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Date of publication April 13, 2020

PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 
EPIDEMIC OUTBREAK  

Lessons from the Italian Experience

By Micaela La Regina, Michela Tanzini, Francesco Venneri, Giulio Toccafondi, Vittorio Fineschi, Peter Lachman, 
Luca Arnoldo, Ilaria Bacci, Alessandra De Palma, Mariarosaria Di Tommaso, Andrea Fagiolini, Marco Feri, Raffaele 
La Regina, Antonino Morabito, Stefano Parmigiani, Mario Plebani, Elisa Romano, Chiara Seghieri, Pierfrancesco 
Tricarico, Giorgio Tulli, Riccardo Tartaglia.

International Society For Quality In Health Care
Version – 1.1 (30 March 2020)

SUMMARY

INTRODUCTION             8

1. GENERAL RECOMMENDATIONS FOR THE WORK SYSTEM        8

2. RECOMMENDATIONS FOR DIAGNOSIS          9

3. RECOMMENDATIONS FOR HOSPITAL TREATMENT         11

4. THE ETHICS OF TREATMENT DECISIONS          12

5. RECOMMENDATIONS RELATED TO SURGERY         12

6. RECOMMENDATIONS RELATED TO PREGNANT WOMEN        13

7. RECOMMENDATIONS RELATED TO PEDIATRIC PATIENTS        14

8. RECOMMENDATIONS RELATED TO HOSPITAL DISCHARGE        14

9. RECOMMENDATION RELATED TO HOME ISOLATION        15

10. RECOMMENDATIONS RELATED TO PERSONS IN QUARANTINE (39)       15

11. RECOMMENDATIONS RELATED TO ONCOLOGIC AND IMMUNOSUPPRESSED PATIENTS    15

12. MORTUARY/MORGUE OPERATING PROCEDURES         15

13. PSYCHOLOGICAL SAFETY OF STAFF AND MENTAL WELLBEING OF PATIENTS      17

14. MEASURES (51,52,53)            19

15. REFERENCES             19

16. APPENDIX - MEDICATIONS           23

This document is re-posted with permission from Riccardo Tartaglia (President of Italian Network for Safety in Health Care)

Copyright © 2021. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY): Creative Commons - Attribution 4.0 International 
- CC BY 4.0. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original 
publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

J Global Clinical Engineering, Special Issue 3, 2020  8

INTRODUCTION
On the basis of reports and questions forwarded to the 

Clinical Risk Managers of the Italian Network for Health 
Safety (INSH) from physicians working on the front line, 
a series of recommendations have been developed re-
ferring to documents and papers published by national 
institutions (ISS) and Italian and international scientific 
societies and journals. We have arranged the process to 
describe organising the work system according to the 
SEIPS Human Factors approach (1).
1. Assess the work system:

a. Team and organisational culture and communication
b. Environment
c. Tasks required and skills to complete tasks
d. Equipment for patient care and to protect staff
e. The people needed to provide care
f. The patients who will receive care

2. Develop reliable pathways of care.
3. Measure the outcomes of care.

ISQua is honoured to publish these recommendations 
with our partners in Italy. The document is work in prog-
ress and will be subject to updates by all professionals 
on a continuing basis. We appreciate and welcome the 
contribution of all those involved in COVID- 19, both 
providers of care and patients who have received care: 
(e-mail info@insafetyhealthcare.it). 

1. GENERAL RECOMMENDATIONS FOR THE WORK 
SYSTEM

Building the Team including communication and team 
culture
1. Emergency taskforce should be promptly activated 

with a clear chain of command, roles and responsibili-
ties, reliable information sharing tools and proactive 
approach.

2. Check frequently every day the communications sent 
by your institutions. Read carefully and respect them. 
Alternatively, print and make such communication 
available in the ward and share such information dur-
ing handovers.

3. Clinical risk management units can support dis-
semination of documents, guidelines issued by the 
national institutions for supporting the emergency 
management, relatively for measures of prevention to 
be taken.  Knowledge about Coronavirus transmission 
and spreading and clinical characteristics of related 
disease (COVID-19) are constantly evolving, so that 
indications for clinical practice change frequently, i.e. 
case or suspicion definition, criteria for making swabs, 
etc.

4. The clinical risk management units must keep con-
tact with front line workers and provide support. 
The reporting of adverse events must occur within 
the task-force activity and be primarily related to the 
core activities in time of the pandemic. Secondly, the 
reporting of Adverse Events should be encouraged in 
order to maintain the underpinning safety climate in 
order to prompt corrective and improvement actions. 
Consider quick reporting tools such as confidential IM 
or audio-messages (e.g. WhatsApp, WeChat, Telegram, 
Line etc.)

5. The clinical risk management units should also receive 
evidence of good practice so this can be disseminated.

Tasks to be undertaken and skills required
1. Organise brief educational training on the correct 

use of medical and protective devices targeted to all 
healthcare workers and develop video tutorials to be 
available on the healthcare trust website.

2. Hold refresher courses on hand-hygiene, the preven-
tion of VAP (Ventilator Associated Pneumonia) and 
CLABSI (Central Line Associated Bacterial Infection) 
bundles and the SEPSIS bundle for early sepsis recog-
nition and management to all healthcare workers (2), 
but in particular to the staff not in the frontline of the 
emergency who could be called as replacements.

3. Organise early support of expert doctors/nurses with 
young or colleagues from other specialties who may be 
called upon to replace them to properly educate them

4. Do not forget appropriate instructions for environment 
disinfection (detergents, contact time, frequency) to 
cleaners (3).

mailto:info@insafetyhealthcare.it


9 J Global Clinical Engineering, Special Issue 3, 2020 

PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

Equipment needed to protect staff
1. Contact and droplet precautions can be used in routine 

patient care of patients with suspected or confirmed 
COVID-19 (4).

2. Contact and airborne precautions are recommended 
when performing aerosol generating procedures (AGPS), 
including intubation and bronchoscopy (4).

3. Prevent biosafety precautions shortage by extended 
use and limited re-use of full-face shields and dispos-
able facial filtering masks (5), by identifying a priority 
order to the different wards and by supply of reusable 
tyvek suits. Store such devices in a locked or secured 
area and distribute to staff appropriately (5).

The infection spreads so quickly that a depletion of reserve 
medical supplies is almost unavoidable. 

Equipment needed to treat patients
1. Give suspected or confirmed patients a surgical mask 

to put on, at their first contact with healthcare services 
(6).

2. In the dedicated care areas for patients with COVID-19, 
ensure that:
a. haemo-gas analyzers
b. pulse oximeters
c. oxygen therapy
d. ventilator therapy equipment e.
e. suction pumps.
are available and well-functioning (7).

Environment
1. Strictly apply, without exceptions, the indications 

for disinfection of environments and tools    (sodium    
hypochlorite    at    0.5%    or    70%    ethyl    alcohol    
solution)    (8).    It is not yet well known how long the 
virus resists in the environment, but it is inactivated 
by solutions based on hypochlorite and alcohol.

2. Prevent germicide deficiency by using galenic preparations.
3. Keep in mind that the creation of dedicated hospitals 

may divert from the emergencies /emergencies network. 
Evaluate carefully the fallout of the timing of treatment 
decisions for time-dependent diseases. Consider the 
use of underused or quiescent equipped hospitals to 

meet this need.4. Unless activity is suspended, in 
the outpatient (public or private) clinics:
a. avoid gatherings in waiting rooms (recommend 

people wait outside, respecting the distance of at 
least 1m between seats);

b. inform symptomatic subjects with fever and / or 
cough and / or dyspnea (shortness of breath) not 
to go to clinics;

c. disseminate hygiene and health standards recom-
mendations in the waiting room.

Patients
1. Reduce hospital admissions, routine outpatient clinic 

appointments and routine surgical procedures and 
regulate hospital visits. Even in absence of strong 
evidence, it would be a good practice for authorized 
family members to enter the wards wearing medical 
masks, due to patients’ frailty.
In the full-blown epidemic phase:
a. consider all patients with flu-like symptoms who 

access hospitals as potentially affected until proven 
otherwise (2 negative swabs at least 48-72h apart);

b. create separate unclean/clean paths, even with 
the help of external mobile structures (i.e. tents).

2. Contacts of positive patients must follow the instruc-
tions provided by those who carry out epidemiological 
investigation and be clinically evaluated in the locally 
designated sites, only if symptomatic.

