Recommendations on management of

the SARS-CoV-2 coronavirus pandemic

(Covid-19) in kidney transplant patients
Verónica López
Visit to download the full and correct content document:
https://ebookmass.com/product/recommendations-on-management-of-the-sars-cov-2-
coronavirus-pandemic-covid-19-in-kidney-transplant-patients-veronica-lopez/
Journal Pre-proof

Recommendations on management of the SARS-CoV-2 coronavirus

pandemic (Covid-19) in kidney transplant patients

Verónica López Teresa Vázquez Juana Alonso-Titos Mercedes

Cabello Angel Alonso Isabel Beneyto Marta Crespo Carmen
Dı́az-Corte Antonio Franco Francisco González-Roncero Elena
Gutiérrez Luis Guirado Carlos Jiménez Cristina Jironda Ricardo
Lauzurica Santiago Llorente Auxiliadora Mazuecos Javier Paul
Alberto Rodrı́guez-Benot Juan Carlos Ruiz Ana Sánchez-Fructuoso
Eugenia Sola Vicente Torregrosa Sofı́a Zárraga Domingo
Hernández, Grupo de Estudio GREAT

PII: S2013-2514(20)30048-1
DOI: https://doi.org/doi:10.1016/j.nefroe.2020.03.017
Reference: NEFROE 708

To appear in: NEFROLOGIA (English Edition)

Received Date: 22 March 2020

Accepted Date: 30 March 2020

Please cite this article as: Verónica LópezTeresa VázquezJuana Alonso-TitosMercedes

CabelloAngel AlonsoIsabel BeneytoMarta CrespoCarmen Dı́az-CorteAntonio
FrancoFrancisco González-RonceroElena GutiérrezLuis GuiradoCarlos JiménezCristina
JirondaRicardo LauzuricaSantiago LlorenteAuxiliadora MazuecosJavier PaulAlberto
Rodrı́guez-BenotJuan Carlos RuizAna Sánchez-FructuosoEugenia SolaVicente
TorregrosaSofı́a ZárragaDomingo HernándezGrupo de Estudio GREAT, Recommendations
on management of the SARS-CoV-2 coronavirus pandemic (Covid-19) in kidney transplant
patients (2020), doi: https://doi.org/10.1016/j.nefroe.2020.03.017
This is a PDF file of an article that has undergone enhancements after acceptance, such as
the addition of a cover page and metadata, and formatting for readability, but it is not yet the
definitive version of record. This version will undergo additional copyediting, typesetting and
review before it is published in its final form, but we are providing this version to give early
visibility of the article. Please note that, during the production process, errors may be
discovered which could affect the content, and all legal disclaimers that apply to the journal
pertain.

© 2020 Published by Elsevier.

 SPECIAL ARTICLE

Recommendations on the management of the SARS-Co V-2 coronavirus

pandemic (Covid- 19) in kidney transplant patients

Recomendaciones en el manejo de la pandemia por coronavirus SARS-

CoV-2 (Covid-19) en pacientes con trasplante renal

f
Authors

oo
Verónica López a , Teresa Vázquez a , Juana Alonso-
Titos a , Mercedes Cabello a , Angel Alonso b , Isabel Beneyto c , Marta

pr
Crespo d , Carmen Díaz-Corte d , Antonio Franco e , Francisco González-
Roncero f , Elena Gutiérrez a , Luis Guirado g , Carlos Jiménez h , Cristina
e-
Jironda a , Ricardo Lauzurica i , Santiago Llorente j , Auxiliadora Maz uecos k ,
Javier Paull , Alberto Rodríguez-Benot m , Juan Carlos Ruiz n , Ana Sánchez-
Pr
Fructuoso o , Eugenia Sola a , Vicente Torregrosa p , Sofía Zárraga q ,
and Domingo Hernández a . GREAT Study Group
al

a
Clinical Nephrology Management Unit. Regional University Hospital of
Malaga, University of Malaga, Malaga Biomedical Research Institute
rn

(IBIMA), REDinREN ( RD16 / 0009/0006), Malaga, Spain

b
Nephrology Service. Aryan Hospital Complex A Coruña, Spain
u

c
Nephrology Service. La Fe Polytechnic University Hospital , Valencia,
Jo

Spain
d
Nephrology Service. Hospital del Mar, Barcelona, Spain
d
Nephrology Service. Hospital Central de Asturias, REDinREN RD16 /
0009/0021, Asturias, Spain
e
Nephrology Service. Alicante Hospital, Alicante, Spain
f
Nephrology Service. Virgen del Rocío Hospital, Seville, Spain
g
Nephrology Service. Puigvert Foundation, REDinREN RD16 / 0009/0019,
Barcelona, Spain.

Page 1 of 19
h
Nephrology Service. La Paz Hospital, Madrid, Spain
i
Nephrology Service. Trias i Pujol Hospital, REDinREN RD16 /
0009/0032 , Barcelona, Spain
j
Nephrology Service. Virgen de la Arrixaca Hospital, Murcia, Spain
k
Nephrology Service. Puerta del Mar University Hospital, Cádiz, Spain
l
Nephrology Service. Miguel Servet Hospital, Zaragoza, Spain
m
Nephrology Service. Reina Sofía Hospital , Maimonides Institute for
Biomedical Research of Córdoba , Córdoba, Spain .
n
Nephrology Service. Marqués de Valdecilla Hospital, IDIVAL, REDinREN

f
RD16 / 0009/0027, Santander, Spain.

oo
o
Nephrology Service. Hospital Clinico San Carlos, Complutense University
of Madrid, Madrid, Spain

pr
p
Nephrology Service. Hospital Clinic, Barcelona, Spain
q
Nephrology Service. Cruces Hospital, Bilbao, Spain
e-
Great, Spanish Group of Transplant Updates
Pr
Correspondence:
Domingo Hernández

Nephrology Clinical Management Unit, Malaga Regional University

al

Hospital
rn

Avda. Carlos Haya s / n.

29010 Malaga
u

e-mail domingohernandez@gmail.com
Jo

Page 2 of 19
 f
oo
pr
e-
SUMMARY
Pr
The SARS-CoV-2 (Covid-19) coronavirus pandemic is evolving very quickly
and means a special risk for both immunosuppressed and comorbid
patients. Knowledge about this growing infection is also increasing
al

although many uncertainties remain, especially in the kidney transplant

population. This manuscript presents a proposal for action with general
rn

and specific recommendations to protect and prevent infection in this

vulnerable population such as kidney transplant recipients.
u

Keywords : Covid-19, kidney transplantation, immunosuppressed, SARS-

Jo

CoV-2

RESUMEN

La pandemia de coronavirus del SARS-CoV-2 (Covid-19) está

evolucionando muy rápidamente y significa un riesgo especial para
pacientes inmunosuprimidos y con comorbilidad.. El conocimiento
sobre esta creciente infección también está aumentando, aunque

Page 3 of 19
persisten muchas incertidumbres, especialmente en la población de
trasplante de riñón. Este manuscrito presenta una propuesta de acción
con recomendaciones generales y específicas para proteger y prevenir
la infección en esta población vulnerable, como los receptores de
trasplante de riñón.
Palabras clave: Covid-19, trasplante renal, inmunodeprimido, SARS-CoV-2.

