DR HATEM EL BITAR MEDICAL files د حاتم البيطار 01005684344 استشاري ادارة الرعاية الصحية ادارة المستشفيات ومكافحة العدوي

1. ‫اجمللس‬
‫اجلامعية‬‫للمستشفيات‬‫األعلى‬
Management ofCOVID-19 patients

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Managementof COVID-19 patients
Novel Coronavirus Disease (COVID-19) has become a rapidly growing pandemic involving several
nations. It is of serious concern and extreme challenge not only to the health personnel but also to
the countries for containment. The causative organism is SARS-CoV-2, RNA virus of subgenus
Sarbecovirus, similar to the SARS virus, and seventh member of the human coronavirus family
responsible for this zoonotic infection. It binds to the human angiotensin converting enzyme
(hACE-2)receptorand causes constitutionalandrespiratorysymptoms.
Incubation period for COVID-19 is defined as the interval between the potential earliest date of
contact of the transmission source (wildlife or person with suspected or confirmed case) and the
potentialearliestdateofsymptomonset(i.e.cough,fever,fatigueormyalgia)andiswithin14days
following exposure. Median incubation period being 4 days (interquartile range, 2–7 days; means
50% casesare dispersed during thisperiod)
Diagnosisand ClinicalTyping
COVID-19 diagnostic criteria include epidemiological history (including clustered onset), clinical
symptoms(feverandrespiratorysymptoms), pulmonaryimaging,SARS-CoV-2nucleic acidtesting.
Diagnostic Criteria
SuspectedCases
➢ HistoryofcontactwithaCOVID-19infectedperson(positivenucleicacidtesting)within14
days prior toonsetof illness.
➢ Clusteredonset(twoormorecasesoffeverand/orrespiratorysymptomsin2weekswithin
a smallpopulation, such as a home, office, andschool).
➢ ClinicalManifestation

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1. Having fever (temperature ≥37.2°c) and/or respiratory symptoms, loss of /or
changein,normalsenseofsmell(anosmia)ortaste(ageusia),newonsetofdelirium
(acute confusion) in older people, or in those with dementia or cognitive
impairment.
2. Having characteristicimagingofCOVID-19.
3. Showing normal or decreased total WBC count and normal or decreased
lymphocyte count in the early stagesof onset.
➢ Exhibitinganyoneitem ofepidemiological historyand anytwo itemsof clinicalpicture;
➢ No explicitepidemiological history,butexhibitingthree itemsof clinicalpicture.
ConfirmedCases
• Showing positive for COVID-19nucleic acidtestingbyreal-timefluorescentRT-PCR.
• Positive for SARS-CoV-2nucleic acid is the gold standard for COVID-19 diagnosis, but false
negatives do occur. Therefore, even if the nucleic acid test is negative, patients highly
suspected for COVID-19 upon lung CT, can still be treated in isolation as if clinically
diagnosed, andrepeatedlytestedfor SARS-CoV-2.
ClinicalTyping
COVID-19 shows a complex profile with many different clinical presentations. Similar to
many other viral infections, the characteristics of currently infected patients and their
clinicaloutcomesmayrepresentthetipoftheiceberg.
Patients may be asymptomatic; experience mild, moderate, or severe symptoms; and
presentedwith orwithoutpneumonia.

