which
had been left uncreate by the great rebellion of 1642–48. Before
leaving this Scotch rebellion of 1745, let us remark that there took
part in the suppression thereof a young ensign of the 47th Foot,
named John Hale—a mere boy of seventeen, it is true, but a
promising officer, of whom we shall hear more.
The Scotch rebellion over, the Duke of Kingston’s Light Horse
were disbanded and re-established forthwith as the Duke of
Cumberland’s own, a delicate compliment to their distinguished
service. As such they fought in Flanders in 1747, but were finally
disbanded in the following year. For seven years after the British
Army possessed no Light Cavalry, until at the end of 1755 a single
troop of Light Dragoons—3 officers and 65 men strong—was added
to each of the eleven cavalry regiments on the British establishment,
viz., the 1st, 2nd, and 3rd Dragoon Guards, and the 1st, 2nd, 3rd,
4th, 6th, 7th, 10th, and 11th Dragoons. These light dragoons were
armed with carbine and bayonet and a single pistol, the second
holster being filled (sufficiently filled, one must conclude) with an
axe, a hedging-bill, and a spade. Their shoulder-belts were provided
with a swivel to which the carbine could be sprung; for these light
troops were expected to do a deal of firing from the saddle. Their
main distinction of dress was that they wore not hats like the rest of
the army, but helmets—helmets of strong black jacked leather with
bars down the sides and a brass comb on the top. The front of the
helmet was red, ornamented with the royal cypher and the
regimental number in brass; and at the back of the comb was a tuft
of horse-hair, half coloured red for the King, and half of the hue of
the regimental facings for the regiment. The Light Dragoon-horse,
we learn, was of the “nag or hunter kind,” standing from 14.3 to 15.1,
for he was not expected to carry so heavy a man nor such cumbrous
saddlery as the Heavy Dragoon-horse. Of this latter we can only say
that he was a most ponderous animal, with a character of his own,
known as the “true dragoon mould, short-backed, well-coupled,
buttocked, quartered, forehanded, and limbed,”—all of which
qualities had to be purchased for twenty guineas. At this time, and
until 1764, all troop horses were docked so short that they can hardly
be said to have kept any tail at all.
In the year 1758 nine of these eleven light troops took part in an
expedition to the coast of France, England having two years before
allied herself with Prussia against France for the great struggle
known as the Seven Years’ War. So eminent was
the service which they rendered, that in March 1759.
1759, King George II. decided to raise an entire
regiment of Light Dragoons. On the 10th of March, accordingly, the
first regiment was raised by General Elliott and numbered the 15th.
The Major of this regiment, whom we shall meet again as Brigadier
of cavalry in America, was William Erskine. On the 4th August
another regiment of Light Dragoons was raised by Colonel
Burgoyne, and numbered the 16th. We shall see the 16th
distinguished and Burgoyne disgraced before twenty years are past.
And while these two first Light Dragoon regiments are a-forming,
let us glance across the water to Canada, where English troops are
fighting the French, and seem likely to take the country from them.
Among other regiments the 47th Foot is there, commanded (since
March 1758) by Colonel John Hale, the man whom we saw fighting
in Scotland as an ensign fourteen years ago. Within the past year he
has served with credit under General Amherst at the capture of Cape
Breton and Louisburg, and in these days of August, while Burgoyne
is raising his regiment, he is before Quebec with General Wolfe.
Three months more pass away, and on the 13th of October Colonel
John Hale suddenly arrives in London. He is the bearer of
despatches which are to set all England aflame with pride and
sorrow; for on the 13th of September was fought the battle on the
plains of Abraham which decided the capture of Quebec and the
conquest of Canada. General Wolfe fell at the head of the 28th
Regiment in the moment of victory; and Colonel Hale, who took a
brilliant share in the action at the head of the 47th, has been
selected to carry the great news to the King. Colonel Hale was well
received; the better for that Wolfe’s last despatches, written but four
days before the battle, had been marked by a tone of deep
despondency; and, we cannot doubt, began to wonder what would
be his reward. He did not wonder for long.
Very shortly after Hale’s arrival the King reviewed the 15th Light
Dragoons, and was so well pleased with their appearance that he
resolved to raise five more such regiments, to be numbered the 17th
to the 21st.

