Interim Recommendation on Clinical Management of Adult Cases with COVID 19.pdf

HA Central Committee on Infectious Diseases  Ref No.
CCIDER-COVID19-001(v1.4)
and Emergency Response (CCIDER)
Issue Date
21 September 2021
Review Date  13 February 2023
Interim Recommendation on Clinical Management of  Approved by  CCIDER
Adult Cases with Coronavirus Disease 2019 (COVID-
  19)
Page
Page 3 of 18

1.  Purpose
1.1.  To provide guidance on clinical management of patients with Coronavirus
Disease 2019 (COVID-19)

2.  Scope
2.1.  For all healthcare workers at hospitals

3.  Introduction
3.1.  A new strain of coronavirus (SARS-CoV-2)  which has not been previously
identified in human, was reported in Wuhan, China in December 2019.  It
belongs to a clade of betacoronavirus distinct from those associated with
human severe acute respiratory syndrome (SARS) and Middle East respiratory
syndrome (MERS).  Coronavirus Disease 2019 (COVID-19)  causes acute
respiratory infection and pneumonia.    Symptoms include fever, malaise, dry
cough, shortness of breath, anosmia and ageusia. Some patients may have
respiratory symptoms without fever and some patients may also have diarrhea.
People of older age or having underlying chronic disease are at a higher risk
of deterioration into serious condition.

4.  Surveil ance and reporting criteria
4.1.  Please report suspected cases fulfil ing the reporting criteria of Coronavirus
Disease 2019 (COVID-19) to the Central Notification Of ice (CENO) of CHP
via fax (2477 2770), phone (2477 2772)  or CENO On-line
(https://cdis.chp.gov.hk/CDIS_CENO_ONLINE/ceno.html). The case definition
is available on the above website of CENO On-line. Both reporting criteria and
case definition are subject to change upon availability of further
epidemiological, clinical and virological data.

5.  Clinical Management
5.1.  Isolate the patient(s) in airborne infection isolation room (AI R) with standard,
contact, droplet and airborne precautions

HA Central Committee on Infectious Diseases  Ref No.
CCIDER-COVID19-001(v1.4)
and Emergency Response (CCIDER)
Issue Date
21 September 2021
Review Date  13 February 2023
Interim Recommendation on Clinical Management of  Approved by  CCIDER
Adult Cases with Coronavirus Disease 2019 (COVID-
  19)
Page
Page 4 of 18

5.2.  Notify via NDORS/ eNID,  and update the confirmed patient data  when
necessary

5.3.  Diagnosis:
5.3.1.  Specimens for RT-PCR of SARS-CoV-2
  Lower respiratory tract  (always  preferred): sputum or tracheal
aspirate (TA) if intubated or bronchoalveolar lavage (BAL) (if
bronchoscopy)
OR
  Upper respiratory tract: Nasopharyngeal Flocked swab (NPFS) or
Nasopharyngeal Aspirate (NPA) [Pooled with throat swab in viral
transport medium] or Deep throat saliva (DTS)
  Stool: For patient fulfil ing reporting criteria with diarrhea, stool can
be sent to PHLSB for RT-PCR for SARS-CoV-2 testing
5.3.2.  For preliminarily positive cases, specimen should be re-tested and
sent to PHLSB for confirmation
5.3.3.  Repeated testing may be necessary to exclude the diagnosis. Please
consult the clinical microbiologists or infectious disease physicians for
advice
5.3.4.  If patient has any stool sample being tested positive for SARS-CoV-2
previously, contact precaution should  be maintained until negative
result from stool has been obtained
5.3.5.  Microbiological workup as appropriate, e.g.
  Sputum, urine and blood culture
  NPA +/- Tracheal aspirate for flu A/B and other respiratory viruses
  NPA +/- Tracheal aspirate for atypical pneumonia PCR
  Urine for legionella and pneumococcal antigen
5.3.6.  Other investigations e.g. CBP with D/C, L/RFT, CaPO4, glucose, ESR,
CRP, procalcitonin, CXR and ECG, etc.

