Q&A with Malaysia-China ID Physicians

Q&A with Malaysia-China ID Physicians

Q1: Role of Favipravir in Treatment of COVID-19 Case

  • A broad spectrum anti-viral.
  • Proven useful for many viruses such as SARS, MERS, Ebola, etc.
  • Preliminary small clinical trials suggest Favipravir may be effective in treating COVID-19.
  • More clinical evidences is needed to determine its effectiveness and safety.
  • Can be considered to use in mild cases, but more scientific evidences is needed.
  • Not included in China’s COVID-19 treatment protocol.


Q2: Comment of Malaysia Treatment Protocol

(MY's protocol table: Clinical Stage 1 - 5, sign and symptoms and treatment plan) Refer to: https://cutt.ly/atQRllw

Overall comments:

  • Similar as China’s COVID-19 treatment protocol.
  • Antiviral should not be the only component in the treatment protocol.
  • Supportive measures (e.g. isolation, quarantine, treatment of complications, etc) should be added.
  • More indicators (e.g. CD4 cell count, T-c ell count, cytokines level, etc) to be added to monitor disease progression.
  • Patient monitoring should be real time dynamic monitoring, instead of single time laboratory testing.
  • Monitoring shouldn’t be neglected in mild cases in view of the possibility of disease progression.

On hydroxychloroquine / chloroquine:

  • Current evidence demonstrated its effectiveness as a treatment for COVID-19.

On lopinavir / ritonavir:

  • No evidence to support the use of Lopinavir / Ritonavir.

On ribavirin:

  • No evidence to support its effectiveness to treat COVID-19.



Q3: Cytokine Release Syndrome

  • Common in lots of viral cases, but its prognosis is yet to be studied.
  • More commonly seen in severe and critical COVID-19 cases.
  • Progression to severe disease usually happen during Day 7 - 10 of illness.
  • If situation permit, monitoring of cytokine levels will be helpful in identifying cytokine release syndrome.
  • Warning signs suggesting the possibility of Cytokine Release Syndrome:
    • Worsening of chest-imaging
    • Acute exacerbation of patient’s condition
    • Rapid elevation of inflammatory markers
    • Increasing trend of cytokine level (IL-1, IL-6, IL-8)



Q4: Role of Steroids in Treatment of COVID-19 Cases

  • No sufficient evidence of steroids provide benefit to COVID-19 patients.
  • Usage of steroids remain controversial.
  • High dose of steroids may prolong viral clearance and increase risk of secondary infection.
  • Steroids may be used to slow down disease progression, especially in cases which progress rapidly.
  • Role of steroids in Cytokine Release Syndrome is yet to be proven.
  • Recommended approaches in using steroid:
    • Start only if clinically indicated.
    • Can be started at early stage of disease when disease progress rapidly and/or cytokine release syndrome is expected and/or patients having comorbidities that may lead to rapid disease progression.
    • Should be used in low dose, and short period of time.
    • Usage of steroid in clinical trials requires patient informed consent.



Q5: Role of Interleukin-6 Inhibitor in Treatment of COVID-19 Cases

  • Elevation of IL-6 is observed in the case of Cytokine Release Syndrome.
  • IL-6 monoclonal antibody (Tocilizumab) has been used in China for severe cases.
  • Limited evidence on the efficacy and safety of IL-6 monoclonal antibody (Tocilizumab).
  • Immunal therapy (IL-6 inhibitors) has been incorporated in China’s COVID-19 treatment protocol (version 7) for treatment of severe COVID-19 cases.
  • Selection of patient for IL-inhibitors need to be done carefully.



Q6: Experience in Usage of Convalescent Serum

  • It has been used in treating emergent diseases (e.g. SARS, MERS, COVID-19).
  • Preliminary clinical data demonstrated the safety of convalescent serum, but more data is needed for further interpretation.
  • No noticeable benefits on patients who received convalescent serum.
  • Six patients in China received convalescent serum as a form of treatment for COVID-19.
  • In China, convalescent serum only be considered for severe and critical cases.
  • Very severe and critical condition patients accompanied by anaemia will be appropriate candidate for convalescent plasma.