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Mild: Showing mild clinical symptoms, no pneumonia manifestations on imaging. In most
of thepeoplewith COVID-19, almost >80% havemildillness
o Patients with mild suspected or confirmed COVID-19 should not require
hospitalization,unlessthereisaclinicalconcernforrapiddeterioration,significant
underlying co-morbidities, extenuating sociodemographic circumstances, or an
inabilitytoreturn promptlyto hospital.
o Patients with mild COVID-19 and their caregivers should be provided with
information on symptom management and informed of the signs and symptoms of
complications thatshouldprompt medicalre-evaluation.
Moderate: Having fever and respiratory symptoms, with pneumonia manifestations on
imaging.
o It is recommended that patients with any one of thefollowing factors be treated as
a severe case: age ≥65 years, with underlying diseases (coronary heart disease,
severe hypertension, insulin-dependent diabetes, COPD, rheumatic autoimmune
disease, other infectious diseases, etc.), received immunosuppressive therapy,
organtransplant,dialysis,radiotherapy or chemotherapyofactivetumors.
o PatientswithmoderatesuspectedorconfirmedCOVID-19(i.e.withclinicalsignsof
pneumonia, SpO2 ≥ 90% on room air, but no signs of severe pneumonia) who are
not determined to be at high risk of deterioration may not require hospitalization,
buttheyshouldself-monitorandbecounseledalongwiththeircaregiversaboutthe
signs and symptomsof complications thatshouldprompt medicalreevaluation.
Severe: Adults with any of the following should be treated as severe cases: respiratory rate
≥30times/min;restingfingertipoxygensaturation≤93%;arterialpartialpressureofoxygen
(PaO2)/fraction of inspired oxygen (FiO2) ≤300 mmHg; pulmonary imaging shows
significantprogressionof lesions >50% within 24–48h.
o Patients with severe suspected or confirmed COVID-19 should receive
supplemental oxygen therapy immediately with target saturations of > 94% SpO2
during resuscitation. Patients with severe illness should be closely monitored for
signs of clinical deterioration, specifically rapidly progressive respiratory failure or
shock

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Critical:Anyonewithoneofthefollowingconditions:respiratoryfailureandonmechanical
ventilation;shock;ICUmonitoringandtreatmentincombinationwithotherorganfailures.
▪ ItisrecommendedthatCOVID-19patientswhoareelderly(≥75yearsold)andhave
organ dysfunction or poorly controlled underlying diseases, be treated as critical
cases.
▪ The goalis toachieveearlydiagnosis, early isolation, and earlytreatment.
▪ In order to discover the patient early who is suffering from severe or critical illness,
some clinical parameters should be dynamically monitored during diagnosis and
treatment, including oxygenation index, pulmonary imaging, and the levels of
plasma inflammatorymarkersand cytokines.
▪ It is recommended that patientswhohave been sickfor morethan aweekandwho
have not seen significant improvement during initial treatment should be treated
as potential severe/critical cases, and be placed under enhanced clinical
observationand given more frequentauxiliaryexaminations.
▪ Iftheconditionisgettingworse,empiricalfirstresponsetreatmentisimplemented
immediately according tothe standards for severe cases.
ClinicalCourseof COVID-19
The symptoms of COVID-19 initially begin with symptoms of fatigue, low-grade
intermittent fever of prolonged duration, myalgia, dry cough and shortness of breath, which then
eitherimproveswithearlyidentificationandconservative managementor worsensandprogresses
to dyspnea and productive cough. The median time to onset of dyspnea from various cohorts was
found to be 6 days following exposure. The median time to admission, development of ARDS and
need for mechanicalventilation andICU care was 8,8.2 and10days,respectively.

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RoutineBiochemistryLabFindingsand ImaginginCOVID-19
Major lab findings as in all other respiratory viral illness include leukopenia and lymphopenia,
elevated transaminasesand D-dimer.
Severe lymphopaenia, thrombocytopenia, elevated C-reactive protein (CRP), elevated D-dimer (>1
μg/L), IL-6, ALT, serum ferritin, lactate dehydrogenase, creatine kinase, high-sensitivity cardiac
troponinI,creatinine,prothrombin timeand procalcitonin are associatedwithhighermortality.
ThemostcommonradiologicalfindingsonX-rayandCTthoraxobservedare bilateralground-glass
opacities (GGOs) with or without consolidation. Lesions predominantly involve bilateral lower
lobeswithperipheral distribution.
Poor Prognostic FactorsinCOVID-19
Strong independent predictors of high mortality are elderly (age >70 years); underlying co-
morbidities such as uncontrolled hypertension, diabetes and coronary artery disease, chronic
obstructive pulmonary disease and malignancy; severe lymphopenia (< 800), thrombocytopenia
and D-dimer (>1 μg/L), elevated C-reactive protein, LDH, ALT, serum ferritin, IL-6 and high-
sensitivitycardiac troponin.