3. Use a screening interview to identify suspected cases 
before admission to the examination room in case of 
infection symptoms or to healthcare services for other 
reasons (i.e. surgery, coronary angioplasty, labour and 
delivery, etc.)
a. If the criteria of case or suspicion are met, refer the 

patient for evaluation, according to local procedures.
b. General practitioners will provide their patients 

with useful information by social networks, email 
or other tools and keep them updated.

2. RECOMMENDATIONS FOR DIAGNOSIS
1. The adequate specimen for Real Time-Polymerase 

Chain Reaction (RT-PCR) testing is nasopharyngeal 



PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

J Global Clinical Engineering, Special Issue 3, 2020  10

and oropharyngeal sampling. Prefer lower respira-
tory tract (LRT; expectorated sputum, endotracheal 
aspirate, or bronchoalveolar lavage) when readily 
available (for example, in mechanically ventilated 
patients). Quality of RT-PCR testing is a crucial issue. 
Both pre-analytical and analytical variables should be 
carefully considered, and a validation process should 
be performed according to ISO 15189 (3 protocols). 
(9)

2. Many of the most common symptoms of novel coro-
navirus disease (COVID-19) are like those of common 
flu or cold. So, it is also suggested knowing which 
common symptoms of flu or cold are not symptoms 
of COVID-19. COVID-19 infection seems to rarely 
cause a runny nose. Rhinorrhea ("runny nose") is not 
a symptom of COVID-19 and nasal congestion ("stuffy 
nose) is reported only by 4.8% of patients (10).

3. The most common COVID-19 symptoms are: fever 
(88%), dry-cough (68%), fatigue (38%), thick sputum 
production (34%), shortness of breath (19%), arthro-
myalgia (15%), sore throat (14%), headache (13.6%), 
chills (11%), nausea/vomiting (5%), nasal congestion 
(4.8%), diarrhoea (3.7%). Data from a series of 55,924 
laboratory confirmed cases of COVID-19 in China in 
the period up to February 2020 (11).

4. Beware of patients with gastrointestinal symptoms. 
Nausea / vomiting and / or diarrhea can be present 
in about 9% of cases. These symptoms have so far 
been one of the most frequent causes of omission or 
diagnostic delays (11).

5. Unexplained hyposmia, anosmia  and dysgeusia could 
be other  symptoms  of COVID-19. This issue is cur-
rently under investigation (12).

6. Vital signs measurements (do not forget respiratory 
rate, please) and blood gas analysis in room air, if SpO2 
<94%, at triage or as soon as possible, are essential 
to correctly assess patients coming to the emergency 
room (13, 14).

7. Do not rely only on PO2 <60 for the diagnosis of 
respiratory failure, always calculate the PaO2/ FiO2 
ratio (P/F ratio), especially in young subjects.

8. Define a “COVID-19 profile” for the rapid order entry of 
blood tests, including the following tests: blood count, 

C-RP, creatinine, electrolytes, blood glucose, albumin, 
AST ALT, LDH, bilirubin, pneumococcal and legionella 
urinary agents, PT-INR, troponin and procalcitonin.

9. Chest X-rays have limited sensitivity in early stages of 
COVID-19 pneumonia. CT scan is more sensitive but 
raises logistical problems. If ultrasounds competencies 
are available, use chest US, but disinfect US probes 
after contact with every COVID-19 suspected patient 
(15).

10. Monolateral lung infiltrates do not exclude COVID-19. 
They have been described in 25% of cases (15).

11. The most common reported laboratory abnormalities 
in COVID-19 patients are: Lymphopenia (35-75%), 
increased C-RP (75-93%), LDH (27-92%), ESR (up 
to 85% of cases), hypoalbuminemia (50-98%) and 
anemia (41-50%). Data from a systematic revision 
of literature (16).

12. The following negative prognostic factors have been 
reported: leukocytosis, neutrophilia, increased 
procalcitonin, LDH, AST, ALT, total bilirubin, creati-
nine, troponin, d-dimer, PT and hypoalbuminemia, 
lymphopenia. Even thrombocytopenia is associated 
with severe disease (16, 17). Severe lymphopenia 
and lymphocytes count fall during the first 4 days 
since hospital admissions have been associated with 
a higher mortality. Increased white blood cell count, 
neutrophil count and procalcitonin could reflect bacte-
rial superinfection, while increased d-dimer and PT 
a diffuse intravascular coagulation (DIC), reported in 
up to 75% of patients who died (16).

13. History of smoking, respiratory failure, maximum body 
temperature on admission 37.3°C, albuminemia<4 
mg/dl would be risk factors for disease progression 
(severe or critical disease/death). esults from a mul-
tivariate analysis on a small sample (OR ranging from 
7 to 15) (18).

14. Do not forget other respiratory infections (legionella, 
pneumococcus, mycoplasma, chlamydia, other re-
spiratory viruses) even if during epidemics, so look 
for other pathogens and consider antibiotics. During 
epidemics it is important to avoid availability bias that 
means diagnose all infections due to epidemic agents. 



11 J Global Clinical Engineering, Special Issue 3, 2020 

PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

WHO recommends investigating other pathogens, as 
co-infections have been reported (2).

15. Use disease severity stratification for the choice of 
the treatment setting (home, ordinary, sub-intensive 
or intensive care unit). WHO distinguishes 6 clinical 
syndromes associated with COVID-19: uncomplicated 
disease, mild pneumonia, severe pneumonia, ARDS, 
sepsis and septic shock. Patients with uncomplicated 
upper respiratory tract viral infection, may have non-
specific symptoms such as fever, cough, sore throat, 
nasal congestion, malaise, headache, muscle pain 
or malaise. These patients do not have any signs of 
dehydration, sepsis or shortness of breath and can 
be treated at home (2).

16. Pay attention to elderly people and immunocom-
promised subjects as they can present vague and/or 
atypical symptoms (2).

17. Immediately notify the Public Health Officials of 
COVID-19 positive patients (use infectious disease 
notification forms) (19).

3. RECOMMENDATIONS FOR HOSPITAL TREATMENT
1. Before prescribing antiviral drugs, verify drug-drug 

and drug-disease interactions, pay particular attention 
to oral anticoagulants that could be substituted by low 
molecular weight heparin. Current antiviral therapy 
schemes include drugs such as lopinavir / ritonavir, 
chloroquine or hydroxychloroquine, darunavir, cobi-
cistat, tocilizumab, remdesivir (14,20) which present 
interactions with antibiotics, antiarrhythmics, statins, 
anti-angina, etc. (Table 1, 2, 3, 4).

2. Angiotensin-converting enzyme (ACE) inhibitors 
and angiotensin II receptor blockers (ARBs) are safe 
and should not be discontinued during Coronavirus 
epidemics (21).

3. There is no proof that ibuprofen can aggravate CO-
VID-19 clinical picture and the European Medicines 
Agency is monitoring this issue (22).

4. Start oxygen therapy at 5 L/min and titrate flow rates 
to reach SpO2 ≥90% in non-pregnant adults and SpO2 
≥92-95 % in pregnant patients (2).

5. High-flow nasal oxygen (HFNO) or non-invasive ven-
tilation (NIV, mainly c-PAP) should only be used in 
selected patients with hypoxemia, respiratory failure 
(P/F next to 300 for HFNO and 250-300 for NIV), but 
with alerts and with preserved ventilator dynamics. 
Monitor closely for clinical deterioration (7, 23).

6. Do not prolong HFNO or NIV for over 2 hours in the 
case of failure to improve (HFNO: respiratory rate ≥24/
min, NIV: respiratory rate ≥28/min and/or worsening 
P/F for both) (7, 23). High flow nasal cannulas and 
non-invasive ventilation are not recommended in viral 
pandemics, based on studies conducted in influenza 
and MERS (2).

7. Avoid nebulisation therapies for the potential spread 
of bacteria. Nebulisers generate aerosol particles 
that can carry bacteria and viruses deep into the 
lung. The risk of infection transmission may increase 
with nebulisers as they can generate a high volume 
of respiratory aerosols that may be propelled over a 
longer distance than in natural dispersion pattern. 
Nevertheless, the larger particles may cause cough in 
both patients' and bystanders' and increase the risk 
of spreading the disease. Nebulisers in patients with 
pandemic COVID-19 infection have the potential to 
transmit potentially viable COVID-19 to susceptible 
bystander hosts (24).