f
oo
pr
Introduction .
On December 31, 2019, the Wuhan Health Commission reported about
e-
groups of people with pneumonia who were epidemiologically linked to a
seafood and live animal market in Wuhan, China 1 . The etiology was
Pr
identified as a new coronavirus, with a supposed zoonotic origin. The virus
has been recently named the coronavirus of severe acute respiratory
syndrome type 2 (SARS-CoV-2) and the disease has been called
Coronavirus Disease 2019 (COVID-19) 2 .
al

So far, there is uncertainty regarding the transmission capacity of the

rn

virus. Recent studies show the presence of a high viral load in the
oropharynx at early stages of the disease, which increases the concern
u

about the high risk of infectivity during incubation periods or with only
Jo

mild symptoms 3 . The average incubation period has been estimated to

be 5-6 days, with a range of 1-14 days. In over 80% of cases the symptoms
of the disease are mild (fever, cough, expectoration, general malaise),
while approximately 20% may have serious clinical manifestations
( pneumonia and other clinical complications) that require hospital
admission. . Pregnant women, newborns , the elderly ,
immunocompromised and patients with comorbidities such as
diabetes mellitus, hypertension and cardiovascular disease , are more to
be infected by COVID-19 , and they are more likely to suffer severe

Page 4 of 19
illness that often requires to be admitted to ICU. The impact of COVID-19
on chronic kidney disease has been scantily reported 4 . Current mortality
rate in China is 3.9 % of the cases confirmed by the lab, which is very
similar to that of Spain 3.7% (Data as of March 16, 2020) 5 . However, it is
still premature to establish the true mortality rate in our country .

General considerations in kidney transplant patients .

In kidney transplant recipients, due to their status of
immunosuppression, the clinical manifestations, treatment, and prognosis

f
of COVID-19 pneumonia may differ from the general population , hence

oo
the importance of early diagnosis by SARS-CoV-2 screening , in those
cases where the infection is suspected. In the general population,

pr
lymphopenia has been observed in up to 63% of patients, 6 but many
kidney transplant recipients have drug-induced lymphopenia, therefore,
this finding does not help the diagnosis. Therefore, special attention
e-
should be paid to this type of immunosuppressed patients, evaluating
the early detection of this infection by appropriate diagnostic test
Pr
and the admission to the hospital in case of infection.
The first case of COVID-19 pneumonia in a kidney transplant recipient has
been published recently7 . The clinical features (symptoms, laboratory
al

tests and chest CT scan) were similar to non - transplanted patients with
rn

COVID-19.

There have not been published relevant reports on the progress of this
u

disease in the renal transplant population . Most of the transplant centers

Jo

in Spain already have cases of kidney transplant patients affected by

COVID-19 that have not been published . Therefore, it is essential the
collaboration between countries in the preparation of national and
European registries to learn with detail the epidemiological
characteristics of this infection in patients with solid organ transplants,
including kidney transplantation.

To our knowledge, COVID-19 has not been described in donor-recipient

transmission of solid organ transplants . However, related viruses such as

Page 5 of 19
the severe acute respiratory syndrome coronavirus (SARS-CoV) and the
Middle East respiratory syndrome coronavirus (MERS-CoV) were reported
in transplant recipients during previous outbreaks of these viruses 8 , 9 .

Based on experiences with previous coronaviruses , it is known that an

transplant recipient exposed to the virus would become infected in a high
percentage of cases ; however, less is known about the risk of donor-
recipient transmission. The possibility of a donor-derived infection may be
influenced by exposure of the donor, the infectivity of individuals during
the incubation period and by asymptomatic people. The extent and

f
oo
duration of viremia and the viability of the virus within specific blood or
organ compartments would also affect the risk of donor
transmission. Therefore, despite the possible negative consequences ,

pr
temporary interruption of kidney transplantation may be necessary in
areas where the virus is being exposed intensively . 10
e-
The current epidemic of COVID-19 in Europe is still in its early stages, and
although the acquisition knowledge is increasing rapidly, there are many
Pr

unknowns for the community in general and particularly for the transplant
patients. However, it is imperative to anticipate the potential impact on
al

the transplant population to avoid serious consequences. The

recommendations may change as we learn more about the infection.
rn

In order to acquire the maximum knowledge to protect the population of

kidney transplant recipients, the transplant centers have to develop
u

connections with their local infectious disease specialists and infection

Jo

prevention professionals . At the same time, it is important to be aware of

local and national public health policies to report suspected cases of
COVID-19. The Ministry of Health of the Government of Spain periodically
publishes a implementation technical report 11 , which at this time does
not include any special consideration for kidney transplant patients.

The Spanish Nephrology Society ( www.senefro.org ) and the Spanish

Transplant Society ( www.setrasplante.org ) are conveying the

Page 6 of 19
recommendations of measures for prevention and contingency against
COVID-19 in kidney patients , including kidney transplant patients .

Specific considerations regarding donation and transplantation

The National Transplant Organization (ONT) in collaboration with

the Transplant Coordination in the Autonomies (Regions) with the advice
of the Study Group of Infection in the Transplanted patient and in the
Immunocompromised Host (GESITRA-IC) , recommends preserving the
donation and transplant activity for as long as to pandemic allows

f
( http://www.ont.es/ ) carrying out universal screening of donors and

oo
potential organ recipients.

Any transplant program in the affected areas should make a case-by-case

pr
assessment when evaluating the convenience of performing a transplant
based on:
e-
1. Availability of resources in the ICU / resuscitation areas .
2. Assessment of the risk / benefit of exposing an
Pr
immunosuppressed patient to the risk of SARS-CoV-2 infection
(based on the number of cases and the possibility of admission
under ideal isolation conditions) versus the need for transplantation
al

(patient's clinical situation).

rn

General recommendations for kidney transplant patients

u

1. Maintain adequate hygiene. Wash your hands frequently with

Jo

soap and water for at least 20 seconds, or with an alcohol-based

hand sanitizer (at least 60% alcohol), especially: after using the
bathroom, before eating, after blowing , coughing or sneezing and
after direct contact with sick people or their surroundings. Avoid
touching your eyes, nose and mouth before washing your hands.
2. Cleaning of house surfaces should be done regularly. Clean
and disinfect frequently touched objects and surfaces.

Page 7 of 19
 3. Avoid contact or maintain a distance of at the least two
meters with people with respiratory infection symptoms (fever,
cough, generalized sore muscle, sore throat or respiratory difficulty)
and do not share personal belongings.

