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

The third wave of Covid-19 is already spreading and turning into a tsunami, and, along with it a wave of knowledge and key observations and a wave of misinformation as well.

Frequently Asked Questions

This is an attempt by the author to answer some common questions about Omicron and third wave of Covid-19. The author has tried to compile all necessary information useful for the clinicians and common people.

The author thankfully acknowledges use of various sources like guidelines, personal clinical observations, clinical experience and opinions of other clinicians and leading national level Covid experts, personal views of some state and national task force members and CMEs conducted by various organizations, academic groups like CME India and offers due credit to them.

The views however remain personal and user discretion is advised. Views are subject to change as new scientific studies, data, guidelines and experiences are available.

1. Has the Third Wave Arrived?

• Of course, YES! It’s already all over and spreading with each blink!

2. Is the Third Wave Of Covid-19 – Omicron Variant A Hope, Hype Or Really Scary?

• HOPE– Not at all. As perceived and as per many articles it is a hope to wipe off covid completely! But not really. The next mutation might be a dangerous one!
• HYPE– Not at all. It is very real and at our doorsteps!
• SCARY– YES! Because of sheer numbers despite the disease being much less severe than Delta!

3. What Are Expected Numbers?

• Just huge! Pure geometric progression. Our peak of documented cases will be in between 10-15 lakh cases per day for ALL INDIA.
• It is said that for every confirmed patient, there can be 5-30 undiagnosed ones. So, one can imagine the total burden!

4. What Is R Value for Omicron?

• Secondary attack rate is very high. The R value for Omicron is 3.5. It means every patient of Omicron will transmit it successfully to other 3.5 individuals.
• The R value for Delta was just 1. So, if a family member is affected, in all probability all family members will turn positive. Not just family, the entire floor or the workplace may turn positive!

5. What About Incubation Period and Transmission?

• Incubation period is lower than previous variants. As low as 2 days! As inferred from history of probable exposure and development of symptoms. Consider it as 2-5 days.
• Transmissible period begins 1-2 days before becoming symptomatic and lasts up to 5-7 days after symptom onset.

6. What in Case of Full Vaccination or Previous Covid?

• Omicron escapes immunity conferred by vaccines or previous disease at large.
• That makes almost all population vulnerable! It is possible that the mildness of Omicron may be secondary to vaccination itself. The T cells may still be at work. Hence vaccination has to be valued and continued.

7. Is It All Omicron?

• At large YES! The speed of transmission, clinical pattern all point to Omicron.
• Genomic sequencing is done only in few cases to understand the trends. It’s a very resource sensitive test and cannot be done on all. We can assume that Omicron is rapidly taking over Delta and will eventually replace it or may have already replaced!

8. Is It a Mild Disease?

• So far, YES! Next 2 weeks will make the picture clearer.
• But the sheer numbers will make it equally or more challenging than previous waves.

9. What About Admission Rate and Mortality?

• Only 1-2% will need admission – as against 10% for Delta.
• Mortality is also very low. Actually, too early to comment. In some European countries, it is as low as 0.1-0.2%.
• Please keep in mind that there is a difference or lag of 10-14 days between first symptom/ diagnosis and mortality. So, while interpreting data especially of mortality, please remember that the number of deaths today are a result of infection 10-14 days back. Interpret accordingly.

10. Then Why at All to Test? And, Let It Spread So That Everyone Is Exposed and Gets Immune. Many Scientists Are Talking the Same and So Lot Many Articles!

• First part of the question – People with comorbidities and elderly are equally vulnerable for complications like previous variants. We need to care for them. Hence diagnosis becomes important for self-isolation purpose
• The Second part- Again, the number game! Simple mathematics than any science in this. Due to immune and vaccine escape, let us consider at least 100 crores of our population is susceptible out of 135 crores and is affected over next 2 months.
• Even 1 percent admission rate will translate into 1 crore admissions and 0.1 percent Mortality into 10 lakh deaths.
• These are over optimistic figures. Are we ready to accept above fact for the theoretical herd immunity it is supposed to provide? And what’s the chance that future variants will also be covered? Omicron itself escapes previously attained immunity!
• So better not to write off this variant! It’s too early to comment that it is very benign.
• Even if the admission rate and morbidity, mortality is close to Zero, which doesn’t look even a distant possibility, 100 crores falling sick within a short span is also not acceptable. Imagine the condition of our healthcare system!

