Covid-19

COVID-19
Initial management and
treatment options
Dr Swayam Sahu
Army Hospital (Research and Referral), New Delhi

Triage and early recognition of patients with SARI
Suspect COVID-19 in a patient with SARI that
–Resides or has traveled to countries with ongoing human or
animal infections.
–Exposure to live or dead animals (i.e. birds, swine, camels).
–Close exposure to patient with SARI of unclear etiology.
https://www.who.int/emergencies/diseases/novel-coronavirus-2019

Appropriate IPC at triage (any ARI)
Apply droplet precautions
• Give the suspect patient with ARI a medical mask.
• Instruct the patient to practice respiratory hygiene and hand hygiene and to avoid
movements within the facility.
• Locate the suspect patient in separate area.
• Keep at least 1 m distance between patients.
• Do not delay medical treatments.

If suspect COVID-19, avian influenza, MERS-CoV or SARS-CoV
Droplet isolation measures :
used for diseases or germs that are spread in tiny droplets caused by
coughing and sneezing (examples: pneumonia, influenza, whooping
cough, bacterial meningitis).
Healthcare workers should:
• Wear a surgical mask while in the room. Mask must be discarded in
trash after leaving the room.
• Clean hands (hand washing or use hand sanitizer) when they enter the
room and when they leave the room.

Add contact to droplet precaution measures.
• HCW wears gown, gloves, medical mask and eye protection when
examining patient.
• Use dedicated patient equipment when possible, (such as
stethoscopes) or wash and disinfect between patients.
• Add airborne precautions if there is an emergent need for intubation or
cardiopulmonary resuscitation

Airborne isolation precautions:
used for diseases or very small germs that are spread through the air from
one person to another (examples: Tuberculosis, measles, chickenpox).
• Ensure patient is placed in an appropriate negative air pressure room (a
room where the air is gently sucked outside the building) with the door
shut.
• Wear a fit-tested NIOSH-approved N-95 or higher level respirator while in
the room. Mask must be discarded in trash after leaving the room.

Airborne isolation precautions:
used for diseases or very small germs that are spread through the air from
one person to another (examples: Tuberculosis, measles, chickenpox).
• Clean hands (hand washing or use hand sanitizer) when they enter the
room and when they leave the room.
• Ensure the patient wears a surgical mask when leaving the room.
• Instruct visitors to wear a mask while in the room.

Triage
Conduct triage at the sick patient’s first point of contact with health
care system.
• Pre-hospital stage:
– ambulance
– clinic.
• Hospital stage:
– admissions ward
– emergency area or department, accident and emergency
department, casualty area
– general ward.

Triage
Prioritize and sort patients based on their severity of
illness and need for immediate care.
• Use standardized triage tools to ensure reliability and
valid sorting of patients.
• Avoid “under-triage” and “over-triage”.
• Identify high priority patients that need immediate care.

WHO – ICRC Integrated Triage Tool ≽ 12 years

Check for RED
Criteria Check for
YELLOW Criteria
Move to High Acuity
Area immediately
Move to Clinical Area
Move to Low
Acuity or Waiting
NO NO
NO
YES
YES
YES

WHO – ICRC Integrated Triage Tool < 12 years

Risk factors for severe disease (influenza)
Comorbidities
• cardiovascular disease (cardiac failure)
• pulmonary disease (asthma and COPD)
• metabolic disease (diabetes)
• kidney disease
• hepatic disease
• Haemoglobinopathies
• chronic neurologic conditions ( neuromuscular, neurocognitive and seizure disorders).

Extremes of age
– infants and young children (< 2 years).
– elderly (≥ 65).
Immunosuppressive conditions
– HIV, immunosuppressive medication, malignancy.
Special situations
– children receiving chronic aspirin therapy.
– pregnancy (up to 2 weeks’ postpartum).