4. During the state of alarm, you must remain at home except

for the stipulated exceptions, according to the rules established
by the political and health authorities. Phone the kidney transplant
clinic at your referral center or the phone numbers authorized by
the health authorities.

f
oo
5. Try to follow a correct diet. Avoid smoking and alcohol. In
addition to being harmful to health, these substances weaken the

pr
immune system, making the body more vulnerable to infectious
diseases. e-
6. Avoid sharing food and utensils (cutlery, glasses, napkins,
handkerchiefs, etc.) and other objects without cleaning them
properly.
Pr

7. The Centers for Disease Control and Prevention and (CDC) :

does not recommend to the general population that people who are
al

well to wear a face mask to protect himself from respiratory

diseases, including COVID-19. Today, the kidney transplant
rn

population must comply with the recommended measures of

protection in the general population, especially if they are
u

asymptomatic at home. However, the responsible physicians will

recommend the use of a mask on an individual basis, mainly in cases
Jo

where the patient goes to a health center or other place with

agglomeration. People who show symptoms of being infected with
SARS-CoV-2 should wear masks to prevent the spread of the disease
to others.
8. It would advisable to authorize a sick leave in patients whose
profession entails a high risk for infection.

Page 8 of 19
 9. To monitoring your kidney transplant through
teleconsultation is recommended to reduce the time spent in health
centers and minimize the risk of infection.

Specific recommendations for kidney transplant patients suspected of

SARS-CoV-2 infection.

According to the latest document from the Ministry of Health ( COVID-19

Clinical Management Technical Document: Medical Treatment of March

f
oo
19, 2020) , kidney transplant recipient patients with suspected SARS-CoV-
2 infection have indication of diagnostic test and assessment of admission
if the result is positive, and the initiation of a specific treatment .

pr
All kidney transplant patients with symptoms compatible with COVID-19
are recommended to contact their transplant specialist or primary
e-
care physician (preferably by telephone), indicating clearly their chronic
diseases and the type of treatment they take regularly. Depending on the
Pr
symptoms presented, it is recommended:

 Mild symptoms (without dyspnea / tachypnea) and temperature

al

<38° C in a kidney receptor with adequate functional reserves: the

patient will be asked to contact by phone with phone number that
rn

has been designed by the Health Authorities in each Autonomic

Community to have the diagnostic test performed and remain at
u

home monitoring symptoms and alarm signs with telephone

monitoring by the transplant team every 24-48 hours.
Jo

 Moderate / severe symptoms, temperature > 38ºC or fragile

receptor: the patient will be instructed to go to the Hospital
Emergency Department to be clinically evaluated .

Treatment of SARS-CoV-2 disease.

Currently there is no evidence from controlled clinical trials to

recommend a specific treatment for the SARS-CoV-2 coronavirus in the
general population in patients with suspected or confirmed COVID-19 12 .

Page 9 of 19
In the absence of conclusive data on the treatment of this infection in
kidney transplant patients, the drugs used to date for the control of this
disease in the general population are the following:

Hydroxychloroquine: Usually used for the treatment of malaria and

amebiasis. Antiviral activity has been documented in vitro and no data is
available in humans but favorable results have been observed. It
interferes with the ECA2 receptor and with the intercellular traffic of the
virus.

f
Dose: 400mg every 12 hours the first 24 hours, then 200mg every 12

oo
hours for a total of 10 days. Requires adjustment in dialysis and liver
failure.

pr
Chloroquine: alternative to hydroxychloroquine. Lower in
vitro activity than hydroxychloroquine.
e-
Dose 500 mg every 12 h .
Lopinavir / Ritonavir: Combination of protease inhibiting antiretroviral
Pr
agents. Both are inhibitor is of CYP3A, so should be reduced dosages of
calcineurin inhibitors and mTOR inhibitors. Concomitant use with
tacrolimus causes a severe increase in immunosuppressant levels far
al

greater than that produced when a single protease inhibitor is used, with
a high risk of toxicity . 13 It is advisable to suspend the administration of
rn

anticalcineurin and to start monitoring levels after 48 hours.

u

There is little evidence to support its possible effect on COVID-19

infection 14 , 15 . An ongoing clinical trial ( MIRACLE) is looking at
Jo

the association between Lopinavir and IFN- β for 14 days for the
treatment of MERS. Compared to Remdesivir, Lopinavir / Ritonavir has the
advantage of being widely available with and acceptably tolerated toxicity
profile. It has been suggested to use a triple therapy with Lopinavir /
Ritonavir / Ribavirin 16 .
Dose: 200mg / 50mg 2 comp p.o. each 12h up to a maximum of 14 days .
Table 1 describes the interactions of drugs for COVID-19 infection with
different immunosuppressants .

Page 10 of 19
Systemic corticosteroids: Not widely recommended. No benefit has been
demonstrated in SARS or MERS epidemics. They can increase the spread
of the virus . Consider and weight it use in cases of adult respiratory
distress syndrome (ARDS) , septic shock, encephalitis, hemophagocytic
syndrome and in case of bronchospasm with wheezing.
Interferon-ß1b (INF-ß1b): Dose: 0.25 mg sc . every 48h for 14 days (total 7
doses) . Risk of acute rejection due to induction of alloreactivity, therefore
its use should be individualized, strictly evaluating the risk-benefit in
kidney transplant patients.

f
oo
Remdesivir: Thus is the prodrug of a nucleotide analog with potent
activity in vitro against a broad spectrum of virus RNA, as
the virus Marburg, Ebola, MERS-CoV, respiratory syncytial virus, Nipah

pr
virus and Hendra virus. Its mode of action is based on the premature
termination of viral RNA transcription 17 . It is suggested that it helps to
e-
reduce viral load and improves respiratory parameters in animals and in
vitro models 18 . Several clinical trials with this drug are currently
Pr
underway. It is for compassionate use.
Dose: loading dose in the first day of 200 mg / iv followed by a
maintenance dose of 100 mg / iv per day from day 2 to day 10.
al

Tocilizumab: it is a humanized monoclonal anti interleukin-6 receptor . It

rn

is used in severe cases taking into account the role of IL-6 together with
other proinflammatory cytokines in the development of ARDS .
u

Dose: 8mg / kg (maximum dose 800mg) iv single dose; consider to repeat

Jo

dose according to clinical response at intervals of at least 8-12h up to a

maximum of 3 doses 19 .
Ascorbic acid: The CITRIS-ALI multicentre trial suggests an
improvement in mortality in ARDS 20 . However, there is no further
evidence supporting this effect .
Intravenous immunoglobulins : They have been used in severe cases but
their indication and efficacy must be evaluated. The recommended doses

Page 11 of 19
are: 1 g / kg / day, 2 days, or 400 mg / kg / day, 5 days. Treatment highly
questioned, there is no evidence for its use.
Antibiotic treatment: It is used in case of bacterial superinfection. A study
has recently been published demonstrating a synergistic effect of the
combination of hydroxychloroquine with azithromizine (500 mg on the
first day, followed by 250 mg/d for 4 days) . 21
Given the possibility of drug interactions, it is recommended to carefully
review the therapeutic combinations well before starting any treatment.

f
Kidney transplant patients frequently receive drugs that block the renin-

oo
angiotensin-aldosterone system . It is currently unclear what is the role
that these drugs may play in patients with COVID-19 disease. The

pr
American Society of Cardiology recommends not stopping these drugs in
patients who are taking it . 22 e-
Immunosuppressive treatment in patients with SARS-CoV-2 disease.