8. Administer intravenous fluids only if needed and avoid 
steroids, unless for other indications. Excessive fluid 
administration could aggravate oxygenation and be 
dangerous, especially in settings where mechanical 
ventilation is not readily available. Steroids were not 
associated with benefits, but rather with damage in 
the 2003 SARS epidemic and a delay in virus clearance 
in Middle-Eastern Respiratory Syndrome (MERS) of 
2012 (2).

9. Assess thromboembolism and bleeding risk of every 
patient and provide appropriate thromboprophylaxis.
Consider that recovery times and therefore hypo 
mobility of a subject with COVID-19 are long (at least 
15 days in mild forms and up to 6 weeks in severe / 
critical ones) and diffuse intravascular coagulation 
(DIC) can complicate the course (2,15).

thromboprophylaxis.Consider
thromboprophylaxis.Consider


PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

J Global Clinical Engineering, Special Issue 3, 2020  12

10. The Respiratory rate, peripheral oxygen saturation 
(SpO2) and arterial blood gas analysis results must 
be monitored closely during hospital stay due to 
insidious presentation of severe hypoxemia in this 
disease. Intra-arterial radial catheters insertion is 
to be considered to reduce arterial punctures, even 
outside ICU.

11. Also monitor white blood cells, lymphocytes and 
platelets count, LDH, procalcitonin and d-dimer are 
considered alarm flags (13, 15, 17).

12. Be aware of an eventual development of severe form 
+/- 7 days after symptom onset (13).

13. If a patient reports a SpO2 ≤90% in free air or ≤92% 
in conventional oxygen therapy and/or presents ≥30 
acts/min and/or severe respiratory distress, intensive 
care therapist consultation must be required (25).

14. Use biosafety precautions when handling oxygen 
therapy devices (23); cover the patient's face with a 
surgical mask during HFNO or C-PAP (23); to reduce 
the risk of aerosolization, possibly use a dual or single 
circuit non-invasive ventilator with an integrated 
expiratory valve and a helmet that allows to insert a 
filter as interface (7).

4. THE ETHICS OF TREATMENT DECISIONS
This is a complex issue which will be decided upon in 

the local setting as per previous ethical frameworks. We 
recommend that the ethical decision-making process be 
developed in anticipation of making complex decisions, 
rather than in reaction to the need to decide.

With regard to management of the patient affected by 
COVID-19 in intensive care, we offer a number of refer-
ences which will assist in developing the local ethical 
guidelines. (19, 25, 26, 27). Other important publications 
(not included among references): These provide recom-
mendations that can assist in developing local, though 
may be context specific.

Giacomo Grasselli, Antonio Pesenti, Maurizio Cecconi. 
Critical Care Utilization for the COVID- 19 Outbreak in 
Lombardy, Italy Early Experience and Forecast Dur-
ing an Emergency Response. JAMA published online 
March 2020 https://jamanetwork.com/journals/jama/
fullarticle/2763188

Robert D. Truog, Christine Mitchell and George Q. 
Daley, Robert D. Truog., Christine Mitchell, George Q. 
Daley. The Toughest Triage — Allocating Ventilators in a 
Pandemic This article was published on March 23, 2020, 
at NEJM.org. https://www.nejm.org/doi/pdf/10.1056/
NEJMp2005689?listPDF=true

Ethical Framework for Health Care Institutions Re-
sponding to Novel Coronavirus SARS-CoV- 2 (COVID-19) 
Guidelines for Institutional Ethics Services Responding 
to COVID-19 Managing Uncertainty, Safeguarding Com-
munities, Guiding Practice Hastings Institute https://
www.thehastingscenter.org/wpcontent/uploads/Hast-
ingsCenterCovidFramework20 20.pdf 

5. RECOMMENDATIONS FOR SURGERY
These recommendations apply to the medical staff 

of the operating blocks in case COVID-19. Patients with 
COVID-19 may need to undergo emergency and/or emer-
gency surgery. The following recommendations should be 
observed (29, 30, 31):

COVID-19 patient positive asymptomatic
1. Surgical team wearing disposable masks, caps and 

gloves correctly. Anesthesiologist and assistant nurse: 
FFP2 masks.

2. Patients must wear a medical mask until I.O.T. (oro-
tracheal intubation).

3. Airway protection of the patient also intubated with 
TNT drapes compatible with anesthesiologist assistance.

Symptomatic or having few or minor symptoms 
positive COVID-19 patient
1. Surgical team wears Personal Protective Equipment 

(PPE) and FFP2 or FFP3 masks.
2. Anesthesiologist and nurses assigned to direct assis-

tance: FFP2 / FFP3 masks and PPE.
3. Patients must wear a medical mask for the entire time 

of surgery and / or after the IOT procedure for airway 
protection with compatible TNT drapes.

https://jamanetwork.com/journals/jama/fullarticle/2763188
https://jamanetwork.com/journals/jama/fullarticle/2763188
NEJM.org
https://www.nejm.org/doi/pdf/10.1056/NEJMp2005689?listPDF=true
https://www.nejm.org/doi/pdf/10.1056/NEJMp2005689?listPDF=true
https://www.thehastingscenter.org/wpcontent/uploads/HastingsCenterCovidFramework20
https://www.thehastingscenter.org/wpcontent/uploads/HastingsCenterCovidFramework20
https://www.thehastingscenter.org/wpcontent/uploads/HastingsCenterCovidFramework20
20.pdf


13 J Global Clinical Engineering, Special Issue 3, 2020 

PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

Patient COVID-19 sick and in invasive airway 
management.
1.  All professionals must wear PPE and FFP2 / FFP3. While 

staying in the operating room it is recommended to 
utilise laminar flow according to current legislation 
and post-intervention sanitisation for at least 1 hour.

Team working and organisation
Surgical teams in order to stay healthy and maintain 

continuity of care should divide into teams of senior and 
junior doctors and work for a 2-week period. After the 2 
weeks, teams will come in to release the other. This will 
allow easier replacement of team members should they 
fall ill and potential containment of the virus to smaller 
staff numbers and an ability to maintain some service 
provision and clinical care.

6. RECOMMENDATIONS RELATED TO PREGNANT 
WOMEN
1. Reduce access of pregnant women to prenatal care, 

limiting only to high-risk cases (32). There is no evi-
dence of an increased risk of unfavourable maternal 
or foetal outcomes in the case of COVID-19. However, 
evidence relating to influenza and SARS-COV1 must 
induce to consider the pregnant woman as a high-risk 
patient.

2. Infants born to mothers with confirmed COVID-19 
should be considered as suspects. As such, these 
infants should be isolated from others (33).

3. Separation (i.e. in an individual room) of the infant from 
the mother with COVID-19 confirmed or suspected, 
until the precautions based on the transmission risk 
of the mother are suspended. The decision should be 
discussed carefully between the caring team and the 
mother, evaluating risk and benefits of this choice, 
including the protective potential of colostrum, breast 
milk and feeding time. (32,33).

4. The discharge of mothers after childbirth must follow 
the recommendations for discharge of COVID-19 or 
suspected patients (32).

5. In the case of a woman with suspected SARS-CoV-2 
infection or with COVID-19, according to her clinical 
conditions and desire, breastfeeding should be started 

and / or maintained directly on the breast or with 
expressed breast milk (33). If mother and child must 
be temporarily separated because of mother clinical 
conditions, one should help the mother to maintain 
milk production  through  manual  or  mechanical/
electric  expressing  (33).  In a limited series reported 
to date, the presence of the virus in the breast milk 
of infected women has not been reported, but anti-
SARS-cov2 antibodies have been found (31). So breast 
milk would be protective.

6. A mother with confirmed COVID-19 or ongoing swab 
samples because symptomatic should take all possible 
precautions to avoid spreading the virus to the baby, 
including washing hands before touching the baby 
and wearing a face mask, if possible. during breast-
feeding. If using a manual or electric breast pump, 
the mother must wash her hands before  touching 
the breast pump or parts of the bottle. If possible, 
have another person administer the milk to the baby 
(33). It is not yet known whether COVID-19 can be 
transmitted through breast milk. At present, the main 
concern is not whether the virus can be transmitted 
through breast milk, but rather whether an infected 
mother can transmit the virus through respiratory 
droplets during breastfeeding (32).

