Topic: Looking back to move forward a Centennial of sharing world experiences

Speaker: Dr Monica Vasudev, Allergist & Clinical Immunologist, Fellow of American

Academy of Asthma, Allergy and Immunology, Advocate Aurora Health, Wisconsin, USA

5^th March, 2022, Saturday, 9.30am-11am

• There have been several publications describing the origin of the pandemic. A recent preprint publication which is a geospatial analysis that was conducted by researchers looking at the south western section of Huanan market where live animals were sold as recent as 2019. This area was seen as the potential epicenter of the outbreak. Researchers looked at the first covid-19 cases in China that were found during the WHO investigation from newspaper articles and audio-video recordings of doctors and patients in Wuhan. They found 156 cases in December 2019 that were tightly clustered around the market with cases gradually becoming more dispersed during January-February 2020. It is important to understand the origin so as to prevent and understand future pandemics that may arise.
• Analysis of the relationship between the four variants (the ancestral strain, alpha, delta and omicron) shows that the omicron has been the most infectious but the fatality rate is lower. It is always good to understand where are these viruses in relationship to the other viruses like bird flu, measles we have understood in our prior experience and in our training.
• We have also seen an incredible example of vaccination innovation. It took 10 months from having the sequence of SARS-CoV-2 to development of mRNA vaccine and completion of large-scale trials with 70,000 participants with no less than 95% efficacy against symptomatic infection in the time they were available. 
• The first Covid case was documented on December 1, 2019 and on December 11 the next year, phase Ia vaccination started for healthcare professionals.
• The Omicron cases rose sharply and then started going down except for Hong Kong, which is still showing an upward trajectory. Information relating to the pandemic is rapidly changing.
• Death toll in the US due to the pandemic is nearly one million.
• We have seen the appearance of vaccination as a way to address and to prevent the lives lost. Vaccines are effective in preventing severe illness, hospitalization and deaths. Vaccine (Pfizer-BioNTech) efficacy is high in children and teens, aged 5-17 years, who received two doses within 149 days after the second dose. The efficacy seems to drop after 150 days following the second dose.
• The efficacy of natural infection was recently examined in a seroepidemiological study published in the New England Journal of Medicine. It was a survey of 7000 individuals in Gauteng province of South Africa. This was before the Omicron variant outcompeted the delta strain. The study shows that 80% of those aged 50 years and older had antibodies against the virus with seropositivity that was likely generated by prior infection. The researchers thought that decoupling the incidences of Covid 19 cases with incidence of hospitalization and deaths during the Omicron wave heralded a turning point in the Covid-19 pandemic. 
• The primary goal is protection against severe disease and death rather than prevention of infection. 70% of the vaccine effectiveness against severe disease with Pfizer vaccines in South Africa might have been due to hybrid cell immunity induced by vaccination and natural infection. 
• When you have natural infection along with vaccine immunity, you get larger than expected immune response. This could result in 25-100 times higher antibody response drive by memory B cells and CD4 T cells and broader crossprotection from variants.
• Different types of vaccines are now available and in use today; mRNA vaccine from Pfizer and Moderna, inactivated vaccines from Sinopharm & Sinovac and AstraZeneca, the viral vector vaccine. Novavax is available in Australia and is up for EUA in the US.
• Multiple factors can increase or decrease the vaccine effectiveness at both the individual or population level. We have to understand the factors that either have made an improvement or had a negative effect on vaccine effectiveness on both either individual or community. Host factors, demographic factors, vaccine access factors, viral variant factors, immune factors can lead to change in vaccine effectiveness.
• Older age, immunocompromised or having underlying health conditions will have a negative impact on vaccine effectiveness. But with hybrid immunity, vaccine effectiveness will be better. Genetic polymorphisms can have positive or negative effect on effectiveness of the vaccine. If vaccine uptake is high in the community, then there is high level of herd immunity, which can have positive effect. But if there are people who live close together or have viral local surge, it can cause decline in vaccine effectiveness. Vaccine access factors (type of vaccine, number of doses, heterologous prime-boost, timing between the doses, limited access to vaccines) will limit the ability of the vaccine do its job. 