High risks groups should be considered for
hospitalization even with mild disease, for close
monitoring to detect deterioration and
treatment

Assess patients with ARI (during seasonal influenza)
Fever or history of
fever (≥ 38 °C)
+
Cough
+
Onset within
last 10 days
Uncomplicated
Influenza-like
illness
Low-risk
Patient
Discharge home with instructions to return if worsens or
fails to improve
High-risk
Patient
Treat with antivirals, and consider hospitalization
SARI*
complications
Low risk patients with non-severe pneumonia may
be treated at home with antivirals.
Hospitalization, consider ICU if critically ill. Treat with supportive
care, antivirals, antibiotics.

Assess patients with ARI (suspect COVID-19)
Fever or history
of fever (≥38 °C)
+
Cough
+
Epidemiologic
link
Uncomplicated
Influenza-like
illness
Low-risk
Patient
Discharge home with instructions to return if
worsens or fails to improve
High-risk
Patient
Hospitalization for close monitoring.
SARI*
complications
Hospitalization, consider ICU if critically ill. Treat
with supportive care, antibiotics. Enroll in clinical
trial for investigational therapeutics.

Recapitulation: Uncomplicated illness
• Symptoms are non-specific:
– fever and cough within 10 days
– sore throat, nasal congestion or rhinorrhea
– headache, muscle pain or malaise
– diarrhea or vomiting.
•Elderly or immunosuppressed patients may present with atypical symptoms
and may not have fever.
•Patient with uncomplicated disease are without signs of:
– dehydration
– shortness of breath
– Sepsis.

Recapitulation: Clinical symptoms suggestive of SARI
• Decreased activity, dizziness, decreased urine output.
• Increasing breathing difficulties, cyanosis, bloody or coloured
sputum, chest pain, noisy breathing.
• Confusion, lethargy, coma, weakness, seizures.
• Persistent high fever and other symptoms beyond 3 days without
signs of resolution.
• Children may also present with poor feeding, excessive diarrhea
and vomiting.

Recapitulation: Clinical signs suggestive of SARI
• Respiratory distress:
–fast breathing, shortness of breath, accessory muscle use, cyanosis,
grunting, severe chest indrawing, wheezing, stridor.
• Cardiovascular/circulatory instability
–delayed capillary refill, weak pulse, cool extremities, reduced
urine output, low blood pressure.
• Neurological instability
–alteration of mental status, seizures, irritability, confusion, lethargy.
• Severe dehydration, stridor
–sunken eyes, very low skin pinch, unable to drink, lethargy.

Caring for SARI patient at pre-hospital setting
• Apply IPC interventions at all times.
• Provide available emergency care; call for help.
• Refer to local emergency medical service (EMS) protocols.
• Arrange for safe transfer to hospital with isolation and ICU
capacity.

Caring for SARI patient in the emergency area of hospital
• Apply IPC interventions at all times.
• Provide available emergency care, call for help.
• Refer to local ward and ICU admission criteria.
• Arrange for safe admission to ward or ICU.

Emergency care
• Based on clinical condition and available resources:
– administer oxygen +/- advanced ventilatory support.
– insert peripheral IV and start fluid therapy (if in septic shock).
– give appropriate antimicrobial therapies before transfer.
– obtain appropriate laboratory testing (i.e. respiratory tract swabs,
blood cultures, chest radiograph, CBC).
• Do NOT delay life-saving treatments. Early treatment reduces
mortality.

Fluid management
• Use conservative fluid management in patients with SARI when
there is no evidence of shock.
• Patients with SARI should be treated cautiously with intravenous
fluids, because aggressive fluid resuscitation may worsen
oxygenation, especially in settings where there is limited
availability of mechanical ventilation. 1
1. Abbott TE et al. A single-centre observational cohort study of admission National Early Warning Score (NEWS).
Resuscitation. 2015;92:89-93.

ICU admission
• ICUs care for critically ill patients
– impending or ongoing acute, life-threatening organ dysfunction.
– need intensive and continuous monitoring.
– need intensive therapies that cannot be delivered on the general
ward (i.e. oxygen therapy, ventilation).
– depending on local resources, many SARI patients will require
ICU admission.