Kidney transplant patients, due to immunosuppression, the immune

Pr
response have been altered and particularly the T-cell immune response .
There is little evidence regarding the minimization or management
pattern of immunosuppression, especially in the kidney transplant
al

population infectedby COVID-19. There has been a very short period of

time since the appearance of COVID-19 with very limited accumulated
rn

experience and the insufficient published scientific evidence. To date, only

one case of a patient with COVID-19 pneumonia in a kidney transplant
u

recipient has been published, whose clinical manifestations were similar

Jo

to those of the population not carrying a kidney transplant 7 . In this

case, the triple immunosuppressive therapy that he had received so
far was discontinued (prednisone, mycophenolate mofetil (MMF) and
tacrolimus and starting methylprednisolone at a dose of 40 mg / day plus
nonspecific immunoglobulin). In this patient, fever remitted the fifth day
after discontinuation of the treatment. ,Then, at that moment, tacrolimus
was restarted at half the dose, although the radiological signs of
pneumonia still persisted. Resolution of the clinical and radiological
symptoms with a negative microbiological sample for COVID-

Page 12 of 19
19 occurred two weeks after the onset of the clinical symptoms, and the
previous dose of tacrolimus and MMF were reintroduced 7 .

Therefore, given the limited experience accumulated and the high

probability of torpid evolution in a short period of time, with the
development of multi-organ failure and the need for respiratory support,
the immunosuppressive strategy recommended a priori , at least in the
most severe cases of kidney transplant patients with COVID-
19 pneumonia , should involve the temporary interruption of
immunosuppressants and the start of methylprednisolone at low doses

f
oo
between 20-40 mg / day, to confer the rapid acquisition of the necessary
cellular immunity to control the infection and thus prevent vital
complications. Low-dose systemic corticosteroids have several beneficial

pr
effect due to their immunomodulatory, anti-inflammatory and vascular
properties, which confer immunological protection of the renal
e-
allograft; 23. Corticoids produce inhibition of proinflammatory cytokines,
reduction of white blood cell traffic and maintenance of integrity and
Pr
permeability of the endothelium, thus maintaining homeostasis and
controlling dysregulation of the immune system 23 .
al

In less severe cases, an alternative could be the withdrawal of MMF and

the reduction of the dose of calcineurin inhibitors, but so far there are no
rn

studies that support this strategy. Given the trophism of the virus by the
lung tissue, it seems undesirable to use anti-mTOR drugs , at least in
u

patients with pathology of the lower respiratory tract .

Jo

The Spanish group at the Hospital de la Paz has recently communicated its
protocol for managing immunosuppressive treatment in patients with
Covid-19 infection 24 (Table 2) .

As far as resuming immunosuppressive therapy, it is not clear either

when to restart and at what dose, and each case should be evaluated
individually . In general, it is reasonable to recommend resuming the
calcineurin inhibitor at half dose after obtaining the first microbiological
culture negative for COVID-19 or a negative PCR, and if the patient

Page 13 of 19
remains asymptomatic, add progressively MMF during the following
days..

We need more time and experience to be able to optimize the treatment

protocol and the immunosuppressive strategy to be followed in kidney
transplant patients with COVID-19 infection.

Key concepts

f
 To prevent the transmission in the renal transplant population is

oo
essential to comply with the general recommendations, with
particular emphasis on measures of self-hygiene.
 To minimize the risk of infection, teleconsultation is

pr
recommended for the follow-up of patients with a kidney transplant.
 It is recommended to preserve the donation and transplant activity
e-
to the extent that the pandemic allows it , individualizing in each
case depending on the characteristics and epidemiological situation
Pr
of each health center .
 Due to the high probability of torpid evolution ,
the immunosuppressant strategy recommended in kidney transplant
al

recipients with COVID-19 pneumonia should consist in the reduction

, or ultimately, the temporary interruption of immunosuppressants .
rn

Financing
u

This article was funded in part by the Ministry of Economy, Industri to and
Jo

Competitiveness of Spain, of the ISCIII (PI17 / 02043), funded by the

European Regional Development Fund-ERDF, RETIC (REDinREN RED16 /
0009/0006 ; RD16 / 0009 / 0021; RD16 / 0009/0019 ; RD16 /
0009/0027 ; RD16 / 0009/0032

Page 14 of 19
 Conflict of interests

The authors declare that they have no conflict of interest related to the
content of the article.

References

1. Zhu, N. et al. A Novel Coronavirus from Patients with Pneumonia in China,

2019. N. Engl. J. Med. 382 , (2020).

2. Coronavirus disease 2019.

f
https://www.who.int/emergencies/diseases/novel-coronavirus-

oo
2019.

3. Holshue, ML et al. First Case of 2019 Novel Coronavirus in the United

pr
States. N. Engl. J. Med. 382 , (2020).

4. Ma, Y. et al. 2019 novel coronavirus disease in hemodialysis (HD) patients:

e-
Report from one HD center in Wuhan,
China. medRxiv 2020.02.24.20027201 (2020) doi: 10.1101 /
Pr

2020.02.24.20027201.

5. https://www.who.int/docs/default-source/coronaviruse/situation-
al

reports/20200316-sitrep-56-covid-19.pdf?sfvrsn=9fda7db2_2.

6. Naicker, S. et al. Journal Pre-proof The Novel Coronavirus 2019 Epidemic and
rn

Kidneys The Novel Coronavirus 2019 Epidemic and Kidneys. Kidney

Int. (2020) doi: 10.1016 / j.kint.2020.03.001.
u

7. Zhu, L. et al. Successful recovery of COVID ‐ 19 pneumonia in a renal

Jo

transplant recipient with long ‐ term immunosuppression. Am. J.

Transplant. ajt.15869 (2020) doi: 10.1111 / ajt.15869.

8. Kumar, D., Tellier, R., Draker, R., Levy, G. & Humar, A. Severe acute
respiratory syndrome (SARS) in a liver transplant recipient and guidelines
for donor SARS screening. Am. J. Transplant. 3 , 977–981 (2003).

Page 15 of 19
9. Alghamdi, M., Mushtaq, F., Awn, N. & Shalhoub, S. MERS CoV infection in two
renal transplant recipients: Case report. Am. J. Transplant. 15 , 1101–1104
(2015).

10. Michaels, MG et al. Coronavirus Disease 2019: Implications of Emerging

Infections for Transplantation. Am J Transpl. 10.1111 / ajt.15832 (2020)
doi: 10.1111 / ajt.15832.

11. ACTION PROCEDURE AGAINST CASES OF INFECTION WITH THE NEW

CORONAVIRUS (SARS-CoV-

f
2) . https://www.mscbs.gob.es/profesionales/saludPublica/ccayes/alertas

oo
Actual/nCov-.

12.https:

pr
//www.semg.es/images/2020/Coronavirus/20200319_Protocolo_manejo
_clinico_tto_COVID-19.pdf.
e-
13. Schonder, KS, Shullo, MA & Okusanya, O. Tacrolimus and Lopinavir /
Ritonavir Interaction in Liver Transplantation. Ann. Pharmacother. 37 ,
Pr
1793–1796 (2003).

14. Baden, LR & Rubin, EJ Covid-19 - The Search for Effective Therapy. N. Engl. J.
al

Med. (2020) doi: 10.1056 / NEJMe2005477.