7. For assisting the delivery of women with confirmed 
or suspected COVID-19, staff must use the safety 
precautions provided for non-pregnant patients (33).

8. Pregnant women with suspected or confirmed SARS-
COV2 infection should be treated with supportive 
therapies, however taking into account the physi-
ological characteristics of pregnancy (2).

9. The use of experimental therapeutic agents outside 
of a research study should be guided by an individual 
risk-benefit analysis based on the potential benefit 
to the mother and the safety of the foetus, with the 
consultation of an obstetrician specialist and an ethics 
committee (2).

10. The decision to proceed to a pre-term birth is based 
on many factors: gestational age, maternal conditions 
and foetal stability and requires a collegial evaluation 
by obstetric, neonatal and intensive care specialists 
(depending on the mother's condition) (2).



PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

J Global Clinical Engineering, Special Issue 3, 2020  14

11. Positivity in itself to Coronavirus is not an indication 
for a caesarean section which in these patients should 
only be performed based on other obstetric or medi-
cal indications (33).

12. In COVID-19 pregnant women, it is useful to be very 
cautious in inducing maturity of the lung by means 
of corticosteroids, since these drugs seem to worsen 
the course of the infection. If possible, evaluate each 
case with a neonatologist.

7. RECOMMENDATIONS RELATED TO PEDIATRIC 
PATIENTS

Keep in mind that:
1. To date there is a paucity of information regarding 

COVID-19 in children.
2. Children and infants are affected and with milder forms 

(X-ray more often negative; CT more sensitive) (34, 
35).

3. A small series of children with COVID-19 has shown a 
greater prevalence of peripheral halo (halo-sign) lung 
consolidations on CT (35).

4. The criteria for the definition of Acute Respiratory 
Distress Syndrome (ARDS) and septic shock, the guide-
lines for the management of sepsis and septic shock 
and the use of non- invasive ventilation in children are 
different from those of adults (2).

5. Children desaturate more easily during intubation; 
therefore, it is important to pre- oxygenate with 100% 
O2 with a mask with a reservoir before intubating (2).

6. A rectal swab may be useful in children to determine 
the timing of the termination of  quarantine. Some au-
thors have used the cycle threshold values of the serial 
rectal and nasopharyngeal swab tests to indicate viral 
load. Interestingly, the measurements have indicated 
that viral shedding from the gastrointestinal system 
could be greater and last longer than the respiratory 
tract (36, 37).

8. RECOMMENDATIONS RELATED TO HOSPITAL 
DISCHARGE
1. The patient with fever without respiratory failure (nor-

mal EGA and walking test) and normal chest x-ray, <70 

years and without risk factors (lung disease, diabetes 
mellitus and/ or heart disease) can be discharged 
from the emergency room (14, 20) with indication of 
home isolation, waiting to run the swab sampling or 
its result.
The discharge physician:
• obtains a telephone number to contact the patient for 

swab sampling and / or to communicate the result;
• provides information on how to access the pad 

(where and when).

If the swab test does not take place in the emergency 
department, but is performed elsewhere to another area 
or hospital, it is strictly suggested to use systems to avoid 
the loss of information. The facility / service running the 
buffer

• must report the result as soon as it is available to the 
patient and, if positive, to the Public Health Depart-
ment for establishing active surveillance.

2. At the end of the hospitalisation, write clearly on the 
discharge letter:
• CLINICALLY CURED patient (patient with clinical 

symptoms resolution, but still positive for swab) (38)

or
• CURED patient (patient who, in addition to resolving 

the symptoms, is negative in two consecutive swabs, 
carried out at least 24 hours apart) (38).

or
•  CLINICALLY CURED PATIENT: write clearly on the 

discharge letter the indication to be observed at the 
home quarantine until the swab is negative on two 
determinations after 24 hours and the execution 
methods of the control buffer.

Although there is no clear supported evidence, it is 
considered appropriate to suggest patient retesting no 
earlier than 7 days and, if negative, confirm the negativity 
after at least 24 hours (38).

Or DISABLED PATIENT, roommate of patient with 
positive swab or whose result is not yet known:

• Write clearly the indication of home isolation on the 
discharge letter (up to 14 days from contact with the 
infected person) and indication to call the appropriate 
number (in Italy 112) if symptoms appear;



15 J Global Clinical Engineering, Special Issue 3, 2020 

PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

• Assure a telephone number to communicate buffer 
result;

• Communicate swab results as soon as available to 
the patient and, if positive, to public health trusts, in 
order to establish active surveillance (38).

9. RECOMMENDATION RELATED TO HOME ISOLATION
1. Provide prevention measures and explain them to pa-

tients in home isolation also by using designs, charts 
or pictures.

2. Give also clear indications on alarm symptoms:
a. promote information
b. diffusion of telephone numbers to call in case of 

occurrence of symptoms
c. Arrangements for support e.g. shopping

3. Provide call centres, online chats, FAQs and video tu-
torials to consult when there is doubt.

10. RECOMMENDATIONS RELATED TO PERSONS 
IN QUARANTINE (39)
1. Information represents the key success factor; quar-

antined persons must be constantly informed and 
updated on the epidemic progress.

2. It is necessary to provide food and other materials 
and any necessary drugs without making people feel 
abandoned or alone.

3. The quarantine period should be short, and the duration 
should not be modified except in extreme circumstances.

4. Most of the side effects derive from the freedom restric-
tion imposition; voluntary quarantine is associated 
with less stress and fewer long-term complications; 
therefore, it is necessary to explain clearly the reasons 
for such suggested behaviours.

5. Public health officials should stress the selfless choice 
of self-isolation. 
Quarantined healthcare workers can be helpful in 

producing useful documents or other materials while 
at home for their colleagues. They could contribute by 
making suggestions and stay in touch with social media.

11. RECOMMENDATIONS RELATED TO ONCOLOGIC 
AND IMMUNOSUPPRESSED PATIENTS
1. Do not indiscriminately discontinue antineoplastic or 

immunosuppressive therapies. (40-42).
2. In cancer patients, consider the possibility of postpon-

ing the treatment cycle on a case-by-case basis (40).
3. Immunosuppressant withdrawal is indicated if symp-

toms suggestive of infection appear (41); in this case 
it is good practice to inform the physician responsible 
for the treatment promptly.

4. Steroids can be continued, but with caution (41).
5. New immunosuppressant prescriptions or dose in-

creases are not recommended during an epidemic (42).
6. Consider the switch from parenteral drugs to others 

that can be administered at home (e.g. subcutaneously) 
to reduce access to outpatient clinics (41).

7. Ensure non-deferred outpatient visits and postpone 
visits for long-term follow-up, after remote evaluation 
(telephone, email, etc.) (40, 41).

8. Do not allow visitors in therapy rooms and allow the 
presence of a maximum of one visitor per patient in 
hospital stays (40).
Please refer also to General Recommendations (sec-

tion 1) for other indications relating to outpatient clinics.

12. MORTUARY/MORGUE OPERATING PROCEDURES
Management of the deceased body with suspect, prob-

able or confirmed COVID-19 respiratory infection. The 
proposed procedure is aimed at the safe management of 
the phases of acceptance, handling, custody, and discharge 
of the body with suspected, probable or confirmed diag-
nosis of COVID-19 (43). The objective has been pursued 
by drawing up the following recommendations:
1. The acceptance and handling of the body must be done 

by personnel equipped wearing the recommended 
PPE;

2. The body must be positioned on a sanitised metal 
stretcher for custody and subsequent investigations.

3. At the end of the investigations, the body must be 
placed in the coffin with the clothes and wrapped in 
a sheet soaked in disinfectant solution.



PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

J Global Clinical Engineering, Special Issue 3, 2020  16

4. If the corpse is required to remain in the mortuary is 
necessary, pending or at the conclusion of the inves-
tigations, the same must take place inside a special 
closed body bag and dedicated refrigerated room.

5. At the end of the handling and transport operations, all 
the equipment used must be subjected to sanitisation.

Recommendations for autopsy investigation in cases 
of suspect, probable or confirmed COVID-19. For the 
safe and effective performance of HG3 (Hazard Group 3) 
autopsy investigations, is required:

• generic risk assessment and adoption of universal 
standard precautions;

• knowledge of possible pathological findings that can 
be highlighted;

• the definition of SOP (Standard Operating Proce-
dures) for the management of autopsies with high 
biological risk.