5.4.  Monitor vital signs and organ functions, and recognize complication(s) early

5.5.  Liaise with ICU early for intensive care if anticipate clinical deterioration

HA Central Committee on Infectious Diseases  Ref No.
CCIDER-COVID19-001(v1.4)
and Emergency Response (CCIDER)
Issue Date
21 September 2021
Review Date  13 February 2023
Interim Recommendation on Clinical Management of  Approved by  CCIDER
Adult Cases with Coronavirus Disease 2019 (COVID-
  19)
Page
Page 7 of 18

Setting and severity of il ness
Mild-to-moderate disease
Severe but non-critical
Critical disease (e.g. in ICU
without need of suppl. oxygen
disease (SaO2 <94% on
needing HFNO, mechanical
room air)
ventilation (MV), or septic
shock, ECMO)
Anti-virals
1
Interferon beta-1b
Can be considered for early
Can be considered for early
Can be considered for early
onset disease (<14 days
onset disease (<14 days
onset disease (<14 days
symptom)
symptom)
symptom)
2
Remdesivir
Can be considered in high risk  Suggest use
Suggest against routine use
patients

3
Ribavirin
Can be considered as part of
Can be considered as part
Can be considered as part of
interferon-based regimens
of interferon-based regimens
interferon-based regimens
4
Lopinavir + ritonavir  Can be considered as part of
Can be considered as part
Can be considered as part of
interferon-based regimens
of interferon-based regimens
interferon-based regimens
Anti-inflammatory or immunotherapeutic
1
Corticosteroids
Suggest against use
Suggest use
Recommend use
Dexamethasone 6mg QD or
equivalent glucocorticoids
2
Convalescent
Suggest against use
Suggest against use
Can be considered at
plasma
discretion of ID physicians/ ICU
intensivist, or use in the context
of a clinical trial
3
Tocilizumab
Suggest against routine use
Suggest use in addition to
Suggest use in addition to
standard of care (steroid)
standard of care (steroid)
In patients with CRP
In patients with CRP
>=75mg/L
>=75mg/L
4
Baricitinib +
Suggest against use
Suggest use
NA
remdesivir +/-
at discretion of ID physicians/
corticosteroids
ICU intensivist
Anti-SARS-COV-2 Antibody products
1
Casirivimab +
Can be considered in high risk
Suggest against use
Suggest against use
imdevimab
patients at discretion of ID
physicians

HA Central Committee on Infectious Diseases  Ref No.
CCIDER-COVID19-001(v1.4)
and Emergency Response (CCIDER)
Issue Date
21 September 2021
Review Date  13 February 2023
Interim Recommendation on Clinical Management of  Approved by  CCIDER
Adult Cases with Coronavirus Disease 2019 (COVID-
  19)
Page
Page 8 of 18

6.3.  Interferon-based regimen
6.3.1.  May consider the following regimen in confirmed patients (Not a
standard therapy)

Interferon beta-1b 0.25mg (8 MIU) subcutaneous alt day*
(maximum 7 doses),
up to 14 days of symptom onset
+
Ribavirin 400mg BD po for 7-14 days depending on clinical response
OR
  lopinavir/ ritonavir 400mg/100mg (Kaletra) BD po for 7-14 days
depending on clinical response

6.3.2.  Interferon beta-1b is considered as the backbone therapy  and
combination therapy with ribavirin or kaletra  is preferred. Interferon
beta-1b monotherapy may be considered if use of ribavirin or kaletra
is contraindicated or there is significant side ef ect due to either drugs
6.3.3.  Reserve syrup formulation of kaletra in patients in ICU, paediatric
patients or patients with swallowing dif iculty
6.3.4.  Dosage adjustment of ribavirin is required for renal impairment
6.3.5.  Pre-treatment workup
-
Check blood x CBP, LRFT, RG, LDH, CK, HBsAg, anti-HCV,
anti-HIV
-
+ blood x TFT, ANA (for starting interferon)
-
CXR (+/- HRCT thorax if indicated)
-
ECG (if preexisting cardiac abnormalities or disease or
clinically indicated). For patients with underlying pre-existing
cardiac problems, fol ow-up monitoring of the cardiac
condition is suggested.
-
Pregnancy test for females with reproductive potential
(Before starting interferon or ribavirin)
-
Avoid pregnancy in female patients and female partners of
male patients during ribavirin therapy; use ef ective
contraceptive measures during treatment and for at least 6

HA Central Committee on Infectious Diseases  Ref No.
CCIDER-COVID19-001(v1.4)
and Emergency Response (CCIDER)
Issue Date
21 September 2021
Review Date  13 February 2023
Interim Recommendation on Clinical Management of  Approved by  CCIDER
Adult Cases with Coronavirus Disease 2019 (COVID-
  19)
Page
Page 11 of 18

(vi)  Obtain consent for treatment. Major side effects: Phlebitis,
Nausea, vomiting, ALT elevations, hyperglycemia,
hyperbilirubinemia, hypersensitivity reactions, bradycardia
(vii)  Coadministration of remdesivir and interferon beta-1b may be
considered in the discretion of ID physicians, particularly in
severe patients with early onset of disease
(viii)  Stopping criteria:
Remdesivir should be discontinued in patients who develop any
of the following:
-  ALT >= 5 times ULN during treatment with remdesivir
-  ALT elevation accompanied by signs and symptoms of liver
inflammation or increasing conjugated bilirubin, alkaline
phosphates, or INR
-  EGFR <30 ml/min