11. How to Diagnose?

• Clinical suspicion – has to be very high. Don’t pass off as common cold.
• Rapid Antigen-60-70% sensitive. Positive is positive. Negative may not be negative.
• RT PCR-More sensitive test than RAT.

12. Is Genomic Analysis Needed?

• Not needed.
• It is not a routine test. It is impossible to test all samples for genomic analysis even though desirable.

13. How to Differentiate Between Omicron and Delta on Clinical Grounds?

Most important for clinicians. Symptoms pointing towards Omicron are as follows:

• Low incubation period.
• Fever usually high grade, sometimes mild-moderate, lasting not more than 3 days.
• Severe upper respiratory symptoms- Throat pain in particular is very classical and initial symptom. Difficulty or pain during swallowing.
• Many a times less of pain and more of irritation, itchy feeling in throat.
• COUGH with or without scanty/mucoid expectoration. We used to rule out Covid if patient presented with cough and expectoration during earlier waves!
• Change in voice – Laryngitis.
• Severe Headache, Backache, Myalgias, Sometimes Arthralgias- Same like Influenza or Dengue.
• Loss of smell and taste is usually not seen.
• Nausea, Anorexia, Dyspepsia, Eructation.
• Breathlessness or Chest pain are usually not seen.
• Overall, a typical flu like syndrome and an upper respiratory syndrome.

14. Any Atypical Presentations?

• Yes, sometimes only upper GI symptoms lasting for 3-5 days.
• Need to observe more and collect data!

15. How to Differentiate Between Omicron and Delta on Investigations?

Yes, we can get some clues from the RT PCR report and there are few other surrogate markers as well.

• RT PCR test uses segments of DNA as primers which bind to the genome of the virus and specifically amplify a genomic region.
• The test uses multiple such primers to detect multiple targets specific for the virus. In the first step, which is a screening step, usually E Gene band is tested [E is Envelope – All SARS-COV2 VIRUSES and all their variants/Mutants will have this Envelope and hence used as a screening test]. If this is positive confirmation has to be done by detecting one more target out of -N [Nuclear], S [Spike] , RdRP (RNA dependent RNA Polymerase ) and ORF1ab. If any one of the 3 is detected, the Presence of SARS COV2 in the given sample is confirmed.
• So, E positive, and either of N/S/RDRP positive means positive. Preferably 2 out of later 3 becomes more reliable. But to curtail costs usually one is tested.

What happens in omicron is that the spike protein is heavily mutated and hence the S gene band will not be detected in PCR by the S gene primer used. This is called as S gene target failure and is considered as one of the surrogate marker for omicron.

• If the lab doesn’t test for S gene, or doesn’t mention which confirmatory gene out of 3 were used, there is no way to interpret for S gene target failure. This is happening with most of the labs and most of the times making a clinician’s job difficult.
• AND IF ONLY E + S is tested, the test will be reported as negative despite being positive for Omicron due to S gene dropout. FALSE NEGATIVE.
• IDEALLY E + S + N o/ RdRP/ORFab has to be tested to pick up Omicron and avoid false negatives as well.
• Hopefully such protocol will be made mandatory by ICMR.
• Sometimes S GENE TARGET FAILURE can also be seen in DELTA, complication things further.

There are two other surrogate markers, although very crude.

• If the Anti-Spike antibodies in the concerned patient are tested and are found to be very low, it is an indirect pointer to Omicron. The reason is same – mutated spike protein. While in Delta, they will be high, especially in vaccinated.
• The CT value in RT PCR, which is now being given less importance, can be another but very crude surrogate marker. As Omicron is predominantly upper respiratory virus and the viral load is very high (both reasons making it highly infectious), the CT value in RT PCR is low. Usually below 20, below 15. CT means CYCLE THRESHOLD/ TIME – cycles of amplification needed to detect a target. Higher the viral load, lower is the CT value. In vaccinated people with Delta infection, CT values are usually above 20.

16. Why It Is Important to Differentiate Between Omicron and Delta?

• For the simple reason that disease course, complications and treatment vary a lot, especially for the milder version.

