Minutes of Virtual Meeting of CMAAO NMAs on “COVID-19 variants & Country Updates”

22^nd May, 2021, Saturday, 9.30am-10.30am

 

Participants: Member NMAs: Dr Yeh Woei Chong, Singapore Chair CMAAO, Dr Marthanda Pillai, India, Member World Medical Council, Dr Debora Cavalcanti, Brazil, Dr Marie Uzawa Urabe, Japan Medical Association, Dr Md Jamaluddin Chowdhury, Bangladesh Medical Association, Dr Salma Kundi, President, Pakistan Medical Association, Dr Qaiser Sajjad, Secretary General, Pakistan Medical Association, Dr Akhtar Husain, South African Medical Association, Dr Tony Bartone, Australia

Dr Shiv Prasad Shrestha, Nepal Medical Association

 

Invitee: Dr Russell D’Souza, Australia UNESCO Chair in Bioethics, Dr Monica Vasudev, USA, Mr Vivek Kumar, Dr S Sharma, Editor IJCP Group, Dr Meenakshi Soni Barnwal

 

Key points from the discussion

 

#1: Covid variants

Dr Monica Vasudev, Allergist Immunologist, Advocate Aurora Health, WI, USA

• The SARS-CoV-2 genome is made of about 30,000 letters (A, T, C and G) of RNA. The RNA produces four structural proteins: S (spike), E (envelope), M (membrane) and N (nucleocapsid). The S, E and M proteins form the viral envelope, while the N protein has the RNA. The virus attaches to the human cells by the spike protein.
• Viruses mutate at a much higher rate. They also replicate very rapidly in a very short period of time. Hence, mutants invariably develop.
• Mutants may be inferior to the original virus i.e. the mutations make the virus less able to replicate or spread from one host to another. Such strains die out. Or, the mutants may have selective advantage i.e. they infect more readily, replicate and also spread more easily. These variants are causing the surge in cases in certain areas.
• Mutations are changes in the genetic composition that occur naturally over time. Mutations cause variants.
• When variants of the same class develop different genome sequences due to mutation, they are called variants. They may either strengthen or weaken the virus.
• A distinct branch of viral classification is termed as part of a lineage.
• Clade means the different ways in which species of a virus relate to each other. It is used to track how the virus bounces around various geographical regions.
• Each variant mutation is named with letters and numbers. For e.g. D614G (earliest mutation that occurred in 2020 and is the most prevalent variant worldwide), N501Y, this mutation helps the virus to bind more tightly to human cells.
• Variant of interest: A variant with specific genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity (CDC).
• Variant of concern: A variant for which there is evidence of an increase in transmissibility, more severe disease (e.g.,  increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures (CDC).
• Variant of high consequence: A variant of high consequence has clear evidence that prevention measures or medical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants (CDC).
• There is evidence of impact on diagnostics, treatments or vaccines for variants of concern. They interfere with diagnostic test targets, decrease susceptibility to neutralising antibodies, reduce vaccine-induced protection from severe disease and increase resistance to treatment.
• The three variants of concern are B.1.1.7 (first found in the UK), B.1.351 (first found in South Africa), P.1 (first found in Brazil) and B.1.617 (first found in India).
• B.1.1.7 variant is 50% more transmissible and has spread to other countries. Many mutations in this variant are present in the gene that encodes for the spike protein.
• The Pfizer, Moderna, AstraZeneca and J&J vaccines appear to protect against B.1.1.7.
• The B.1.351 was first detected in October 2020 in South Africa. It is the predominant variant in South Africa now. Some mutations are similar to that seen in B.1.1.7.
• The P.1 strain was discovered in Brazil. It has at least two key mutations that may make the strain more transmissible and more able to reinfect. It has the potential to make vaccines less effective.
• The B.1.617 or the “double” variant was first detected in India in the state of Maharashtra in October last year. It is very contagious and is spreading very rapidly and may soon become the dominant variant in Europe. It shows potentially slightly reduced susceptibility to neutralising antibodies.
• Most antigen-based tests will continue to work with these variants as most test the N antigen of the virus, where there are fewer mutations. So far, the N antigen has remained conserved in these variants. However, efficacy of genome sequence testing is still unknown.
• 85.4% of diagnostic tests have targets other than the spike gene, so they should still be effective for these variants, and would not produce a “failed” test if the infection is caused by a variant with mutations in the spike gene. Of the remaining 14.6% of tests, 7.3% have multiple targets within the SARS-CoV-2 genome in addition to the spike gene, such as ORF1ab and N genes, so they should continue to yield accurate results; 90.1% of rapid antigen tests with EUA detect nucleocapsid protein, rather than spike protein, so they should be unaffected (Johns Hopkins).
• The percentage of cases that are being sequenced is very low. Hence, there is very little insight into emerging new variants.
• We still have a long to go to ensure equitable distribution of vaccines in terms of the number of population.
• The Novavax vaccine (NVX-CoV2373) was tested against B1.351 variant at 16 sites in South Africa in 4387 participants. Two doses of the vaccine or placebo were administered 21 days apart. The overall efficacy of the vaccine was 49.4% and the efficacy against the variant in HIV-negative subjects was 51%. The Novavax vaccine was efficacious against Covid-19, including the B.1.351 variant.
• The efficacy of Pfizer-BioNTech was found to be 75% against B.1.351; the efficacy against B.1.1.7 was 89.5% 14 days after the second dose. Efficacy against severe outcomes against any variant was 97.4% (NEJM).
• The Moderna trial evaluated three types of booster vaccines: B.1.351, multistrain version and its original vaccine. The single dose of 1273 and 1273.351 had increased neutralizing titers against the virus and two variants of concern (B.1.351, P.1). 1273.351 achieved higher titers against B.1.351 vs 1273. Both booster doses were generally well tolerated.