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MultidisciplinaryCollaborativeand PersonalizedTherapy
✓ A multidisciplinaryteam(MDT) is an important hospital management strategy to improve
the quality of clinical diagnosis and treatment, and has played an important role in the
treatment of critical COVID-19 patients. COVID-19 can affect multiple organs and systems
in the human body. At thesame time, elderly patients often suffer from several underlying
comorbidities. Cases can turn severe rapidly, often involving multiple organs, resulting in
failureofmultipleorgans,andrequiringmultidisciplinaryassistance.Inordertoeffectively
treat severe and critical cases, and prevent mild cases from becoming severe, hospitals
should establish amultidisciplinarycollaborative treatment andearly warningsystem.
✓ Multidisciplinary Team (MDT) conduct daily meetings, and allow doctors in isolated ward
areas to participate in daily video conferences over the Internet, coordinate diagnosis and
treatment, formulate scientific, systematic, and individualized treatment plans for each
severeandcriticalpatient,andprovidemultidisciplinaryconsultationsas needed.
✓ Discussion should rely on expertise from the various disciplines, as well as focus on key
issues in diagnosis and treatment. The various opinions and suggestions of experts who
understand the overall situation and have extensive experience must be combined to
determinethefinal treatment plan.
✓ Multidisciplinary collaborative personalized treatment provides comprehensive,
standardized, individualized diagnosis, and treatment programs for COVID-19 patients. At
the same time, seminars also provide a platform for all subspecialties to learn and
communicate, while also creating conditions for further improving medical staff’s
knowledgeandabilityregardingdiagnosis andtreatmentof COVID-19.

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SymptomaticandSupportiveTreatment
Initial symptoms of COVID-19 include fever, cough, and fatigue. Treatment principles
include antiviral therapy, general symptomatic therapy, respiratory and circulatory support,
managementof acutekidney injury,andrenal replacement therapy.
Antipyretic treatment: Fever is generally controlled by physical cooling and oral rehydration.
Paracetamol (acetaminophen) is recommended. the use of NSAIDs is not contraindicated.
Glucocorticoid is not recommended for a fever, however It can be cautiously used after weighing
the prosand cons.
Cough and expectoration: We found that most patients complained of cough but with less
expectoration during managing the COVID-19 patients. Ambroxol hydrochloride and
acetylcysteine are commonly used during practice. If the patient suffers severe cough, an
antitussivecanbeappropriatelyadded.
Fatigue: In the early stages, fatigue is pronounced due to fever, poor appetite, and low oral intake.
Propernutritional supportcanbe administeredwhilepaying attention to therest.
Electrolyteimbalanceandnutritionalsupport:Manypatientswerecomplicatedwithhypokalemia,
hypocalcemia,hyponatremia,andsignificantweightlossduringadmission.Interventionalmethods
can betakenby dietitiansupportorrelated medications.
Empiricalantimicrobialtreatment
Severe COVID-19 patients are prone to bacterial and fungal infections, so attention should bepaid
to the clinical microbiological detection of patients with severe and critical diseases. Elevated C-

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reactiveproteinhaspoorspecificityforthediagnosisofsecondaryinfection.Elevatedprocalcitonin
levelsareof great significance forclinical diagnosisof sepsis.
Empiricantibacterialagentsshouldbeconsideredtotreatalllikelypathogenscausingsevereacute
respiratory bacterial infection and sepsis as soon as possible, and optimally within 1 hour of initial
patient assessment forpatientswith sepsis.
✓ Oralantibiotics for mild/moderatecases
o Doxycycline:200mgon first day, then 100mgonce aday
o Clarithromycin: 500mgtwice a day
o Levofloxacin: 500 mg once or twice a day (consider the safety issues with
fluoroquinolones)
✓ Intravenous antibioticsformoderateor severepneumonia
o Levofloxacin: 500mg once a day for 5days
o Ceftriaxone1gmIM for 5days
✓ Intravenous antibiotics for moderate or severe pneumonia when there is a higher risk of
resistance.
o Piperacillinwithtazobactam:4.5gthreetimesaday,increasedto4.5gfourtimesa
dayifinfectionis severe
o Ceftazidime: 2gthree timesa day
o Levofloxacin:500mgonceortwiceaday(usea higher dosageif infection is severe
✓ Antibiotictobeaddedifmethicillin-resistantStaphylococcusaureusinfectionissuspected
or confirmed(dual therapywith an intravenous antibiotic listed above)

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o Vancomycin:15mg/kgto20mg/kgtwoorthreetimesadayintravenously,adjusted
accordingto serum vancomycin concentration. Maximum 2gper dose.
o Linzolid600mg IV/12hrs.
o TiecoplaninIV.
Use of antibacterial therapy should be judicious with a reassessment after 3 days for de-escalation
and/or optimization of therapy, in accordance with the principles of stewardship, after review of
the clinical status, laboratoryandradiologic findings, cultureand susceptibilityresults.

