CME INDIA Presentation by Dr Anand Malani, MD, Sangli (Maharashtra). Interest – Critical care/ Infectious diseases/ Rheumatology.

COVID PEARLS: From personal experience.

I will like to put up some observations from my experience in treating COVID, from myself and all my family members getting infected and two becoming critical.

I was pretty confident that being using adequate protective and preventive measures, I am not going to get it. I also used to give advice about the same to many, write articles about it, give interviews etc. And to my embarrassment it hit us quite hard and bad.

ABOUT INFECTION AND INFECTIVITY

• You are more likely to get COVID in non-hospital settings – at home, outside home, than in hospital settings.
• 100% fool proof preventive measures does not  exist.
• All are vulnerable.
• Kids are more likely to catch infection and bring it home.
• Infection in kids is asymptomatic or mildly symptomatic.
• CT values of RT PCR in kids are extremely low making them highly infectious.
• If a kid brings infection home, by virtue of their high infectivity, all family members will be affected in some time span. I mean secondary attack rate is almost 100%.
• Social distancing and use of masks at home sounds weird but essential. Sleep in separate rooms. No meals or tea/ coffee together. This will at least minimize secondary attack rate.
• Very high chance of getting infection from maids/ servants/ gardener etc. Standard operating procedures needs to be established for them.
• For social distancing 6 feet distance is minimally required and not 3 feet as claimed.
• Incubation period varies from 4-12 days. It was surprising to see incubation period of 12 days in an 85-year-old member who later went on to develop severest form of disease. So, a negative RT PCR done on 5th or 6th day doesn’t rule out infection. To repeat RT PCR on onset of symptoms or on day 10-11.

ABOUT VARIOUS MEDICATIONS

• Doxycycline – Ivermectin – Even though included in Indian guidelines, there is no great evidence. It is not recommended in Australian guidelines or CDC guidelines.
• Same is true about HCQS.
• Same is true about Favipiravir. Used only in clinical trial settings.
• Many people use quadruple therapy – combine above all – can be extremely dangerous.
• About Favipiravir – I have personally observed 2 types of responses – Responders and Non-responders. If no symptomatic relief in first 72 hours after initiation, it is likely that the patient is non-responder. Genetics needs to be studied for this observation. This observation is very important as non-responders may land up with complications.
• Favipiravir is usually well tolerated. Can cause hyperuricemia which is usually asymptomatic, and transaminitis which resolves on discontinuation.
• About Methylene blue – again nothing proved. Not in any guidelines national or international. Experience of few is very good. Actually, it acts finally on the bradykinin pathway. So, use of H1 and H2 blockers may have similar effect if not same. G6PD deficiency makes therapy ineffective. Those on psychiatric medications should avoid. Fatal serotonergic syndrome with SSRIs, SNRIs, & MAOIs. I won’t personally recommend. But no harm if no contraindications. Benefits not assured.

INTERVENTIONS AND MEDICINES WHICH WORK!

• The four things which surely work and reduce morbidity and mortality are Remdesivir, Steroids, LMWH and of course oxygen therapy with various devices.
• All other things including plasma therapy are in clinical trial settings and results are still not encouraging.

REMDESIVIR

• Remdesivir works well in moderate and severe cases. Relatively safe drug. Well tolerated by most of the patients.
• It is included in US / Australian / Indian guidelines as well. Indian guidelines recommend only in patients requiring oxygen. Now US FDA have recommended in all hospitalised patients irrespective of oxygenation status, means used even in non hypoxics.
• There should be no hesitation in using Remdesivir. I personally feel it should be used more freely and used in all moderate patients even without hypoxia.
• Rather waiting for hypoxia will delay therapy and response as well.
• Preferably the 5 days therapy should be completed by day 10 of symptoms. Means aim to begin on day 6 of disease with borderline indications. Of course, those with severe disease or hypoxia should receive at the earliest.
• It is now known that viral replication stops after day 9-10, hence antivirals don’t work beyond this. Personally, I have seen patients benefiting even beyond this period and even in cytokine storm. No harm in using even if no benefits. Don’t deny the potential benefits to a deserving patient just because theory says no benefit.
• Indications for using it as per my personal recommendation will be
• All severe cases by definition.
• All hypoxic patients or those requiring oxygen.
• All symptomatic patients, who remain symptomatic with cough, myalgias, fever, profound weakness beyond 5 days despite treatment with any of the used drugs, especially Favipiravir non-responders. These patients may be classified as mild to moderate as per guidelines and as per CT scan and Remdesivir is not indicated as per guidelines. I strongly differ over here and will recommend it. This intervention will prevent many patients from developing hypoxia and further needs. This may also prevent cytokine storms which I will discuss later.
• All patients in cytokine storm should receive it irrespective of disease duration.
• Even geriatric patients can be given if necessary. Age should not be a contraindication.
• All patients with worsening HRCT scores or x ray findings.
• All patients with HRCT scores above 13, irrespective of oxygenation levels.
• All patients with positive walk test.
• If one family member has needed Remdesivir, there is a high chance that others may need. We are not aware of the role played by genetics as of now, but it certainly needs to be studied. The same stands true for Favipiravir non-responders.
• Threshold for using Remdesivir should be low in high risk patients with comorbidities, toxic patients, and those with high markers.

STEROIDS

• Should be used in all patients receiving oxygen, and all patients on Remdesivir. That’s the top and bottom line.
• Dexamethasone 8 mg iv od or Methyl Prednisolone 1mg/kg iv bid should be used for 5-10 days.
• Hyperglycemia will be inevitable and should not preclude from using steroids. Even diabetics should receive in same doses. Glycemic control to be achieved by insulin.
• Avoid in mild cases. Viremia may aggravate.
• Antibiotic coverage is essential but not necessarily of very higher order. Simple oral antibiotics may also suffice. Policy differs from case to case basis.
• For all those with moderate and severe disease, a 3 week tapering doses of oral steroids should be used to prevent pulmonary fibrosis.