6.5.  Corticosteroids
6.5.1.  Consider dexamethasone 6mg daily PO/IV up to 10 days in patients
with pneumonia, and requiring oxygen supplement or invasive
mechanical ventilation, Prolonged  duration or higher dose of
dexamethasone  may be considered according to individual clinical
condition
6.5.2.  Equivalent total daily doses of alternative glucocorticoids are
methylprednisolone 32mg and prednisolone 40mg
6.5.3.  Dexamethasone may cause hyperglycemia, viral rebound of SARS-
CoV-2 and increased risk of bacterial, fungal and parasitic infections
6.5.4.  Use of short-period, stress dose steroids (hydrocortisone 200mg max
daily) for refractory septic shock or other clinical indications on
physician discretion

6.6.  Convalescent Plasma (CP)
6.6.1.  Transfusion with convalescent plasma in COVID19 patients is
unlicensed. The use may be considered in patients with severe COVID-
19 infection, at the discretion of intensivist and ID Physician
6.6.2.  Obtain consent for treatment. Potential side ef ects: transfusion allergic
reactions, transfusion-associated circulatory overload (TACO),

HA Central Committee on Infectious Diseases  Ref No.
CCIDER-COVID19-001(v1.4)
and Emergency Response (CCIDER)
Issue Date
21 September 2021
Review Date  13 February 2023
Interim Recommendation on Clinical Management of  Approved by  CCIDER
Adult Cases with Coronavirus Disease 2019 (COVID-
  19)
Page
Page 12 of 18

transfusion-related acute lung injury (TRALI)
6.6.3.  Limited by availability
6.6.4.  It is recommended the use of CP to be arranged through clinical trial.
Meanwhile, liaise with QMH  (HKU)  and  Hong Kong Red Cross  for
arrangement if indicated
6.6.5.  The safety and ef ectiveness during pregnancy have not been
evaluated
6.6.6.  Potential side ef ects: transfusion-transmitted infections (e.g. Human
immunodeficiency virus (HIV), hepatitis B, hepatitis C), allergic
reactions, anaphylactic reactions, febrile nonhemolytic reactions,
transfusion-related acute lung injury (TRALI), transfusion-associated
circulatory overload (TACO), and hemolytic reactions. Hypothermia,
metabolic complications, and post-transfusion purpura

6.7.  Tocilizumab
6.7.1.  Monoclonal antibody to IL6 receptor
6.7.2.  There are data from clinical trials suggesting use of tocilizumab in
combination with dexamethasone in certain hospitalized patients who
are exhibiting rapid respiratory decompensation due to COVID-19,
including:
-
Recently hospitalized patients (i.e. within first 3 days of admission)
who have been admitted to intensive care unit (ICU) within the
prior 24 hours and who require invasive mechanical ventilation,
noninvasive ventilation, or high-flow nasal cannula (HFNC)
oxygen (>0.4 FiO2/ 30L/min of oxygen flow) or
-
Recently hospitalized patients (i.e. within first 3 days of admission)
not admitted to the ICU who have rapidly increasing oxygen
needs and require noninvasive ventilation or HFNC oxygen and
who have significantly increased markers of inflammation (CRP
>=75mg/L)
6.7.3.  Dose: 8mg/kg (Max: 800mg/dose), one dose
6.7.4.  Use  at  the  discretion of Infectious Disease (ID)  Physician  and
intensivist  for  severe  patients with evidence of cytokines release
syndrome (Supported by elevated inflammatory markers like CRP, d-
dimer, ferritin, etc)

HA Central Committee on Infectious Diseases  Ref No.
CCIDER-COVID19-001(v1.4)
and Emergency Response (CCIDER)
Issue Date
21 September 2021
Review Date  13 February 2023
Interim Recommendation on Clinical Management of  Approved by  CCIDER
Adult Cases with Coronavirus Disease 2019 (COVID-
  19)
Page
Page 13 of 18

6.7.5.  Contact QMH and arrange serum IL-6 level test  prior to giving
tocilizumab if possible
6.7.6.  Major side ef ects: hypertension, increased ALT, injection site infections,
risk of opportunistic infections particularly bacterial, anaemia; serious
side ef ects: gastrointestinal perforation, neutropenia
6.7.7.  Live vaccines should be avoided for at least 3 months, after
commencement of tocilizumab.