15. Cao, B. et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe

rn

Covid-19. N. Engl. J. Med. (2020) doi: 10.1056 / NEJMoa2001282.

u

16. Ruan, Q., Yang, K., Wang, W., Jiang, L. & Song, J. Clinical predictors of
mortality due to COVID-19 based on an analysis of data of 150 patients
Jo

from Wuhan, China. Intensive Care Med. (2020) doi: 10.1007 / s00134-
020-05991-x.

17. Ko, W.-C. et al. Arguments in favor of remdesivir for treating SARS-CoV-2
infections. Int. J. Antimicrob. Agents 105933 (2020) doi: 10.1016 /
j.ijantimicag.2020.105933.

18. Wu, C. et al. Risk Factors Associated With Acute Respiratory Distress
Syndrome and Death in Patients With Coronavirus Disease 2019

Page 16 of 19
 Pneumonia in Wuhan, China. JAMA Intern. Med. (2020) doi: 10.1001 /
jamainternmed.2020.0994.

19. xiaoling Xu. Effective treatment of severe covid-19 patients with

tocilizumab. ChinaXiv .

20. Fowler, AA et al. Effect of Vitamin C Infusion on Organ Failure and

Biomarkers of Inflammation and Vascular Injury in Patients with Sepsis
and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical
Trial. in JAMA - Journal of the American Medical Association vol. 322

f
1261–1270 (American Medical Association, 2019).

oo
21. Gautret, P. et al. Hydroxychloroquine and azithromycin as a treatment of
COVID-19: results of an open-label non-randomized clinical trial. Int. J.

pr
Antimicrob. Agents (2020) doi: 10.1016 /
j.ijantimicag.2020.105949.
e-
22. HFSA / ACC / AHA statement addresses concerns re: using RAAS antagonists
in COVID-
Pr
19. https://professional.heart.org/professional/ScienceNews/UCM_50583
6_HFSAACCAHA-statement-addresses-concerns-re-using-RAAS-
antagonists-in-COVID-19.jsp.
al

23. Lansbury, L., Rodrigo, C., Leonardi-Bee, J., Nguyen-Van-Tam, J. & Lim, WS
rn

Corticosteroids as adjunctive therapy in the treatment of

influenza. Cochrane Database of Systematic Reviews vol. 2019
u

(2019).
Jo

24. López-Oliva, MO, González, E., Miranda, RJ & Jiménez, C. Management of

kidney transplant immunosuppression in positive coronavirus infection
requiring hospital admission .

Page 17 of 19
 f
oo
pr
e-
Pr

Table 1 . Pharmacological interactions of antiviral drugs with

al

immunosuppressants
LPV / r RDV FAV1 CLQ HCLQ NITAZ RBV
rn

Adalimumab ↔ ↔ ↔ ↔ ↔ ↔ ↔
Anti- ↔ ↔ ↔ ↔ ↔ ↔ ↔
thymocytic
u

globulin

Azathioprine ↔ ↔ ↔ ↔ ↔ ↔ ↑
Jo

Basiliximab ↔ ↔ ↔ ↔ ↔ ↔ ↔
Belatacept ↔ ↔ ↔ ↔ ↔ ↔ ↔
Cyclosporine ↑ ↔ ↔ ↑ ↑ ↔ ↔
Mycophenolate ↑↓ ↔ ↔ ↔ ↔ ↔ ↔
Sirolimus ↑ ↔ ↔ ↑ ↑ ↔ ↔
Tacrolimus ↑ ↔ ↔ ↑ ↑ ↔ ↔

Table 2 . Immunosuppressive protocol in kidney transplant patients with

COVID-19 infection at Hospital La Paz in Madrid

Page 18 of 19
 Kidney transplant <60 YEARS > 60 YEARS
recipients

Without lung infiltrates -Maintain, do not change the -Suspend MMF and maintain with
immunosuppressive treatment. tacrolimus1 (levels 4-6 ng / ml) and
prednisone (usual dose, do not go up to 20
-If you start treatment with mg)
hydroxychloroquine, decrease the
dose of tacrolimus and iMTOR by
20% of entry (due to the interactions
between tacrolimus and iMTOR and
chloroquine) and then always
monitor levels every 48 hours and
maintain tacrolimus levels: 4-6 ng /
ml.

f
Without - Discontinue MMF only. Maintain Discontinue MMF, reduce tacrolimus1 to

oo
hypoxemia or with tacrolimus1 (levels 4-6 ng / ml) levels of 3-5 ng / ml and maintain
fever and prednisone 20 mg daily prednisone (usual dose, do not go up to 20
mg)
With pulmonary
infiltrates

pr
More hypoxemia 1.- Discontinue tacrolimus and MMF
(need oxygen) or (or iMTOR) and maintain only with
fever prednisone 20 mg a day for the first 4
days.
e-
2.- After the 5th day of admission, if
there is clinical improvement
(he/she does not have a fever and
does not need oxygen): Resume
Pr
tacrolimus1 to maintain levels of 4-6
ng / ml associated with prednisone of
20 mg.
3.- After the 5th day of admission, if
the clinical situation is not improved
(persists fever or requires oxygen),
al
1.- Discontinue tacrolimus and MMF (or
iMTOR) and maintain only with
prednisone 20 mg a day for the first 4 days.
2.- After the 5th dayof admission , if the the
patient improves (does not have a fever and
does not need oxygen): Resume
tacrolimus1 to maintain levels of 3-5 ng /
ml associated with prednisone of 20 mg.
3.- After the 5th day, if the clinical situation
does not improve (persists fever or requires
oxygen), maintain only with prednisone 20
mg/day. Tacrolimus will be started again as
in point 2 when the patient improves.
1If you start or are already on

maintain only with prednisone 20 hydroxychloroquine, decrease the dose of

mg/day. Tacrolimus will be started tacrolimus and iMTOR by 20% of entry
again as in point 2 when the patient (due to the interactions between tacrolimus
rn

improves. and iMTOR with chloroquine)

Patients who have been in Start with Hydroxychloroquine 200mg every 12 hours for 5 days. Reduce tacrolimus or iMTOR doses by
contact with a case of 20% during these days and then return to the usual dose. Maintain unchanged the rest of
u

confirmed coronavirus immunosuppression.

infection and have no
Jo

symptoms

Page 19 of 19
Another random document with
no related content on Scribd:
 I cannot explain to you in this place how this gas is formed by
plants. It would be a good plan for you to study up this subject, for it
is quite curious, and very interesting. The gas is fatal to animal life.
Neither man, beast, or bird can breathe it for even a short time and
live. But the gas is heavier than the common air, and sinks in it. In
this valley, as I have said, it extended only about two feet above the
ground, and a man’s lungs were above it, so he could not inhale it.
On horseback of course he was far above it. But low animals, and
birds that alighted on the ground at once fell victims to it.
This led to an examination of the Upas tree stories, and most of
them were found to be fables. Grass and flowers do grow around
these trees in most places; birds sport upon their branches, and
lizards run up and down unhurt; and it is possible to remain under
them without injury of any kind.
But it is true that the juice of the upas is a powerful poison. The
savages use it as a weapon to kill their enemies in war, and to slay
the wild beasts. They dip the points of their spears and arrows in the
poisonous sap. An animal dies in five or six minutes after being
struck with one of these poisoned weapons. They take great
precautions in collecting the sap, so terrible is their fear of this tree.
On some plants the blossoms are so small they can scarcely be
seen by the naked eye, and on others they are of enormous
proportions.
An African flower, the Aristolochia, has a large and curiously
shaped blossom. It is shaped like a helmet with flaring edges, and
the opening is so large that it will admit the head of a man, and can
be worn as a hat.
The flowers of the Victoria Regia, which are shaped very much like
those of our water lily, are a yard in circumference.
But the giant of blossoms is the Rafflesia Arnoldi. This is a long
name, but the flower can bear it very well.
 RAFFLESIA ARNOLDI.