Collection of Specimens
• Collect blood cultures for bacteria that cause pneumonia and
sepsis, ideally before antimicrobial therapy. DO NOT delay
antimicrobial therapy to collect blood cultures.
• Collect specimens from the upper respiratory tract (URT;
nasopharyngeal and oropharyngeal) AND, where clinical
suspicion remains and URT specimens are negative, collect
specimens from the lower respiratory tract when readily available
(LRT; expectorated sputum, endotracheal aspirate, or
bronchoalveolar lavage in ventilated patient) for SARS-CoV-2
testing by RT-PCR and bacterial stains/cultures.

Collection of Specimens
• In hospitalized patients with confirmed COVID-19, repeat URT
and LRT samples can be collected to demonstrate viral clearance.
The frequency of specimen collection will depend on local
epidemic characteristics and resources. For hospital discharge, in
a clinically recovered patient two negative tests, at least 24 hours
apart, is recommended.

Safe patient transfer
• Ensure IPC measures are always applied.
• Ensure appropriate diagnostics and emergency treatments have been
given and patient is stable and ready for transport.
• Ensure all monitors and ongoing treatments are secured and can be
maintained during transport.
• Ensure appropriate documentation and handover of care to next
responsible clinicians.
• Ensure the responsible health care worker is prepared.

Treatment options: Oxygen Therapy
• Hypoxaemia is a life-threatening condition that can be easily
treated with oxygen therapy: - oxygen therapy saves lives.
● Oxygen therapy is an essential medicine that should be available
in all areas that may care for SARI patients.
● Oxygen therapy is cost-effective.
● Oxygen therapy is safe in newborns (preterm and term) that are
hypoxic.

• In the hospital setting, give oxygen immediately to patients (adults
and children) with SARI who have signs of severe illness:
– severe respiratory distress
– sepsis with hypoperfusion or shock
– alteration of mental status
– or hypoxaemia
• SpO2 < 90% (if patient is haemodynamically normal)
• SpO2 < 94% (if patient with any emergency signs of airway,
breathing or circulation)
• SpO2< 92–95% (if pregnant woman).

• In children, clinical signs that should trigger oxygen therapy
include (when pulse oximeter not available):
– central cyanosis
– nasal flaring
– inability to drink or feed (when due to respiratory distress)
– grunting with every breath
– depressed mental state (i.e. drowsy, lethargic)
– and in certain conditions (severe lower chest indrawing, RR
≥ 70 bpm, head nodding).

• If patient is critically ill, give higher flow rates
– In adults and older children, start with 10–15 l/min via face
mask
with reservoir bag.
- Less ill patients can start with 5 L/min by nasal cannula.

• In children < 5 years, preference is nasal cannula

• For severe hypoxaemia: Nasopharyngeal catheter
– For severe hypoxaemia:
– place past uvula into the pharynx
– provides higher oxygen levels at similar flow rates
because of PEEP
– needs to be humidified
– neonates, dose is 0.5 L/min
– infants, dose is 1 L/min
– use with nasogastric tube.

• Monitor oxygen levels
Clinical signs are not reliable indicators of hypoxaemia.
● Pulse oximeters should be available in all settings caring for
patients with SARI and used to measure the SpO2 - pre-hospital,
emergency area, ward, and ICU.
● Blood gas analyser should be available in the ICU:
– measures pH, PO2, and PCO2 for patients on mechanical
ventilation, with severe hypoxaemia, risk of hypercapnea
and shock states.

• Oxygen titration to reach target
• Titrate oxygen to target:
– SpO2 ≥ 90% in adults and children
– SpO2 ≥ 92–95% in pregnant patients
– SpO2 ≥ 94% if child or adult with signs of multi-organ failure,
including shock, alteration of mental status, severe anaemia until
resuscitation has stabilized patients, then resume target ≥ 90%.
• Titrate oxygen up and down to achieve target.
• Wean oxygen when patient is stable.

Appropriate dose and delivery device

Treatment options: IPC and oxygen therapy
• Ensure single patient use of nasal prongs, simple face masks and
face masks with reservoir bag to prevent nosocomial infection.
• Humidification is not necessary when delivering low flow rates.
The oropharynx and nasopharynx provide sufficient humidity.
• In children, flow rates are considered high when > 2 L/kg/min.
• Avoid bubble bottles because of risk of infection.