6.8.  Baricitinib
6.8.1.  An orally administered, selective inhibitor of Janus Kinase (JAK) 1 and
2. Baricitinib inhibits the intracellular signaling pathway of cytokines
known to be elevated in severe COVID-19.
6.8.2.  Among hospitalized adults with severe COVID-19 having elevated
inflammatory markers but not on invasive  mechanical ventilation,
concomitant use of baricitinib with remdesivir can be considered.
Baricitinib appears to demonstrate the most benefit in those with severe
COVID-19 on high flow oxygen or non invasive ventilation at baseline.
The benefits for persons on mechanical ventilation are uncertain.
6.8.3.  Dosing:  oral 4mg once daily for  up to  14 days of treatment or until
hospital discharge, whichever is first. Longer duration can be
considered at the discretion of ID physician/ ICU intensivist.
6.8.4.  Renal adjustment: oral 2mg daily (30 to <60 ml/min), 1mg daily (15 to
<30 ml/min)
6.8.5.  Use in combination with remdesivir. Limited information on the use of
baricitinib in combination with systemic corticosteroids. Consider use at
ID physician’s discretion
6.8.6.  Potential side ef ects: Infection  (particularly upper respiratory tract
infection, herpes zoster), nausea, raised ALT, neutropenia, arterial
thrombosis, malignant lymphoma (<1%), malignant neoplasm (<1%)
6.8.7.  Not recommended for patients on dialysis, having eGFR <15ml/min,
having acute kidney injury, or having known active tuberculosis
6.8.8.  Pregnancy: Should be used during pregnancy only if potential benefit
justifies the potential risk for the mother and the fetus
6.8.9.  Avoid use of live vaccines with baricitinib
6.8.10.  Monitoring: CBP, LRFT (Consider interruption if ALC <0.2 or ANC <0.5)

HA Central Committee on Infectious Diseases  Ref No.
CCIDER-COVID19-001(v1.4)
and Emergency Response (CCIDER)
Issue Date
21 September 2021
Review Date  13 February 2023
Interim Recommendation on Clinical Management of  Approved by  CCIDER
Adult Cases with Coronavirus Disease 2019 (COVID-
  19)
Page
Page 14 of 18

6.9.  Casirivimab plus imdevimab
6.9.1.  Anti-SARS-CoV-2 monoclonal antibody products currently have
Emergency Use Authorizations (EUAs) from the Food and Drug
Administration (FDA) for the treatment of mild to moderate COVID-
19 patients who are at risk of progressing to severe disease and/or
hospitalization.
6.9.2.  Casirivimab plus imdevimab: These are recombinant human
monoclonal antibodies that bind to nonoverlapping epitopes of the
spike protein RBD of SARS-CoV-2.
6.9.3.  Dosing: Casirivimab 600mg plus imdevimab 600mg intravenous
infusions for one dose. If intravenous route is not feasible,
administration by four subcutaneous injections (2.5ml per injection)
can be used as an alternative.
6.9.4.  The use of casirivimab plus imdevimab can be considered in patients
with mild to moderate severity and at risk of progression to severe
COVID-19 infection.
6.9.5.  Medical conditions or other factors that were represented in clinical
trials that evaluated anti-SARS-CoV-2 monoclonal antibodies
•  Age >=65
•  Obesity (BMI >30)
•  Diabetes
•  Cardiovascular disease (including congenital heart disease) or
hypertension
•  Chronic lung disease (e.g. COPD, moderate to severe asthma,
interstitial lung disease, cystic fibrosis, pulmonary hypertension)
6.9.6.  Monoclonal antibodies should be used at discretion of ID physicians,
particularly for other conditions or factors at risk of progressing into
severe disease.
6.9.7.  Side ef ects: Uncommon (up to 1 %): allergic reactions or reactions
following infusions: fever, chil s, headache, dif iculty breathing,
hypotension, facial swelling, itching, myalgia
6.9.8.  Pregnancy: The safety for use in pregnancy is inadequate. Use if
potential benefits of treatment outweigh the potential risks to the
mother and fetus.