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AntithromboticTherapyin PatientswithCOVID-19
The incidence of venous thromboembolism (VTE) in patients with COVID-19 may be up to
30% of infected patients managed in intensive care units. The rate of VTE reported in
generalwardsranges from5%to 10% ofpatients with COVID-19.
Most of patients with COVID-19 diagnosed with VTE have no history of previous VTE
episodes. Of note, VTE in about 30% of patients with COVID-19 in the scenario of viral
infection can be asymptomatic, which increases the risk of death. The diagnosis of VTE in
COVID-19increasesmortality 2.5-fold.
D-dimer levels should be monitored and a sudden rise of this marker after an initial
decrease inbloodwith concomitantrespiratoryfailuremight suggestVTE.
• In all patients with COVID-19, VTE risk should be assessed using a risk assessment model
validated foracutelyillmedicalpatients.
• The VTE risk stratification should be repeated along with bleeding risk assessment during
the courseof COVID-19.UseIMPROVEriskassessment models inpatients withCOVID-19.

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• OutpatientswithmildCOVID-19shouldnotreceivepharmacologicalthromboprophylaxis,
but increased mobility and appropriate hydration, in particular in the presence of fever or
vomiting,shouldbe encouraged.
• Patientswhoarereceivinganticoagulantorantiplatelettherapiesforunderlyingconditions
should continue these medications iftheyreceive adiagnosisof COVID-19.
• Thromboprophylaxis may be considered in outpatients with mild / moderate COVID-19
patients who have, in addition to a significant reduction in mobility, at least one of the
followingriskfactors:
o BMI > 30kg/m2;
o age > 70years;
o active cancer;
o personalhistoryof VTE;
o major surgerywithinthelast threemonths.

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• Inthese cases,thromboprophylaxis for 7to14daysis suggested eitherwith Low Molecular
Weight Heparin (LMWH) or Fondaparinux at standard dose (e.g. Dalteparin, Enoxaparin,
Fondaparinux,TinzaparinandNadroparin)withself-injectionsifpossibletolimittheuseof
anurseathomeandavoidcontact,ortheuseofDOACs( Rivaroxaban10mgdaily,apixaban
2.5 mg orallytwice aday).
• In hospitalized patients with COVID-19, hematologic and coagulation parameters are
commonlymeasured.
• PharmacologicprophylaxisisrecommendedforallCOVID-19inpatientswithconsideration
of intermediate or therapeutic dosing for prophylaxis in low bleeding risk ICU/sick floor
patients
• OptimalACdosing for VTEpreventioninCOVID-19patientsis unknown
• For hospitalized COVID-19 patients, the possibility of thromboembolic disease should be
evaluated in the event of rapid deterioration of pulmonary, cardiac, or neurological
function,orofsudden, localized loss ofperipheralperfusion .
• Patients with COVID-19 who experience an incident thromboembolic event or who are
highly suspected to have thromboembolic disease at a time when imaging is not possible
should be managedwith therapeutic doses of anticoagulant therapy as per thestandard of
care forpatientswithout COVID-19.

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Pharmacologic AnticoagulationRegimens
Prophylactic/TreatmentIntensity
Clinical
Consideration
Standard Intermediate Therapeutic
CrCl ≥30
LMWH 40mg
Q24H
LMWH 0.5 mg/kg
Q12H
LMWH 1 mg/kg Q12H
15≤ CrCl < 30
LMWH 30mg
Q24H
UFH7500Q8H LMWH 1 mg/kg Q24Ha
CrCl<15 -or- on
RRT
UFH5000Q12H
or Q8H
UFH7500Q8H
UFHbolusinfusion
Goal aPTT 60-85sec
Spinal/Epidural
Anesthesia
UFH5000Q12H
or Q8H
UFH5000Q12H
or Q8H
Discuss choice of agent
withAnesthesia
HistoryorNew
DiagnosisHIT
CrCl ≥30:
Fondaparinux
2.5mg Q24h
Crcl ≤ 30: Consult
Heme
Consult
Hematology
ConsultHematolo
On ACPrior to
Admission
Warfarin: Continueifno criticalillnessor anticipatedprocedures
DOAC:GivenICUrisk,switchtotherapeuticregimenaboveperCrCl