Treatment options: Oxygen therapy
• Recognize acute hypoxaemic respiratory failure
• Patients not responding to increasing oxygen therapy are developing
acute hypoxaemic respiratory failure:
• Signs of severe respiratory distress
• Hypoxaemia (SpO2 < 90%) despite escalating oxygen therapy
• SpO2/FiO2 < 300 while on at least 10 L/min oxygen therapy
• Cardiogenic pulmonary oedema not primary cause.

• High-flow oxygen system for acute hypoxemic respiratory failure
• High-flow oxygen systems can be used for adults and children:
• Selected patient must be awake, cooperative, haemodynamically
stable without urgent need for intubation.
• May generate aerosols so should be used with airborne precautions.

• Comfortable nasal cannula interface.
● Reliably titrates FiO2 up to 100%.
● Humidification prevents dryness.
● In adults, delivers flow rates as high as 60 L/min.
● In infants and young children, maximum flow rates are less, based on
age and weight:
– i.e. 2 L/kg/min up to maximum of 60 L/min

• Aims to match patient’s inspiratory demand.
• Reduces work of breathing.
• Washes out nasopharyngeal dead space.
• Provides low level of PEEP.
• May induce less injury to the lung in ARDS.
• Monitor closely for need for intubation.

Treatment options: Antimicrobial therapy
• Give appropriate, empiric broad-spectrum antimicrobials as soon
as possible of recognition of patient with SARI and sepsis/severe
pneumonia (in the emergency area when possible).
• Preferably after the clinical specimen collection (upper and/or
lower respiratory samples and blood cultures).
• Each hour delay in administration of effective antimicrobial
therapy in septic shock is associated with increased mortality.

Treatment options: Antimicrobial therapy
• Empiric therapy may include one or more effective drugs to treat
all likely pathogens:
– i.e. antibiotics for suspected bacterial pathogens, antiviral
for suspected viral pathogen (if effective antiviral is known),
antifungal for suspected fungal pathogen, etc.)
● For patients with septic shock, can consider combination therapy:
– i.e. using two antibiotics of different antimicrobial classes
aimed at most likely bacterial pathogen.

Treatment options: Antibiotic regimens for severe CAP
• Examples of antibiotic regimens for severe CAP: IDSA and BTS guidelines
• Combination therapy:
ampicillin or penicillin G for fully immunized child if local epidemiology documents lack of
substantial high-level penicillin-resistance for invasive S. pneumoniae.
•OR third generation cephalosporin (e.g. cefotaxime or ceftriaxone) for non-fully
immunized child, known high-level, penicillin-resistance for invasive S. pneumoniae or life-
threatening infection.
• And antibiotic against atypical pneumonia (i.e. macrolide).
• If community-acquired S. aureus suspected:
•add vancomycin or clindamycin based on local susceptibility data.
• Flouroquinolones and doxycyline are not used to treat CAP in children.

Treatment options: Antibiotic regimens for severe CAP
• Paediatric recommendation from IDSA
• Combination therapy:
• •B-lactam e.g. ampicillin-sulbactam, cefuroxime, cefotaxime or ceftriaxone and antibiotic
against atypical pneumonia (e.g. macrolide or doxycycline) or respiratory flouroquinolone
(e.g. levofloxacin).
• If community-acquired methicillin-resistant S. aureus (CA-MRSA) suspected:
•add vancomycin or linezolid.
• If immunosuppressed (i.e. PL-HIV):
• consider anti-pneumocystis treatment (e.g. sulfamethoxazole/trimethoprim).
• In pregnant women the use of macrolides, cephalosporins and penicillins are
safe. Do not use flouroquinolones or doxycyline.