 

#2: Country Update

• Singapore Update:  The B.1.617 is a concern. Four generations of spread from the Changi Airport cluster have been seen in just 8 days. The index cases was detected on 4^th May, the second generation spread was estimated to be from May 3-7, the third generation spread was estimated to be between 8^th and 11^th May and the fourth generation spread between 10^th and 12^th May.
• Bangladesh Update: The country has the variant from India as well as South Africa. There are about 1400-1600 new cases every day. The country is under a lockdown but only educational institutes, public transport, markets are closed. Only about 50% people use masks. There is a shortage of vaccines in the country.
• India Update: the country is struggling with the second wave. More than 4 lakh new daily cases were recorded, though the numbers have started declining. Although the second wave had initially overwhelmed the healthcare system, the situation seems to be somewhat under control. Many states are under lockdown with different restrictions. The infection is spreading to the rural areas. Both vaccines in India (Covaxin and Covishield) appear to be effective against variants though confirmatory reports are awaited.
• Pakistan Update: The country is experiencing the third wave; in some parts of the country, the numbers are rising, whereas they are decreasing in other parts. More than 4000 cases were recorded in last 24 hours. Vaccines used are Sinopharm, AstraZeneca and Sputnik.
• Malaysia Update: More than 6000 cases were recorded in 24 hours. There is lockdown called the “movement control order (MCO)” although businesses are allowed to operate. Five cases of the variant found in India have been detected. The Government is planning a 21 day quarantine for travellers coming from India.
• Japan Update: Japan is currently in the midst of the fourth wave. The IOC has said that the Olympics will be held, which is a concern.
• Brazil Update: Two cases of B.1.617 have been detected. The vaccines used are Coronavac, Pfizer and AstraZeneca.
• South Africa Update: the country is experiencing the third wave. More than 3500 new cases are reported daily. People with comorbidities are more affected and their oxygen requirement is very early. The Pfizer vaccine is being used for the general public, but the vaccination is occurring at a slow pace.
• Australia Update: there are no community cases; there is some complacency and vaccine hesitancy. Poor logistics hampered vaccine rollout. There is battle between government zero tolerance strategy vs open up and back to normal living with the virus. The borders may be closed for much longer.