Focus on middle east respiratory syndrome coronavirus (mers-cov) a. bleibtreu 2024 Scribd Download by Education Libraries

https://ebookmass.com/product/focus-on-middle-

More products digital (pdf, epub, mobi) instant download maybe you interests ...

Identification and evaluation of potent Middle East respiratory syndrome coronavirus (MERS-CoV) 3CLPro inhibitors Vathan Kumar

https://ebookmass.com/product/identification-and-evaluation-ofpotent-middle-east-respiratory-syndrome-coronavirus-merscov-3clpro-inhibitors-vathan-kumar/

Middle East respiratory syndrome coronavirus (MERS-CoV)

Surveillance and testing in North England from 2012 to 2019 Hamzah Z. Farooqa

https://ebookmass.com/product/middle-east-respiratory-syndromecoronavirus-mers-cov-surveillance-and-testing-in-north-englandfrom-2012-to-2019-hamzah-z-farooqa/

Middle East Respiratory Syndrome-Corona Virus (MERSCoV) associated stress among medical students at a university teaching hospital in Saudi Arabia Abdulkarim Al-Rabiaah

https://ebookmass.com/product/middle-east-respiratory-syndromecorona-virus-mers-cov-associated-stress-among-medical-studentsat-a-university-teaching-hospital-in-saudi-arabia-abdulkarim-alrabiaah/

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges Chih-Cheng Lai

https://ebookmass.com/product/severe-acute-respiratory-syndromecoronavirus-2-sars-cov-2-and-coronavirusdisease-2019-covid-19-the-epidemic-and-the-challenges-chih-chenglai/

Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths Chih-Cheng Lai

https://ebookmass.com/product/asymptomatic-carrier-state-acuterespiratory-disease-and-pneumonia-due-to-severe-acuterespiratory-syndrome-coronavirus-2-sars-cov-2-facts-and-mythschih-cheng-lai/

First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA Isaac Ghinai

https://ebookmass.com/product/first-known-person-to-persontransmission-of-severe-acute-respiratory-syndromecoronavirus-2-sars-cov-2-in-the-usa-isaac-ghinai/

Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation Guangming Ye

https://ebookmass.com/product/clinical-characteristics-of-severeacute-respiratory-syndrome-coronavirus-2-reactivation-guangmingye/

Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence Yu-Chen Cao

https://ebookmass.com/product/remdesivir-for-severe-acuterespiratory-syndrome-coronavirus-2-causing-covid-19-anevaluation-of-the-evidence-yu-chen-cao/

Severe Acute Respiratory Syndrome (SARS) and Coronavirus disease-2019 (COVID-19): From Causes to Preventions in Hong Kong Siukan Law

https://ebookmass.com/product/severe-acute-respiratory-syndromesars-and-coronavirus-disease-2019-covid-19-from-causes-topreventions-in-hong-kong-siukan-law/

Review

Focus on Middle East respiratory syndrome coronavirus (MERS-CoV)

A. Bleibtreu a , M. Bertine b , C. Bertin a , N. Houhou-Fidouh b , B. Visseaux b,∗

a Service des maladies infectieuses et tropicales, hôpitaux universitaires Pitié-Salpêtrière Charles Foix, AP–HP, Paris, France

b Inserm, Laboratoire de Virologie, IAME, UMR 1137, Hôpital Bichat, Sorbonne Paris Cité, Université Paris Diderot, AP–HP, Paris, France

a r t i c l e i n f o

Article history:

Received 16 September 2018

Received in revised form 22 October 2018

Accepted 8 October 2019

Keywords: Emerging disease

MERS-CoV Coronavirus Pneumonia

a b s t r a c t

Since the ﬁrst case of human infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia in June 2012, more than 2260 cases of conﬁrmed MERS-CoV infection and 803 related deaths have been reported since the 16th of October 2018. The vast majority of these cases (71%) were reported in Saudi Arabia but the epidemic has now spread to 27 countries and has not ceased 6 years later, unlike SARS-CoV that disappeared a little less than 2 years after emerging. Due to the high fatality rate observed in MERS-CoV infected patients (36%), much effort has been put into understanding the origin and pathophysiology of this novel coronavirus to prevent it from becoming endemic in humans. This review focuses in particular on the origin, epidemiology and clinical manifestations of MERS-CoV, as well as the diagnosis and treatment of infected patients. The experience gained over recent years on how to manage the different risks related to this kind of epidemic will be key to being prepared for future outbreaks of communicable disease.

Mots clés :

Maladies émergentes

MERS-CoV

Coronavirus

Pneumonie r é s u m é

Depuis le premier cas d’infection liée au Middle East Respiratory Syndrome – Coronavirus (MERS-CoV), détecté en Arabie Saoudite en juin 2012, le MERS-CoV a donné lieu, au 16 octobre 2018, à plus de 2260 cas d’infections conﬁrmées et à 803 décès. La grande majorité des cas (71 %) ont été déclarés en Arabie Saoudite mais l’épidémie a depuis touché 27 pays et n’est toujours pas enrayée 6 ans après son émergence, contrairement au SRAS-CoV qui a disparu un peu moins de deux ans après sa première détection. En raison du taux important de décès observé parmi les patients infectés par le MERS-CoV (36 %), beaucoup d’efforts ont été déployés pour comprendre l’origine et la physiopathologie de ce nouveau coronavirus ainsi que pour lutter contre une éventuelle installation endémique de ce virus au sein de la population humaine. Cette revue s’attache plus particulièrement à retracer l’origine et l’épidémiologie du MERS-CoV à décrire la clinique observée chez les patients ainsi que la prise en charge diagnostique et thérapeutique des patients infectés. L’expérience acquise au cours des dernières années dans la gestion des différents risques liés à ce type d’épidémie est importante pour pouvoir faire face à la prochaine émergence d’infection transmissible.

1. Introduction

The ﬁrst case of infection attributed to Middle East respiratory syndrome coronavirus (MERS-CoV) was detected in Saudi Arabia in June 2012 [1]. MERS-CoV then spread to several neighboring countries, mainly Jordan and Qatar (see Fig. 2), and imported cases of the disease were reported throughout the world in Asia, Africa, Europe and the Americas [2] By the 16th of October 2018, 2260 con-

∗ Corresponding author.

E-mail address: benoit.visseaux@aphp.fr (B. Visseaux).

ﬁrmed cases of infection with MERS-CoV had been documented in 27 countries by the World Health Organization (WHO) and were associated with 803 deaths [2] The vast majority of the cases (73%) were reported in Saudi Arabia and only one widespread outbreak was observed outside of the Arabian peninsula in South Korea in 2015 [3] (Figs. 1 and 2). Due to the disease’s high fatality rate (36%) [2], much effort has been put into understanding the origin and pathophysiology of this novel coronavirus to prevent it from becoming endemic in humans.

This review focuses in particular on tracking down the origin of MERS-CoV, its epidemiology and clinical manifestations, as well as the diagnosis and treatment of infected patients.

(MERS-CoV).

2. Origin and emergence of the virus

2.1. Human coronaviruses

The first two coronaviruses demonstrated to cause respiratory infections in humans, the coronaviruses 229E and OC43, were identified in the 1960s. They were held responsible for respiratory infections of moderate severity in humans. Despite these viruses being identified in several reports as causing lower respiratory tract infections, it was generally accepted that coronaviruses were of low pathogenicity until the emergence of SARS-CoV (Severe Acute Respiratory Syndrome Coronavirus) in 2002, a virus with a fatality rate estimated at 10%. The SARS outbreak that resulted in more than 8400 cases was finally contained two years later, in 2004, and the virus has not been detected again since [4] There was renewed interest in coronavirus research following the SARS epidemic, and two novel endemic human coronaviruses were identified, NL63 and HKU1 respectively in 2004 and 2005, but could not be replicated in cell culture. Both of these new viruses were responsible for respira-

tory infections of moderate seriousness like the coronaviruses 229E and OC43. Great effort has been made to identify coronaviruses in animal populations, both before and after the SARS outbreak, in order to better understand and control the risk of animal-to-human transmission. This resulted in the discovery of coronaviruses in numerous animal species, with a few exceptions such as sheep and goats, ﬁsh and non-human primates [5].

2.2. Emergence of the MERS epidemic

The ﬁrst case of MERS-CoV infection was reported in Jeddah, Saudi Arabia, in June 2012 [1]. The patient, a 60-year-old man, died from lung and kidney failure 11 days after being admitted to hospital. Very shortly afterwards, in September 2012, a second patient was admitted to hospital in the United Kingdom for severe respiratory infection related to a novel coronavirus following travel to the Middle East. The new virus was found to replicate in a tissue culture model and was rapidly isolated and identiﬁed for both cases [6,7]. Retrospectively, other cases of the disease were found to have

Fig. 1. Geographical distribution of conﬁrmed cases of MERS-CoV infection. World Health Organization (WHO) data on September 10th, 2018.

Fig. 2. Distribution over time of conﬁrmed cases of MERS-CoV infection worldwide. World Health Organization (WHO) data on September 10th, 2018.

occurred before the 2 aforementioned cases: in April 2012, an outbreak at Zarqa hospital in Jordan affected the staff of the intensive care unit, with two fatal cases. The respiratory samples collected were later conﬁrmed to be positive for MERS-CoV [8]

These initial cases were rapidly followed by a series of outbreaks in all Saudi Arabian provinces that were characterized by the infection of health professionals in direct contact with the patients. Other similar outbreaks were observed in several neighboring countries: Qatar, Bahrain, Kuwait, Jordan and Tunisia. Health authorities reacted quickly to the reports of these epidemics and the strong resemblance with observed clinical features of SARS-CoV infections. Indeed, although a few patients developed mild infections, the fatality rate for patients infected with MERS-CoV was over 30% [2]

2.3. Natural reservoir of MERS-CoV

Following the identification of MERS-CoV, great effort was put into finding which animal species it originated from in order to stop the further spread of the disease to humans. MERS-CoV was very rapidly determined to be genotypically closely related to the betacoronavirus lineage C viruses identified in bats [9] Based on these findings, and the major role of bats in the genetic diversity and spread of coronaviruses, much of the initial work aiming at finding the natural reservoir of MERS-CoV focused on bats. However, no conclusive evidence demonstrating that bats were the natural reservoir of MERS-CoV in the Arabian peninsula were found, despite the identification of closely related viruses in bats in SubSaharan Africa [10], far from the existing outbreaks. Very strong epidemiological links were identified between the human cases and camels and resulted in the isolation in camels of viruses that were directly related to MERS-CoV and that could replicate in cultured human cells [11] The investigation of dromedary camel serum collections, some of which collected as early as 1983, demonstrated that the virus was already widespread (seropositivity rate

> 80%) in the East African countries (Somalia, Sudan and Egypt). These countries export dromedary camels to Arabian countries, but also in Kenya, Nigeria, Tunisia, Ethiopia, Burkina Faso and Morocco [12–14] Phylogenetic analysis revealed 5 distinct coronavirus lineages in dromedary camels, including one recombinant lineage that led to the MERS-CoV epidemic in humans [15].

3. Virus structure and cycle

MERS-CoV is a betacoronavirus belonging to lineage C. It is an enveloped virus with a positive-sense single-stranded RNA genome of about 30 kb. Under electron microscopy, virions are generally spherical with surface projections (spikes) formed by the surface protein S creating an image reminiscent of a crown or solar corona. The positive-sense single-stranded RNA genome acts as messenger RNA (mRNA) with a 5 cap and a 3 polyadenylated tail. It plays three roles during the host cell cycle: (i) it acts as the initial RNA molecule for the infection cycle; (ii) it is the template for replication and transcription; (iii) it is the substrate that is packaged into the newly assembled viral particles [16]

The MERS-CoV genome is organized in the same way as other coronavirus species. The first two thirds of the MERSCoV genome contain two overlapping reading frames (ORF1a and ORF1b) that translate into the replication-transcription complex including 16 non-structural proteins. The remaining third of the genome encodes the four structural proteins, the spike (S), envelop (E), membrane (M) and nucleocapsid (N) proteins, as well as five accessory proteins (ORF3, ORF4a, ORF4b, ORF5 and ORF8b) that are not required for genome replication but are probably involved in virulence. The flanking sequences, on both ends of the genome, contain untranslated 5 and 3 regions (UTR) (Fig. 3) [17]

The viral particle can enter the cell in two ways, which probably contribute to the broad tissue tropism of this virus that replicates mainly in respiratory epithelial cells but can also infect many other

Fig. 3. Structure and genomic organization of MERS-CoV.

cell types. Via the endosomal pathway, the S1 domain of the MERSCoV spike protein (S) binds its receptor, dipeptidyl peptidase 4 (DPP4) [18], induces endocytosis of the viral particle and a change in the conformation of the S2 subunit of the S protein that then mediates virus-host membrane fusion and uncoating of virus RNA. MERS-CoV can also enter host cells via a non-endosomal mechanism by direct fusion of the virus with the plasma membrane following S protein cleavage by human proteases [19]

Following entry into the cytoplasm and uncoating of the virus nucleocapsid, the viral genomic RNA is translated to produce two polypeptides, pp1a and pp1b, that form the replicase-transcriptase complex. This initial replicase-transcriptase complex uses the genomic RNA to produce 16 non-structural proteins that assemble into the replication complex. The replication complex then replicates the genomic RNA and produces other subgenomic RNAs that ensure the translation of the structural proteins.