It grows in the islands of Java and Sumatra, and the buds and
blossoms seem to be pretty much all there is of the plant. And quite
enough too. The full blown flower is a yard wide. Each of its five
petals is a foot long, and they stand at about the distance of a foot
from each other. In the centre there is a deep honey-cup, which is
capable of holding a dozen pints of fluid. The whole weighs fifteen
pounds. The central cup is violet and red, and the petals are of a
brilliant orange color, so that it makes a gorgeous display indeed.
But this flower, so magnificent in size and color, has such a
disagreeable smell, that after having satisfied your curiosity by
looking at its gigantic blossom, you will be glad to get away from its
neighborhood.
From the bark of a tree, the Cinchona, we get one of our most
useful and powerful medicines. The bark is known under the name of
Peruvian bark, and there are several preparations from it—quinine
being the one most generally used. It is a valuable medicine
everywhere, but is especially so in the hot countries where it grows,
for very malignant fevers prevail in those localities. It got its name,
Cinchona, from the first European who used it. The Countess
Chinchon of Spain, while living in Peru was attacked by one of the
terrible fevers of the country, and was near dying, when she heard
that in such fevers the natives cured themselves with the bark of a
tree. She tried it, and recovered; and, after she got well, she took
pains to make known the virtues of this bark, and gave away great
quantities of it. It is now a very important article of export from Peru,
and a source of great wealth.
There are other barks of plants and trees used in medicine. A
great many are useful as dyes. The inner bark of a species of oak
furnishes us with corks. Some trees have aromatic barks. The black
birch of our own woods is highly spiced. Of some the flavor is so
pleasant that they are used as spices. Cinnamon bark, for instance,
which, of course, you know all about.
So you see that even in the bark of vegetables there are pleasant
things stored away, and wonderful secrets, if we choose to take the
trouble to get at them.
The fragrance of a plant, if it has any, we expect to find in its
blossoms. But this quality is not confined to the flowers. It is found
sometimes in the leaves, occasionally in the bark, and very
frequently in the fruit. We are familiar with the fragrance of
strawberries, raspberries, peaches, grapes, bananas, lemons, and
oranges; and many others might be named. In fact nearly all eatable
fruits have some sort of a pleasant odor, though in some it is very
faint.
Sometimes the fragrance is in the nuts. There are but few
examples of this. The Black Walnut has an agreeable smell. The
most famous of fragrant nuts is the Nutmeg, with which we are all
familiar in the spice-boxes. But perhaps you don’t know how
beautifully it looks growing upon the tree. So we will break off a
branch for you to look at.
 BRANCH OF A NUTMEG TREE.

This nut ripens under the hot sun of India. Not only is the nut itself
fragrant, but the second coat of its envelope, or shell, that you see in
the picture, also has a pleasing perfume of its own, entirely distinct
from its nut. This you are also familiar with in the spice box, broken
up into thin yellow chips, and called Mace.
No more delicious fragrance can be found than that of a South
American bean, the Vanilla.
As for leaves, you can think of a great many fragrant kinds in a few
minutes, not only green-house plants, like some of the geraniums,
but many of the weeds of the fields.
Some vegetables produce very remarkable fruits.
 FRUIT OF THE BREAD FRUIT TREE, REDUCED IN SIZE.
A species of fig-tree bears loaves of bread! It is quite a large tree,
about forty feet high, and has wide spreading branches, thickly
covered with very large leaves. It bears fruit abundantly, and during
eight months of the year, there is always some ripe fruit to be found
on the boughs.
This fruit is round; is larger than a child’s head; weighs three or
four pounds, and is rough and hairy on the outside.
The thick green rind encloses a pulp, which is as white as wheat
bread, and, when cooked, tastes very much like it, and is equally
nourishing. To prepare it to be eaten, it is cut into thick slices, and
laid upon a gridiron over a bed of hot coals. In a few minutes the
“bread” is ready.
Thus the natives of the countries where this fruit grows have bread
for eight months of the year with very little trouble. If they did not
have this kind they would not have any bread at all, for wheat and
rye will not grow there.
But they want bread the rest of the year too. So they take
advantage of the time when the fruit is most abundant, and, from that
which they do not want for immediate use, they prepare a paste that
can be kept a long time without turning sour. And, during the four
months the tree is without ripe fruit, they live upon this preparation.
Tapioca is the singular production of a vegetable root. It is singular
because, though wholesome and nutritious as food, it is produced
from a strong poison. It is prepared as follows by native women.
Roots of the manioc plant are gathered, and bruised into pulp with
a wooden pestle. This pulp is wrapped in a net made of lily leaves.
This is stuck upon a fork, and a heavy weight tied to the bottom of
the net so as to press it tightly to squeeze out the manioc juice. A
calabash receives the juice, which is very poisonous. Arrows and
spear heads are dipped into it to make them certainly fatal. While
this is going on the liquid is all the time depositing a white, starch-like
substance in the bottom of the calabash. When all of this that the
poisonous liquid contains is deposited, the juice is poured off, and
the white substance is passed through clear water, and becomes
tapioca.
 A FOREST OF MANGROVES.
When we are in the tropics we must not forget to visit the
Mangroves. These trees grow thickly together in the ocean mud near
the shore, and are very queer specimens of the vegetable world. To
look at them from a little distance you would hardly know whether
they were trees, or fishes, or sea-serpents. Their upper branches
and trunks are like the first, their lower branches covered with
oysters and other shell-fish appear like the second; and their long
curiously twisted roots, standing partly out of the water, seem like the
third. Sometimes, in passing over wet and swampy places, men walk
on these roots. In such a case, a naked savage gets along much
more easily than an European, with his boots and clothes, and
perhaps a heavy gun.
But there is a strange thing about this tree, apart from its
uncommon growth. And that is the way that its seeds germinate. We
put a seed into the ground, and when it sends up its little stalk and
leaves we say it has germinated or sprouted. Now the mangrove
seeds germinate on the branches, in the fruit. The seed sends forth
the little stalk which grows up there until it is a foot long. This stalk is
shaped like a pointed club and is quite heavy. When it is ready to fall,
it goes plump down through the leaves and branches of the tree,
sharp end downwards, and sticks itself firmly upright in the mud at
the bottom of the water. And, after some time, it thrusts itself above
the surface, and grows into a comical mangrove tree.
If you will study the marvels of vegetable life you will find strange
things of which I have said nothing.
Many wonderful plants grow high up in the air on the branches of
trees; and many very curious ones thrive only in the water.
 BRON AND KRUGE.