1. The use of universal precautions effectively protects 
against most risks related to SARS- CoV-2 infection. 
Professionals have a duty to carry out risk assessment 
for each case in order to prevent actions that could put 
operators at risk (44).

2. At the end of the autopsy investigations, the body 
must be positioned in a body bag and transported in 
a refrigerated room.

3. Disinfect the outside of the body bag with a hospital 
disinfectant applied according to the manufacturer's 
recommendations. It is also recommended in this phase 
the use of suitable PPE by each operator involved in 
the movement and exit phases of the body.

Disinfection of autopsy rooms
In addition, following an autopsy on a subject with 

suspect or confirmed COVID-19, the following recom-
mendations for disinfection of autopsy rooms should be 
applied (45):
1. keep ventilation systems active during cleaning;
2. wear disposable gloves when cleaning and handling 

cleaning or disinfectant solutions;
3. dispose of gloves after cleaning; do not wash or reuse 

the gloves in any case;

4. use eye protection, such as a visor or goggles, if splash-
ing is expected;

5. if necessary, use respiratory protection based on the 
type of detergent or disinfectant;

6. wear a long-sleeved waterproof device to protect skin 
and clothing;

7. use disinfectants with indications of efficacy against 
human coronaviruses;

8. clean the surfaces and apply the disinfectant ensuring 
an adequate contact time for effective disinfection;

9. comply with the safety precautions and warnings 
indicated on the product label (for example, allow ad-
equate ventilation in restricted areas and ensure correct 
disposal of the unused product or used containers);

10. avoid product application methods that cause the 
production of splashes or aerosols.

Regarding environmental disinfection, the available 
evidence has shown that coronaviruses are effectively 
inactivated by adequate sanitisation procedures that 
include the use of common hospital disinfectants, such 
as sodium hypochlorite (0.1% -0.5%), ethanol (62- 71%) 
or hydrogen peroxide (0.5%). There is currently no evi-
dence to support a greater environmental survival or a 
lower sensitivity of SARS-CoV-2 to the aforementioned 
disinfectants.
1. Hard and non-porous surfaces can be cleaned and 

disinfected as previously described.
2. Handle with gloves and disinfect properly after use, 

equipment such as cameras, telephones and keyboards, 
as well as all objects that remain in the autopsy room.

3. Cleaning activities must be supervised and periodically 
checked to ensure that correct procedures are followed. 
Sanitation personnel must be properly trained and 
equipped with suitable PPE.

4. After cleaning and removing the PPE, wash the hands 
immediately. Avoid touching the face with gloved or 
unwashed hands.

5. Environmental disinfection must include cleaning with 
water and detergent soap on all vertical and horizontal 
surfaces, followed by disinfection with hospital disin-
fectants effective against SARS-CoV-2.



17 J Global Clinical Engineering, Special Issue 3, 2020 

PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

6. For environmental decontamination, it is necessary 
to use dedicated or disposable equipment. Reusable 
equipment must be decontaminated after use with a 
chlorine-based disinfectant. The use of special trolleys 
is strongly recommended, different from those used 
for cleaning common areas.

7. The instruments used for autopsies should be auto-
claved or treated through chemical sterilisers.

13. PSYCHOLOGICAL SAFETY OF STAFF AND MENTAL 
WELLBEING OF PATIENTS

Psychological safety of staff (46, 47, 48, 49)
1. Create a healthy work, ethos and environment during 

crises and also to have systems in place to deal with 
subsequent distress and disorder.

2. Organisations which have the foresight to prepare 
their staff to deal with trauma might consider using 
interventions such as PFA (Psychological First Aid is a 
humane, supportive response to a fellow human being 
who is suffering and who may need support).

3. Consider that factors negatively affecting the psycho-
logical well-being of staff are:
• concerns over the contracting the illness
• concerns for safety of their family
• witnessing the death of colleagues
• isolation from family and colleagues
• sense of being underappreciated
• extended length of epidemic

4. Reduce mental health stigma. The best ways of reduc-
ing stigma were believed to be raising awareness of 
mental health issues and telling people that it’s quite 
normal to feel that way and have those feelings;

5. Educate healthcare workers who are exposed to trauma 
about the effects of cumulative stress. The training 
should be delivered either online ‘because they can do 
it at their own convenience’ or via educational leaflets 
‘rather than finding the time to spend on a day course’. 
The education about psychological trauma may lead to 
better understanding, better recognition of symptoms 
in oneself and in others, less judgement, and therefore 
reduced stigma, and that positive relationships with 

others in the workplace can have a positive impact on 
psychology.

 6. Maintain teamwork and effective leadership while at 
the same time providing individuals the opportunity to 
provide input into the decisions that affect their lives. 
Staff often experience severe emotional stress during 
viral outbreaks. It is often the nursing staff who feels 
the greatest level of stress due to their constant contact 
with sick patients, who may not be improving despite 
the nursing staff's best efforts. Physicians usually cope 
somewhat better with this situation because they are 
in a position to make treatment decisions and are less 
directly involved in implementing patient care.

7. Be receptive to suggestions from nursing staff and sup-
port personnel. Input is empowerment and provides 
a sense that these critical staff retain some control 
over their situation. If suggestions are not acted on, 
clear explanations as to why they were not should be 
provided and alternatives should be explored.

8. Administration needs to be supportive of staff and not 
be seen as pedantic and overly controlling.

In cases where staff and support personnel did not feel 
appreciated or listened to, there was a high degree 
of dissatisfaction and an increased occurrence of 
absenteeism and staff strikes, which further reduced 
personnel in an already-strained system.

9. Take care of yourself and your loved ones. Healthcare 
providers are not invulnerable to experiencing their 
own emotional distress during outbreaks, and this 
distress can be compounded by caring for sick and 
distressed patients.

10.  Make sure your basic needs are met, including: eating, 
drinking, and sleeping; take a break when you need 
one; check in with loved ones; practice the strategies 
to reduce distress listed above; and monitor yourself 
for stress reactions too.

11.  Make efforts to ensure that your office and/or or-
ganisation has a viable plan to monitor the course of 
the outbreak and take rapid and appropriate action if 
needed.



PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

J Global Clinical Engineering, Special Issue 3, 2020  18

 Mental well-being of Patients (50)
1. Medical and mental health clinicians are likely to en-

counter patients who are experiencing various levels of 
emotional distress about the outbreak and its impact on 
them, their families, and their communities. We must 
consider that COVID-19 patients have long hospital 
stays and in the early stages they will experience the 
anguish of having an aggravation of the disease with 
the possibility of being intubated. Furthermore, the 
limited staff available will not be able to guarantee 
them continuous assistance and their relatives as well.

2. Providers should acknowledge uncertainty about 
emerging diseases and help patients understand that 
there is often an emotional component to potential 
health concerns.

3. Providers should be cognisant that the symptoms 
might extend beyond classical mental health symptoms 
to include relational struggles, somatic, academic, or 
vocational issues.

4. Every person, including mental health providers, can 
either react in fear, anger, or despair and regress, or 
can choose resilience and play as an active part of the 
solution.
In addition, providers should consider the following 

recommendations for promoting patients’ mental wellbe-
ing during emerging infectious disease outbreaks:

Be informed: Obtain the latest information about the 
outbreak from reliable public health resources in order 
to provide accurate information to your patients.

Educate: Healthcare providers are on the front lines 
of medical intervention and in a position to influence 
patient behaviours for protecting individual, family, and 
public health. Psycho-education is of utmost importance 
in the aftermath of disasters. Patient education plays a 
critical role in both containing the disease and mitigating 
emotional distress during outbreaks. Depending on the 
nature of the outbreak, this can range from education 
about basic hygiene such as hand-washing and cough 
etiquette to more complex medical recommendations 
for prevention, diagnosis, and treatment.
5. Let patients know what you, your office, or your or-

ganisation is doing to reduce the risk of exposure.

6. Correct misinformation. In this age of social media, 
misinformation can spread quickly and easily, causing 
unnecessary alarm. If patients present you with inac-
curate information related to the outbreak, correct 
their misconceptions and direct them to vetted public 
health resources.

7. Limit media exposure. The excess media exposure 
to coverage of stressful events can result in negative 
mental health outcomes. Use trusted media outlets 
to gather the information you need, then turn them 
off— and advise your patients to do the same.