Virions are assembled at the endoplasmic reticulum membrane as viral proteins and genomic RNA are grouped together and then bud into the lumen of the endoplasmic reticulum. The virions are then exported via the secretory pathway of the endoplasmic reticulum into the Golgi intermediate compartment and then into the extracellular environment. The M protein drives the packaging process by selecting and organizing the viral envelop components at the assembly sites and interacting with the nucleocapsid to allow budding [20]

4. Transmission mechanisms and preventive measures

4.1. Transmission mechanisms

Several large serology studies suggest that cases of asymptomatic or mild MERS-CoV infection occur regularly, although infrequently. The importance of such cases is difficult to assess [10] It is therefore difficult to determine whether these cases are due to or take part in human-to-human transmission. Several studies suggest that less than 50% of infected patients transmit the virus to individuals they come into contact with, even at the beginning of an outbreak [10]. The disease therefore seems to spread due to frequent animal-to-human transmission, from camels to humans, with limited subsequent human-to-human transmissions [21] There are unfortunately exceptions to this observation and local outbreaks caused by human-to-human transmission have been observed on a regular basis, mostly in hospitals. To date, the most poignant example is the outbreak that occurred in South Korea in which the index case caused 185 secondary cases, among whom 30 were care providers, leading to 24 fatalities [3] This outbreak was characterized by the key role of a few “super spreaders”, delayed diagnosis, high doctor shopping behavior and the importance of confined spaces (waiting room, hospital room, ambulance). In this example, the resemblance with SARS-CoV’s spreading mechanisms is striking, despite lower degrees of transmission to care providers for MERS-CoV [22] These regular cases of importedMERS, the most recent was reported in England in August 2018 [23], represent a real threat of local epidemics outside Saudi Arabia and special screening and isolation procedures need to be implemented in units likely to receive patients suspected of MERS-CoV infections.

4.2. Preventive measures for travelers

When possible, the ﬁrst measure to be taken is to delay departure, in particular for individuals over 65 or with chronic disease, and for pregnant women or children. Such measures are nevertheless challenging to maintain today as that the virus is still present 6 years after its apparition.

All other preventive measures aim at preventing both animalto-human transmission and human-to-human transmission. It is therefore recommended to avoid any contact with domestic animals (ﬁrstly dromedary camels), their secretions, raw milk and insufﬁciently cooked meat. It is also advised to avoid eating fruit and vegetables that might have been in contact with animal secretions if not washed and peeled by oneself.

To avoid human-to-human transmission, the usual recommendations for preventing the spread of any respiratory virus should be applied: hand washing with soapy water or an alcohol-based solution, covering one’s nose and mouth when sneezing, refraining from shaking hands and touching one’s mouth and nose with one’s hands, avoiding contact with people with respiratory symptoms.

Finally, a last series of recommendations focus on how to behave in case of suspicious symptoms: (i) consult a doctor as soon as symptoms occur during travel and delay the return until symptoms disappear; (ii) if symptoms occur with 14 days of returning home, consult a doctor and tell him/her about the recent travel [24]

5. Diagnostic laboratory testing

PCR-based detection methods are currently the preferred option for detecting the virus in respiratory samples and making a diagnosis of MERS-CoV infection. Serology tests can also be performed and are often used for second-line diagnostic investigation in patients with a high suspicion of MERS-CoV but negative results by direct PCR testing.

5.1. Direct PCR detection

Various respiratory matrices can be used: nasopharyngeal swabs, nasopharyngeal or tracheal aspirates, bronchoalveolar lavage (BAL), and even in some cases, induced sputum. The deepest samples, tracheal aspirates and BALs, show the greatest sensitivity and signiﬁcantly higher viral loads [25]

The genome ampliﬁcation and detection methods used (PCR) were initially mostly developed in situ and performed in biosafety level 3 (BSL-3) reference facilities. The time to results is generally relatively long, 24–48 h, due to the usual time required for conventional PCR testing to which must be added the additional preparation and sample neutralization time needed to protect the laboratory staff against this virus. The PCR methods used are generally semi-quantitative and some studies suggest a correlation between the amount of virus detected and the severity of the symptoms [26] Nevertheless, no consensus has been reached yet regarding a threshold level that could actually predicts clinical severity. Targeting the envelop gene upE is recommended with conﬁrmatory testing for ORF 1A or 1B or the N gene. If results diverge, sequencing is sometimes required to obtain conclusive results [27] Today, an increasing number of commercial tests are becoming available (Altona Diagnostics, Fast Track Diagnostics, Primerdesing Ltd.) some even with a time to results of less than 1 hour (BioFire–bioMérieux). Some of these tests are point-of-care, or can be performed in BSL3 facilities or a standard laboratory following sample neutralization in a BSL3 facility. These commercial tests must always be validated before use to check their sensitivity and compare their performance with reference methods.

5.2. Indirect serological testing

As with any other acute viral infection, antibodies can only generally be detected about 10 days after the onset of symptoms. In some patients, especially those with severe infections, the time interval to antibody detection may be even longer [28]. Serological testing is therefore of little help for the initial diagnosis of

symptomatic patients, but can be useful for epidemiological investigations.

The highly immunogenic S and N viral proteins are widely used targets for serological tests and are found on all coronaviruses. Various approaches have been developed: serum neutralization assays [29], microarrays [30], or more recently ELISA conﬁrmed by a microneutralization test [31] All methods are technically complex and require a high level of expertise that restrict their use to a few highly specialized facilities.

6. Clinical presentation

The ﬁrst cases of infection with MERS-CoV were reported in 2012 [1] Hospital-acquired MERS-CoV infections have been described worldwide and represented a third of all cases reported in Saudi Arabia in the early stages of the epidemic [1,32,33]. Clustered hospital-acquired infections were frequently observed during the ﬁrst outbreaks and probably contributed to spreading the disease from the primary site of virus infection to the whole Arabian peninsula, the most striking example of hospital-acquired outbreak being the Korean outbreak in 2015 [34]. Care providers are often affected and represent 15–22% of cases [33–39].

Most of the cases are described in Middle East countries, in particular Saudi Arabia (73%), with a predominance of male patients (66–69% in various studies) and a mean patient age ranging from 40 to 55 years [34,38,40]

Comorbidities are found in 46–68.6% of patients, in particular diabetes and high blood pressure, followed by other heart conditions and ﬁnally obesity [34,37,38,41]

The mean incubation time is 5 to 6.5 days. The generation interval (time between the onset of symptoms of the ﬁrst case and those of the second case) is 7.6 days, which is identical to that of the respiratory syncytial virus (RSV) but threefold more than the inﬂuenza virus [36,42–44]

6.1. Clinical symptoms

The main challenge of MERS-CoV infection is the absence of specific clinical features for differential diagnosis with other viral respiratory diseases [37,45] This difficulty, combined with precautionary action taken to avoid potential secondary contamination with MERS-CoV [46], can result in medical confusion and inappropriate patient management due to prolonged, difficult isolation that makes it impossible to perform the necessary complementary tests while waiting for PCR results [47]

The clinical features of MERS-CoV infection are extremely variable, ranging from an absence of symptoms (14–80% of cases) to a ﬂu-like syndrome, pneumonia and acute respiratory distress syndrome (ARDS) [37,48].

The three most frequent symptoms are: fever (77% [IQR: 59–82]), cough (90% [52–69]), and dyspnea (68% [22–69]).

Many other secondary symptoms have been reported, such as sputum production (40%), odynophagia (39%), digestive system signs (20%), hemoptysis (4.3%), myalgia (43%) and headache (20%) [34,37,41,42].

Diarrhea is signiﬁcantly more frequent in patients infected with MERS-CoV than in patients with another acute, febrile respiratory conditions [45]

6.2. Severe MERS

Severe MERS is characterized predominantly by ARDS, acute kidney failure, and in the most severe cases, by multiple organ failure that can be fatal [49,50]. One third of patients develop pneumonia and 20% develop ARDS [51].

The median time to respiratory failure is 12 days after the onset of symptoms. Depending on studies, 53 to 89% of hospitalized patients are admitted to an intensive care unit (ICU) [43,52]

6.3. Fatality rate

Since the ﬁrst MERS outbreak, WHO had documented, in October 2018, 2260 cases of MERS-CoV infection conﬁrmed by laboratory testing and 803 related deaths in 27 different countries.

The retrospective fatality rate varies between outbreaks, ranging from 36.5 to 60% [33,35,37,38,42] The mortality rate of 20.4% observed for the Korean outbreak is probably the most reliable epidemiologically due to the comprehensive investigations carried out [34] The death rate is highest among patients admitted to an ICU, ranging from 58% to 90% [49,53]. In the only cohort study performed in Saudi Arabia, the fatality rate for MERS-CoV patients was of only 10% (8/80). However, the patients of this cohort were younger, had less symptoms, showed less radiological features and only 17% were admitted to an ICU [37] The findings of the latter study diverge therefore with the situations observed in other hospitals, but are perhaps a better reflection of the infection profile in the general population in which younger subjects are less symptomatic and therefore less frequently admitted to hospital.

The time interval between the onset of symptoms and death ranges from 11.5 to 27 days [34,44,54]

Finally, co-infection with other respiratory viruses, in particular inﬂuenza, has been described although the impact of such combined infections have not been evaluated [44,55] Co-infections with bacteria have also been reported in the patients developing the most severe disease [49,51]

6.4. Laboratory ﬁndings

There are no speciﬁc laboratory ﬁndings related to MERS-CoV infection. Nevertheless in patients with acute respiratory infection in MERS-endemic areas, MERS-CoV infections have been associated with normal leukocyte and/or polymorphonuclear neutrophil counts but elevated transaminases [37,45].

Moreover, hyperleukocytosis, lymphocytopenia, thrombocytopenia, hypoalbuminemia, elevated serum creatinine, LDH and CRP levels, and hypoxemia (PaO2/FiO2 < 300) have been repeated reported in MERS-CoV infected patients and are associated with severity and death [34,45].

Imaging (chest X-ray and sometimes chest CT) has revealed infection-related features in 51–75% of cases. The lesions observed are uni- or multi-focal ground glass opaciﬁcations, of subpleural and lower lobe predominance, with sometimes bilateral bi-basal involvement or features of organizing pneumonia [34,37,42,45].

6.5.

Risk factors for mortality

Mortality is highest in elderly, male patients with comorbidities, especially diabetes [38,45,56] Patients from Saudi Arabia and the Middle East have an increased mortality rate compared with patients from Korea or other countries [38,40]. In contrast, being a medical professional signiﬁcantly reduces the risk of mortality [38,45]

Other factors associated with a higher mortality risk have been described in various studies: digestive symptoms, prolonged delay between the onset of symptoms and admission to hospital, smoking, low blood pressure, impaired gas exchange, leukopenia, anemia, disturbance of liver or kidney function, use of mechanical ventilation and prolonged stay in the ICU [42,57]

For the Korean outbreak in 2015, the independent risk factors for mortality were: age > 55 years, dyspnea, diabetes, chronic lung disease, systolic blood pressure at admission < 90 mmHg,

4. Viral cycle of MERS-CoV and targets of the antiviral drugs available or under development.

hyperleukocytosis at admission (> 10,000/mm3 ) and the use of mechanical ventilation [34].

6.6. Risk factors for severe MERS

Positive PCR results for MERS-CoV in blood at diagnosis are associated with an increased risk of requiring mechanical ventilation, extracorporeal membrane oxygenation (ECMO) or to lead to death [58,59]

The lack or delayed detection of MERS antibodies (ELISA IgG and IgA, or PRNT) in the blood or airways is a poor prognostic factor [54,60]. It should however be noted that no seroconversion is observed in asymptomatic MERS-infected patients [54]. Finally, the MERS-CoV viral loads in distal lung samples were higher among deceased patients [60]

In a study including 45 patients in a tertiary referral hospital in South Korea:

• the predictive factors for pneumonia in MERS-CoV patients were: age > 45 years, body temperature > 37.5 ◦ C on day 3, platelet counts < 150,000/mm3 , lymphocytopenia (< 1000/mm3 ), CRP ≥ 20 mg/L and high viral loads (Ct value < 28.5);

• the predictive factors for respiratory failure were male sex, high blood pressure, thrombocytopenia, lymphocytopenia, hypoalbuminemia < 35 g/L and CRP ≥ 40 mg/L.

The patients with at least two, one and none of the predictive pneumonia factors developed pneumonia in 100%, 50% and 0% of cases, respectively [61].

7. Treatment of MERS

Several therapeutic options targeting various viral elements are currently available or under development (Fig. 4) [62]. The different classes of available treatment are (i) immunotherapy with speciﬁc anti-MERS-CoV antibodies, (ii) molecules with antiviral activity, (iii) symptomatic treatment. Few molecules have shown real curative action and the reports in the literature generally describe isolated cases or small series of cases. More studies have focused on associated treatment and supportive care. At this time, preventive therapies are still in preclinical stages.