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Roundenoxaparin dosesto nearest syringe; no upperweight limit
Mechanical ppx should be used for patients unable to receive pharmacologic ppx,
& should be used in addition to pharmacologic ppx for patients in the ICU or with
an ICUtrajectory
Withhold pharmacologic prophylaxis & treatment in active or recent bleeding
(within 24-48h)
• PostDischargeRecommendations
o Indication forTherapeuticAC ContinueACas per usual guidelines
o Received EmpiricTherapeuticAC
▪ Low bleedingrisk:Complete 90-daycourse
▪ Highbleedingrisk: Consider ExtendedPpx
o Received Prophylactic AC: Strongly consider Extended Ppx after in-house standard
or intermediateintensityppx
• Extended Out-of-Hospital Prophylaxis (in pts with LOS≥3 days, low bleeding risk & CrCl ≥
15):
• Duration:30 days startingon thedayofdischarge
• Drug choice: Rivaroxaban 10mg daily, apixaban 2.5 mg orally twice a day or Enoxaparin
40mg daily.

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• Respiratory support: The most obvious manifestation of respiratory impairment is
hypoxemia in COVID-19 patients. When hypoxemia is effectively corrected, it can
significantly mitigate multiorgan damage and dysfunction due to hypoxia, and
significantly improve theprognosisof disease.
• Circulatory support: When COVID-19 turns from severe to critical, we should pay more
attention to circulation problems. Patients in the critical stages of the disease are likely to
suffer from shock. Tissue perfusion disorders and even multiple organ failures may occur.
Early rapid fluid resuscitation can improve the prognosis of shock. We should pay more
attention to fluid balance strategies, avoiding excess or insufficient fluid resuscitation. If
necessary, vasoactive medicine may be considered. See the following sections for more
details.

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AntiviralTreatment
Early antiviral therapy can reduce viral replication and shorten viral clearance times, as well as
reduce the incidence of severe and critical illnesses. Antiviral drugs with clearly demonstrated
clinical efficacy against COVID-19 are lacking. However, there are a few that have received initial
clinicalvalidation.
Currentlyavailabledrugs for clinicaltrial:
o Remdesivir
• It may be consideredinpatientswith moderatedisease ata loadingdoseof 200mg
intravenous over 1–2 hours on day 1, followed by 100 mg intravenous daily for 5–
10days
o Favipiravir (1600mg,q12h onthe firstday, 600mg,q12h thereafter)
• Favipiravir showsactivityagainstRNAvirusesbyconversionintotheribofuranosyl
triphosphatederivativebyhostenzymesandsubsequentselectiveinhibitionofthe
viralRNA-dependentRNApolymerase.
• The drug has also shown effectivenessin the treatment of avian influenza and may
be an alternative option for the treatment of illness caused by pathogens such as
the EbolavirusandCOVID-19
o Lopinavir/ritonavir (KALETRA)
• EffectivedoseofLPVis400mgorallyevery12hours,andbasedontheeffectiveness
of this drug during the previous SARS and Middle East respiratory syndrome virus
outbreaks,itwas initiallyseen asa potentialtreatment option for COVID-19
o α-interferon(5millionIUin2mLnormalsalineforinhalation,bid).Ifinitialefficacyispoor,

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o Chloroquineand hydroxychloroquine
• Chloroquine is awidely used antimalarial drugthat has been shown to have broad-
spectrum antiviral activity. Chloroquine (500 mg every 12 hours) blocks the virus
infection by an increase in the endosomal pH required for virus/cell fusion, as well
as by preventing SARS-CoV receptor glycosylation. It has shown efficacy in
reduction of exacerbation of COVID-19 pneumonia as well as accelerated viral and
symptomatic clearance.
• HCQS(200mgevery12hours)isachloroquineanaloguewithabettersafetyprofile
and an anti-SARS-CoV activity in vitro.HCQS was found to be more potent than
chloroquine in SARSCoV-2-infected Vero cells and also shown to be significantly
associated with viral load reduction.80 81 Although this antiviral effect is seen to
be enhanced by the macrolide azithromycin, the combined use of both drugs can
leadtoanincreasedincidenceofQTintervalprolongationandcardiacarrhythmias.
o Oseltamivir (TAMIFLU)
• Although designed and used against influenza virus outbreaks, oseltamivir (75 mg
two times per day for 5 days) was tested for patients with COVID-19 along with
standard supportive care in two case series from Wuhan, China. As such, no clear
additional benefitof oseltamivir therapy was observed inthesepatients.
o Ivermectin
➢ Ivermectin, an anti-parasitic medicine whose discovery won the Nobel Prize in 2015, has
proven, highly potent, anti-viral and anti-inflammatory properties in laboratory studies. In
the past 4months, numerous, controlled clinical trials from multiple centers and countries