The raising of the first of these regiments, that now known to us

as the Seventeenth Lancers, was intrusted to Colonel John Hale,
who received his commission for the purpose on the 7th November.
For the time, however, the regiment was known as the Eighteenth,
for what reason it is a little difficult to understand; since the apology
for a corps which received the number Seventeen was not raised
until a full month later (December 19th). As we shall presently see,
this matter of the number appears to have caused some
heartburning, until Lord Aberdour’s corps, which had usurped the
rank of Seventeenth, was finally disbanded, and thus yielded to
Hale’s its proper precedence.
On the very day when Colonel Hale’s
commission was signed, which we may call the 7th Nov.
birthday of the Seventeenth Lancers, the Board of
General Officers was summoned to decide how the new regiment
should be dressed. As to the colour of the coat there could be no
doubt, scarlet being the rule for all regiments. For the facings white
was the colour chosen, and for the lace white with a black edge, the
black being a sign of mourning for the death of Wolfe. But the
principal distinction of the new regiment was the badge, chosen by
Colonel Hale and approved by the King, of the Death’s Head and the
motto “Or Glory,”—the significance of which lies not so much in
claptrap sentiment, as in the fact that it is, as it were, a perpetual
commemoration of the death of Wolfe. It is difficult for us to realise,
after the lapse of nearly a century and a half, how powerfully the
story of that death seized at the time upon the minds of men.
Two days after the settlement of the dress, a warrant was issued
for the arming of Colonel Hale’s Light Dragoons; and this, being the
earliest document relating to the regiment that I have been able to
discover, is here given entire:—
George R.
Whereas we have thought fit to order a Regiment of Light
Dragoons to be raised and to be commanded by our trusty and well-
beloved Lieutenant-Colonel John Hale, which Regiment is to consist
of Four troops, of 3 sergeants, 3 corporals, 2 drummers, and 67
private men in each troop, besides commission officers, Our will and
pleasure is, that out of the stores remaining within the Office of our
Ordnance under your charge you cause 300 pairs of pistols, 292
carbines, 292 cartouche boxes, and 8 drums, to be issued and
delivered to the said Lieutenant-Colonel John Hale, or to such person
as he shall appoint to receive the same, taking his indent as usual,
and you are to insert the expense thereof in your next estimate to be
laid before Parliament. And for so doing this shall be as well to you as
to all other our officers and ministers herein concerned a sufficient
Warrant.
Given at our Court at St. James’ the 9th day of November 1759, in
the 33rd year of our reign.
To our trusty and well-beloved Cousin and Councillor John Viscount
Ligonier, Master-General of our Ordnance.

These preliminaries of clothing and armament being settled,

Colonel Hale’s next duty was to raise the men. Being a Hertfordshire
man, the son of Sir Bernard Hale of Kings Walden, he naturally
betook himself to his native county to raise recruits among his own
people. The first troop was raised by Captain Franklin Kirby,
Lieutenant, 5th Foot; the second by Captain Samuel Birch,
Lieutenant, 11th Dragoons; the third by Captain Martin Basil,
Lieutenant, 15th Light Dragoons; and the fourth by Captain Edward
Lascelles, Cornet, Royal Horse Guards. If it be asked what stamp of
man was preferred for the Light Dragoons, we are able to answer
that the recruits were required to be “light and straight, and by no
means gummy,” not under 5 feet 5½ inches, and not over 5 feet 9
inches in height. The bounty usually offered (but varied at the
Colonel’s discretion) was three guineas, or as much less as a recruit
could be persuaded to accept.
Whether from exceptional liberality on the part of Colonel Hale, or
from an extraordinary abundance of light, straight, and by no means
gummy men in Hertfordshire at that period, the regiment was
recruited up to its establishment, we are told, within
the space of seventeen days. Early in December it December.
made rendezvous at Watford and Rickmansworth,
whence it marched to Warwick and Stratford-on-Avon, and thence a
fortnight later to Coventry. Meanwhile orders had already been given
(10th December) that its establishment should be augmented by two
more troops of the same strength as the original four; and little more
than a month later came a second order to
increase each of the existing troops still further by 1760. 28th Jan.
the addition of a sergeant, a corporal, and 36
privates. Thus the regiment, increased almost as soon as raised
from 300 to 450 men, and within a few weeks again strengthened by
one-half, may be said to have begun life with an establishment of
678 rank and file. To them we must add a list of the original officers:
—
Lieutenant-Colonel Commandant.—John Hale, 7th November 1759.
Major.—John Blaquiere, 7th November 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