Old King Rhine sat upon his rocky

throne among the reeds. He had
given his kingly word that for three
months his river, the Rhine, should
not overflow its banks, and that there
should be no manner of tempest
upon its waters. The old gentleman
was sad and gloomy. A month had
passed since he gave this promise,
and all that time he had had nothing
to do. This was hard upon him, for
he had led a very busy life. Many an
army had he helped across his river,
and many a one had he broken to
pieces with floods, and tempests. KING RHINE.
Christians and savages, knights and
nobles, and men of low degree had
fought upon his banks. Men had built castles, and he had swept
them away, or crumbled them into ruins. And, sometimes, he had
helped beautify them, and spread grass and flowers all around them.
And he had occupied himself in many other ways.
And now there was nothing for him to do. He looked up and down
the length of the stream. The waters were still and blue, and vessels
glided over them, and the little boats rocked gaily on the swelling
waves. At the wharves of the cities men were busy loading and
unloading the ships, and all rejoiced in the pleasant and prosperous
season. On the hill-sides the vineyards were as full of grapes as ever
they could be, and the vines found their way up the very walls of the
ruined castles, and hung their purple clusters on the loosened
stones.
 It was very pretty, and the old king took pleasure in it, but he
always liked to have something going on that was not quite in the
ordinary way.
Suddenly he remembered that there were other creatures under
his care besides men. There were Nixies, and Fairies, and Gnomes,
and Dwarfs, and Undines, and Elves, and Sylphs, and Peris, and
Nymphs, and Dryads, and Giants.