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worldwide are reporting consistent, large improvements in COVID-19 patient outcomes
whentreatedwithivermectin
➢ Properties ofIvermectin
• Ivermectin inhibits the replication of many viruses, including SARS-CoV-2, influenza, and
others;
• Ivermectin has potent anti-inflammatory properties with multiple mechanisms of
inhibition;itdiminishes viralload andprotectsagainst organdamage in animalmodels;
• Ivermectin preventstransmissionofCOVID-19when takeneitherpre- orpost-exposure;
• Ivermectin hastens recovery and decreases hospitalization and mortality in patients with
COVID-19.
➢ Uses ofIvermectin
➢ Ivermectinforpostexposureprophylaxis0.2mg/kg(12mg)immediatelythenrepeatday3.
➢ Ivermectin for pre-exposure prophylaxis (in HCW) and for prophylaxis in high-risk
individuals (> 60 years with co-morbidities, morbid obesity, long term care facilities, etc.).
0.15–0.2 mg/kgDay 1,Day3 andthenweeklyfor 10weeks, followedbybiweekly dosing.
➢ Ivermectin intreatment : 4tabletsdailyonanemptystomachfor 4 consecutivedays.

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Corticosteroids
Given the hyper-inflammatory state in COVID-19, immunomodulatory approaches,
including steroids, continue to be evaluated to address both ARDS and systemic
inflammation.
Early treatment with a short course of corticosteroids in patients with COVID-19 may
attenuatetheexcessivehost respiratoryandsystemic inflammatoryresponses.

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Immunomodulatoryagents
Some patients with COVID-19 develop a hyperinflammatory syndrome (HIS) that is
characterizedby elevations inproinflammatorycytokinesandmultiorgandysfunctionalso
knownastheimmunopathologyofSARS-CoV-2infection.Thesignificanceofthesefindings
is unclear, however early descriptions found that those with elevated Il-6 levels and
evidence ofhyperinflammation hadincreasedratesof moreseveredisease.
The reason why a subgroup of COVID-19 patients with pneumonia develops rapidly
progressing respiratory failure remains unknown, which makes the optimal therapeutic
approach to these patients uncertain. The scarcely available evidence suggests that a
hyperinflammatory syndrome (HIS) that resembles secondary hemophagocytic
lymphohistiocytosis (sHLH) may have a pathogenetic role . sHLH may be triggered by viral
infections, and some cases have been linked to the Middle East respiratory syndrome due
to coronavirus (MERS-CoV). The laboratory hallmarks of sHLH are cytopenia, elevated
levels of ferritin, transaminases, triglycerides, lactate dehydrogenase (LDH) and D-Dimer,
and low fibrinogen [9]. In Chinese reports, lower levels of lymphocyte count, higher levels
offerritin,LDH,transaminasesandD.dimerwereassociatedwithaworseprognosis[10,11].
Patients with HIS may benefit from early identification and treatment with anti-cytokine
targetedtherapies
Tocilizumab, a monoclonal anti-IL-6-receptor blocking antibody, has been proposed as a
therapeuticapproachtomitigate hyperinflammationassociatedwith COVID-19.
Tocilizumab is FDA-approved for various rheumatologic conditions as well as cytokine
release syndromeassociated withCAR-T celltherapy.