Details of the regiment’s stay at Coventry are

wanting, the only discoverable fact being that, in 1760
obedience to orders from headquarters, it was
carefully moved out of the town for three days in August during the
race-meeting. But as these first six months must have been devoted
to the making of the raw recruits into soldiers, we may endeavour,
with what scanty material we can command, to form some idea of
the process. First, we must premise that with the last order for the
augmentation of establishment was issued a warrant for the supply
of the regiment with bayonets, which at that time formed an essential
part of a dragoon’s equipment. Swords, it may be remarked, were
provided, not by the Board of Ordnance, but by the Colonel. It is
worth while to note in passing how strong the traditions of 1645 still
remain in the dragoons. The junior subaltern is indeed no longer
called an ensign, but a cornet; but the regiment is still ruled by the
infantry drum instead of the cavalry trumpet.
 Farrier. Officer. Trumpeter.
1763.
Let us therefore begin with the men; and as we have already seen
what manner of men they were, physically considered, let us first
note how they were dressed. Strictly speaking, it was not until 1764
that the Light Dragoon regiments received their distinct dress
regulations; but the alterations then made were so slight that we may
fairly take the dress of 1764 as the dress of 1760. To begin with,
every man was supplied by the Colonel, by contract, with coat,
waistcoat, breeches, and cloak. The coat, of course, was of scarlet,
full and long in the skirt, but whether lapelled or not before 1763 it is
difficult to say. Lapels meant a good deal in those days; the coats of
Horse being lapelled to the skirt, those of Dragoon Guards lapelled
to the waist, while those of Dragoons were double-breasted and had
no lapels at all. The Light Dragoons being a novelty, it is difficult to
say how they were distinguished in this respect, but probably in 1760
(and certainly in 1763) their coats were lapelled to the waist with the
colour of the regimental facing, the lapels being three inches broad,
with plain white buttons disposed thereon in pairs.
The waistcoat was of the colour of the regimental facing—white,
of course, for the Seventeenth; and the breeches likewise. The
cloaks were scarlet, with capes of the colour of the facing. In fact, it
may be said once for all that everything white in the uniform of the
Seventeenth owes its hue to the colour of the regimental facing.
Over and above these articles the Light Dragoon received a pair
of high knee-boots, a pair of boot-stockings, a pair of gloves, a
comb, a watering or forage cap, a helmet, and a stable frock.
Pleased as the recruit must have been to find himself in possession
of smart clothes, it must have been a little discouraging for him to
learn that his coat, waistcoat, and breeches were to last him for two,
and his helmet, boots, and cloak for four years. But this was not all.
He was required to supply out of an annual wage of £13: 14: 10 the
following articles at his own expense:—
4 shirts at 6s. 10d. £1 7 4
4 pairs stockings at 2s. 10d. 0 11 4
2 pairs shoes at 6s. 0 12 0
A black stock 0 0 8
Stock-buckle 0 0 6
1 pair leather breeches 1 5 0
1 pair knee-buckles 0 0 8
2 pairs short black gaiters 0 7 4
1 black ball (the old substitute for blacking) 0 1 0
3 shoe-brushes 0 1 3
£4 7 1

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

Also a pair of saddle-bags, a turn-key, and an awl.