Treatment options: Antivirals for COVID-19
• There are no known effective antivirals for coronavirus infections.
• Various candidates with potential anti-nCoV activity are
being evaluated for clinical trial protocols.
• Use of unregistered or unproven therapeutics for nCoV
should be done under strict monitoring and ethical approval.
• Use WHO Monitored Emergency Use of Unregistered Interventions
(MEURI) framework

• Neuraminidase inhibitors:
• oseltamivir (including Tamiflu™, Antiflu™)
• zanamivir inhaler(including Relenza™),
• IV formulation is investigational drug – peramivir (including RapivabTM).

• Prescribing oseltamivir
• WHO recommends for patient with severe or at risk for severe,
seasonal influenza virus infection and zoonotic influenza virus
infection.
• Oral capsule or suspension, that can be given via nasogastric or
orogastric tube in ventilated patients.
• Dose is 75 mg twice daily for 5 days in adults.
• Give as soon as possible to patient with suspected or confirmed
influenza virus infection of all ages.

• Prescribing oseltamivir (children)
• Dose in children up to 40 kg is 3 mg/kg twice daily for 5
days
• Dose in children over 40 kg is adult dose (75 mg twice daily
for 5 days)
• Available as oral suspension (6 or 12 mg/mL) and tablets
(30 mg, 45 mg, 75 mg)

• IV peramivir:
– Approved for use in China, Japan, Republic of Korea and United
States of America for treatment of uncomplicated influenza in
outpatients via a single infusion.
• IV zanamivir:
– Recent clinical trial found IV zanamivir at 600 mg once daily not
superior to oseltamivir in hospitalized adult and adolescent
patients.
• WHO recommends against use of IV peramivir and IV zanamivir when
compared to placebo for patients with severe or at risk for severe
influenza infection. However, to be considered in patient with
oseltamivir-resistant virus.

• Lopinavir-ritonavir is FDA-approved for treatment of HIV infection. It has
been used for other coronavirus infections;
• It was used empirically for SARS 2 and is being studied in the treatment of MERS 3
• In China this combination is used in conjunction with interferon alfa for
treatment of some patients with COVID-19 4,5
• A trial in 199 patients with COVID-19 comparing lopinavir-ritonavir with
standard care did not show a significant difference in time to improvement or
in mortality at 28 days, nor were there differences in duration of viral RNA in
oropharyngeal specimens. 6
2.Chu CM et al: Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 59(3):252-6, 2004
3. Arabi YM et al: Treatment of Middle East respiratory syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled
trial. Trials. 19(1):81, 2018
4. Harrison C: Coronavirus puts drug repurposing on the fast track [news article]. Nat Biotechnol. ePub, 2020
5. Jin YH et al: A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 7(1):4, 2020
6. Cao B et al: A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. ePub, 2020

• Remdesivir
• Several randomized trials are underway to evaluate the efficacy of remdesivir for moderate or
severe COVID-19. 7
• Remdesivir is a novel nucleotide analogue that has activity against severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) in vitro and related coronaviruses (including SARS and
MERS-CoV) both in vitro and in animal studies. 8,9
• The compassionate use of remdesivir through an investigational new drug application was
described in a case report of one of the first patients with COVID-19 in the United States. 10
• Any clinical impact of remdesivir on COVID-19 remains unknown.
7. Gilead. Gilead Sciences Statement on the Company’s Ongoing Response to the 2019 Novel Coronavirus (2019-nCoV).
8. Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med 2017; 9.
9. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020; 30:269.
10. Holshue ML, DeBolt C, Lindquist S, et al. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med 2020; 382:929.

Treatment options: Chloroquine and derivatives
• Both chloroquine and hydroxychloroquine have been reported to inhibit
SARS-CoV-2 in vitro, although hydroxychloroquine appears to have more
potent antiviral activity. 11
• Use of chloroquine is included in treatment guidelines from China's National
Health Commission and was reportedly associated with reduced progression
of disease and decreased duration of symptoms. 12, 13
• However, primary data supporting these claims have not been published. 14
11. Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome
Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020.
12. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020; 14:72.
13. Colson P, Rolain JM, Lagier JC, et al. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents 2020; :105932.
14. Cortegiani A, Ingoglia G, Ippolito M, et al. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care 2020.