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Among hospitalized patients, Tocilizumab demonstrated a lower relative risk of clinical
deterioration, defined as death, need for mechanical ventilation, or ICU admission,
comparedtoplacebo/usual care.
o Indication criteria for Useof Tocilizumab
▪ SeverecasesspeciallywithelevatedIL-6.
▪ Alternatively, high levels of d-dimer and or CRP or ferritin and / or
fibrinogenprogressivelyincreasing.
▪ Worsening of respiratory exchanges such as to require noninvasive or
invasive support from ventilation
o LaboratoryParametersalso supportiveof cytokinerelease syndrome (CRS)
▪ Serum IL-6> 10xuppernormal limit
▪ Ferritin >300ug/Lwithdoublingwithin24hours
▪ Ferritin >600ug/Latpresentation
▪ LDH >250U/L
▪ ElevatedD-dimer(>1mg/L)
o AdultTocilizumabDosingRegimen
▪ The initial dose should be 4-8mg/kg, with the usual dose 400mg, (round
dosetonearestvialof400andor 200mg) 2ndinfusion 8-12hours afterthe
firstdose
▪ In obese patients (Maximum dose if calculated by mg per kg basis, is 800
mg/dose)

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Severity-dependentprotocol tomanage COVID-19
1.Mild Cases:
Patients present with Fever, sore throat, dry cough, malaise and body aches or Nausea,
vomiting,abdominalpain,loose stools; SpO2≥ 94% on ABG; no chestX-ray findings.
Siteof treatment: Self-isolation at homeunlesstherearerisk factorsfor deterioration
Treatment: Symptomatictreatment
o Vitamin C 500mg BID.
o Zinc75–100mg/day(elemental zinc)
o Melatonin10mgatnight .
o VitaminD32000–4000IU/day.
o Ivermectin 4tablets dailyon an empty stomach for 4consecutivedays.
o B complexvitamins
2. ModerateCases:
Mild casewith comorbidities
Patients present with Fever, sore throat, dry cough, malaise and body aches or Nausea,
vomiting,abdominalpain,loose stools; SpO2< 93% on ABG; or chest X-ray findings.
Siteof treatment: Hospitalization.
Treatment:
o Anticoagulant: LMWH according D. dimer if 0.5-1 prophylactic and therapeutic if
morethan 1.
o Ceftriaxone1gmIV/24Hrs. for 5 days.
o Symptomatic treatment; oxygenation through nasal cannula, face mask or high-
flow nasal cannula

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Antiviraltherapy
o Remdesivir 200 mg iv followed by 100 mg OD (5–10 days according to clinical
evolution) OR
o Lopinavir/ritonavir 400/100 mg BID orally (duration: according to clinical
evolution) OR
o Hydroxychloroquine200mg BID orally (5–20daysaccording to clinical evolution).
OR
o Ivermectin 4tablets dailyon an empty stomach for 4consecutivedays. It should be
noted that ivermectin has potent anti-inflammatory properties apart from its
antiviralproperties
Follow up
Check the following laboratorystudiesdaily:
o Completebloodcount(CBC)withdifferential,withafocusonthetotallymphocyte
counttrend
o Completemetabolic panel
o Creatinekinase (CK)
o C-reactiveprotein(CRP)
check the following studies every other day (or daily if elevated or in the intensive care
unit):
o Prothrombintime(PT)/partial thromboplastin time(PTT)/fibrinogen
o D-dimer
check the following studies at baseline and repeat them if abnormal or with clinical
worsening:
o Lactatedehydrogenase,repeateddaily ifelevated
o Troponin,repeated everytwo tothree daysif elevated
o Electrocardiogram (ECG), with at least one repeat test after starting any QTc-
prolongingagent
Secondary bacterial infection has not been a frequently reported feature of COVID-19; if
thisissuspected(eg,basedonchestimagingorsuddendeterioration),wechecktwosetsof