All these various items were paid for, “according to King’s
regulation and custom,” out of the soldier’s “arrears and grass
money.” For his pay was made up of three items—
“Subsistence” (5d. a day nominal) £9 2 0 per annum.
“Arrears” (2d. a day nominal) 3 1 0 „
“Grass money” 1 11 10 „
£13 14 10 „

We must therefore infer that his “subsistence” could not be

stopped for his “necessaries” (as the various items enumerated
above are termed); but none the less twopence out of the daily
stipend was stopped for his food, while His Majesty the King
deducted for his royal use a shilling in the pound from the pay of
every soul in the army. Small wonder that heavy bounty-money was
needed to persuade men to enlist.
What manner of instruction the recruit received on his first
appearance it is a little difficult to state positively, though it is still
possible to form a dim conception thereof. The first thing that he was
taught, apparently, was the manual and firing exercise, of which we
are fortunately able to speak with some confidence. As it contains
some eighty-eight words of command, we may safely infer that by
the time a recruit had mastered it he must have been pretty well
disciplined. The minuteness of the exercise and the extraordinary
number of the motions sufficiently show that it counted for a great
deal. “The first motion of every word of command is to be performed
immediately after it is given; but before you proceed to any of the
other motions you must tell one, two, pretty slow, by making a stop
between the words, and in pronouncing the word two, the motion is
to be performed.” In those days the word “smart” was just coming
into use, but “brisk” is the more common substitute. Let us picture
the squad of recruits with their carbines, in their stable frocks, white
breeches, and short black gaiters, and listen to the instructions which
the corporal is giving them:—
“Now on the word Shut your pans, let fall the primer and take hold
of the steel with your right hand, placing the thumb in the upper part,
and the two forefingers on the lower. Tell one, two, and shut the pan;
tell one, two, and seize the carbine behind the lock with the right
hand; then tell one, two, and bring your carbine briskly to the
recover. Wait for the word. Shut your—pans, one—two, one—two,
one—two.”
There is no need to go further through the weary iteration of “Join
your right hand to your carbine,” “Poise your carbine,” “Join your left
hand to your carbine,” whereby the recruit learned the difference
between his right hand and his left. Suffice it that the manual and
firing exercise contain the only detailed instruction for the original
Light Dragoon that is now discoverable. “Setting-up” drill there was
apparently none, sword exercise there was none, riding-school, as
we now understand it, there was none, though there was a riding-
master. A “ride” appears to have comprised at most twelve men, who
moved in a circle round the riding-master and received his teaching
as best they could. But it must not be inferred on that account that
the men could not ride; on the contrary the Light Dragoons seem to
have particularly excelled in horsemanship. Passaging, reining back,
and other movements which call for careful training of man and
horse, were far more extensively used for purposes of manœuvre
than at present. Moreover, every man was taught to fire from on
horseback, even at the gallop; and as the Light Dragoons received
an extra allowance of ammunition for ball practice, it is reasonable to
conclude that they spent a good deal of their time at the butts, both
mounted and dismounted.
As to the ordinary routine life of the cavalry barrack, it is only
possible to obtain a slight glimpse thereof from scattered notices.
Each troop was divided into three squads with a corporal and a
sergeant at the head of each. Each squad formed a mess; and it is
laid down as the duty of the sergeants and corporals to see that the
men “boil the pot every day and feed wholesome and clean.” The
barrack-rooms and billets must have been pretty well filled, for every
scrap of a man’s equipment, including his saddle and saddle-
furniture, was hung up therein according to the position of his bed.
As every bed contained at least two men, there must have been
some tight packing. It is a relief to find that the men could obtain a
clean pair of sheets every thirty days, provided that they returned the
foul pair and paid three halfpence for the washing.
The fixed hours laid down in the standing orders of the Light
Dragoons of 14th May 1760 are as follows:—
The drum beat for—
Réveille from Ladyday to Michaelmas 5.30 a.m. Rest of year 6.30
Morning stables „ „ 8 a.m. „ 9.0
Evening stables „ „ 4 p.m. „ 3.0
“Rack up” „ „ 8 p.m.
Tattoo[1] „ „ 9 p.m. „ 8.0