7.1. Immunotherapy

7.1.1. Convalescent plasma

The efﬁcacy and safety of plasma from convalescent patients have not been assessed. Three separate reports concluded that such therapeutic approaches were inappropriate [63] One trial is listed on www.clinicaltrials.gov

7.1.2. Intravenous immunoglobulins (IgGs)

Two cases of therapy with intravenous polyclonal IgGs have been reported. In one of them, the IgGs originated from donors in regions negative for MERS speciﬁc antibodies.

Several monoclonal antibodies were tested and seemed to show anti-MERS-CoV activity in vitro [64] No clinical trials are currently underway. Recently, a phase I placebo-controlled, dose escalation study evaluated the efﬁcacy of polyclonal IgGs produced by transchromosomal cattle with human immunoglobulin genes immunized with the MERS-CoV spike (S) protein [65] The primary outcome of tolerance to a single dose was reached. The secondary pharmacodynamic endpoint (serum neutralization activity) showed efﬁcacy with a dose of 50 mg/kg. No phase II trials are currently underway. A phase I study has been registered to assess the

Fig.

immunogenicity and tolerance of a combination of two monoclonal anti-MERS-CoV antibodies. The study has not yet started recruiting patients.

7.2. Antivirals

7.2.1. Interferons (IFN)

Infection with MERS-CoV reduces the host’s interferon response. MERS-CoV is 100 times more sensitive to IFN- . Treatment with IFN- has been reported for many clinical cases and several retrospective cohort studies have been performed, in combination with ribavirin, lopinavir or mycophenolate mofetil (MMF). None of these studies have demonstrated increased overall survival. One study reported increased survival at D14 but not at D30 for critically ill intubated and ventilated patients [66]. A IFN/MMF combination trial is currently underway (see below).

7.2.2. Ribavirin

High doses of ribavirin have shown anti-MERS-CoV activity in vitro. Ribavirin has been used to treat patients in Saudi Arabia as well as in France for the most severe cases managed in ICUs [67]. No signiﬁcant effects were demonstrated either on the mortality rate or the time spent in the ICU.

7.2.3. Protease inhibitors

Ritonavir-boosted lopinavir has shown efficacy against MERSCoV in vitro. As a result, the FDA has extended the indications of lopinavir to patients infected with MERS-CoV. Two case reports (in Greece and Korea) have described improvement in patients treated with lopinavir, type 1 interferon and ribavirin [68] A phase II-III clinical trial is registered on clinicaltrials.gov. The aim of this study is to evaluate the feasibility, efficacy and safety of the combination lopinavir/ritonavir/recombinant IFN -1b vs. a placebo in patients with confirmed MERS receiving optimal symptomatic care.

7.2.4. Chloroquine

Chloroquine is among the molecules approved by the FDA following in vitro studies. No clinical data or studies support its use in vivo at the present time.

7.2.5. Nitazoxamide

In vitro, anti-MERS-CoV activity has been demonstrated for doses of nitazoxamide that could be reached with two daily oral doses. No clinical data or studies support its use in vivo at the present time [69]

7.2.6. Mycophenolate mofetil (MMF)

In vitro, anti-MERS-CoV activity has been demonstrated for doses of MMF that are acceptable for use in humans. MMF seems to show a synergistic effect with IFN- 1b in vitro [70] But in a non human primate common marmosets model, animals treated with MMF developed more severe lesions and showed a higher case fatality rate compared with untreated animals [70] In contrast with animal model, the combination IFN- 1b/MMF was administered to 8 patients in Saudi Arabia. All the patients survived but had lower APACHE II scores that other patient groups [71]

7.2.7. Alisporivir

Alisporivir has been shown to provide additive in vitro antiMERS-CoV activity when used in combination with ribavirin. No clinical data or studies support its use in vivo at the present time [72]

7.2.8. Silvestrol

Silvestrol is a molecule of the ﬂavagline family found in plants. It binds to eIF4A and enhances the afﬁnity of eIF4A for mRNA.

This blocks helicase activity and inhibits protein translation. A recent in vitro study demonstrated that silvestrol has anti-MERSCoV activity [73] No clinical data or studies support its use in vivo at the present time.

7.2.9. Corticosteroids

Corticosteroid therapy is currently the most widely studied therapeutic option. In a retrospective study, Arabi et al. [67] compared the outcome of 309 patients with conﬁrmed MERS-CoV infection managed in an ICU setting and treated with (151) or without (159) corticosteroid therapy. The overall fatality rate was 67%. Univariate analysis showed that mortality in the ICU, during the hospital stay or at 90 days was higher in the corticosteroid group. Then, following adjustment using a marginal structural model for causal inference, corticosteroid therapy was shown not to be associated with mortality, but delayed virus clearance. These ﬁndings, together with the absence of any description of the adverse effects caused by corticosteroid treatment, argue against the use of corticosteroids.

7.3. Extracorporeal membrane oxygenation (ECMO)

A retrospective study was recently carried out in Saudi Arabia in MERS-CoV patients with refractory respiratory failure [74] The patients were included in the study from 2014 to 2015 in ﬁve ICUs. The study consisted of two patient groups: ECMO versus conventional treatment. The primary endpoint was inhospital mortality. Secondary endpoints included the length of stay in the ICU and in hospital. Thirty-ﬁve patients were included: 17 were treated with ECMO and 18 received conventional care. Both groups had similar baseline characteristics. Inhospital mortality was lower in the ECMO group (65 vs. 100%; P = 0.02) although they stayed longer in the ICU (median stay of 25 days vs. 8 days; P < 0.01). The overall time in hospital was similar in both groups (median stay of 41 vs. 31 days; P = 0.421). In addition, patients in the ECMO group showed improved PaO2/FiO2 values at 7 and 14 days after admission into the ICU (124 vs. 63, and 138 vs. 36, respectively; P < 0.05), and lower levels of vasoactive amines at D1 and D14 (29 vs. 80%, and 36 vs. 93%, respectively; P < 0.05). The results of this study support the use of ECMO as salvage treatment for MERS patients with respiratory failure, as is the case for other respiratory infections.

8. Vaccine development

Two trials with candidate vaccines are currently registered at https://clinicaltrials.gov/ct2/home. A phase-I clinical trial on healthy volunteers was set up to evaluate the safety and immunogenicity of a plasmid DNA vaccine (GLS-5300) that expresses the S protein of MERS-CoV. This trial was planned to last one year and started in 2016. No results are available yet. A second phase-I trial was started by Oxford University in January 2018. It uses a chimpanzee adenovirus vector containing the MERS-CoV S protein gene [75] Patient inclusion is currently underway. Many other candidate vaccines using various different technologies are at a less advanced stage of development.

9. Conclusions

The MERS epidemic started in 2012. In contrast with SARS-CoV that disappeared 2 years after it ﬁrst appeared, MERS-CoV continues to persist in the Middle East 6 years later. Although the disease has not become pandemic, outbreaks have occurred worldwide. Today, it is impossible to predict with certainty whether MERS-CoV will disappear or continue to remain a threat for human populations. Efﬁcient vaccine development for host ani-

(2019), https://doi.org/10.1016/j.medmal.2019.10.004

mals and humans could play a key role in tilting the balance from potentially-pandemic to MERS-CoV elimination. Furthermore, the epidemiological and viral determinants of the emergence of MERSCoV in the Middle East are difﬁcult to comprehend, due to the high seropositivity rate of African dromedary camels but no similar disease in local human populations.

The constant increase of transcontinental travel, in particular towards the main focal points of MERS outbreaks with religious pilgrimages and mass tourism, raises the problem of the management of patients suspected of MERS-CoV infection and the absence of efﬁcient treatment options to this date. The main problem in non-epidemic countries is to detect a MERS-CoV case among a great number of non-MERS patients. In France, with the exception of the ﬁrst 2 cases, no further cases have been detected. The current strategy is to isolate any suspicious cases as rapidly as possible to contain the infection and prevent local outbreaks as seen in South Korea. The ability to rapidly test patients suspected to have MERS-CoV infection is the cornerstone of this strategy. The experience gained over the last few years by the health community will also help deal with any respiratory infections that will emerge in the future.

Disclosure of interest

The authors declare that they have no competing interest.

Acknowledgments

The chapters on the origin, emergence, structure, transmission mechanisms, prevention and diagnostic methods were mainly written MB, NH, and BV.

BV produced the ﬁgures.

The chapters on clinical presentation, prognosis and available treatment options were mainly written by AB and CB.

All authors read, amended and agreed with the entire ﬁnal manuscript.

References

[1] Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus ADME, Fouchier RAM. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012;367:1814–20, http://dx.doi.org/10.1056/NEJMoa1211721

[2] WHO. Middle East respiratory syndrome coronavirus (MERS-CoV). WHO; 2018. http://www.who.int/emergencies/mers-cov/en/.(accessed March 5, 2018).

[3] Cho SY, Kang J-M, Ha YE, Park GE, Lee JY, Ko J-H, et al. MERS-CoV outbreak following a single patient exposure in an emergency room in South Korea: an epidemiological outbreak study. Lancet 2016;388:994–1001, http://dx.doi.org/10.1016/S0140-6736(16)30623-7

[4] World Health Organization. Consensus document on the epidemiology of severe acute respiratory syndrome (SARS). World Health Organization; 2003. https://apps.who.int/iris/handle/10665/70863.

[5] Forni D, Cagliani R, Clerici M, Sironi M. Molecular evolution of human coronavirus genomes. Trends Microbiol 2017; 2017;25:35–48, http://dx.doi.org/10.1016/j.tim.2016.09.001

[6] van Boheemen S, de Graaf M, Lauber C, Bestebroer TM, Raj VS, Zaki AM, et al. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. MBio 2012;3, http://dx.doi.org/10.1128/mBio.00473-12

[7] Bermingham A, Chand MA, Brown CS, Aarons E, Tong C, Langrish C, et al. Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012. Euro Surveill 2012;17:20290.

[8] WHO | Background and summary of novel coronavirus infection–as of 21 December 2012. WHO; 2012. http://www.who.int/ csr/disease/coronavirus infections/update 20121221/en/(accessed March 21, 2018).

[9] Woo PCY, Wang M, Lau SKP, Xu H, Poon RWS, Guo R, et al. Comparative analysis of twelve genomes of three novel group 2c and group 2d coronaviruses reveals unique group and subgroup features. J Virol 2007;81:1574–85, http://dx.doi.org/10.1128/JVI.02182-06

[10] Müller MA, Meyer B, Corman VM, Al-Masri M, Turkestani A, Ritz D, et al. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological stud. Lancet Infect Dis 2015;15:629, http://dx.doi.org/10.1016/S1473-3099(15)00029-8

[11] Memish ZA, Cotten M, Meyer B, Watson SJ, Alsahaﬁ AJ, Al Rabeeah AA, et al. Human infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerging Infect Dis 2014;20:1012–5, http://dx.doi.org/10.3201/eid2006.140402

[12] Müller MA, Corman VM, Jores J, Meyer B, Younan M, Liljander A, et al. MERS coronavirus neutralizing antibodies in camels, Eastern Africa, 1983–1997. Emerging Infect Dis 2014;20:2093–5, http://dx.doi.org/10.3201/eid2012.141026

[13] Corman VM, Jores J, Meyer B, Younan M, Liljander A, Said MY, et al. Antibodies against MERS coronavirus in dromedary camels, Kenya, 1992–2013. Emerging Infect Dis 2014;20:1319–22, http://dx.doi.org/10.3201/eid2008.140596.

[14] Miguel E, Chevalier V, Ayelet G, Ben Bencheikh MN, Boussini H, Chu DK, et al. Risk factors for MERS coronavirus infection in dromedary camels in Burkina Faso, Ethiopia, and Morocco, 2015. Euro Surveill 2017:22, http://dx.doi.org/10.2807/1560-7917.ES.2017.22.13.30498

[15] Sabir JSM, Lam TT-Y, Ahmed MMM, Li L, Shen Y, Abo-Aba SEM, et al. Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia. Science 2016;351:81–4, http://dx.doi.org/10.1126/science.aac8608

[16] van Boheemen S, de Graaf M, Lauber C, Bestebroer TM, Raj VS, Zaki AM, et al. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. MBio 2012:3, http://dx.doi.org/10.1128/mBio.00473-12

[17] Menachery VD, Mitchell HD, Cockrell AS, Gralinski LE, Yount BL, Graham RL, et al. MERS-CoV Accessory ORFs Play Key Role for Infection and Pathogenesis. MBio 2017:8, http://dx.doi.org/10.1128/mBio.00665-17

[18] van Doremalen N, Miazgowicz KL, Milne-Price S, Bushmaker T, Robertson S, Scott D, et al. Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4. J Virol 2014;88:9220–32, http://dx.doi.org/10.1128/JVI.00676-14

[19] Millet JK, Whittaker GR. Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein. Proc Natl Acad Sci U S A 2014;111:15214–9, http://dx.doi.org/10.1073/pnas.1407087111

[20] Neuman BW, Kiss G, Kunding AH, Bhella D, Baksh MF, Connelly S, et al. A structural analysis of M protein in coronavirus assembly and morphology. J Struct Biol 2011;174:11–22, http://dx.doi.org/10.1016/j.jsb.2010.11.021

[21] WHO | Middle East respiratory syndrome coronavirus (MERS-CoV)–update. WHO; 2014. http://www.who.int/csr/don/2014 05 15 mers/en/(accessed April 9, 2018).