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blood cultures and sputum Gram stain and culture. Procalcitonin can be checked to assess
the risk of secondary bacterial infection; however, since elevated procalcitonin levels have
beenreportedasCOVID-19progresses,theymaybelessspecificforbacterialinfectionlater
in the disease course.
3. Severe case:
Fever; severe hypoxia (SpO2 < 88%) on ABG, BUT patient responsive to high flow of O2
(SpO2≥93% with O210–15L/min)
Siteof treatment: Hospitalizationinintermediate careunit.
Treatment:
Anticoagulant:LMWHtherapeutic Dose.
Broad spectrumantibiotics
Symptomatictreatment;Oxygenationthroughnasalcannulas,facemaskorhigh-flownasal
cannulastoreachSpO2target≥93%.Iftargetnotreachedafter30min,evolutiontocritical
case .
Antiviraltherapy
Remdesivir 200mgiv followedby 100mgOD(5–10daysaccording to clinicalevolution)
Lopinavir/ritonavir 400/100mg BIDorally(duration: according to clinical evolution)
Hydroxychloroquine200mg BID orally (5–20daysaccording to clinical evolution).
Ivermectin 4 tablets daily on an empty stomach for 4 consecutive days. It should be noted
thativermectinhaspotentanti-inflammatorypropertiesapart fromitsantiviralproperties
4.CriticalCase.
HighprobabilityofARDSevolution;NIV neededtomaintain acceptableSpO2levels.
Hospitalizationinintensive careunit
Start CPAP/NIVwithSpO2target> 93%

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Trailof awakeproning .
HighdoseSteroid
o Solumedrol2mg/kgon 2 divideddoses
o Dexamethasone20mgdaily
o Assess IL6 forpossibilityofanti-interleukin 6.
Full Anticoagulation and if Plasma d dimer is more than 3 consider heparin infusion and
assesspossibilityofDVTor Pulmonary embolism.
Countering Hypoxemia
Hypoxemia is the most prominent feature of impaired respiratory function due to COVID-19.
Timely and effective correction of hypoxemia and alleviation of secondary organ damage and
dysfunction caused by respiratory distress and hypoxia are of great significance for improving
patientprognosis.
Nasal Cannula
Oxygen therapy shouldbeconsideredimmediatelyin thefollowingcircumstances:
o SPO2<93%,respiratorydistress(RR>24bpm).Adjusttheoxygenflowto2–5L/min
accordingtobloodoxygensaturation(connecttoahumidifierbottle).
Face Mask Oxygen
If the oxygen saturation with the nasal cannula therapy is still <93%, the patient is in
respiratorydistress,orthepatient’sinitialSPO2is<85%,giveoxygenbyfacemask(flow5–
10L/min)to correctthehypoxia assoon aspossible.
High-FlowNasalCannula

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High-flow nasal cannula (HFNC) is used to provide patients with a high flow of oxygen (up
to60–80L/min)atarelativelyconstantconcentration(21–100%),temperature(31–37°C)
intranasally.Itsapplications toCOVID-19areas follows:
o mild-to-moderatetypeI respiratoryfailure(150mmHg ≤ P/F < 300mmHg);
o mildrespiratorydistress(respiratoryrate >24bpm);
o intolerance to traditional oxygen therapy or noninvasive positive pressure
ventilationorwithcontraindications;
o assistancewithwithdrawal ofventilator and extubation.
After beginning HFNC therapy(within 2–4 h), the responseto treatment should be closely
monitored. If the following conditions persist, a different support method should be
utilized:respiratoryrate>35bpm;SpO2<90%;chestandabdominalparadoxicalbreathing;
combined PCO2> 45mmHg; pH< 7.35; unstable circulationandothersituations.
NoninvasivePositivePressure Ventilation
Because CPAP has better human–machine synchronization than BiPAP, the CPAP mode is
preferred; BiPAPmaybeconsideredfor patientswho cannottolerate CPAP, orhaveCOPD.
(1) Set CPAP to 5 cm H2O FiO2 100%, and perform an arterial blood gas analysis after 30–
60mintoevaluatetheARDSseverity.(2)Adjustpressuregraduallyuntilreaching8–10cm
H2O.
Precautions
o Posture:semi-recumbentposition, bedraised 30–45°.
o Givepatientwaterevery2h.
o Themaskshouldnotbewornfor morethan 4–6htoavoidpressureulcers.

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o Choosea facemask suitedto the patient’s face.
o Make surethemask is fixed inplace andnottoo loose ortight.
o Instructthepatienttoclosetheirmouthandbreathethroughtheirnoseasmuchas
possible.
o Ifthepatient’sgastrointestinalbloatingisobvious,considerinsertingagastrictube
forgastrointestinaldecompression.
o Carefullyobservevitalsigns,changesinbreathingpatterns,andbloodgasanalysis,
to identify high-riskfactors forfailure, andavoiddelayed intubation.