8. Anticipate and counsel about stress reactions. Emo-
tional distress is a common mental condition in the 
context of uncertain and potentially life- threatening 
situations, such as COVID-19 epidemic. A good first step 
for mitigating your patients’ stress is to acknowledge 
that it exists and help normalise it (“I see that you’re 
stressed, and that’s understandable. Many people are 
feeling this way right now.”).

9. Teach patients to recognise the signs of distress, in-
cluding worry, fear, insomnia, difficulty concentrating, 
interpersonal problems, avoiding certain situations at 
work or in daily living, unexplained  physical  symptoms,  
and  increased  use  of  alcohol  or  tobacco.  This will 
help them become more aware of the state of their 
mental health and head off distress before it becomes 
harder to manage.

10. Discuss strategies to reduce distress, which can include:
• Being prepared (developing a personal/ family pre-

paredness plan for the outbreak).
• Taking everyday preventive measures (e.g., frequent 

handwashing).
• Maintaining a healthy diet and exercise regimen.
• Talking to loved ones about worries and concerns.
• Engaging in hobbies and activities you enjoy to im-

prove your mood.
• If a patient is experiencing severe emotional distress 

or has a diagnosable mental illness, refer for special-
ized mental health care.



19 J Global Clinical Engineering, Special Issue 3, 2020 

PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

14. MEASURES (51,52,53)
It is important that we measure the impact of our 

actions. We include some measures that may be of use.

Outcome measures
Outcome measures should be collected in order to 

support the monitoring of effective provider (hospital) 
epidemic/pandemic response including the capacity to 
adequately treat patients with other common severe 
conditions like heart attacks, strokes, trauma, COPD in 
order to assure that the health of the public is protected 
to the fullest extent possible:
1. Hospitalisation rate for COVID-19 (indirect outcome 

measure of the territory).
2. In-hospital Mortality rate of patients hospitalized for 

COVID-19.
3. Average Length of Stay of COVID-19 patients.
4. Percentage of COVID-19 patients admitted to ICU.
5. In-hospital mortality rate of NO-COVID-19 patients 

hospitalised for AMI.
6. In-hospital mortality rate of NO-COVID-19 patients 

hospitalized for Stroke.
7. In-hospital mortality rate of NO-COVID-19 patients 

hospitalized for COPD.
8. Percentage of NO-COVID-19 hospitalized patients that 

acquired COVID during the hospitalisation.
9. COVID-19 infection rate among staff / Number of tests 

performed to hospital staff (as process measure)
10. Survival rates

Where possible indicators 1-7 should be stratified by 
age groups. Additionally, the proposed outcome measures 
should be used and interpreted with great caution if used 
to benchmarking care quality between providers. In this 
case, consistent data definitions should be adopted and 
measures from 1 to 7 should be adjusted for potential 
confounding factors (i.e. patient case mix) in order to draw 
meaningful and correct comparisons among providers of 
Mortality rate.

Length of stay measures
1. Length of Stay
2. Average length of stay in ICU of infected

3. Average length of stay in hospital

Process Measures (some examples)
1. Percentage of infected individuals admitted to ICU
2. Percentage of people with comorbidities
3. Percentage of staff with and without correct equipment
4. Number of patients not treated in appropriate level of 

care
5. Percentage staff trained to use equipment

Balancing measures
1. Staff infection rate
2. Staff mortality rate
3. Staff well being
4. Illness and sickness rates
5. Mental illness

Patient profiles to consider
• Age
• Gender
• Ethnicity
• Comorbidity
• Region
• Contacts 

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21 J Global Clinical Engineering, Special Issue 3, 2020 

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37.  Xu, Y., Li, X., Zhu, B. et al. Characteristics of pediatric 
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39. Samantha K Brooks, Rebecca K Webster, Louise E Smith, 
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40. Rischio infettivo da Coronavirus COVID-19 Indicazioni 
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43. Management of the corpse with suspect, probable or 
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44. Health and Safety Executive. Managing infection risks 
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47. Samantha K. Brooks, Rebecca Dunn, Richard Amlôt, G. 
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During Coronavirus and Other Emerging Infectious 
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Novel coronavirus disease 2019 (COVID-19) pandemic: 
increased transmission in the EU/EEA and the UK – 
sixth update – 12 March 2020. Stockholm: ECDC; 2020. 
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DOMICILIARE.pdf
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https://doi.org/10.1016/S2468
https://www.eular.org/eular_guidance_for_patients_COVID
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https://www.hse.gov.uk/pUbns/priced/hsg283.pdf
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https://www.rcpath.org/uploads/assets/d5e28baf
https://www.rcpath.org/uploads/assets/d5e28baf
autopsy-Feb-2020.pdf
https://doi.org/10.1186/s40359
https://doi.org/10.1186/s40359
https://ohsonline.com/Articles/2016/05/01/Providing
https://ohsonline.com/Articles/2016/05/01/Providing
Following-a-Disaster.asp
https://apps.who.int/iris/bitstream/handle/10665/44615/9789241548205
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ita.pdf
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https://www.cstsonline.org/assets/media/documents/CSTS_FS_Caring_for_Patients_
Mental_WellBeing_during_Coronavirus.pdf.pdf
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23 J Global Clinical Engineering, Special Issue 3, 2020 

PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

default/files/documents/RRA-sixth-update- Outbreak-
of-novel-coronavirus-disease-2019-COVID-19.pdf

52. World Health Organization (WHO). Pandemic Influenza 
Severity Assessment (PISA): A WHO guide to assess 
the severity of influenza epidemics and pandemics. 
Geneva 2017. Available online at: https://apps.who.

int/iris/bitstream/handle/10665/259392/WHO-
WHE-IHM-GIP- 2017.2-eng.pdf?sequence=1

53. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 
Hospitalized Patients With 2019 Novel Coronavirus–
Infected Pneumonia in Wuhan, China. JAMA (2020); 
323(11): 1061–1069. Available online at: https://
jamanetwork.com/journals/jama/fullarticle/2761044

TABLE 1. Chloroquine and hydroxy-chloroquine: main Italian drug interactions

DRUGS INTERACTIONS

Chloroquine

Antacids based on aluminum, calcium and magnesium and kaolin can reduce their absorption. 
In association with: 
• Corticosteroids accentuation of any myopathies or cardiomyopathies
• Phenylbutazone can induce exfoliative dermatitis
• Isoniazid, Amiodarone, Carbamazepine, Phenytoin, Phenothiazide, Ketoconazole and 

MAO inhibitors (Mono-Amino-Oxidase Inhibitors) risk of hepatotoxicity
• Mefloquine and bupropion risk of convulsions
• Metronidazole possible dystonic reactions
• Penicillamine serious haematological or renal adverse events
• Pyrimetamine / sulfadoxineskin reactions

Effects of chloroquine on other drugs:
• Ampicillin reduced absorption (administer at least 2 hours after chloroquine)
• Class IA and III antiarrhythmics, Tricyclic antidepressants, Antipsychotics increased 

risk of ventricular arrhythmia
• Antiepileptic antagonism on anticonvulsant effects
• Cyclosporine increase in plasma concentration
• Digoxin increase in plasma concentration and relative toxicity
• Methotrexate potentiation of the action
• Neostigmine and Pyridostigmine antagonism of the effects
• Vaccines antibody response reduction ONLY with rabies vaccine

Hydroxy- chloroquine

In association with:
• Phenylbutazone can induce exfoliative dermatitis
• Isoniazid, Amiodarone, Carbamazepine, Phenytoin, Phenothiazide, Ketoconazole and 

MAO inhibitors (Mono-Amino-Oxidase Inhibitors) can cause hepatoxicity

Effects of hydroxychloroquine on other drugs
• Anti-epileptics antagonism on anticonvulsant effects
• Cyclosporine increased plasma concentrations
• Digoxin increased plasma concentration and relative toxicity
• Insulin and Antidiabetics potentiation of hypo-glycemic effects

16. APPENDIX - MEDICATIONS

https://www.ecdc.europa.eu/sites/default/files/documents/RRA
Outbreak-of-novel-coronavirus-disease-2019-COVID-19.pdf
Outbreak-of-novel-coronavirus-disease-2019-COVID-19.pdf
https://apps.who.int/iris/bitstream/handle/10665/259392/WHO
https://apps.who.int/iris/bitstream/handle/10665/259392/WHO
2017.2-eng.pdf
https://jamanetwork.com/journals/jama/fullarticle/2761044
https://jamanetwork.com/journals/jama/fullarticle/2761044


PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

J Global Clinical Engineering, Special Issue 3, 2020  24

TABLE 2. LOPINAVIR/RITONAVIR: Main Italian interactions and recommendations

Co-administered Drug Mechanism of interaction Clinical Recommendations

RETROVIRAL AGENTS:
Nucleoside reverse transcriptase 
inhibitors (NRTIs), Non-nucleoside 
reverse transcriptase inhibitors 
(NNRTIs), HIV CCR5
- antagonist, Integrase inhibitor, 
Inhibitors of HIV protease

Specialist advice, dose adjustment is not 
required in most cases. Co- administration 
with other HIV protease inhibitors (PIs), 
according to current guidelines, is not 
recommended.