Treatment options: Chloroquine and derivatives
• In an open-label study of 36 patients with COVID-19, use of
hydroxychloroquine (200 mg three times per day for 10 days) was associated
with a higher rate of undetectable SARS-CoV-2 RNA on nasopharyngeal
specimens at day 6 compared with no specific treatment (70 versus 12.5
percent). 15
• In this study, the use of azithromycin in combination with hydroxychloroquine
appeared to have additional benefit, but there are methodologic concerns
about the control groups for the study, and the biologic basis for using
azithromycin in this setting is unclear.
• Optimal dosing is uncertain; various regimens are being used, including 400
mg twice daily on day 1 then daily for five days, 400 mg twice daily on day 1
then 200 mg twice daily for four days, and 600 mg twice daily on day 1 then
400 mg daily for four days. 16
15. Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of Antimicrobial
Agents – In Press 17 March 2020 DOI:10.1016/j.ijantimicag.2020.105949.
16. CDC. Therapeutic options for patients with COVID-19. https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html (Accessed on March 22, 2020).

Treatment options: Tocilizumab
• Treatment guidelines from China's National Health Commission include the
IL-6 inhibitor tocilizumab for patients with severe COVID-19 and elevated IL-
6 levels; the agent is being evaluated in a clinical trial. 17
17. Reuters. China approves use of Roche drug in battle against coronavirus complications. https://www.reuters.com/article/us-health-coronavirus-china-roche-hldg/china-approves-use-
roche-arthritis-drug-for-coronavirus-patients-idUSKBN20R0LF (Accessed on March 11, 2020).

Treatment options: Limited role of glucocorticoids
• The WHO and CDC recommend glucocorticoids not be used in patients with
COVID-19 pneumonia unless there are other indications (eg, exacerbation of
chronic obstructive pulmonary disease). 18, 19
• Glucocorticoids have been associated with an increased risk for mortality in
patients with influenza and delayed viral clearance in patients with Middle
East respiratory syndrome coronavirus (MERS-CoV) infection.
• Although they were widely used in management of severe acute respiratory
syndrome (SARS), there was no good evidence for benefit, and there was
persuasive evidence of adverse short- and long-term harm. 20
18. Centers for Disease Control and Prevention. Interim Clinical Guidance for Management of Patients with Confirmed 2019 Novel Coronavirus (2019-nCoV) Infection, Updated February 12,
2020. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html (Accessed on February 14, 2020).
19. World Health Organization. Novel Coronavirus (2019-nCoV) technical guidance: Patient management. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-
guidance/patient-management (Accessed on February 02, 2020).
20. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; 395:473.

Treatment options: Uncertainty about NSAID use
• Some clinicians have suggested the use of non-steroidal anti-inflammatory
drugs (NSAIDs) early in the course of disease may have a negative impact
on disease outcome. 21, 22
• These concerns are based on anecdotal reports of a few young patients who
received NSAIDs early in the course of infection and experienced severe
disease. In light of these concerns, some providers are using acetaminophen
in place of NSAIDs for reduction of fever.
• However, there have been no clinical or population-based data that directly
address the risk of NSAIDs. The European Medicines Agency (EMA) and the
WHO do not recommend that NSAIDs be avoided when clinically indicated.
23,24
21. https://dgs-urgent.sante.gouv.fr/dgsurgent/inter/detailsMessageBuilder.do?id=30500&cmd=visualiserMessage (Accessed on March 19, 2020).
22. Day M. Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists. BMJ 2020; 368:m1086.
23. Updated: WHO Now Doesn't Recommend Avoiding Ibuprofen For COVID-19 Symptoms. Science Alert 2020. https://www.sciencealert.com/who-recommends-to-avoid-taking-ibuprofen-
for-covid-19-symptoms (Accessed on March 19, 2020).
24. European Medicines Agency. EMA gives advice on the use of non-steroidal anti-inflammatories for COVID-19 https://www.ema.europa.eu/en/news/ema-gives-advice-use-non-steroidal-
anti-inflammatories-covid-19 (Accessed on March 19, 2020).

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