If there was an order for a mounted parade the drum beat—

1st drum—“To horse.” The men turned out, under the eye of the
quartermaster and fell in before the stable door in rank entire.
Officers then inspected their troops; and each troop was told off in
three divisions.
2nd drum—“Preparative.” By the Adjutant’s order.
3rd drum—“A flam.” The centre division stood fast; the right division
advanced, and the left division reined back, each two horses’
lengths.
4th drum—“A flam.” The front and rear divisions passaged to right and
left and covered off, thus forming the troop in three ranks.
5th drum—“A march.” The quartermasters led the troops to their
proper position in squadron.
6th drum—“A flam.” Officers rode to their posts (troop-leaders on the
flank of their troops), facing their troops.
7th drum—“A flam.” The officers halted, and turned about to their
proper front.
 Then the word was given—“Take care” (which meant “Attention”).
“Draw your swords;” and the regiment was thus ready to receive the
three squadron standards, which were escorted on to the ground
and posted in the ranks, in the centre of the three squadrons.
Each squadron was then told off into half-squadrons, into three
divisions, into half-ranks, into fours, and into files. As there are many
people who do not know how to tell off a squadron by fours, it may
be as well to mention how it was done. The men were not numbered
off, but the officer went down each rank, beginning at the right-hand
man, and said to the first, “You are the right-hand man of ranks by
fours.” Then going on to the fourth he said, “You are the left-hand
man of ranks by fours,” and so on. Telling off by files was a simpler
affair. The officer rode down the ranks, pointing to each man, and
saying alternately, “You move,” “You stand,” “You move,” “You stand.”
Conceive what the confusion must have been if the men took it into
their heads to be troublesome. “Beg your honour’s pardon, but you
said I was to stand,” is the kind of speech that must have been heard
pretty often in those days, when field movements went awry.
If the mounted parade went no further, the men marched back to
their quarters in fours, each of the three ranks separately; for in
those days “fours” meant four men of one rank abreast. If field
movements were practised, the system and execution thereof were
left to the Colonel, unhampered by a drill-book. There was, however,
a batch of “evolutions” which were prescribed by regulation, and
required of every regiment when inspected by the King or a general
officer. As these “evolutions” lasted, with some modification, till the
end of the century, and (such is human nature) formed sometimes
the only instruction, besides the manual exercise, that was imparted
to the regiment, it may be as well to give a brief description thereof in
this place. The efficiency of a regiment was judged mainly from its
performance of the evolutions, which were supposed to be a
searching test of horsemanship, drill, and discipline.
First then the squadron was drawn up in three ranks, at open
order, that is to say, with a distance equal to half the front of the
squadron between each rank. Then each rank was told off by half-
rank, third of rank, and fours; which done, the word was given,
“Officers take your posts of exercise,” which signified that the officers
were to fall out to their front, and take post ten paces in rear of the
commanding officer, facing towards the regiment. In other words, the
regiment was required to go through the coming movements without
troop or squadron leaders. Then the caution was given, “Take care to
perform your evolutions,” and the evolutions began.
To avoid tedium an abridgment of the whole performance is given
at some length in the Appendix, and it is sufficient to say here that
the first two evolutions consisted in the doubling of the depth of the
column. The left half-ranks reined back and passaged to the right
until they covered the right half-ranks; and the original formation
having been restored by more passaging, the right half-ranks did
likewise. The next evolution was the conversion of three ranks into
two, which was effected by the simple process of wheeling the rear
rank into column of two ranks, and bringing it up to the flank of the
front and centre ranks. Then came further variations of wheeling,
and wheeling about by half-ranks, thirds of ranks, and fours; each
movement being executed of course to the halt on a fixed pivot, so
that through all these intricate manœuvres the regiment practically
never moved off its ground. No doubt when performed, as in smart
regiments they were performed, like clockwork, these evolutions
were very pretty—and of course, like all drill, they had a disciplinary
as well as an æsthetic value; but it must be confessed that they left a
blight upon the British cavalry for more than a century. It is only
within the last twenty years that the influence of these evolutions,
themselves a survival from the days of Alexander the Great, has
been wholly purged from our cavalry drill-books.