Antacids No contraindications

Alpha antagonists

ALFUZOSIN Increased concentration (CYP3A inhibition) Contraindicated (hypotension)

Analgesic Drugs

FENTANYL Increased concentration (CYP3A inhibition) Close monitoring (risk of respiratory

Antianginal Drugs

RANOLAZINE Increased concentration (CYP3A inhibition) Contraindicated

Co-administered Drug Mechanism of interaction Clinical Recommendations

Antiarrhythmics

AMIODARONE, DRONEDARONE Increased concentration (CYP3A inhibition) Contraindicated (arrhythmia)

DIGOXIN Increased concentration (P-gp inhibition) Plasma level monitoring
BEPRIDIL, SYSTEMIC LIDOCAINE, 
QUINIDINE Increased concentration Plasma level monitoring

Antibiotics

CLARITHROMYCIN Moderate increase of under-curve area 
(CYP3A inhibition)

Dose reduction in kidney failure (CrCL<30 
ml/min); attention in patients with impaired 
liver and kidney function

Antineoplastics Specialist Advice

Anticoagulants

WARFARIN CYP2C9 induction INR monitoring

RIVAROXABAN AUC:   153%, Cmax:   55% (CYP3A and 
P-gp inhibition) Contraindicated (bleeding)

VORAPAXAR Increased concentration (CYP3A inhibition) Contraindicated

Antiepileptic

PHENYTOIN Concentrazioni diminuite (induzione del 
CYP2C9 e del CYP2C19) Plasma level monitoring

CARBAMAZEPINE, PHENOBARBITAL
Increased Carbamazepine concentration (CYP3A 
inhibition); reduced Lopinavir concentration 
(CYP3A induction)

Plasma level monitoring

→ →



25 J Global Clinical Engineering, Special Issue 3, 2020 

PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

Co-administered Drug Mechanism of interaction Clinical Recommendations

Antidepressants and anxiolytics

TRAZODONE AUC:   2,4 times Dose reduction

Antifungals

KETOCONAZOLE Increased concentration (CYP3A inhibition) Dose reduction

Co-administered Drug Mechanism of interaction Clinical Recommendations

Anti-gout

COLCHICINE AUC:    3-times; Cmax:    1,8-times (CYP3A 
and/or P-gp inhibition) Contraindicated

Antihistamines

ASTEMIZOLE, TERFENADINE Increased concentration (CYP3A inhibition) Contraindicated (severe arrhythmias)

Anti-Infectives

Fusidic Acid Increased concentration (CYP3A inhibition) Contraindicated (rhabdomyolysis)

Anti-mycobacterial agents Specialist Advice

Benzodiazepines

MIDAZOLAM
Oral administration: AUC:   13-times
parenteral administration: AUC:   4-times 
(CYP3A inhibition)

Oral administration contraindicated; close 
monitoring for parenteral administration

Beta2 agonists

SALMETEROL Increased concentration (CYP3A inhibition) Contraindicated (severe cardiovascular event 
and arrhythmias)

Calcium Channel Blockers

FELODIPINE, NIFEDIPINE, 
NICARDIPINE

Steroids

DEXAMETHASONE Reduction of Lopinavir concentrations (CYP3A 
induction) Clinical monitoring of anti- viral activity

Phosphodiesterase inhibitors
AVANAFIL, SILDENAFIL Increased concentration (CYP3A inhibition) Contraindicated

Ergot Alkaloids

DIHYDROERGOTAMINE AND 
OTHERS Increased concentration (CYP3A inhibition) Contraindicated

Intestinal Prokinetics

CISAPRIDE Increased concentration (CYP3A inhibition) Contraindicated

Direct anti-HCV agents Increased plasma concentration
(combined mechanisms) Contraindicated

HCV protease inhibitors Contraindicated

→
→ →

→

→



PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

J Global Clinical Engineering, Special Issue 3, 2020  26

Co-administered Drug Mechanism of interaction Clinical Recommendations

Immuno-suppressers

CICLOSPORINE Increased concentration (CYP3A inhibition) Plasma level monitoring

Statins Contraindicated; fluvastatin and pravastatin 
tolerated

Opioids

METHADONE Decrease in concentration Plasma level monitoring

Contraceptives

Ethinylestradiol Decrease in concentration Use additional contraceptive methods

Hormone Replacement Therapy (HRT)

Levothyroxine Potential interactions not well documented
TSH monitoring
during the first month from the beginning 
and / or from the end of the treatment



27 J Global Clinical Engineering, Special Issue 3, 2020 

PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

TABLE 3. DARUNAVIR/COBICISTAT: Main Italian interactions and recommendations

Co-administered Drug Interaction mechanism Clinical Recommendations

Anti-retroviral agents (HIV)

Inhibitors of the strand transfer of ' integrase, 
inhibitors nucleoside / nucleotide HIV reverse 
transcriptase inhibitors (NRTIs)

Specialist advice, no dose adjustment 
necessary, except for Emtricitabine / 
tenofovir alafenamide

Non- nucleoside / nucleotide inhibitors of 
HIV reverse transcriptase (NNRTI)

Specialist advice, non- recommended co- 
administration RILPIVIRINE, the increase 
of which is not considered relevant, is an 
exception

CCR5 A ntagonists No dose adjustment necessary

MAVAVIROC Increased concentration (CYP3A inhibition) Specialist advice for dose adjustment

Al / M or calcium carbonate- based antacids No dose adjustment

Alpha antagonists

ALFUZOSIN Increased concentration (CYP3A inhibition) Contraindicated (hypotension)

Anaesthetic

AL FENTANYL Increased concentration (inhibition of CYP3A4) Dose reduction and monitoring (respiratory 
depression risk)

Antianginal/tymic antiaries

AMIODARONE, DRONEDARONE 
CHINIDINA, BEPRIDILE, IVRABRADINA, 
RANOLAZINA

Increased concentration (inhibition of CYP3A 
and/or CYP2D6) contraindicated

DYSOPYRAMID, FLECAINIDE, SYSTEMIC 
LIDOCAINE, MEXILETINE, PROPAPHENONE

Increased concentration (inhibition of CYP3A 
and/or CYP2D6) Caution and monitoring

digoxin Increased concentration (P- glycoprotein 
inhibition)

Dose titration and accurate monitoring of 
drug concentration

Antibiotics

Clarithromycin Increased AUC (CYP3A inhibition) Caution dose adjustment in patients with 
renal impairment CrCL <30 ml / min

Anticoagulants

WARFARIN Theoretical mechanism of alteration of plasma 
concentrations INR monitoring

APIXABAN, EDOXABAN, RIVAROXABAN Increased plasma concentrations (inhibition 
of CYP3A & P-gp) contraindicated

DAPIGATRAN; ticagrelor Increased plasma concentrations (inhibition 
of CYP3A & P-gp) contraindicated

Anticonvulsants

clonazepam Increased concentration (CYP3A inhibition) Clinical monitoring

CARBAMAZEPINA, FENOBARBITALE, 
FENITOINA

Reduced concentrations of darunavir and/or 
cobicistat (CYP3A induction). Contraindicated



PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

J Global Clinical Engineering, Special Issue 3, 2020  28

Co-administered Drug Interaction mechanism Clinical Recommendations

Antidepressants and anxiolytics

ST. JOHN'S GRASS Reduction of darunavir and / or cobicistat 
concentrations (CYP3A induction). contraindicated