[22] Chowell G, Abdirizak F, Lee S, Lee J, Jung E, Nishiura H, et al. Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study. BMC Med 2015;13:210, http://dx.doi.org/10.1186/s12916-015-0450-0

[23] New case of MERS-CoV identiﬁed in the United Kingdom. European Centre for Disease Prevention and Control 2018. http://ecdc.europa.eu/en/newsevents/new-case-mers-cov-identiﬁed-united-kingdom (accessed October 22, 2018).

[24] Pavli A, Tsiodras S, Maltezou HC. Middle East respiratory syndrome coronavirus (MERS-CoV): prevention in travelers. Travel Med Infect Dis 2014;12:602–8, http://dx.doi.org/10.1016/j.tmaid.2014.10.006

[25] Memish ZA, Al-Tawﬁq JA, Makhdoom HQ, Assiri A, Alhakeem RF, Albarrak A, et al. Respiratory tract samples, viral load, and genome fraction yield in patients with Middle East respiratory syndrome. J Infect Dis 2014;210:1590–4, http://dx.doi.org/10.1093/infdis/jiu292

[26] Feikin DR, Alraddadi B, Qutub M, Shabouni O, Curns A, Oboho IK, et al. Association of Higher MERS-CoV Virus Load with Severe Disease and Death, Saudi Arabia, 2014. Emerging Infect Dis 2015;21:2029–35, http://dx.doi.org/10.3201/eid2111.150764

[27] WHO | Laboratory testing for Middle East Respiratory Syndrome Coronavirus. WHO; 2018. http://www.who.int/csr/disease/coronavirus infections/merslaboratory-testing/en/(accessed April 9, 2018).

[28] Modjarrad K, Moorthy VS, Ben Embarek P, Van Kerkhove M, Kim J, Kieny M-P. A roadmap for MERS-CoV research and product development: report from a World Health Organization consultation. Nat Med 2016;22:701–5, http://dx.doi.org/10.1038/nm.4131

[29] Müller MA, Meyer B, Corman VM, Al-Masri M, Turkestani A, Ritz D, et al. Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study. Lancet Infect Dis 2015; 2015;15:629, http://dx.doi.org/10.1016/S1473-3099(15)00029-8

[30] Reusken C, Mou H, Godeke GJ, van der Hoek L, Meyer B, Müller MA, et al. Speciﬁc serology for emerging human coronaviruses by protein microarray. Euro Surveill 2013;18:20441.

[31] Trivedi S, Miao C, Al-Abdallat MM, Haddadin A, Alqasrawi S, Iblan I, et al. Inclusion of MERS-spike protein ELISA in algorithm to determine serologic evidence of MERS-CoV infection. J Med Virol 2018;90:367–71, http://dx.doi.org/10.1002/jmv.24948

[32] Guery B, Poissy J, el Mansouf L, Séjourné C, Ettahar N, Lemaire X, et al. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission. Lancet 2013;381:2265–72, http://dx.doi.org/10.1016/S0140-6736(13)60982-4

[33] Alhamlan FS, Majumder MS, Brownstein JS, Hawkins J, Al-Abdely HM, Alzahrani A, et al. Case characteristics among Middle East respiratory syndrome coronavirus outbreak and non-outbreak cases in Saudi Arabia from 2012 to 2015. BMJ Open 2017;7:e011865, http://dx.doi.org/10.1136/bmjopen-2016-011865.

[34] Choi WS, Kang C-I, Kim Y, Choi J-P, Joh JS, Shin H-S, et al. Clinical Presentation and Outcomes of Middle East Respiratory Syndrome

in the Republic of Korea. Infect Chemother 2016;48:118–26, http://dx.doi.org/10.3947/ic.2016.48.2.118

[35] Oboho I, et al. 2014 MERS-CoV outbreak in Jeddah–a link to health care facilities. NEJM 2015;372:846–54.

[36] Ki M. 2015 MERS outbreak in Korea: hospital-to-hospital transmission. Epidemiol Health 2015;37:e2015033, http://dx.doi.org/10.4178/epih/e2015033

[37] Mohd HA, Memish ZA, Alfaraj SH, McClish D, Altuwaijri T, Alanazi MS, et al. Predictors of MERS-CoV infection: A large case control study of patients presenting with ILI at a MERS-CoV referral hospital in Saudi Arabia. Travel Med Infect Dis 2016;14:464–70, http://dx.doi.org/10.1016/j.tmaid.2016.09.008

[38] Ahmed AE. The predictors of 3- and 30-day mortality in 660 MERS-CoV patients. BMC Infect Dis 2017;17:615, http://dx.doi.org/10.1186/s12879-017-2712-2.

[39] Memish ZA, Zumla AI, Assiri A. Middle East respiratory syndrome coronavirus infections in health care workers. N Engl J Med 2013;369:884–6, http://dx.doi.org/10.1056/NEJMc1308698

[40] Ahmed AE. Estimating survival rates in MERS-CoV patients 14 and 45 days after experiencing symptoms and determining the differences in survival rates by demographic data, disease characteristics and regions: a worldwide study. Epidemiol Infect 2017;2017:1–7, http://dx.doi.org/10.1017/S095026881700293X

[41] Badawi A, Ryoo SG. Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis. Int J Infect Dis 2016;49:129–33, http://dx.doi.org/10.1016/j.ijid.2016.06.015

[42] Sherbini N, Iskandrani A, Kharaba A, Khalid G, Abduljawad M, Al-Jahdali H. Middle East respiratory syndrome coronavirus in Al-Madinah City, Saudi Arabia: Demographic, clinical and survival data. J Epidemiol Glob Health 2017;7:29–36, http://dx.doi.org/10.1016/j.jegh.2016.05.002

[43] Assiri A, McGeer A, Perl TM, Price CS, Al Rabeeah AA, Cummings DAT, et al. Hospital outbreak of middle east respiratory syndrome coronavirus. N Engl J Med 2013;369:407–16, http://dx.doi.org/10.1056/NEJMoa1306742

[44] Zumla A, Hui DS, Perlman S. Middle East respiratory syndrome. Lancet 2015;386:995–1007, http://dx.doi.org/10.1016/S0140-6736(15)60454-8

[45] Garbati MA, Fagbo SF, Fang VJ, Skakni L, Joseph M, Wani TA, et al. A Comparative Study of Clinical Presentation and Risk Factors for Adverse Outcome in Patients Hospitalised with Acute Respiratory Disease Due to MERS Coronavirus or Other Causes. PLoS ONE 2016;11:e0165978, http://dx.doi.org/10.1371/journal.pone.0165978

[46] eCDC, Rapid risk assessment: Severe respiratory disease associated with Middle East respiratory syndrome coronavirus (MERS-CoV), 22nd update. European Centre for Disease Prevention and Control 2018. http://ecdc.europa.eu/en/publications-data/rapid-risk-assessment-severerespiratory-disease-associated-middle-east-11 (accessed September 16, 2018).

[47] Bleibtreu A, Jaureguiberry S, Houhou N, Boutolleau D, Guillot H, Vallois D, et al. Clinical management of respiratory syndrome in patients hospitalized for suspected Middle East respiratory syndrome coronavirus infection in the Paris area from 2013 to 2016. BMC Infect Dis 2018;18:331, http://dx.doi.org/10.1186/s12879-018-3223-5

[48] Aleanizy FS, Mohmed N, Alqahtani FY, El Hadi Mohamed RA. Outbreak of Middle East respiratory syndrome coronavirus in Saudi Arabia: a retrospective study. BMC Infect Dis 2017;17:23, http://dx.doi.org/10.1186/s12879-016-2137-3

[49] Arabi YM, Ariﬁ AA, Balkhy HH, Najm H, Aldawood AS, Ghabashi A, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med 2014;160:389–97, http://dx.doi.org/10.7326/M13-2486

[50] Joob B, Wiwanitkit V. Middle East respiratory syndrome coronavirus infection: a short note on cases with renal failure problem. Ren Fail 2016;38:1749–50, http://dx.doi.org/10.3109/0886022X.2015.1128772

[51] Who Mers-Cov Research Group. State of Knowledge and Data Gaps of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Humans. PLoS Curr 2013;5, http://dx.doi.org/ 10.1371/currents.outbreaks.0bf719e352e7478f8ad85fa30127ddb8

[52] Al-Tawﬁq JA, Hinedi K, Ghandour J, Khairalla H, Musleh S, Ujayli A, et al. Middle East respiratory syndrome coronavirus: a case-control study of hospitalized patients. Clin Infect Dis 2014;59:160–5, http://dx.doi.org/10.1093/cid/ciu226

[53] Saad M, Omrani AS, Baig K, Bahloul A, Elzein F, Matin MA, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis 2014;29:301–6, http://dx.doi.org/10.1016/j.ijid.2014.09.003

[54] Ko J-H, Müller MA, Seok H, Park GE, Lee JY, Cho SY, et al. Serologic responses of 42 MERS-coronavirus-infected patients according to the disease severity. Diagn Microbiol Infect Dis 2017;89:106–11, http://dx.doi.org/10.1016/j.diagmicrobio.2017.07.006

[55] Alfaraj SH, Al-Tawﬁq JA, Alzahrani NA, Altwaijri TA, Memish ZA. The impact of co-infection of inﬂuenza A virus on the severity of Middle East Respiratory Syndrome Coronavirus. J Infect 2017;74:521–3, http://dx.doi.org/10.1016/j.jinf.2017.02.001

[56] Arabi YM, Al-Omari A, Mandourah Y, Al-Hameed F, Sindi AA, Alraddadi B, et al. Critically Ill Patients With the Middle East Respiratory Syn-

drome: A Multicenter Retrospective Cohort Study. Crit Care Med 2017, http://dx.doi.org/10.1097/CCM.0000000000002621

[57] Nam H-S, Park JW, Ki M, Yeon M-Y, Kim J, Kim SW. High fatality rates and associated factors in two hospital outbreaks of MERS in Daejeon, the Republic of Korea. Int J Infect Dis 2017;58:37–42, http://dx.doi.org/10.1016/j.ijid.2017.02.008

[58] Shalhoub S, Farahat F, Al-Jiffri A, Simhairi R, Shamma O, Siddiqi N, et al. IFN-(2a or IFN-(1a in combination with ribavirin to treat Middle East respiratory syndrome coronavirus pneumonia: a retrospective study. J Antimicrob Chemother 2015;70:2129–32, http://dx.doi.org/10.1093/jac/dkv085

[59] Kim SY, Park SJ, Cho SY, Cha R-H, Jee H-G, Kim G, et al. Viral RNA in blood as Indicator of Severe Outcome in Middle East Respiratory Syndrome Coronavirus Infection. Emerging Infect Dis 2016;22:1813–6, http://dx.doi.org/10.3201/eid2210.160218

[60] Min C-K, Cheon S, Ha N-Y, Sohn KM, Kim Y, Aigerim A, et al. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity. Sci Rep 2016;6:25359, http://dx.doi.org/10.1038/srep25359

[61] Ko J-H, Park GE, Lee JY, Lee JY, Cho SY, Ha YE, et al. Predictive factors for pneumonia development and progression to respiratory failure in MERS-CoV infected patients. J Infect 2016;73:468–75, http://dx.doi.org/10.1016/j.jinf.2016.08.005

[62] McKimm-Breschkin JL, Jiang S, Hui DS, Beigel JH, Govorkova EA, Lee N. Prevention and treatment of respiratory viral infections: presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference. Antiviral Res 2018;149:118–42, http://dx.doi.org/10.1016/j.antiviral.2017.11.013

[63] Arabi YM, Hajeer AH, Luke T, Raviprakash K, Balkhy H, Johani S, et al. Feasibility of using convalescent plasma immunotherapy for MERSCoV infection, Saudi Arabia. Emerging Infect Dis 2016;22:1554–61, http://dx.doi.org/10.3201/eid2209.151164

[64] Mustafa S, Balkhy H, Gabere MN. Current treatment options and the role of peptides as potential therapeutic components for Middle East Respiratory Syndrome (MERS): a review. J Infect Public Health 2018;11:9–17, http://dx.doi.org/10.1016/j.jiph.2017.08.009

[65] Beigel JH, Voell J, Kumar P, Raviprakash K, Wu H, Jiao J-A, et al. Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus antibody produced from transchromosomic cattle: a phase 1 randomised, double-blind, single-dose-escalation study. Lancet Infect Dis 2018, http://dx.doi.org/10.1016/S1473-3099(18)30002-1

[66] Mo Y, Fisher D. A review of treatment modalities for Middle East Respiratory Syndrome. J Antimicrob Chemother 2016;71:3340–50, http://dx.doi.org/10.1093/jac/dkw338

[67] Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Al Mekhlaﬁ GA, Hussein MA, et al. Corticosteroid Therapy for Critically Ill Patients with the Middle East Respiratory Syndrome. Am J Respir Crit Care Med 2017, http://dx.doi.org/10.1164/rccm.201706-1172OC

