CME INDIA Presentation by Dr Pratik Savaj, Infectious disease physician, DNB Medicine FID/FNB Infectious disease Surat, Gujrat. Contact: pratiksavaj2@gmail.com.

Virus came, virus stayed and we will keep dealing with the complications for years – even after the recovery. COVID-19 last month witnessed 20% to 30% jump in post-COVID fibrosis related OPD consultations in metros. Knowing some basics of 15 litre oxygen dependent syndrome is need of the hour.

Post COVID fibrosis

15-Litre Oxygen dependent syndrome: What is this?

  • It is a post COVID condition in which patient becomes oxygen dependent due to progressive lung fibrosis which enables to bring down oxygen requirement.
  • Usually seen in 2nd to 3rd week of illness.
  • After initial improvement, patient might go into repeat exacerbation.
  • Progressive decline in lung function → pulmonary failure → death.

Complexity in the management

From patient side:

  • Emotional disturbance.
  • Increase in the cost of management.
  • Health care associated infections.

From health care side:

  • Bed remains occupied so new patient doesn’t get the bed.
  • Continuous monitoring is needed by staff to check SPO2 and RR.
  • Need to keep ventilator standby.

Who will develop more fibrosis?

  • Age >65.
  • High LDH.
  • Smoking Alcoholism.
  • HTN/DM/IHD.
  • Long ICU stay.
  • Abnormal pressure/volume settings of ventilator.

(Ademola S. Ojo. Hindawi Pulmonary Medicine Volume 2020, Article ID 6175964)

New onset of breathlessness after recovery – Causes & Workup

CausesWork Up
Cardiogenic pulmonary edemaNT Pro-BNP
Acute MIECG, Trop T
Pulmonary embolism2D echo, D-Dimer, pulmonary angiography
Infection– HAP/VAPsend relevant cultures
Unknown reasons (2nd storm)??Send markers – IL6, CRP, TNFalpha

Management of such patient:

 Most important:

  • Anti-fibrotics.
  • Oxygen therapy.
  • Steroids.
  • Prevention of thrombosis.

Not to neglect:

Anti-fibrotics:

Only two drugs are commercially available:

  1. Pirfenidone.
  2. Nintedanib.

Post COVID fibrosis - Pirfenidone
Post COVID fibrosis - Nintedanib

Steroids

  • Steroids should be given till hypoxia as per ICMR guideline. Standard accepted dose.
  • Dexamethasone 8mg IV OD or Methlyprednisolone 40mg OD.
  • Giving high dose steroid not helpful and not recommended.
  • Benefit of giving prolong steroid in chronic hypoxic patient is unknown.

Prevention of thrombosis

  • All COVID-19 patients admitted to the hospital should be given prophylactic dose of heparin unless contraindicated.
  • Therapeutic dose →only for documented thrombosis.
  • Severe disease progression with very high D-dimer and imaging is not possible → can make therapeutic dose of anticoagulant.
  • Pro-coagulant pattern – ↑fibrinogen ↑D-dimer ↑ PT ↓platelet count.

Uncertainty regarding antifibrotics

  • Efficacy has not been established in post COVID fibrosis.
  • Optimal dose is unknown.
  • Rapidity of onset is not studied.
  • Optimal duration is not well defined.

 Oxygen therapy

  • Keep Spo2 target ≥ 88.
  • Encourage patient for prone positioning.
  • Provide extra pillow to make prone position comfortable.
  • Disadvantage of high oxygen support → tracheobronchitis, ARDS, pulmonary fibrosis • Try to reduce oxygen to maintain SpO2 ≥ 88.

Post COVID fibrosis - Anti-coagulant and Prophylaxis dose

Post discharge thrombo prophylaxis

Oral anticoagulant is preferred

  1. Apixaban – 2.5mg BD.
  2. Dabigatran – 150mg OD.
  3. Rivaroxaban – 10mg OD.

Duration will depend upon co-morbid condition, severity of illness, mobility of patient

Post COVID fibrosis - Moderate category and Severe category

Not to neglect:

[1.] Infection control

  • Secondary infections are seen in later stage of the disease.
  • Infection control should be top priority in the effective management of COVID-19.
  • Effective infection control bundle should be followed.
  • Ventilatory patient →regular suctioning, oral care, head up position.
  • Catheterized patient →removal as soon as possible when not required, keep bag down.
  • Central line → remove when not needed, wash hand before and after using it.

[2.] Early identification of sepsis

 It is most difficult task because patient is already on steroids so:

  1. Markers might be normal.
  2. No fever.
  3. Typical signs of inflammation might not be seen on imaging.
  4. ET secretions will be minimal.
    • Repeatedly sending cultures will be useful (blood, urine, ET).
    • Don’t use PCT as a sole marker of sepsis.

[3.] Role of antibiotics?

  • There is no role of prophylactic antibiotics in COVID-19.
  • High WBC could be because of steroids and antibiotics not justified for the same.
  • Bacterial co-infection is rare in COVID-19.
  • Early identification of secondary infection and antibiotics should be chosen based upon site of sepsis.

[4.] Nutrition

  • Severe COVID-19 →Hypercatabolic state.
  • Food intake is reduced by several factors →stress, disease related anorexia, dyssomnia.
  • Hypemetabolism + Poor intake →Severe muscle wasting.
  • Ryle’s tube should be inserted for those who can’t take feed properly.
  • Physical activity should be promoted to preserve muscle mass and function.
  • Carbohydrate – 27-30 kcal/kg/d.
  • Protein – 1 to 1.5gm/kg/day.
  • Lipids.

