HCFI Round Table Expert Zoom Meeting on Delta Plus Variant and third wave of COVID

HCFI Dr KK Aggarwal Research Fund

3rd July, 2021; 11am-12pm

Key points of HCFI Expert Round Table

  • India is currently in between waves. In North India, the second wave is almost over. A potential third wave looms large.
  • The coronavirus is a medium sized virus, but has the largest mRNA genome. The virus has 4 or 5 structural proteins (S, M, N, E and HE). Each of these structural proteins has a function to perform and is better understood today. The spike protein is crucial for receptor binding.
  • The SARS-CoV-2 binds 10-20 times more strongly to ACE2 receptors than the SARS-CoV. The concentration of ACE2 receptors is highest in type 2 alveolar cells followed by the bronchial epithelium, buccal epithelium, upper GI epithelium, myocardial cells, proximal tubule cells of the kidneys and bladder urothelial cells. It is now know that it also binds to the pancreatic beta cells.
  • Antibody dependent enhancement i.e. antibodies can create a backdoor enhancement for viral replication.
  • The delta variant is B.1.617.2, which is predominantly seen as a mutation in the spike protein.
  • Large number of cases in the UK and USA are delta variant.
  • The second wave in India had a geometric spike. As per the prediction SIR model, the wave should have continued for much longer, but there is a sudden decline in the number of cases i.e. a higher peak and a very sharp and precipitous decline. The reasons for this sudden fall in the cases are being explored. The second wave was predominantly driven by the delta variant.
  • New symptoms to watch out for in the second wave are nausea, abdominal pain, hearing impairment, vomiting, diarrhea, GI complications, joint pain, weakness, loss of appetite, skin rash, discoloration of finger and toes.
  • The second wave has not yet ended in the country; around 40,000 new daily cases are still being reported. Of these, around 10,000 are from Maharashtra, another 10,000 are from Kerala and the remaining 20,000 are from the North East, West Bengal, Orissa, Telangana, Andhra Pradesh and Tamil Nadu.
  • The three strains that emerged from genomic sequencing and which predominantly led the second wave are 617.1 (kappa variant), 617.2 (delta variant) and 617.3. The alpha variant was still present in Delhi, Punjab and Haryana.
  • A new variant, delta plus, has become a cause for concern and has been red flagged. Delta plus or AY.1 has a new K417N mutation, similar to the Beta variant (first found in South Africa). This mutation was mainly seen in UK and Nepal prior to being detected in India.
  • The first delta plus was in the UK, where it was found that it was more transmissible, had a tighter binding to the ACE2 receptor and escaped the monoclonal antibodies; it also caused immune escape.
  • Genomic sequencing labs in India documented around 41 cases of delta plus. Genomic sequencing is still ongoing. There were two deaths: one was not vaccinated, the second was >80 years with comorbidities.
  • These genomic samples were taken at the end of May, so the patients have survived for at least 4 weeks with mild to moderate disease; so far this variant does not appear to be sinister in nature.
  • No connection has been found between AY.1 strain found in Nepal and AY.1 strain found in Ratnagiri in Maharashtra (Mango belt).
  • The features of Delta variant are cluster spreading, faster spreading and faster recovery with low case mortality.
  • Delta is a cause for concern as it is rapidly transmissible and cluster spreading. It may be faster recovering but virulence is not known. Delta has immune escape mainly to Covishield.
  • Delta is now the predominant strain in the country; in Mumbai, Kappa strain is still present and in Punjab, the alpha strain is still found.
  • Early observation shows that delta plus is also fast spreading but probably not as fast as the delta variant.
  • Three challenges when unlocking: Keep the test positivity rate by RT PCR <5%, try to saturate 70% of population with vaccination and have zero tolerance for non adherence to Covid-appropriate behavior and Covid-appropriate protocol.
  • The second wave is not abating in some parts of the country because of the rapid unlocking.
  • Earlier we vaccinate, lesser will be the intensity of the next wave, if and when it comes.
  • The factors which may cause an outbreak are immune escape and lack of adherence to Covid-appropriate behavior.
  • To prevent this, make sure to double mask whenever in public, follow Covid-appropriate protocols, take both vaccine doses at the earliest, aggressive vaccination and have better ventilated environments. Avoid crowded and poorly ventilated spaces.
  • The third wave may come faster and the second wave may merge into the third wave, which is expected somewhere between September and November.
  • It appears that the disease is becoming endemic in Maharashtra and Kerala; hence, testing, tracking and treating strategy needs to be ramped up regularly.
  • Five states are contributing to 36% of cases in the country, with Kerala contributing the maximum.
  • Any modelling will take into consideration factors like how we unlock, how much is our susceptible pool (though serosurveys show 60-70% seroconversion; we do not know how long these antibodies will last for), how much of the population is following covid-appropriate behavior, how much percentage of population is immunized and the efficacy of the vaccines. How we manage the second wave will be the most important.
  • Covid-appropriate behavior and immunisation coverage will ultimately decide about the susceptible pool of the population.
  • Efforts are ongoing to educate about the management of children. IAP is closely involved in this.
  • Probably the third wave will not be as ferocious as the second wave, but we have to closely monitor the genetic variations. Genomic sequencing therefore becomes very important.
  • There is a need to be more transparent in sharing data between organisations.
  • Some punitive measure for non-adherence to Covid-appropriate behavior is required.
  • Issues such as the need for a booster dose and mixing of two vaccines are being discussed at the National Technical Advisory Group meetings.
  • Vaccination can prevent development of new variants.
  • The gold standard to detect neutralizing antibodies is the plaque reduction neutralization test (PRNT). It is done in special (BSL3) labs. N serology test is an indirect test; it is expensive and cannot be done as a routine. A test for T cell response is not yet available in routine practice.
  • Hybrid immunity is immunity due to natural infection, immunity due to vaccine and a combination of both.
  • Vaccines are protective; antibody tests may be misleading; antibody tests may not be sufficient; continue to wear the mask.
  • How we unlock and how strictly we follow Covid-appropriate behavior will decide about the next wave.

Participants

Dr AK Agarwal

Dr Shashank Joshi

Dr Suneela Garg

Dr Anita Chakravarti

Dr DR Rai

Dr Alex Thomas

Mrs Upasana Arora

Dr Yang Ing Woei

Mr Saurabh Aggarwal

Dr S Sharma

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