PAROXETINE, SERTR ALINA, AMITRIPTILINA, 
DESIPRAMINA, IMIPRAMINA, 
NORTRIPTILINA, TRAZODONE

Increased plasma concentrations (CYP2D6 
and/or inhibition CYP3A) Dosage reduction and clinical monitoring

Antidiabetic

METFORMIN Increased plasma concentration Dosage reduction and clinical monitoring

Αntiemetics

DOMPERIDONE Not studied contraindicated

Anti-fungals

CLOTRIMAZOLO, FLUCONAZOLO, 
ITRACONAZOLO, ISAVUCONAZOLO, 
POSACONAZOLO

Increased concentration 
(inhibition of CYP3A &/or P- gp)

Caution, clinical monitoring and dosing
Voriconazole contraindicated

Anti-gout

colchicine Increased concentration
(inhibition of P- gp and/or CYP3A4)

Dosage reduction, contraindicated in the 
presence of hepatic or renal impairment

H2 receptor antagonists No dose adjustment necessary

Antimycobacterials Specialized evaluation, tendentially contraindicated

Anti-psychotics / neuroleptics

PERFENAZINA, RISPERIDONE, 
TIORIDAZINA

Increased plasma concentrations
(inhibition of CYP3A, CYP2D6 and/or P- gp) Dose reduction and clinical monitoring

LURASIDONE, PIMOZIDE, SERTINDOLO, 
QUETIAPINA Contraindicated

Anti-cancer Theoretical mechanism of concentration increase 
(CYP3A inhibition) Specialist evaluation, extreme caution

Beta2 agonists

SALMETEROL Increased concentration (CYP3A inhibition) Contraindicated (serious cardiovascular 
adverse events, arrhythmias)

Beta blockers

CARVEDILOL, METOPROLOL, TIMOLOL Plasma concentrations increased
(CYP3A inhibition) Dose reduction and clinical monitoring

Calcium antagonists

AMLODIPINA, DILTIAZEM, 
FELODIPINA, NIFEDIPINA, 
NICARDIPINA, VERAPAMIL

Increased concentration (inhibition of CYP3A 
and / or CYP2D6) Dose reduction and clinical monitoring



29 J Global Clinical Engineering, Special Issue 3, 2020 

PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

Co-administered Drug Interaction mechanism Clinical Recommendations

Corticosteroids

dexamethasone Reduction of Darunavir and / or cobicistat 
concentrations (CYP3A induction) Caution

Proton pump inhibitors No dose adjustment

Inhibitors of phosphodiesterase

TADALAFIL, SILDENAFIL Increased concentration (CYP3A inhibition) Contraindicated

Antivirals direct action against HCV 
(inhibitors NS3-4A protease)

Increased plasma concentrations (combination 
of mechanisms) Contraindicated

Endothelial receptor antagonists (Bosentan) Increased concentration (theoretical consideration) Contraindicated

Immunosuppressant

CYCLOSPORINE Increased concentration (CYP3A inhibition) Monitoring of drug levels

everolimus contraindicated

Narcotics, Opioids

METHADONE Increased concentration (theoretical consideration) Monitoring of drug levels

Buprenorphine / naloxone Increased concentration (theoretical consideration) Clinical monitoring

FENTANYL, OXYCODONE, TRAMADOL Increased concentration (theoretical consideration) Clinical monitoring

Opioid antagonists

NALOXEGOL Not studied contraindicated

Sedatives / hypnotics

BUSPIRONE, CLORAZEPAM, 
DIAZEPAM, ESTAZOLAM, 
FLURAZEPAM, ZOLPIDEM

Increased concentration (CYP3A inhibition) Caution, dose reduction and clinical monitoring

MIDAZOLAM (PARENTERAL) Only in intensive care.

MIDAZOLAM (ORAL) contraindicated

Urological drugs

FESOTERODINA, SOLIFENACINA Not studied Caution, dose reduction and clinical monitoring

DAPOXETINE Not studied Contraindicated

Contraceptives

Alteration of plasma concentrations Use additional methods of contraception

drospirenone Monitoring for possible hypokalaemia

Statins and other hypo-lipidemic agents
(Lomitapide) Contraindicated



PATIENT SAFETY RECOMMENDATIONS FOR COVID-19 EPIDEMIC OUTBREAK: Lessons from the Italian Experience

J Global Clinical Engineering, Special Issue 3, 2020  30

TABLE 4. Serious adverse effects

Lopinavir / 
Ritonavir

Darunavir / 
cobicistat Chloroquine Hydroxychlor 

oquine Tolicizumab

Serious 
adverse 
effects

Hypersensitivity 
reaction, 
angioedema 
Stevens-Johnson 
syndrome / 
Toxic epidermal 
necrolysis 
/ Erythema 
multiforme
QT prolongation 
&
Torsade de Pointes
AV block, PR 
prolongation
Hyperglycaemia, 
hypertriglyceride 
mia
Renal failure
Anemia, 
leukopenia, 
neutropenia 
Pancreatitis 
Hepatotoxicity

Hepatotoxicity

Anorexia,

hyper- cholesterol- 
aemia

hyper- triglyceridemia

Renal failure

Stevens- Johnson 
syndrome rarely

QT
prolongation & 
Torsades de Pointes

Reduction in seizure 
threshold

Anaphylaxis or
anaphylactoid reaction

Neuromuscula r 
impairment

Neuropsychiat ric 
disorders (potential to 
increase
delirium)

Pancytopenia, 
neutropenia, 
thrombocytop enia, 
aplastic anemia

Hepatitis

Hypoglycemia

QT prolongation

Cardio- myopathy

Muscle asthenia

Retinal or visual field 
alterations
Skin reactions

Interstitial 
pneumonia 
Infections

Leukopenia, 
neutropenia hypo- 
fibrinogenaemia

Upper
respiratory 
infections

Herpes simplex and 
zoster

Oral ulcerations

Complicated 
diverticulitis
Hepatotoxicity

Common 
adverse 
reactions

Nausea / vomiting, 
diarrhoea 
Insomnia, anxiety

Nausea / vomiting, 
diarrhoea Insomnia, 
anxiety Headache 
Rash Muscle Pain

Nausea / vomiting, 
diarrhoea, abdominal 
pain

Visual disturbance, 
headache

Extrapyramida l 
symptoms

Nausea / vomiting, 
diarrhoea, 
abdominal pain 
Visual disturbance, 
headache
Skin rash, itching

Extra-pyramidal 
symptoms

Hypertension 
Headache

Skin reactions 
Conjunctivitis
Hyper- 
cholesterolemia

Abdominal pain, 
gastritis
Cough, dyspnoea

Contra- 
indicated 
in:

Cardiac disease 
ischemic 
heart disease, 
cardiomyopathy, 
structural heart 
disease,
QT prolongation
Liver disease

Liver failure (class C 
Child- Pugh)

Haemophilia

Porphyria G6PD
deficiency Epilepsy 
Heart failure Recent 
myocardial
infarction

Porphyria 
Retinopathy 
Maculopathies 
Children
<6a <31 Kg

Administration of 
alive or attenuated 
vaccines

Monitor Transaminases Kidney function Serial complete blood 
count QT interval

Blood count, 
glycemia, QT interval

Cholesterol, 
blood count, 
transaminases


	Introduction
	1. GENERAL RECOMMENDATIONS FOR THE WORK SYSTEM
	2. RECOMMENDATIONS FOR DIAGNOSIS
	3. RECOMMENDATIONS FOR HOSPITAL TREATMENT
	4. THE ETHICS OF TREATMENT DECISIONS
	5. RECOMMENDATIONS FOR SURGERY
	6. RECOMMENDATIONS FOR PREGNANT WOMEN
	7. RECOMMENDATIONS FOR PEDIATRIC PATIENTS
	8. RECOMMENDATIONS FOR HOSPITAL DISCHARGE
	9. RECOMMENDATION FOR HOME ISOLATION
	10. RECOMMENDATIONS FOR PERSONS IN QUARANTINE (39)
	11. RECOMMENDATIONS FOR ONCOLOGIC AND IMMUNOSUPPRESSED PATIENTS
	12. MORTUARY/MORGUE OPERATING PROCEDURES
	13. PSYCHOLOGICAL SAFETY OF STAFF AND MENTAL WELLBEING OF PATIENTS
	14. MEASURES (51,52,53)
	15. REFERENCES
	16. APPENDIX - MEDICATIONS