[68] Spanakis N, Tsiodras S, Haagmans BL, Raj VS, Pontikis K, Koutsoukou A, et al. Virological and serological analysis of a recent Middle East respiratory syndrome coronavirus infection case on a triple combination antiviral regimen. Int J Antimicrob Agents 2014;44:528–32, http://dx.doi.org/10.1016/j.ijantimicag.2014.07.026

[69] Rossignol J-F. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Pub Health 2016;9:227–30, http://dx.doi.org/10.1016/j.jiph.2016.04.001

[70] Chan JF-W, Yao Y, Yeung M-L, Deng W, Bao L, Jia L, et al. Treatment With Lopinavir/Ritonavir or Interferon-(1b Improves Outcome of MERS-CoV Infection in a Nonhuman Primate Model of Common Marmoset. J Infect Dis 2015;212:1904–13, http://dx.doi.org/10.1093/infdis/jiv392

[71] Al Ghamdi M, Alghamdi KM, Ghandoora Y, Alzahrani A, Salah F, Alsulami A, et al. Treatment outcomes for patients with Middle Eastern Respiratory Syndrome Coronavirus (MERS CoV) infection at a coronavirus referral center in the Kingdom of Saudi Arabia. BMC Infect Dis 2016;16:174, http://dx.doi.org/10.1186/s12879-016-1492-4

[72] de Wilde AH, Falzarano D, Zevenhoven-Dobbe JC, Beugeling C, Fett C, Martellaro C, et al. Alisporivir inhibits MERS- and SARS-coronavirus replication in cell culture, but not SARS-coronavirus infection in a mouse model. Virus Res 2017;228:7–13, http://dx.doi.org/10.1016/j.virusres.2016.11.011

[73] Müller C, Schulte FW, Lange-Grünweller K, Obermann W, Madhugiri R, Pleschka S, et al. Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses. Antiviral Res 2017;150:123–9, http://dx.doi.org/10.1016/j.antiviral.2017.12.010

[74] Alshahrani MS, Sindi A, Alshamsi F, Al-Omari A, El Tahan M, Alahmadi B, et al. Extracorporeal membrane oxygenation for severe Middle East respiratory syndrome coronavirus. Ann Intensive Care 2018;8:3, http://dx.doi.org/10.1186/s13613-017-0350-x

[75] Alharbi NK, Padron-Regalado E, Thompson CP, Kupke A, Wells D, Sloan MA, et al. ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice. Vaccine 2017;35:3780–8, http://dx.doi.org/10.1016/j.vaccine.2017.05.032

Please cite this article in press as: Bleibtreu A, et al. Focus on Middle East respiratory syndrome coronavirus (MERS-CoV). Med Mal Infect (2019), https://doi.org/10.1016/j.medmal.2019.10.004

Another random document with no related content on Scribd:

in with some blue chalk from the Straits of Baffleman, and then I shall chalk out all your wants; so be off, or I shall get the boatswain’s mate to measure you with the end of the fore brace before her arrival, which you may think rather premature.’

When asking him for leave to go on shore he would frequently say, ‘As soon as I have time to chalk you out a barge to take you, I shall attend to this most important business.’ Once on a rainy day he was making some of those remarks, when his foot slipped and he fell on his bottom on the quarter deck. One of the lieutenants said, ‘Had the deck been chalked, sir, it would have saved your fall.’ This vexed him greatly, and seeing us laugh he started us up to the masthead for the remainder of the watch, saying, ‘Take care! As the rigging is not chalked you may slip and get an ugly fall.’

I have already mentioned our bringing home 75 dogs. I messed in the main hatchway berth on the lower deck, with four midshipmen and a scribe. We had eight of those dogs billeted on us. One of them had the name of Thunder. At dinner I once gave him a piece of beef with plenty of mustard rolled up in it. The moment he tasted it, he flew at me and I was obliged to run for it. He never forgot it, and whenever I offered him victuals he would snap at me directly. Another of those dogs used to sleep at the foot of Charley Bisset’s cot, and when the quartermaster would call the watch this dog would fly at him if he came near Bisset, who would often plead ignorance of being called, and by that means escape going on deck for the first hour of the watch. We had a drunken Irishman, by the name of Collins, who, when sent to the hospital at St. John’s, contrived to get liquor in spite of all precaution to prevent it. At last it was found out by the following circumstance. He had one of those dogs that could do anything but speak. He used to sling a bottle round his neck and then put a shilling in his mouth and send him off in the evening. The dog knew well where to go, for he had been often there with Collins. It was to a public-house, between the hospital and St. John’s. He’d howl as soon as he got there; the landlord knew well what he wanted, and would fill the bottle with rum. The dog would then drop the shilling, but not before, and scamper off to return to his master; not at the gate of the hospital—he was too cunning for that—but like a Roman conqueror, through a hole in the wall; when one night he was discovered by the watch going their rounds, and by that means the

business was brought to light. From the ingenuity of the master and his dog, both escaped punishment.

Our armourer was a man who would drink like a fish, and one morning coming to the brewery complaining of thirst, the cooper, a droll and wicked fellow, gave him some essence of spruce, and the armourer took a good swig before he found out his mistake. The moment he could speak he asked what it was he had taken. The cooper said he was very sorry for what had happened, but he thought it right to acquaint him it was some stuff they had to poison rats. The armourer was struck dumb with terror, but at last, in a paroxysm of rage, swore that the cooper should die first; and drawing out a large knife, gave chase and certainly would have put an end to his joking had he not locked himself up in the brewery in great tribulation, as the armourer was trying all in his power to break open the door. However, the poor fellow was at last made sensible it was a joke, and had some double spruce given him to make amends—which had the desired effect.

Our second assistant surgeon was another wet soul, and coming from the play half drunk went to sleep in an empty cask that was lying on Quigley’s Wharf, when a squall of wind rolled the cask overboard and poor old Andrew Reardon would have been drowned, had it not been for the boat-keeper of the cutter. Old Andrew is now dead. He dearly loved grog, and when told that new rum was a bad article he said he didn’t care; if it fractured the brain it was all he wanted.

With a few exceptions we had a terrible lot of wild midshipmen. Some of them were members of the Hell-fire Club,[36] and used to dress, when going to that place, in scarlet coats with black velvet collars and cuffs, black waistcoat, breeches, and stockings, and hair powdered. Those chaps would play all manner of wicked pranks on board, such as pouring molasses under the heads of those who slept in the tier, and others would have a hook and line with which they’d haul our quilts and blankets off in the night, and then heave water over us, at the same time making a squeaking noise; while others, in the secret, would say it was the gibbering of a ghost, and that the tier was haunted; but that they would ask the parson (a wet soul) to lay the spirit, not in the Red Sea, but in the large pond near St. Johns. One poor fellow, a clerk whose name was Newnham, but nicknamed

Newcome, they got in the tier one night in the dark, and swore it was the admiral’s cow that had got adrift. It was no use for the poor fellow to say he was not that personage; for a selvagee was clapped round him in an instant with a hauling line made fast, with which they roused him up the hatchway in a moment, terrified almost to death.

I must here mention the shifts my old messmate, Ben Morgan, and myself were put to the last year we were at St. John’s. Our captain used to pay our mess and washing bills, for which he was repaid on our return to England. It happened one morning when the washing bill was sent in, that he observed our towels were inserted with other articles; upon which he sent for us, and after a severe reprimand upon our extravagance, adding that we ought to have washed the towels ourselves, he dismissed us, saying he should give no more money to be fooled away in that manner, and that we deserved to be well flogged in the bargain. We were glad enough to steer clear of him. In respect of the money he was as good as his word; for devil a farthing more would he let us have, and we were sadly put to it; for we had only Tom Cod (caught alongside) for breakfast, salt beef or pork for dinner, and Tom Cod for tea in the evening. At last we in some measure got over our difficulties by going to the hills and gathering a weed called maidenhair, a good substitute for tea; and with molasses instead of sugar, poor Ben and myself fared gloriously.

While at St. John’s two of our seamen deserted and got into the woods on their way to an out port; and they had nearly been devoured by the wolves who attacked them in a hut, where they remained three days without provisions, and had great difficulty and danger in coming back to the ship, where they were treated with two dozen apiece.

Our captain to keep us in good order placed a Mr. Stack as father of our mess. He was cursed surly and disagreeable, but I believe meant well; only [he had] an ugly way of showing his kindness. When in good temper (which was seldom) he would say ‘My son,’ when he addressed any of us; but generally, ‘I’ll split your ear.’ This man drew a very long bow and would frequently tell the most unaccountable stories. I have heard him relate that the ghost of Commodore Walsingham[37] (who he had served under, and who was

lost in the Thunderer, 74, in the West Indies, in the hurricane of 1780) appeared to him when he was a slave on the coast of Barbary, where he was chained by the leg for upwards of a twelvemonth, and after undergoing innumerable hardships he was released by a Moorish lady who fell in love with him and paid his ransom to a considerable amount. This was too much to swallow from a fellow as ugly as the old Diligente’s [figure-] head.

When at Spithead and in the harbour, our ship’s company had a violent quarrel with the crew of the Grampus 50, commanded by Ned Thompson[38] the poet, who had the Coast of Guinea station, and several battles were fought with various success. The quarrel originated in some of our fellows saying they of the Grampus, when on the coast, lived chiefly on monkey soup, except on Sundays, and then they were regaled on roast parrots. For this they swore to murder every snow-eating son of a bitch belonging to the Salisbury whenever they could catch them. One of the mates of the Grampus had the impudence, while we were in harbour, to drop under our bows with a launch-load of his people who had been for stores to the dockyard, and challenge ours to fight; for which he had very near been brought to a court martial.

Our quarrelsome blades had another row with the riggers; and when the latter would pass the ship in their launches, our fellows would thrust their heads out of the ports and sing out—‘I say, Mortimer, drop in the launch, make fast a hawser to the NW buoy, take three round turns and a half hitch, seize the end back and come on board with the launch.’ This occasioned many a battle, and the riggers generally got the worst of it; for we had some from that land which produces the finest peasantry in the world on board, and woe betide those who came in contact with them. We had the O’Ryans, the O’Gallaghers, the Macartys, the O’Donovans, the Murphys, the O’Flahertys, the O’Tooles and the O’Flanagans, and great part of the ship’s company were Irish and very quiet when not disturbed. One of those fellows—Darby Collins, who had the dog that I have mentioned at the hospital—did positively beat at the back of the Point, Portsmouth, eleven men by cracking their heads at single-stick one after the other. He was a tall, raw-boned Irishman, a Garry-owen boy that stood up manfully for the honour of his country.

The following are the names of the officers belonging to the Salisbury:—

J C, F.R.S., Vice-Admiral.

Dead [1790]. An admiral; a most able officer and great astronomer. He was captain of the fleet on board the Royal George with Admiral Hawke when he defeated the French under Conflans.—[D.N.B.]

J B, Esq., Captain.

Dead. A retired rear-admiral.

H D, 1st Lieutenant.

Dead. He was the senior commander on the list; had the outpension of Greenwich Hospital. A good seaman, but satirical, and too fond of mastheading.

R R, 2nd Lieutenant.

Dead. A commander; a fine-looking fellow and the best officer in the ship.

J L, 3rd Lieutenant.

Dead. A good sailor, very passionate, and swore like the devil.

J S, 4th Lieutenant.

Dead. A rear-admiral of the white. Fond of mastheading for little or nothing. More of him when I come to the Edgar.

[G] T, Master.

Dead. A quiet, good man. [William Henry Brown Tremlett (captain, 1802), his servant].

[J] P, Captain of Marines.

Dead. A strange fish.

[W] G, Lieutenant of Marines.

Dead. A good officer.

T P (I forget his name).

Dead. Had no dislike to grog.

[J] C, Purser.

Drowned. Took care of his eights.[39]

[E] P, Surgeon.

Dead. Crabbed as the devil.

A G, Admiral’s Secretary.

Dead. A very clever fellow; was magistrate at Bow Street.

[C] S, Gunner.

Dead. Fractious from long illness. [D.D. in pay-book: no date.]

D—— (I forget his name) [E D], Gunner.

Dead. Lethargic; always dozing on the forecastle; a sleepy, good man.

[S] B, Carpenter.

Dead. A quiet, good man; clever in his profession.

[J] H, Boatswain.

Dead. An infernal tyrant; a good sailor; a sycophant, a Hun, a Goth, a Vandal; a fellow that was made too much of by those who ought to have kept him at proper distance.

[J] MC, 1st Assistant Surgeon.

Dead. A surgeon at St. John’s; a very excellent fellow, and clever in his profession.

A R, 2nd Assistant Surgeon.

Dead. A surgeon, R.N. A very worthy fellow, who loved his glass of grog.

D B, Master’s Mate.

Dead. A lieutenant; a gentleman very much respected.

[S] S, Master’s Mate.

Uncertain. A tyrant who I well remember, although it is upwards of fifty years since I saw the blustering, swaggering bully.

R L, Midshipman.

Vice-admiral of the white; a baronet and K.C.B. A most excellent officer, seaman, and gentleman. [Admiral, 1846; died 1848.—O’Byrne.]

C B, Midshipman.