A RHINE VINEYARD.
Giants! Here was something for him to attend to! There were not a
great many giants left on the banks of the Rhine, but the few that
were there were capable of doing a great deal of mischief; and king
Rhine had been hearing bad reports of them for a long time. But he
had been so busy with men and their affairs that he had neglected
looking after anything else. It was high time that these giants were
taught better manners.
 But who was to teach them? Who should he employ to subdue
these giants, who were as tall as oak trees? Men could do nothing
against them. Since the death of Jack the Giant-Killer no man had
ever been known to conquer a giant.
In his perplexity he summoned a wise woman, who lived on the
highest peak of the highest mountain on the river, and who always
gave wise counsel; but would never leave her rocky home except
when some one was in great need of good advice. She came to the
king at his bidding and this is what she said:
“Good dwarfs can conquer bad giants.”
Not another word would she utter. She made this same answer to
every question the king put to her, until, finally, he flew into a rage,
and shook his reedy sceptre at her. Whereupon this wise woman
disappeared.
The king spent several days thinking about this matter. He could
not fight the giants himself, for that would be beneath the dignity of a
king. As for what the wise woman had said about the dwarfs, that
was ridiculous. A little creature, scarcely a foot high, to conquer a
mighty giant! But, after considering the matter a good while, it did not
seem quite so absurd. He recalled to mind something the gnomes
had done some years before.
Now a gnome is as small a being as a dwarf, and his home is
under the ground, so that he seldom sees the light of day.
Consequently he is not as bright and quick-witted as a dwarf. And
yet a few of these creatures had first astonished all the civilized
nations on the globe, and then set them all to quarreling. In order to
make you understand how this was I must go back for a minute to
the world before the Flood.
 THE GNOMES AT WORK.
A long time before the Flood, before man was created, the world
was inhabited by beasts, fishes, and reptiles of enormous size; very
much larger than any at present upon the earth. We know this
because parts of the skeletons of these animals have been found in
various places; and the learned men of different countries have
written a great deal about them.
Now it happened that some years before this trouble had arisen
between King Rhine and the giants, and before his talk with the wise
woman, some gnomes while digging in a cave for gold, found buried
in the earth the skeleton of an immense head. Astonished at this
sight they determined to let gold hunting alone for a while, and to see
if they could not find the rest of the animal to which the head
belonged. They worked carefully and industriously for many months
with their little picks and spades, and, finally they laid bare the whole
skeleton of a monstrous creature of the very queerest shape the
gnomes had ever seen. I say the whole of it, but there were a few
bones wanting here and there, for which the gnomes searched in
vain in the earth around the spot where the creature lay.
This animal measured thirty-three feet in length. It was shaped
somewhat like a great lizard, but it had the back-bone of a fish, and
the fins of a dolphin, with the head and teeth of a crocodile. But what
eyes it must have had while living! The gnomes amused themselves
by crawling in and out of the sockets! The ball of the eye must have
been as large as a man’s head!
When the gnomes had finished this great piece of work they did
not know what to do with the huge creature they had found. It was of
no use to them, and, after they had taken a few of the smallest
bones for drum-sticks, they would have nothing more to do with it.
After a time, the sight of this terrible, fleshless monster was hateful to
them, and they could not move it away.
In this dilemma they went to King Rhine to know what it was best
to do with this fruit of their long labors. He told them they had been
very foolish gnomes to spend so much time on a thing that was of no
use to anybody, and that ought to be covered up from the sight of
men. He advised them to put all the earth and stones back again,
and bury the horrid creature.
The gnomes could not make up their minds to do this, and they
moved out of the cave into another part of the same mountain, and
left the lizard in possession of their old home.
Soon after a wood-cutter, being caught in a storm, took refuge in
this cave; and the sight of this gigantic skeleton frightened him more
than the storm. He ran to his village with the wonderful news. A very
learned man who lived there, hearing the story, went to look at the
skeleton, and was filled with astonishment, for he had never even
imagined such an animal.
He immediately wrote a book about it.
And then old Rhine found that, in this case, the gnomes were
wiser than their king. For, so far from this creature they had dug out
of the ground being of no account, it caused a greater stir than
anything that had happened in his kingdom since the last army had
been driven across the river a good many years ago. People flocked
from all quarters to the cave, and business was lively the whole
length of the river.
Learned men came from every country in the civilized world. And
each one wrote a book about the lizard-fish. But the worst of it was
that no two of them agreed as to what it was. They disputed so long,
and so earnestly over this skeleton that, at last, the unlearned took
up the quarrel, each country feeling bound to support its own learned
men. And in this way the governments were drawn into the dispute,
and there had liked to have been a war over the old bones. Letters of
instruction to Consuls were flying about, and there was a great
examination into treaties; when, all at once, it became known that
the learned men all agreed that the animal was the Ichthyosaurus,
and that the last one had died thousands of years ago. So the war
was happily averted.
Then the dispute was as to who had first found out this fact, but
this was amicably settled by the discovery that all the learned men
had found it out at precisely the same time.
During all this the gnomes had worked away in their new home at
their own affairs, and knew nothing of the great commotion they had
caused. But king Rhine nodded his old head, and said to himself;
“The gnomes are a very little people, but they have managed to set
the whole world by the ears.”
He recalled all this now, and thought perhaps the wise woman
meant what she said about the dwarfs and giants.
He despatched a trusty messenger to a colony of dwarfs who lived
in a large ruined castle. These dwarfs, or Kobolds, as they are called
in that part of the country, sleep all day, and do their work at night.
Therefore the king chose an owl, venerable with age and wisdom, for
his messenger. He was to travel in the night-time, and rest in the
day.
On the second night, quite early, the owl arrived at the castle. He
flew quietly into the ruin, so as not to frighten the dwarfs, but he
found they had already gone. He was afraid he was too late; and that
they had all dispersed to perform their several duties; but, hearing a
great noise outside, on the opposite wall from that he had entered,
he flew up into a narrow window where there was no glass, and
looked solemnly down, with his great staring eyes, upon a very
merry scene.
 THE KOBOLDS.
The little kobolds were having a frolic before they separated for the
night’s adventures. They were chiefly employed in running up and
down the wall, chasing lizards, though some were dancing on the
grass at the foot of the castle, and others were swinging on the
vines, and gathering grapes. They were making such a hubbub that
the owl thought he had better wait for them to get quiet before
attempting to make himself heard.
He soon noticed that there were three dwarfs who took no part in
the fun, and these sat upon the root of a tree near the castle talking
very earnestly together. The owl knew something of the habits of the
kobolds, and he supposed this trio to be the Council, chosen yearly
by the colony. It was the business of the Council to assign to each
dwarf his nightly task, and the affairs of the colony were mainly
placed in its hands.
While the three are holding counsel together, and the owl is
waiting, I will tell you something about these dwarfs.
They were generally larger than Fairies, although some of them
were very small indeed.
There were three or four kinds of these little people, all called
dwarfs, although there was a great difference in their characters, and
labors. Some were wicked, and thought only of doing spiteful tricks;
some were lazy drones, some mingled publicly with men, and
became kings’ fools; some would never show themselves to human
beings; and some were gnomes and worked underground.
The kobolds were the brightest, and most industrious of all the
dwarfs, and were famed for being good-tempered and obliging.
Every night these little creatures were busy in the fields, and the
stables, and the kitchens of the neighborhood. They never quarrelled
among themselves, and they gave nobody any trouble. Hence they
were spoken of as the Peaceful People.
Sometimes field laborers, on going out in the morning to weed, or
to reap, would find the work already done. A poor farmer’s wife
coming into her kitchen in the morning to make the fire would find the
wood all cut, and laid in order, and a pail of water brought from the
spring. Sometimes the little people would go into the dining room,
and wash the glasses, and clean the silver. Occasionally they would
go to work, and drive all the mice and spiders out of a house. They
washed dishes, and cleaned vegetables, and made themselves
useful about the house in every possible way. All they required in
return was a little food. A bowl of milk, or some nice fresh bread, was
set upon the kitchen table, and that was supper enough for a kobold.
Some of them preferred to work in
stables. They would curry the
horses; comb out their manes; shake
down straw for the litters, and clean
the stables. But this is hard work,
and the little things would get very
tired. So the coachmen, and the
farmers used to tie knots in the
manes of the horses to afford resting
places for the kobolds. They would
sit in these to rest their weary limbs
and often take a little nap there to
refresh themselves.
They visited the sheep in the fold,
or on the hill-sides, and kept the
fleeces white and clean.
TAKING A REST.
There were many other things the
kobolds did, but I have told enough
to give you an idea of the busy, and helpful life they led; and will now
return to the colony that lived in the old castle.
The owl looked down and watched the frolic of the dwarfs for
nearly an hour. Then one of the three dwarfs, who formed the
Council, blew a shrill blast upon a whistle. At this signal the whole
colony gathered into a group in front of the Council. Now all were
quiet, and the owl knew this was his time to speak, for the tasks of
the night were to be given out, and as each one received his
commission, he would go away.
The owl flapped his wings, and they all looked up. Some of them
had seen him before, and knew him to be one of the king’s
messengers. So they invited him to a seat on a rock near them, and
listened with respectful attention while he told them of the bad
behavior of the giants, and of the advice of the wise woman. He took
good care not to tell them that the king at first thought this advice
ridiculous, but made it appear that his majesty relied upon the good
dwarfs to conquer the giants, and to make them behave peaceably.
The method of accomplishing this he left entirely to their wisdom.
It was a very flattering speech, and the owl looked so grave while
delivering his message that the dwarfs believed every word of it.
Never in all the history of kobolds had anything like this happened.
The giants were the beings that the dwarfs feared more than any
other creatures, and they took very good care always to keep out of
their way. And now their king thought them capable of vanquishing
these gigantic enemies! The whole colony became at once puffed up
with pride and vanity, and clamored to the Council to lead them forth
immediately to fight the giants.
Two of the members of the Council had their wits completely
carried away by the enthusiasm of the colony, and waved their hats,
and shouted, “On to the giants!” But the third member sat quiet until
all the company had shouted themselves hoarse, and were still once
more. Then he said:
“My friends, we can never conquer the giants in an open fight. One
of these huge creatures could crush a dozen of us at a time with one
foot, and a giant’s club would knock our whole colony higher than a
kite. Moreover we know nothing about fighting. The kobolds have
been peaceable people from the beginning of time, and all warfare is
distasteful to us. The giants are big and strong, but everybody knows
they have not much wit, while our small heads are full of brains. The
giants do nothing but mischief, and any fool can do that. But we
spend our time in work that requires intelligence and skill. The king
has honored us by selecting us to punish the giants for their bad
behavior, and I feel sure we can conquer them; but we must do it by
using our brains, and not with weapons of war.”
The name of the dwarf who thus spoke, was Bron, and he was
looked upon by the whole colony as the brightest wit among them.
So they listened attentively to all he had to say. But they were not in
the humor for following this good advice. The king evidently
expected them to fight the giants, and fight them they would.
They sent a message back to the king that they were going forth to
battle, and, in three days, would bring to him, as a trophy, the head
of Kruge, the chief giant.
The dwarfs now consulted as to a plan of action. It was agreed
that they should, in a body, march upon the stronghold of Kruge,
surprise him while asleep, and tie him down, fast and firm, with a
great number of small cords. Then they would cut off his head.
If Kruge was killed, or submitted to them, the remaining giants
were as good as conquered, for they all depended upon Kruge.
The kobolds sharpened their little swords that had only been used
for cutting twigs, and strings. They made bows and arrows, and
gathered sharp sticks, and armed themselves with brooms, and
hoes, and spades, and reaping-hooks. They organized companies,
and drilled, and marched, and counter-marched all night long; and
enjoyed it immensely. They slept soundly the next day; and by night,
they were ready for action.
They marched gaily forth in four bands of a hundred each. The
first band was assigned to Bron. He did not approve of the
expedition any more than at first, and his heart was sad, for he
thought his tribe was marching to certain death. But, as they were
determined to fight, he resolved to go with them, and do his best. It
was better to die with them than to live alone.
Kruge lived a long distance from the castle, and, as the dwarfs had
to rest most of the day, it was late in the second night when they
drew near the great cave where the giant dwelt. Fortune favored
them, for Kruge lay outside of the cave stretched upon the ground
fast asleep. He did not hear the delicate footfalls of the tiny creatures
who had come to him with such evil intent, and they could easily tie
him down without awaking him. But the dwarfs saw that their small
cords would avail nothing when the giant did awake. He would snap
them in a minute. And the probability was that as soon as they
commenced sawing at his throat to cut his head off he would wake