Initiation of convalescent serum therapy:

  • Collection of convalescent serum (~400ml) at 2-4 weeks after the patients are discharged from hospital.
  • Titre of antibody requires 1 to 160 ratio , more ideal is 1 to 320 ratio.
  • Amount of plasma to be infused: 200 - 400ml.
  • Infusion can be done multiple time if conditions permit.
  • Monitoring of clinical symptoms, change in imaging, change in immune cells, viral load level and antibody level.



Q7: Management of Healthcare Workers who Exposed to Positive COVID-19 Patients without Proper Personal Protection Equipment (PPE)

Evaluation of exposure risk:

  • How long has the patient admitted to hospital?
  • How long has the HCW exposed to the patient without proper PPE?
  • Does the patient’s investigation showing viral clearance (negative result)?

Recommendations:

  • Full infection control and PPE training should be given to all HCW.
  • Exposure of healthcare workers (HCW) to positive COVID-19 cases without proper PPE should be reduced.
  • If it happened, respective HCW should be isolated for 14 days.

In the case if isolation of respective HCW is not possible:

  • Evaluate how high is the risk of exposure.
  • Perform full self hygiene → wash the skin surface which may come into contact with patient’s droplets.
  • Immediately put on PPE.
  • Can consider post-exposure prophylaxis (e.g. lopinavir/ritonavir, inhalation of interferon). However, efficacy not proven yet, and proper consent need to be taken.
  • Perform swab nuclear test.
  • Closely monitoring of the respective HCW.
  • Minimize his/her contact with others → may work at an isolated environment. 
  • Precautions for other HCW who work with him/her.



Q8: Re-infection of COVID-19

  • Immune response differ between one and another.
  • Patient’s body will usually develop antibody after emergence of the infection.
  • It is still unclear if such immunity is long or short-term. Based on China’s observation, such immunity is most probably short term.
  • No re-infection has been identified in Shanghai, China thus far.
  • The surrounding environment may precipitate re-infection.
  • Recovered patients are advised to stay at home.
  • Positive result in “recovered” patients may be a result of false negative swab previously.

Swab sampling method and its result:

  • Swab results can be affected by technical issues such as sampling method / technique and type of test kit used.
  • Positive result in recovered patients does not mean there’s still live virus in the body. Without live virus, the patient is not contagious.

Recommendation on choice of specimen in the case of re-testing:

  • Sputum (most preferred)
  • Lower respiratory tract secretion
  • Nasopharyngeal swab
  • Pharyngeal swab (least preferred)



Q9: Infectivity of Patients who had Recovered from The Illness, but PCR Remains Positive Beyond 14 Days

Recommended discharge criteria:

  • Two consecutive negative result with 24 hours apart.
  • PCR result shouldn’t be the only discharge criteria.
  • Comprehensive assessment need to be done prior to discharge.
    • Firstly, clinical assessment → significant improvement of clinical presentation.
    • Secondly, afebrile for at least 3 consecutive days.
    • Thirdly, significant improvement in chest imaging.
    • Re-test if the above criteria abide.
  • Patient should continue to be isolated at home after discharged.

Discharge criteria if patients met all criteria mentioned above except laboratory results has always been COVID-19 positive:

  • If only faecal specimen remains positive, patient may be discharged.
  • If swab specimen remains positive, monitoring is needed for additional 1-2 weeks. It will usually return negative after a few days.
  • If test result remains positive for a long time, one may be considered as intermittent viral shedding. Patient can be discharged in a very cautious manner. He/She needs to stay at home, and avoid going to public places.

Viral shedding:

  • In mild cases:
    • Swab / urine specimen turns negative after 8 days of illness.
    • Faecal (stool) turns negative after 10 days of illness.
    • Blood turns negative after 14 days of illness.
  • In severe cases:
    • Swab specimen turns negative after 15-20 days of illness.

Others:

  • Traditional and Complementary Medicine (TCM) has also been used in reduction of sustained positive result post-recovery.





We would like to thank Dr. Woon Yuan Liang and Ms. Teh Hoon Shien for transcribing and summarizing the live teleconference discussion.



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