Dead. Wild and thoughtless, but a good-natured, harmless fellow.

[H] P, Midshipman [afterwards A.B.].

Dead. A tyrannical fellow and member of the Hell-fire Club.

[J] S, Midshipman [afterwards A.B.].

Dead. A member of the Hell-fire Club; a dandy and droll fellow.

[R] H, Midshipman. [A.B.].

Uncertain. A noisy, tyrannical fellow; member of the Hell-fire Club; nicknamed Hawbuck.

[T J] S, Midshipman. [A.B.]

Uncertain. This fellow wanted to be a tyrant, but was too great a fool.

[C] M, Midshipman.

East India House.

[T] M, Midshipman.

Uncertain. A good fellow; called Old Siolto.

[J W] H, Midshipman. [A.B.]

A post captain; played the violin well. [Died 1841.]

R M, Midshipman.

Dead. A commander. Bob was a good fellow.

R. B. V, Midshipman.

Dead [1831]. A post captain; C.B.; fought well; called Don Diego Del Vinsanti Hispaniola Whiskerando. More of him when I come to the Victory.—[D.N.B.]

P B, Midshipman.

Dead. A loss to the service.

B B, Midshipman, son of the captain. [A.B.]

Dead. A commander; a very worthy character. [Two other (presumably) sons of the captain, Matthew Barton and Daniel, were rated captain’s servants.]

C G, Midshipman.

This gentleman was Captain of the Aurora, 32, and was unfortunately drowned in Yarmouth Roads, Isle of Wight, going off to his ship in the evening [1796].

J M, Midshipman.

A commander; good-natured and droll. [Captain (retired), 1840; died 1852.—O’Byrne.]

R. B. L, Midshipman.

A retired rear-admiral. [Vice-admiral, 1840: died 1847.— O’Byrne.]

J T, Midshipman.

Marshal at Gibraltar.

B M, Midshipman.

Dead. A lieutenant. Poor Ben! you and I have spent many an hour at the masthead for little or nothing.

H B, Midshipman.

Dead. A lieutenant. An old schoolfellow of mine. Harry was passionately fond of grog, which made him an ungrateful return by taking him out of this world before it was agreeable. Nicknamed Ram, Cat, Batt, and Rammon the Butcher.

W G, Midshipman.

Dead. A lieutenant. A very good fellow and good sailor, but fond of grog and boasting.

N T, Midshipman.

A rear-admiral. [Died 1844.—Marshall, iii. 294.]

I, Midshipman.

Dead. A worthy fellow; a loss to the service.

R S T, Midshipman.

Killed in a duel with Lord Camelford.

G. N[] T, Midshipman.

A commander. Brother of the above; a very good fellow. [Died 1865.—O’Byrne.]

A D, Midshipman.

Dead. A drunken Hun.

F G, Midshipman.

Dead. A lieutenant; wonderfully great, in his own opinion.

[W] E, Midshipman.

Dead. A commander, sickly and proud.

L A B, Midshipman.

An admiral, G.C.B. and G.C.H.; chief naval aide-de-camp to the king. [Died 1846.—D.N.B.]

S, Midshipman.

Uncertain. Remember little of him, and that no good.

J. A. G, Midshipman. [Entered Dec. 12, 1783.]

A commander.

W P, Schoolmaster.

Dead. A purser; Fit Pye, Fit man.

J A, Captain’s Clerk.

A purser and retired storekeeper of Portsmouth yard.

H R H, Admiral’s Office.

Was a purser in the navy but resigned the situation; a most worthy fellow. We were in four ships together.

[W] W, Admiral’s Office. [A.B.]

Uncertain. A very droll and noisy fellow.

[T] L, Admiral’s Office. [Admiral’s servant.]

Dead. A purser; a very satirical gentleman.

C, Admiral’s Office.

Dead. A purser; another noisy, droll fellow.

N, Admiral’s Office.

Uncertain. A quiet, easy, poor fellow; made a butt of.

[T] S, used to keep the forecastle watch as Midshipman

Uncertain. Made a gunner; I have mentioned him before with his long bow.

ORESTES, 18.

I joined the son of Agamemnon early in 1786, fitting in Portsmouth Harbour for Channel service, to cruise after smugglers from Dunnose to the Start; Manley Dixon, Esq., commander.

This brig was considered the finest in the service. She measured 32 ft. 9 in. on the beam, and drew 17 ft. 4 in. abaft, 13 ft. 4 in. forward, and [was] nearly 450 tons, mounting 18 long nines, and pierced for 26. She and the Pylades (called the Hercules and Mars) were taken from the Dutch by Macbride in the Artois, 44.[40] She sailed remarkably well, but was a wet soul, shipping seas over the bows and washing the men at the wheel. She would never condescend to rise to a sea, but dash right through. After a few cruises, when off the Isle of Purbeck we observed two large Hogboats[41] among the rocks, and several people on horseback upon the cliffs above the spot. Sent our boats to examine, and found them to be smugglers with seven hundred tubs of liquor, which we seized, and landed the smugglers at Swanage. After landing our tubs at the Custom House, Portsmouth, we anchored at Yarmouth, in the Isle of Wight, our place of rendezvous, where we remained a short time, and then resumed our cruising; sometimes in company with the Hebe, 36, on the same station; and then put into Guernsey, where we stayed but a short time and ran out in a gale of wind. Caught fire in the master’s cabin over the magazine, by the candles rolling against his curtains. It created great alarm, but was soon got under. During the time, it occasioned the utmost terrors among the ship’s company. Several of them got into the forechains, the head, and on the bowsprit, ready to jump overboard. However, they seemed to have as much dread of water as they had of the fire and remained stationary. It was ludicrous to see the captain with a speaking trumpet, exerting himself to keep order, and the carpenter’s wife catching him round

the legs, and while he was calling for Water, she was screaming out Fire.

When our cruise was over we returned to Yarmouth, where our surgeon turned mad and cut some unaccountable capers. One morning early, he came upon deck and gave some orders to the officers of the watch, who paid no attention to them. Upon this he got hold of a crow[42] that was in the becket over one of the guns, and began to run a-muck,[43] and cleared the deck in a moment. Sentries and all took to their heels, and it was some time before an opportunity offered to get him below. At last he was got to his cabin in the gunroom, with four marines and a midshipman to guard him; but he soon made a start from his den and made no more of the marines than if they were sparrows. He first caught hold of two and knocked their heads together, and then punished the others, who from fear, made little resistance. He next attacked Patterson, the master, and swore he should stand auctioneer as it was his intention to sell his effects. I never saw a more ludicrous scene when the master, to humour him, began to put his things up to auction and we, outside (for we were afraid to go in) the gunroom, bidding for them. After the sale was over, he made Patterson put on two of his coats— one of them the Windsor uniform[44]—and then upset him and rolled him about the gunroom, swearing he was a beer cask. Then rushing out, he belaboured all that he met with, and went upon deck and remained cock of the walk until he came down of his own accord, and went to bed, saying, ‘You shall hear from me presently.’ However, good care was taken to secure him, and he was soon after sent to sick quarters, being a dangerous subject, and glad enough we were to get rid of him.

There was at Yarmouth a truly hospitable gentleman, a Captain Urry[45] of the Royal Navy, well known to officers in the service, who kept open house and gave large parties. He was the life and soul of Yarmouth, which place has never been worth going to since his death. On one of these parties, our barge (for we had a barge) was ordered to attend and tow a sloop full of company (it being calm) from Yarmouth to Lymington, and I was the midshipman sent, and had directions to land them, and to take orders from a captain in the navy, who was one of the party. This being done, a half-guinea was given to the men to drink, and I was desired to let them go on shore

for that purpose. After they had their grog I missed the strokesman of the barge, a tall Irishman named McCarthy, who was nowhere to be found; in fact he had deserted. On my return I reported this to Lieutenant Jeynes who abused me and said he would write against me to the captain (who lived on shore) for suffering this tall Paddy to run away. The next morning he was as good as his word, and sent me with the letter. The captain, on reading it, gave me a severe reprimand, and sent me on board in a hurry, saying I should hear more of it very shortly. In a day or two after he came on board and we left Yarmouth for Spithead. I was in hourly expectation of some terrible explosion, as my friend the lieutenant was constantly reminding me of the subject. After the ship was moored the captain went on shore, and Jeynes soon followed. The master being commanding officer, I asked him permission to go and see my friends, which he granted, and I never joined the Orestes after.

I was but a youngster then. Had I known as much as I did soon after, I would have demanded a court martial on myself, and would have brought Lieutenant Jeynes to another for tyranny and oppression, which he was guilty of in many instances and had laid himself open to anyone who might think proper to bring the charges forward. He was obliged to leave the Orestes soon after. He had formerly (as I have understood) been a purser, and was broken by court martial; but having served his time as midshipman, got to be made a lieutenant, and died a retired commander.

Whenever the Orestes came in I used to keep out of the way. I lived at Gosport and was always on the watch, and when she came into Spithead I had timely notice and would set off for the country. After returning from one of those excursions, I was hiding behind a screen in our parlour; on the other side sitting by the fire was an old schoolfellow of mine and a young lady in earnest conversation about me. The former among other remarks said he believed I had made away with myself. This observation I could not brook, and catching hold of a large family Bible that was on a table near me (and which I have at this moment) I hove it over the screen and hit my friend on the jaw and knocked him down as flat as a flounder. I set off as fast as I could, leaving them in the utmost consternation; and he told me a long time after that he thought it was the devil that had felled him, until he saw the Bible. Captain Dixon, I believe, was aware that

Lieutenant Jeynes had blamed me wrongfully, as he sent me my prize money and gave me a good certificate, and offered to take me again, for which he has my most grateful thanks, and I hope to live to see him admiral of the fleet.[46]

He was a very smart officer, and did everything in his power to teach the midshipmen their duty. We used to take helm and lead, and reef the main topsail; also pull in the boats upon particular occasions, such as going along shore in the night after smugglers, &c. When we were at Guernsey, the captain in the kindest manner allowed the petty officers a moderate quantity of liquor in each of their messes; but the sergeant of marines, not content with this indulgence, smuggled twenty kegs into the ship. When this was told the captain, he ordered all the kegs to be brought on deck and stove. The sergeant stood, like Niobe, in tears for his loss. It was a most laughable sight, as the liquor was running out mixed with salt water (for the ship rolled a great deal), to see the fellows laying down like beasts on the deck and licking up, while the boatswain’s mates were thrashing them to no purpose. The sergeant, I believe, was reduced to the ranks.

I shall mention a few strange fellows we had on board, and first Mr. Quinton the mate. This gentleman was a good sailor, and was very fond of gin grog, and used to say it agreed with him so well and made his flesh so firm. It was determined one day to count how many glasses he drank from morning until evening; and, if I remember correctly, twenty-six tumblers of good Hollands and water made the number; for in the good old times we never sported Cockney gin. I must in justice declare that Mr. Quinton was no drunkard; I never saw him disguised with liquor the whole time I belonged to the ship. The next was Mr. Stevens, who went by the nickname of Tommy Bowline, a rough knot; full of wise saws and strange dry sayings, but rather slack in his movements, and was what we call a hard officer and droll middy. When belonging to a guardship commanded by Sir Roger Curtis, while lying at Spithead the mizen topsail was ordered to be loosed, to swing the ship the right way. Tommy Bowline was the first to go aloft and was highly complimented by Sir Roger for his activity, saying ‘You are a fine fellow, Mr. Stevens; a most active officer, Mr. Stevens; you are a wonder, Mr. Stevens.’ Now it unfortunately happened that Tommy

was left behind by the other midshipmen and was last on the yard. Sir Roger observing this called out ‘I recall all my compliments, Mr. Stevens; you are a damned lubber, Mr. Stevens; a blockhead, Mr. Stevens; come down, Mr. Stevens.’ This poor Tommy never heard the last of.

Our gunner (McKinnon) was another strange hand. He was troubled with sore eyes and would sit in his cabin damning them from morning till night. Two of our men having deserted while in Yarmouth Roads, our boat, manned by midshipmen with Lieutenant Jeynes, left the ship in the evening and pulled for Cowes, where we arrived about eleven at night. Mr. Jeynes having received some information respecting the deserters, set off in the boat for Ryde, leaving me at Cowes with two marines to go round by land and meet him there. I had no money to get any refreshment, and never shall I forget the fatigue I went through that night. After pulling in the boat thirteen miles, I had to walk seven miles on a wild goose chase, for we never heard anything more of the runaways; and the wind shifting, we had to pull all the way back to Yarmouth. Before I close my account of the Orestes, I must say a word or two respecting Lieutenant Jeynes (letting the law of Solon sleep for a day). He was without exception the most cold-blooded and bad fellow I ever met with. I have seen him thrash the men with the end of a rope in the most unfeeling manner, until he was tired, making use of the most abusive language; and for his tyranny was obliged to quit the ship; but, to give the devil his due, [he] was what we call a bit of a sailor, and if he pleased (which was seldom) could make himself agreeable. In the year 1793, the Orestes was lost in the Indian Seas and every soul perished.

NAMES OF OFFICERS

M D, Esq., Captain.