17. How to Evaluate Further?

• Need to hold our horses this time!
• Asymptomatic positive- No investigations needed.
• Mild patients- Baseline investigations like CBC, BSL, CREAT, SGPT make sense (so that further therapeutics if at all needed can be managed well) but are not mandatory!
• A CBC, CRP, and possibly D-DIMER on day 5-6 will be useful and reassuring. Not a strict recommendation. It has been observed that CRP/ D DIMER doesn’t rise in OMICRON, thus indicating that there’s not much of systemic inflammation.
• No much role of FERRITIN/ LDH/ IL-6 etc. Absolutely unnecessary for mild-moderate patients, sometimes even in critical ones! We have overused/ misused them in past.
• HRCT as a routine – NO.
• HRCT as a routine on DAY 1 – Big NO.
• HRCT as a routine for low risk, mild cases, anytime in the course of disease – NO.
• HRCT for very high-risk patients but mild/moderate disease -Can consider on day7/8 by proper case selection. Not for all.
• Immediate HRCT – for hypoxic, breathless patients.

18. How to Manage Asymptomatic Patients?

• Isolation and observation only.
• No investigations. No treatment.

19. How to Manage Mild Patients Without Any Risk Factors or Comorbidities?

• Symptomatic treatment only! Paracetamol SOS, anti-histamine cough Syp.
• No role of azithromycin/ doxy / ivermectin / vit c / zinc / antivirals/ monoclonal antibodies/ bronchodilators/ lmwh/ rivaroxaban/ aspirin etc.
• Vit D supplements in those deficient or likely to be deficient. No need to test.
• Inhaled budesonide 800 MCG BID x 5 days IF PERSISTENT COUGH beyond 3-5 days.

20. How to Manage Mild Patients with Risk Factors or Comorbidities?

• Symptomatic treatment as above.
• Plus, antivirals- molnupiravir – available in India.
• Paxlovid [nirmatrelvir+ritonavir] and sotrovimab [monoclonal antibody working against omicron] are better choice but still remain unavailable in India.

21. How to Manage Severe/ Hypoxic Patients?

• On same lines as DELTA.
• Admission / Oxygenation / Remdesivir/ Steroids/ Anticoagulation etc.

22. How to Use Molnupiravir?

• 30% risk reduction for severe disease and hospitalization- not very great!
• Only for high-risk cases! Not as a routine for all patients!
• Dose- 800 mg twice a day x 5 days only.
• Each capsule is 200 mg- so 4 caps twice a day.
• Contraindicated in pregnancy/ lactation/ under 18 years.
• Mutagenic but unlikely to cause malignancy in future with such short course.
• Causes cartilage damage in children.
• No dose adjustment needed for mild to moderate renal and hepatic impairment. Full dose to be taken if E-GFR >30.
• No major adverse effects otherwise.
• Will be replaced by Paxlovid and Sotrovimab once available.
• Till then use without hesitation wherever indicated and avoid indiscriminate use.

23. What About Antibody Cocktail Casirivimab-Imdevimab?

• Again, it is not useful in Omicron because it acts by binding to spike protein of the Virus which itself is mutated.
• As per CDC, mutations in the Monoclonal antibody binding site do not always result in loss of binding or neutralization.
• Do not use if your area is predominant Omicron and the clinical picture matches.
• Consider the surrogate markers.
• Please use if S gene target is detected- it is likely to be Delta.
• Can still use if your region is showing both Omicron and Delta and there is no way to discriminate, or the clinical picture and investigations point towards non- Omicron especially in very high-risk candidates.

24. Is Any Other Treatment Available in India or Western World?

• As discussed above, paxlovid and sotrovimab are available in western countries.
• REMDESIVIR can be used if patient doesn’t respond to MOLNUPIRAVIR within 3 days. Can be used even in non-hypoxic patients on day care basis for 3days. 200 mg on day 1, and 100 mg on day 2&3. Again, need to use very appropriately and on MERIT basis.

25. What Is the Best Preventive Strategy?

• Masking is the best policy.
• Double mask for general population – double surgical, or thick cotton mask outside and surgical inside.
• Proper use has to be encouraged.
• Good quality fit tested N95 mask with 100% uptime for health care workers.
• Social distancing should be encouraged but many times practically impossible. Social dismantling (lockdown) may be needed if healthcare systems collapse. Hope this stage won’t arise.
• Vaccination – has to be encouraged and continued without any ifs and buts. Maybe Omicron will remain a mild disease in those vaccinated and a cause of concern in unvaccinated!

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