HA Central Committee on Infectious Diseases  Ref No.
CCIDER-COVID19-001(v1.4)
and Emergency Response (CCIDER)
Issue Date
21 September 2021
Review Date  13 February 2023
Interim Recommendation on Clinical Management of  Approved by  CCIDER
Adult Cases with Coronavirus Disease 2019 (COVID-
  19)
Page
Page 15 of 18

6.10.  Monitoring during treatment
6.10.1.  Blood x CBP, LRFT, LDH, CRP
6.10.2.  Repeat NPS +/- Throat swab or deep throat saliva x SARS-CoV-2 twice,
24 hours apart before isolation release
6.10.3.  Blood x SARS-CoV-2 antibody for patients who are asymptomatic or 7
days after symptom onset or with SARS-CoV-2 RT-PCR CT value >=30
6.10.4.  Repeat Stool x SARS-CoV-2  if there are previous positive results
before isolation release
6.10.5.  Monitor for any concomitant bacterial or fungal infections
6.10.6.  Observe for any side ef ects

7.  Release from Isolation
7.1.  Confirmed cases can be released from isolation if they fulfil the following criteria:
For symptomatic patients:
(i)  Clinical conditions improve and afebrile; AND
(ii)  Either one of the following criteria:
  With two clinical specimens of the same type* (i.e. respiratory or stool)
tested negative for nucleic acid of severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase
chain reaction (RT-PCR) taken at least 24 hours apart; OR three
clinical specimens of the same type* taken at least 24 hours apart in
which RT- PCR test results showed consistent Ct value 33 or above;
AND 10 days have passed since the onset of il ness; OR
  With a transition of the test results for SARS-CoV-2 IgG from negative
to positive results with at least one PCR Ct value 33 or above
For patients who did not develop any COVID-19 compatible symptoms all
along:
Either one of the following laboratory criteria:
(i)  With two clinical specimens of the same type* (i.e. respiratory or stool)
tested negative for nucleic acid of SARS-CoV-2 by RT-PCR taken at least
24 hours apart; OR three clinical specimens of the same type* taken at
least 24 hours apart in which RT-PCR test results showed consistent Ct
value 33 or above; AND 10 days after the first positive RT-PCR for SARS-

HA Central Committee on Infectious Diseases  Ref No.
CCIDER-COVID19-001(v1.4)
and Emergency Response (CCIDER)
Issue Date
21 September 2021
Review Date  13 February 2023
Interim Recommendation on Clinical Management of  Approved by  CCIDER
Adult Cases with Coronavirus Disease 2019 (COVID-
  19)
Page
Page 16 of 18

CoV-2; OR
(ii)  Serology test result for SARS-CoV-2 IgG change from negative to positive
with at least one PCR Ct value 33 or above

7.2.  Discussion with MCO of CHP for lifting of isolation order is necessary

* For patient ever with stool specimen(s) tested positive, they should have two
negative stool specimens collected 24 hours apart before release from isolation OR
three stool specimens taken at least 24 hours apart in which RT-PCR test results
showed consistent Ct value 33 or above.

8.  Follow-up arrangement
8.1.  Follow-up arrangement should be subject to parent team’s decision. In general,
patients who developed pneumonia or complications during hospitalization
should be monitored for any long term sequelae from COVID-19 infection

8.2.  Subject to patient’s need, referral may be sent to clinical psychologist, medical
social worker, physiotherapist, occupational therapist, traditional Chinese
medicine practitioner or District Health Centre

8.3.  Monitoring during follow-up
  Blood tests (e.g. CBP, LRFT, CRP) +/-  2 clotted blood for SARS-CoV2
antibody if not taken previously
  CXR
  Consider lung function tests for moderate to severe cases
  Consider HRCT for cases with residual lung changes

9.  References
1.  Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human
cases. Interim guidance 19 March 2020. WHO.
2.  Q&A on coronaviruses. 2 February 2020. WHO
3.  HA Communication Kit – Coronavirus disease 2019 (COVID-19) Version 6.5. 31

HA Central Committee on Infectious Diseases  Ref No.
CCIDER-COVID19-001(v1.4)
and Emergency Response (CCIDER)
Issue Date
21 September 2021
Review Date  13 February 2023
Interim Recommendation on Clinical Management of  Approved by  CCIDER
Adult Cases with Coronavirus Disease 2019 (COVID-
  19)
Page
Page 17 of 18

Dec 2020
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7.  JFW Chan, et al. A familial cluster of pneumonia associated with the 2019 novel
coronavirus indicating person-to-person transmission: a study of a family cluster,
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8.  Zhu, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019,
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9.  Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical
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https://www.info.gov.hk/gia/general/202005/06/P2020050600679p.htm
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HA Central Committee on Infectious Diseases  Ref No.
CCIDER-COVID19-001(v1.4)
and Emergency Response (CCIDER)
Issue Date
21 September 2021
Review Date  13 February 2023
Interim Recommendation on Clinical Management of  Approved by  CCIDER
Adult Cases with Coronavirus Disease 2019 (COVID-
  19)
Page
Page 18 of 18

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