An admiral and K.C.B. He commanded the Lion, 64, when the William Tell, 84, was taken. The Foudroyant, 80, and Penelope, 36, in company. He was also port admiral at Plymouth. Since dead.—[Marshall, i. 375.]

T. J, Lieutenant.

Dead. I have said enough of him. A commander on the retired list.

[G] P, Master.

Uncertain. Was master attendant abroad.

D, Lieutenant of Marines.

A barrack-master.

[J] S, Purser.

Took care of his eights.

W, Surgeon.

Uncertain. Mad from drink.

[A] P, Surgeon’s Assistant. A surgeon. Proud as the devil.

[H] L, Clerk.

Uncertain. A clever little pedant.

[J] H, Boatswain.

Uncertain. A good sailor.

[T] S, Carpenter.

Uncertain. A good man, and good bread-and-cheese carpenter.

[P] MK, Gunner.

Uncertain. A good sailor, but used to damn his poor eyes so.

[J] Q, Mate.

Dead. A good sailor; fond of gin grog.

D. H,} Brothers, Midshipmen.

H,}

Dead. Good young men.

[C] G, Midshipman.

Dead. A lieutenant. See Queen.

S, Midshipman.

Tommy Bowline. Was made a gunner.

W. M, Midshipman.

Dead [1830]. A captain, C.B.; a very good fellow.—[Marshall, vi. 20.]

A. G, Midshipman.

A commander; a good old sailor.—[Died 1853.—O’Byrne].

N, Midshipman.

Dead from insanity.

M, Midshipman.

Dead. A lieutenant. Was broke for tyranny, which he richly deserved. Afterwards restored to his rank. Nicknamed Mantrap, from taking up deserters.

J. A. G, Midshipman. A commander.

EDGAR, 74

Early in 1787 I joined the Edgar, a guard-ship in Portsmouth Harbour—Charles Thompson, Esq., captain, formerly of the Boreas; and soon after went to Spithead and hoisted the broad pennant of the Honorable John Leveson Gower as commodore of the squadron of observation; but the Dutch armament taking place prevented their sailing. Several ships of the line assembled at Spithead, and others fitting in the harbour; but to no purpose, as the business was soon settled, and the ships returned to their stations, and those fitting were paid off. Next spring we were again ordered to Spithead, and a promotion of flags having taken place, we hoisted the flag (blue at the mizen) of Rear-Admiral the Hon. John Leveson Gower, as commander-in-chief of the fleet of observation, consisting of the following men of war:

Edgar 74

Colossus 74

Magnificent 74

Culloden 74

Crown 74

Scipio 64

Hebe 36

Andromeda 32

Trimmer 18

{Rear-Admiral Honorable John Leveson Gower.[47]

{Captain Charles Thompson.[47]

Captain Hugh Cloberry Christian.[47]

Captain Hon. Geo. C. Berkeley.[47]

Captain Sir Thomas Rich, [Bart.][48]

Captain Charles Morice Pole.[47]

Captain Skeffington Lutwidge.[49]

Captain Edward Thornbrough.[50]

Captain H.R.H. Prince William Henry.[50]

Captain Charles Tyler.[50]

Sailed with the squadron to the westward of Scilly, and off the Irish coast for nearly two months, putting in occasionally to Cawsand Bay and Torbay, and then returned to our station as guard-ship on Portsmouth Harbour. We were very glad to get rid of our admiral. He

was what we call a tight hand of the watch; one that would make a fellow jump where there was no stile. He used to play hell and turn up Jack, and would spare nobody. He had an ugly trick of getting up as early as three and sometimes before it in the morning, and would walk the quarter deck in a flannel jacket, and most of the time without a hat, until breakfast was ready; a happy dog of a midshipman walking between two of the quarter deck guns with a signal book, which ever and anon he would call for in the voice of Stentor—

Stentor the strong, endued with brazen lungs, Whose throat surpassed the force of fifty tongues.

Coming out of his cabin early one morning in a great hurry, he fell over a signal lantern, and was going to play hell with the lieutenant of the watch for having lanterns upon deck at that time of day—about half-past two in the morning. The Crown being out of her station, he was going to make the signal for an officer from that ship, and going to the office to write the order he could not get in, the clerk having the key; which put him into such a rage that he swore he would flog the clerk and those that wrote under him. However, his rage abated and he did not make the signal, it blowing very hard; but he would not suffer the clerk or his under-scribes to show themselves in the office while his flag was flying.

Culverhouse was at this time signal lieutenant and was not so quick in getting up this unlucky morning as the admiral, although a very active and able officer. The admiral, not seeing him, roared out to me (which made me jump a foot off the deck) ‘Where’s that little son of a bitch? Go down for him directly.’ Down I went to the gunroom where Culverhouse slept, and told him the news. In great tribulation he instantly got up and came upon deck, and kept some time behind the admiral thinking to weather the storm; but the moment he got sight of him he sang out like a lion, ‘Go on the poop and be damned to you. Why were you not out of your nest before?’ I must here state that, notwithstanding this, the admiral was a great friend to Lieutenant Culverhouse, and I have been told first took notice of him from the following circumstance. When on board the Victory, he was on the gangway with his glass, sitting on the weather clue of the mainsail, when the main tack suddenly gave way and

threw him into the lee clue of the sail unhurt. He was an excellent signal officer, a good sailor, an agreeable messmate, and in every respect a very clever fellow. He was made a post captain, but was unfortunately drowned at the Cape of Good Hope.[51] The admiral was like Sylla the Dictator; that is, he would go any length to serve his friends, but was the reverse to those he had a dislike to. He appeared to be well acquainted with the character of most of the officers in the service; his memory in that respect was astonishing. He was an able tactician, and in every respect a great officer, with a look ‘that withered all the host.’

He was a mortal foe to puppyism, and one of our midshipmen going aloft with gloves on, attracted his eye; for which he got such a rub down that I am certain he remembers to the present day, although he is a post captain, and as proud as the devil, without any reason. Another of his freaks was threatening to have a bowl put upon our heads and our hair cut round in the newest fashion by that measure. He told one of our midshipmen (Pringle) who was a very stout man and who happened to be in his way when looking at the compass, ‘That he was too big for a midshipman but would do very well as a scuttle butt,’ and, Pringle having his hands in his pockets, he was going to send for the tailor to sew them up. When he first came on board to muster, a little before we sailed, everyone was dressed in full uniform to receive him. He took notice of this, and with a smile (a lurking devil in it), complimented us on our good looks, at the same time observing, ‘You knew who was coming; but notwithstanding your looking so well, I think I can see a little rust on you yet which I shall endeavour to rub off.’[52]

Our captain was as gruff as the devil, and had a voice like a mastiff whose growling would be heard superior to the storm. He was very particular respecting dress as the following order will shew:

Memo.:

If any officer shall so far forget himself as to appear when on shore without his uniform, I shall regard it as a mark of his being ashamed of his profession and discharge him from the ship accordingly. (Signed) C T, Captain.

He had very near caught some of us in Middle Street, Gosport, but fortunately an alley was at no great distance through which we made a hasty but safe retreat, and by that means prevented a few vacancies for midshipmen taking place in the Edgar.

And now according to promise let me speak a few words about my old mastheading friend, Lieutenant John Stiles. When the guardships went out for a cruise to blow the dust off the harbour duty men, their complement was made up of men and officers from those ships that remained in port. It happened that my aforesaid friend was sent on board of us. Now it so turned out that he had not so much to say on board the old Edgar as he had when on board the Salisbury (of cruel memory). In the latter ship he had lambs to look after; in the Edgar he had devils to look after him. In working ship this gentleman was stationed on the forecastle, and got the nickname from the admiral of ‘Knight of the Belfry,’[53] because he always planted himself there when the hands were turned up; and from being in such a conspicuous situation, when things went slack—which was sometimes the case— the admiral, who had an eye like a hawk, would damn him up in heaps, and the captain, as an able assistant, would run forward like a bull-dog, and roar out the second part of the same tune. I was also stationed on the forecastle, and when those freaks were going on, I used to look at my old mastheading friend and grin, and he knew damned well what I was grinning at, as the good old times could not be forgotten. And now, John, I am done with you.

I subscribed to a concert in Gosport and one evening I went with a messmate (the late Captain Philpot) and some girls who I gave tickets to; we did not break up until 12 o’clock and then went on board. It happened unfortunately to be our middle watch, and the rest of the watch being on shore we relieved the deck; but, being tired and sleepy, we thought it no harm to go to our hammocks instead of keeping a vile watch; so, singing the old song:

I hate this damned watching and trudging the deck; The most we can get, boys, at best is a check; Sit still then, and let the lieutenants all rail, We’ll ride out the breeze says Commodore Gale we thought ourselves perfectly secure; and so we should have been, had not a quarrel taken place between two of the quartermasters’

wives, for which one of them was turned out of the ship; but in revenge she accused the other of smuggling four tubs of liquor into the ship, stating the time to the first lieutenant. Now as ill luck would have it, it proved to be on the concert night, or rather the morning, when the transaction took place. He then made his report to the captain, who sent for us and with a ferocious aspect demanded the reason of our leaving the deck. We could give none, only Philpot said, ‘The concert, sir.’ ‘The concert, sir?’ retorted the captain; ‘What had the concert to do with liquor getting into the ship, and officers sleeping in their watch? I have a great mind to try you both by a court martial;’ and turning to the first lieutenant he said, ‘Mr. Yetts, let them be prisoners for three months’—or, in other words, not to be suffered to leave the ship, even upon duty, during that time.

Our first lieutenant (Yetts) was a very droll and strange personage, in dress as well as in manners. When he commissioned the Edgar he had on a uniform coat made in days of yore, with sleeves that reached to his hips, a very low collar, huge white lappels and cuffs, the buttons behind at a good fighting distance, and the skirts and pockets of enormous size. A red waistcoat, nankin breeches, and black worsted stockings, with great yellow buckles on round-toed shoes, a hat that had been cocked, but cut round, with a very low crown, so that he was obliged to keep his hand to his head to prevent its blowing off in the lightest breeze. When he came on board in this costume, the warrant officers thought he had made his escape from a madhouse; and Grey, the gunner, swore he was an understrapper from Bedlam that was come to take Johnny Bone the boatswain (at that time half mad from drunkenness) to the lunatic hospital. When this was told Johnny it brought him to his reason, and in great tribulation he locked himself up in his storeroom and remained there the most of the day, to the great amusement of everyone on board.

This Johnny Bone was a devil of a fellow at Cap-a-bar,[54] and would stick at nothing. It is related that the late Lord Duncan, when he commanded the Edgar, once said to him, ‘Whatever you do, Mr. Bone, I hope and trust you will not take the anchors from the bows.’

But to return to Lieutenant Yetts; he was a very active old man; extremely passionate, and swore as well as his brother officers of the present day; an excellent sailor, and though violent at times, would

hurt no one. He was also well read in ancient and modern history. In asking him leave to go on shore, his answer was (if out of temper), ‘No; damn my brains if you shall go.’ It happened one night when he went on shore that Jack Kiel (one of the midshipmen) and myself took the opportunity and set off on a cruise in the long boat’s punt (small boat), and landed on Gosport beach; and having secured the boat, we took a stroll up Middle Street, when who should pop upon us but old Yetts, who, we thought, had gone to Portsmouth. We took to our heels and he called after us, but was not certain (so it appeared) to our persons. We, without loss of time, got on board and went to our hammocks. The moment he returned, down came the quartermaster to acquaint us that Mr. Yetts wished to see us. When we came upon deck he addressed us with ‘——, Mr. Kiel and Mr. Gardner, who gave you leave to go on shore? and why did you not come when I called you?’ We brazened it out that we had not been on shore and had gone to our hammocks a considerable time, and that he must have mistaken somebody else for us. This seemed to stagger him, but he swore, ‘damn his brains, but it must be us.’ He then made inquiry of the midshipmen of the watch, but we had taken devilish good care not to come up the side but crept in through the gunroom port, so that they could give him no information. By these means we weathered him; but for more than a week after, whenever he saw us on deck, he greeted us with, ‘Damn my brains, but it was you.’

There was a song at this time by Storace[55]—it began as follows:

I left the country and my friends To play on my little guitar; It goes tang-tang-tang, It goes tang-tang-tang, It goes tang-tang-tang, It goes ta etc.

One of our midshipmen (Vosper) altered this, and used to sing with a thundering voice the following burlesque to the same tune.

The other day I asked old Yetts For leave to go on shore; He said no, no, you shall not go, He said no, no, no, he said no, He said no no, you shall not go,

By Christ, you shall not go, etc.

I had nearly got into a second scrape about the confounded middle watch. My friend Jack Kiel and myself relieved the deck at 12. The rest of the watch were absent as before. The night was as dark as pitch, and blowing and raining most furiously, when about five bells we got rather hungry and went to our berth in the cockpit to stew beef steaks. This was done by lighting several pieces of candle in the bottom of a lantern, and sticking forks (not silver ones) in the table round it with a plate resting on them over the candles (the head of the lantern being off), which stewed the steaks remarkably well. We had scarcely finished when old Davy Jacks, the quartermaster, came hobbling down the cockpit ladder to inform us that the Endymion was going out of harbour, and had made the signal for assistance (we had then the command). ‘Why, Davy,’ says Kiel, ‘you must be mad to think of such a thing. Is that all the news you have?’ ‘Nothing more, sir,’ says Davy; ‘only Mr. Yetts wants you.’ This was the unkindest cut of all. Away we flew upon deck, saw how things were, and went into the wardroom to answer the bell for the officer of the watch, and found the old man nearly dressed. ‘J—— ——,’ say he, ‘What’s the matter? and why did you not come when I rung before?’ I told him we were looking out on the Endymion, who had broke from her moorings and had made the signal, and that I was just coming to acquaint him of the circumstance. This satisfied him, and we took good care never to be off deck again.