LOW MOLECULAR WEIGHT HEPARIN

• For all those with moderate and severe disease.
• For all those on Remdesivir / steroids/ oxygen.
• Enoxaparin 1mg/kg – od if moderate disease and d-dimer normal, bid if d-dimer high [> 2 times the upper limit of normal].
• At least 7 days – maximum 14 days.
• Watch for platelet count / bleeding.
• Dosing adjustments necessary in case of deranged LFT/RFT.
• For all severe cases, and even some moderate cases with high d-dimer values, a 6-week course of Novel oral anticoagulant agents like Dabigatran or Rivaroxaban should be used.
• Otherwise Aspirin 75/150 mg should be given.
• It will be dangerous to combine Steroids + Aspirin + Anticoagulants.

OXYGEN THERAPY

• Of course, for all patients with spo2 below or equal to 94.
• For those on home treatment make sure your pulse oximeter is of good quality. Wrong readings will cause lot of problems- over or under estimation of disease severity resulting in anxiety as well as risks.
• Usually fingertip pulse oximeters show saturation lower by 1-3% as compared with Nellcor probes of multipara monitors. But its better to err on safer side.
• Make sure to have a long oxygen delivery set. Patients can carry to the bathroom if in private room/ or use at bedside if in a ward/icu – of course for modest cases.
• Going to washrooms by removing oxygen support is too dangerous and will add to mortality. This is a common scenario at many hospitals due to scarcity of staff.
• Target SPO2 IS 91-92% and not 98-99%. Adjust oxygen accordingly.
• Oxygen requirement from 1-15 litres per min is low flow and can be given with routine flowmeters.
• Requirements above 15 lit per min are to be fulfilled with high flow oxygen equipment. The equipment needs a strong oxygen supply backup otherwise is of no use. If a patient is on 60 lit per min with 60% fio2 he will consume approx 30-35 litres of oxygen per min. A jumbo cylinder can deliver 7000 litres of oxygen. So, one cylinder will be exhausted in 3-4 hours.
• Of course, if HFNO is also not sufficient to achieve target saturation, then NIV should be considered. Results of invasive ventilation are still not very encouraging due to various medical and non-medical reasons.

ABOUT CYTOKINE STORM

• It’s the most dreaded complication and can be fatal.
• Occurs usually after 7 days, and up to 15 days. Some cases as late as 3 weeks reported.
• Can occur after apparent recovery from mild infection as well.
• High chances in moderate or severe infections.
• And its not uncommon!
• Diagnosis may be difficult if not suspected.
• Presents with increased symptoms, a new fever which is usually high grade, myalgias, increased cough, progressive respiratory distress and hypoxia.
• Can quickly aggravate – in a matter of hours.
• CT scan will show new lesions and increased scores
• Needs very prompt treatment in best possible set up.
• Any new worsening, new hypoxia, new CT lesions after 6-7 days should be considered as storm.
• Many patients who were all right with home treatment and who suddenly become sick and need admission are in storm unless proved otherwise. Aggravated viral pneumonia is also a possibility but more or less treatment will be same.
• Sudden increase in markers – especially CRP and IL6 are seen. These may be near normal or slightly elevated a day before and suddenly rise. So markers should be monitored frequently –may be every 3 days in all cases and sos.
• Ferritin and LDH are less specific.
• D dimer may not rise. Not very specific for storm.
• Needs aggressive treatment with Steroids, LMWH, Remdesivir, antibiotic cover, oxygen support with all possible levels of escalation including ventilator.
• Tocilizumab/ Itolizumab – Now these are not being used as they have failed in trials. But still compassionate use is recommended. Many have good personal experience with this.
• Need to do procalcitonin level to r/o bacterial infection. Sometimes just proceed without any investigations along with antibiotics. Time is the key. Please don’t waste time in blood culture. It doesn’t make sense to wait for 24-48 hours.
• Many a times patients improve in 24 hours!
• But very close observation and escalation of treatment at appropriate times required.

POST COVID RECOVERY

• It’s a long game for moderate to severe infection. Mild cases recover quite early.
• Profound weakness and fatigue, tachycardia on minimal exertion expected up to 3-4 weeks. No specific treatment for same.
• Weight loss expected.
• New diabetes/ Hyperglycemia due to steroids expected. To be treated with insulin preferably.
• Graduated exercise and low volume spirometry/ pranayama should be carried out.
• Resuming work may take time. Better not to hurry otherwise may land up in chronic fatigue syndrome.
• Be watchful for delayed complications especially thrombotic.
• Get an ECG/ ECHO done.
• Be careful and loyal to medication schedule. Watch for adverse effects.

INTERNATIONAL GUIDELINES

We all know and follow Indian Guidelines. Have a look at US and Australian guidelines too!

USA:

https://files.COVID19treatmentguidelines.nih.gov/gui delines/COVID19treatmentguidelines.pdf

Australia:

https://COVID19evidence.net.au/#living-guidelines

SANGLI – IS IT DIFFERENT? FEW QUESTIONS TO PONDER!

• Large number of cases suddenly exploding.
• All over ratio of mild/moderate/severe case per 100 patients is 85/10/5.
• I personally feel it is skewed for Sangli – may be 65-70 are mild and all others are moderate to severe. A proper statistical analysis required.
• I also find the disease is also more severe, more storms and more deaths. Secondary attack rate is also very high.
• Is it time to study the virus for mutations?
• And our people, still enjoying freedom and failing us repeatedly! Can someone talk to them?

STAY SAFE – ALWAYS

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