Post COVID fibrosis - Respiratory insufficiency and Lipid

  • The use of EN enriched with omega-3 fatty acids should be preferred in case of ARDS.
  • Take help of dietician.

[5.] Psychological support

  • Take help of psychiatrist.
  • Early shifting to non-COVID area.
  • Early home care.

[6.] Take help of psychiatrist Common psychological conditions

  • Depression.
  • Anxiety.
  • Post-traumatic stress disorder (PTSD).
  • To give Psychiatry reference in such cases would be helpful.
  • Treating doctor or nurse can be counsellor.
  • Low dose benzodiazepine would be useful to deal with early insomnia.

[7.] Early shifting to non-COVID area

  • If patient had completed 14 days of illness or repeat RT-PCR is negative, he/she can be shifted to non-COVID area
  • Advantages:
    1. Less burden on COVID staff.
    2. Relatives can stay with patients →more psychological comfort and care.
    3. Less cost of the treatment in non-COVID area.

[8.] Early home care

  • If patient’s relative can arrange home oxygen and monitoring facilities at home then he can be shifted to home with oxygen therapy.
  • Nearby hospital should be available.
  • Relatives should be taught to identify warning signs (tachypnea, hypoxia, fever).
  • Oxygen requirement should be < 5 litre.
  • Advantages →more psychological benefit.

[9.] Glycemic control

  • Because of ongoing steroids there will be hyperglycemia.
  • Pre-existing diabetic patient will have very high sugar.
  • Hyperglycemia →Risk of infection + Hyper-coaguable state.
  • After each dexa/MPS injection → Peak of sugar will be seen after 6 to 8 hours.
  • Useful OHA to control peak in sugar level → Glicalzide.
  • Useful Insulin → NPH (Neutral Protamine Hagedorn) or basal + bolus.

Post COVID fibrosis - Common mistakes during treatment
Post COVID fibrosis - Post COVID Immunization

Presentation has been reviewed by Dr Sudhir Kumar, Pulmonologist, Patna and Dr Nishith Kumar, Pulmonologist, Ranchi.

Dr Nishith Kumar opines:

  • There is no established role of antifibrotics in post COVID sequelae.
  • Dexamethasone was used in the Recovery Trial in oral or intravenous preparation 6 mg once daily for ten days.
  • In pregnancy or breastfeeding women, prednisolone 40 mg administered by mouth (or intravenous hydrocortisone 80 mg twice daily) should be used instead of dexamethasone. So basically, the recommendation (from Recovery trial) is for 6mg Dexamethasone.
  • No rationale OF EARLY USE OF STEROID. In fact, prolonged use of steroid can lead to Secondary infection, uncontrolled BSL, GI bleed & other complications.

CME INDIA Learning Points

  • The pathogenesis of post-infective pulmonary fibrosis includes dysregulated release of matrix metalloproteinases during the inflammatory phase of ARDS causing epithelial and endothelial injury with unchecked fibroproliferation. There is also a vascular dysfunction which is a key component of the switch from ARDS to fibrosis, with vascular endothelial growth factor and cytokines such as interleukin-6 and tumor necrosis factor alpha being implicated (CollinsBF, Raghu G. Antifibrotic therapy for fibrotic lung disease beyond idiopathic pulmonary fibrosis. Eur Respir Rev2019;28:190022).
Post COVID fibrosis
Courtsey: Kacper Lechowicz et al.J. Clin. Med. 2020, 9, 1917
  • Role of presently available antifibrotic drugs (pirfenidone and nintedanib) needs further research in the present pandemic. There is no evidence that antifibrotic therapies (nintedanib and pirfenidone) impact the risk or severity of COVID-19.
  • There is overlap between adverse effects of these medications and symptoms of COVID-19 (eg, diarrhea, fatigue, loss of appetite), which can confound early identification and lead to worse manifestations of COVID-19.
  • The increase of LDH reflects tissue destruction and is regarded as a common sign of cell damage. In patients with severe pulmonary interstitial disease, the increase of LDH is significant and is one of the most important prognostic markers of lung injury For critically ill patients with COVID-19, the rise in LDH level indicates an increase of the activity and extent of lung injury.
  • About 60% to 80% of the individuals who have recovered from COVID-19 may have some form of sequelae. It can be mild in the form of fatigue and body aches. But it can also be very serious in the form of individuals requiring to be on long-term oxygen therapy. (AIIMS Delhi observation).
  • Despite the use of short term steroids, HRCT in many cases show reticulation of suggesting a post-inflammatory pulmonary fibrosis. Due to fear of side effects from long term use of steroids, many pulmonogists use Pirfenidone in order to avoid the progress into irreversible pulmonary fibrosis.
  • Few case reports show absorption of the interstitial abnormalities including reticulation, GGO and patchy consolidation, indicating the potential use of Pirfenidone as an effective medication for the post-inflammatory pulmonary fibrosis of COVID-19 patients.

CME INDIA Tail Piece:

  • The consequences of “steroid” avoidance – CT scan after 23 days of “supportive care” demonstrating the late fibroproliferative (irreversible) phase of COVID-19 lung disease (Courtsey: evms.edu/COVIDcare).
Post COVID fibrosis

Question which haunts today – had steroids been used timely in this case, such scary situation could have been prevented?

Answer is probably UNKNOWN.


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