Meanwhile at this time (and for full forty years after for that matter)
an immense deal of time was given up to dismounted drill; for the
dragoons had not yet lost their character of mounted infantry. To
dismount a squadron, the even numbers (as we should now say)
reined back and passaged to the right; and the horses were then
linked with “linking reins” carried for the purpose, and left in charge
of the two flank men, while the rest on receiving the word,
“Squadrons have a care to march forward,” formed up in front,
infantry wise, and were called for the time a battalion. This
dismounted drill formed as important a feature of an inspection as
the work done on horseback. Probably the survival of the march past
the inspecting officer on foot may be traced to the traditions of those
days.
If it be asked how time was found for so much dismounted work,
the explanation is simple. From the 1st of May to the 1st October the
troop horses were turned out to grass, and committed to the keeping
of a “grass guard”—having, most probably, first gone through a
course of bleeding at the hands of the farriers. It appears to have
mattered but little how far distant the grass might be from the men’s
quarters; for we find that if it lay six or eight miles away, the “grass
guard” was to consist of a corporal and six men, while if it were
within a mile or two, two or three old soldiers were held to be amply
sufficient. Men on “grass guard” were not allowed to take their cloaks
with them, but were provided with special coats, whereof three or
four were kept in each troop for the purpose. “Grass-time,” it may be
added, was not the busy, but the slack time for cavalrymen in those
days—the one season wherein furloughs were permitted.
The close of the “grass-time” must have been a curious period in
the soldier’s year, with its renewal of the long-abandoned stable
work and probable extra tightening of discipline. On the farriers
above all it must have borne heavily, bringing with it, as we must
conclude, the prospect of reshoeing every horse in the regiment.
Moreover, the penalty paid by a farrier who lamed a horse was
brutally simple: his liquor was stopped till the horse was sound.
Nevertheless the farrier had his consolations, for he received a
halfpenny a day for every horse under his charge, and must
therefore have rejoiced to see his troop stable well filled. The men,
probably, in a good regiment, required less smartening after grass-
time than their horses. Light Dragoons thought a great deal of
themselves, and were well looked after even on furlough. At the
bottom of every furlough paper was a note requesting any officer
who might read it to report to the regiment if the bearer were
“unsoldierly in dress or manner.” We gather, from a stray order, “that
soldiers shall wear their hair under their hats,” that even in those
days men were bitten with the still prevailing fashion of making much
of their hair; but we must hope that Hale’s regiment knew better than
to yield to it.
Every man, of course, had a queue of leather or of his own hair,
either hanging at full length, in which case it was a “queue,” or partly
doubled back, when it became a “club.” Which fashion was favoured
by Colonel Hale we are, alas! unable to say,[2] but we gain some
knowledge of the coiffure of the Light Dragoons from the following
standing orders:—
“The Light Dragoon is always to appear clean and dressed in a
soldier-like manner in the streets; his skirts tucked back, a black
stock and black gaiters, but no powder. On Sundays the men are to
have white stocks, and be well powdered, but no grease on their
hair.”
Here, therefore, we have a glimpse of the original trooper of the
Seventeenth in his very best: his scarlet coat and white facings neat
and spotless, the skirts tucked back to show the white lining, the
glory of his white waistcoat, and the sheen of his white breeches.
“Russia linen,” i.e. white duck, would be probably the material of
these last—Russia linen, “which lasts as long as leather and costs
but half-a-crown,” to quote one of our best authorities. Then below
the white ducks, fitting close to the leg, came a neat pair of black
cloth gaiters running down to dull black shoes, cleaned with “black
ball” according to the regimental recipe. Round on his neck was a
spotless white stock, helping, with the powder on his hair, to
heighten the colour of his round, clean-shaven face. Very attractive
he must have seemed to the girls of Coventry in the spring of 1760.
What would we not give for his portrait by Hogarth as he appeared
some fine Sunday in Coventry streets, with the lady of his choice on
his arm, explaining to her that in the Light Dragoons they put no
grease on their heads, and in proof thereof shaking a shower of
powder from his hair on to her dainty white cap! Probably there were
tender leave-takings when in September the regiment was ordered
northward; possibly there are descendants of these men, not
necessarily bearing their names, in Coventry to this day.