The Phaëton, 38, having arrived from the Mediterranean and a court martial ordered on her captain (Geo. Dawson), and also on Messrs. Wall and Lucas, the first and second lieutenants, and likewise on a man by the name of Wilkie, her master—Rear-Admiral J. Peyton hoisted his flag (white at the mizen) on board of us as president of the court. The lieutenants were tried the first, and sentenced to be dismissed from their ship; and then the abovenamed Wilkie, as prosecutor, exhibited fifteen charges against Captain Dawson. The trial lasted several days, when twelve of the charges and part of another were brought in Scandalous, Malicious, Ill-founded, and Derogatory to the discipline of his Majesty’s Service; but two of the charges and part of another being proved, he was dismissed from his Majesty’s Service.

Captain Dawson then tried Wilkie on four charges; part of which being proved, he was sentenced to be dismissed from his ship—a sad punishment, she being paid off the next day. The surgeon (Wardrope) had been tried before the ship arrived and was a long time under sentence of death.[56]

Captain Dawson was an officer who had greatly distinguished himself in the American War when he commanded the Hope [schooner]. He was captain of the Renown, 50, when she engaged and would have taken a French 84,[57] one of the Count D’Estaing’s fleet, had she not been rescued by some of the enemy’s ships coming to her assistance. This trial occasioned a great party spirit among the midshipmen, some siding with Wilkie the prosecutor, and others with Captain Dawson. I was for the latter, because I thought there was malice prepense in the prosecution. I hated the basilisk look of Wilkie, and wished him at the devil. A violent altercation taking place upon this subject, my old messmate Philpot, a strong adherent to the house of Wilkie, in the moment of irritation threw a black jack full of beer in my face; for which compliment I instantly knocked him down, and after a hard battle in which he got two black eyes, I came off conqueror. Things were going to be carried farther, but a stop was put to it and we made it up.

Like all ships we had some droll hands, and with the exception of about half a dozen, all good and worthy fellows. One or two of the half dozen I shall mention, and begin with Geo. Wangford, who had been in the Boreas, and was a follower of the captain. He was an immoderate drinker, and from his fiery countenance had the nickname of Bardolph. While in the Edgar his mother died and left him one thousand pounds. He lived about six months after receiving the money in one scene of debauchery; and with the assistance of a noted prostitute, named Poll Palmer, in that short time made away with nearly five hundred pounds. I remember his being taken ill after a hard drinking match, and then he got religious and requested one of the midshipmen (Patrick Flood), another strange fish, to read the Bible to him. This Patrick readily agreed to; but before he got through a chapter pretended to have a violent pain in his stomach, upon which Wangford requested him to take capillaire[58] and brandy, and that he would join him, and desired that, in mixing, two thirds should be brandy. Flood was immediately cured, and began to

read a chapter in Job; and when he came to that part, ‘Then Job answered and said,’ Wangford started up and roared out—‘that I am going to hell before the wind.’ I lay close by them and heard every word. He soon after turned to upon Hollands, his favourite beverage, and thought no more of Job or the Bible. Soon after he was sent to the hospital, where he remained some time and died mad. A little before his death Pringle (one of the midshipmen) went to see him, and while sitting on the foot of his bed he started up and seized hold of Pringle by the hair singing out, ‘—— —— ——, catch that bird’; the other calling out for the nurse to assist him, which was of little use for he nearly broke her arm before others came up to secure him. Several of us attended his funeral.

Our time passed cheerfully in the harbour; plenty of fun and going on shore. One night several of us supped in the main hatchway berth on the orlop deck, when old Andrew Macbride, the schoolmaster (a man of splendid abilities but unfortunately given to drinking, though the goodness of his heart made him much respected and did away in a great measure with that infirmity) on this occasion got so drunk that Ned Moore (my worthy messmate) handed him a couple of tumblers of the juice of red pickled cabbage and told him it was brandy and water, which he drank without taking the least notice. I believe it did him good as an aperient, for he was cruising about all night and next day, and could not imagine what it was that affected him so.

One of our midshipmen (Millar), as worthy a fellow as ever lived, told me the following anecdote of himself and Macbride. On his joining the Hector, 74, a guard-ship in Portsmouth Harbour, Morgan, the first lieutenant, came up to him and said, ‘Millar, my boy, how glad I am to see you. You must dine with me to-day.’ Millar, who had never seen him before, thought it rather queer that he should be so friendly at first sight; however, he accepted the invitation. When dinner was over, Morgan declared that he was under a great obligation to him and that he should at all times be happy to acknowledge it. Poor Millar said he was really at a loss to understand him. ‘Well then,’ says Morgan, ‘I’ll tell you. It is this. I was considered the ugliest son of a bitch in the fleet before you came on board, but you beat me dead hollow, and surely you cannot wonder at my being sensible of the obligation.’ Millar laughed

heartily, and they were ever after on the best terms. It happened in about three months after this, Macbride also joined the Hector. The moment he came on board, down came the quartermaster to Millar saying that Lieutenant Morgan wanted to see him immediately. As soon as Millar came on the quarter deck, Morgan went up to him and wished him joy; and pointing to Macbride observed, ‘You, Millar, are a happy dog for being relieved so soon. I was considered the ugliest son of a bitch in the fleet for more than a year; you then came on board and outdid me; but there stands one that beggars all description, and if they were to rake hell they could not find his fellow.’ Then going and shaking Macbride by the hand, asked him and Millar to dine with him that day to celebrate the happy relief.

Poor Andrew once made a vow that he would not get drunk, and said that not only the taste but the smell of the liquor was so disagreeable that he could not bear to stay where it was. He also gave Watson, the boatswain, leave to thrash him with his cane if ever he found him drunk. Poor fellow, he kept his promise for about three months, and then turned to as bad as ever, and Watson did not forget to give him a lacing with his cane, which occasioned the following song written by John Macredie:—

Of all the delights that a mortal can taste,

A bottle of liquor is surely the best; Possessed of that treasure my hours sweetly glide, Oh! there’s nothing like grog, says sweet Andrew Macbride.

When I sit in my school I think my time lost Where with dry sines and tangents my temper is crossed; But how sweetly I smile with the glass by my side: Grog helps mathematics, says Andrew Macbride.

The boatswain, God damn him, would fain me control With a promise when sober I made like a fool; With his cursed rattan he so curried my hide, That I’ll drink his damnation, says Andrew Macbride.

When the sweet powers of grog have my reason betrayed, And free from sad care on the deck I am laid, Then the boys black my face, and my actions deride; The whelps may be damned, says Andrew Macbride.

From the raptures of grog shall a sage be controlled,

And a man like myself submit to be schooled? If I’m drunk, the lieutenant and captain may chide; But I’ll drink till I die, says sweet Andrew Macbride.

When I said the smell hurt me, the fools did believe; Och hone! my dear friends, I did you deceive; When the taste or smell hurts me, may hell open wide, And I, damned there with water to drink, says Macbride.

Nothing disrespectful was intended by this song. Every officer in the ship was a friend to poor Andrew, and Macredie would have been one of the first to resent an insult offered to him. It is a strange coincidence that on the day we were paid off, I saw Macbride sitting on the taffrail reading Ossian’s poems, and looking at a fine engraving of the Spirit of Crugal.[59] Twelve years after in Port Royal Harbour, Jamaica, I went to answer the signal for lieutenant on board the Leviathan, 74 (I then belonged to the Brunswick), and going on the poop to write the order, I saw a figure sitting on the taffrail, who I thought I knew, in deep meditation. On going up to him I recognised my old messmate Macbride, with the identical book and the engraving of the Spirit of Crugal in his hand. The poor fellow was most happy to see me, but how altered! He went back with me to dinner, and I gave him some classical books that pleased him greatly. His bones are lying at the Palisades. He was one of the first mathematicians in Europe; an excellent writer in prose and verse, an able disputant, and possessed a mind remarkable for the strictest integrity. ‘Tread lightly on his ashes, ye men of genius, for he was your kinsman.’[60]

I must here say a word about poor unfortunate Patrick Flood. When first I knew him in the American War, he was a fine officerlike looking fellow; but when he joined the Edgar he was sadly reduced from long illness in the West Indies; and from domestic troubles, and disappointment at not getting promotion, grew regardless of himself and reckless of his character. Cynical to a degree and used to caricature us upon every occasion, I remember his making a very ludicrous drawing of Macbride, representing him sitting on the deck with the boys blacking his face and a bottle and a glass alongside of him; and [underneath it, some scurrilous verses, which Macbride answered with others still more indecent].

When the Edgar was paid off, Captain A. J. P. Molloy[61] was appointed to the command of her, and Flood was continued as one of the midshipmen. Having obtained leave to go to London to try and raise friends to get his promotion, he succeeded in getting the promise from Lord Chatham; but unfortunately having staid a short time above his leave, Captain Molloy, in answer to Lord Chatham’s letter respecting him, cruelly said he considered Mr. Flood in no other light than that of a deserter. This was the ruin of poor Flood, who died in penury, but lived long enough to witness the downfall of his enemy. And now let me mention my worthy messmate John Macredie, a gentleman that did honour to society and one that was highly respected by a numerous acquaintance. He had seen a great deal of service and was on board the Hercules, 74, in Rodney’s action on the 12th of April 1782. He was also on board the Princess Royal, 98, and Pégase, 74, and then joined the Edgar, and was a messmate of mine for three years, and again in the Barfleur for upwards of a twelvemonth. He was an excellent scholar, being well acquainted with the Greek and Latin, and was deeply read in ancient history and nearly equal to Macbride in mathematics. The author of many plays that were never printed, as he would not allow them to be sent to the press, although strongly urged by those who were competent judges of their merit. He was also a good poet and possessed undaunted courage, and was as generous as he was brave. At the same time he was one of the most absent [minded] men that can be imagined. I have known him when going to answer a signal come on deck with one boot and one shoe on; and when sent below in consequence, come up again with his black stock with the inside turned out. One morning when alongside of the flagship, on stepping from the boat to the accommodation ladder he dropped the order book overboard, and in trying to get hold of it he let go his sword, which sunk in a moment. I have also known him walk nearly two miles out of Gosport before he recollected that he had only to go to his tailor’s, who lived near the beach.

I must not forget another worthy fellow and messmate of mine, the late Lieutenant Edward Moore, at this time one of the mates. Ned was as brave and generous a soul as ever lived; a determined enemy to tyranny, as the following circumstance will shew. When the present Retired Rear-Admiral Shield[62] was first lieutenant of the Saturn, 74, at Spithead in the year 1791 or 1792, one evening in the

first watch he ordered one of the midshipmen (Mr. Leonard) on some trifling occasion to the masthead for punishment. Mr. L. said he would go there with pleasure if it was on duty, but not for punishment; upon which Mr. Shield had him made fast to a girtline and triced up to the main topmast-head without a guy to keep him clear of the top etc. This made a great stir both on board and on shore, and Mr. Leonard was advised to commence proceedings by entering an action against Shield; and a subscription was set on foot to defray the expenses attending it. My friend Ned at this time belonged to the London, 98, lying at Spithead; and he wrote letters to the midshipmen of the other men of war to subscribe also. This coming to the knowledge of Lord Hood, he considered it as a conspiracy injurious to the discipline of the navy, and Moore was put under an arrest. A court of inquiry was held, and then a court martial, where Sir Hyde Parker stood as prosecutor; and after a long examination of witnesses, Moore was found guilty of contempt of court and sentenced to be confined in the Marshalsea for one month, a fortnight of which he remained on board the guard-ship. The other charge was not proved. The late Admiral Macbride, who commanded the Cumberland, 74, at that time, was a member of the court, and was a friend to Moore ever after, and made him lieutenant.

One of our midshipmen, who lately died a post captain, was an infernal tyrant. While in the Edgar, this chap one evening began his tricks by thrashing one of the youngsters, a messmate of Ned’s, and for so doing Ned gave him, to the great joy of all, the most severe drubbing I ever witnessed. Ned had been a shipmate of this person’s before in the Queen, 98, when a guard-ship, and had seen some of his pranks there and now paid him on the old score.

While lying at the Hardway moorings, about three o’clock one morning we heard a voice halloing out ‘Come here, you sleepyheaded hounds, and take me out of a hole that I have got into.’ It being low water, the voice appeared to come from the mud. Two or three of us got into the cutter (for we always kept a boat out)[63] and went in the direction of the voice, where we found Moore up to his middle, and being a stout fellow it was no easy matter to extricate him. Had we not gone when we did he would have been suffocated as the tide was flowing. He had been keeping it up and missed his way to the Hard. He was one that would part with his last shilling to serve