• If vaccine does not protect against antigenic determinants of virus then the vaccine is not going to be effective.  
• The burden of this pandemic has been tremendous. In the US, 140,000 children lost a primary or secondary caregiver due to the Covid-19 pandemic. We are going to face unprecedented downstream issues related to pandemic whether mental health whether restructuring our healthcare systems as a result of the pandemic.
• We are seeing a mental health epidemic during this pandemic. We have observed stress at a level unheard of before. As healthcare providers we need to take care of each other and acknowledge the fact that this is going to have an impact on us as we enter the next stage.
• As part of long Covid, people can have neurological and neuromuscular symptoms like headaches, tremors, muscle pain, joint pain; cluster of GI symptoms such as nausea, vomiting, diarrhea, systemic symptoms such as fatigue, weakness, neurocognitive memory fatigue, brain fog, psychological and social anxiety, upper respiratory (sore throat, nasal congestion), cardiopulmonary and others. All these systems have been affected in those hospitalized as well as those not hospitalized.
• A preprint publication in Cell looked at more specific details of long Covid, also known as post-acute sequelae of Covid-19. Patients who have associated comorbidities like type 2 diabetes had viremia (SARS-CoV-2 viremia, Epstein Barr viremia) and reactivation of latent viruses during the initial infection and autoantibodies.
• In terms of vaccination, the US is 67^th in the world for being fully vaccinated and 54^th in the world for receiving a booster dose. 
• In the US, we are moving to community levels that are now considered to be where we are safer. New guidance from the CDC related to this has classified counties as being low, medium, high based on hospital beds being used, hospital admissions and total number of new cases per 100,000 in that area in the previous week. If you live in a low-risk county, which is 90% of the country you can wear a mask based on your personal preference. If you live in a medium risk county, you discuss with your healthcare provider if you need to wear a mask and take additional precautions if you are immunocompromised or at high risk of severe illness. If you live in a high-risk county, you need to wear a well-fitted mask regardless of vaccination status or individual risk.
• In his State of the Union address, President Biden said that keeping businesses and schools open was a priority along with improving the access to testing and treatment using the approach of “test to treat”, which is to expand access to antiviral drugs and other covid-19 treatments and testing and treatment at the same place at local pharmacy clinics, community health centers, veterans’ health facilities and long-term care facilities. The strategy also includes wastewater surveillance program, genomic sequencing efforts, funding to get more vaccines, treatments. Long Covid and mental health is also a focus.
• The path to becoming endemic requires becoming endemic on individual level, epidemiological level and economic level. Individual level occurs when fluctuation in disease burden causes minimal change in peoples’ economic and social behavior. On epidemiological level, when Covid-19 is at a  predictable level and does not require society defining interventions. Economic when epidemiology decouples from economic activity and secondary economic impacts are largely resolved.
• It is important that we get a vaccine which is effective against different viruses. A panvirus vaccine could be the answer to prevent the next pandemic.
• Novavax has asked federal regulators for emergency use authorization for its new COVID-19 vaccine. Sanofi and GlaxoSmithKline have also requesting full approval for their COVID-19 vaccine. Both these vaccines use older technology than the mRNA vaccines currently in use. Hopefully, this can address vaccine hesitancy. They also do not require storage at very low temperatures. The new vaccines must also fulfil the needs of children under the age of 5 years for whom we do not have a vaccine and so remain a vulnerable population. 
• As we move forward, we need to learn from our experiences to produce better outcomes. 
• Hospitals dedicated to treating only COVID-19 patients appeared to yield better outcomes for them than other, mixed-use hospitals. The reason being the higher use of COVID-specific therapies that have been proven in clinical trials (JAMA Network Open).
• We should be able to get the resources consolidated so that we can quickly assemble them and quickly provide the best care possible to minimize the morbidity and mortality of any new variants or any new pandemics.
• We need to continue to repurpose existing therapeutics. Data from the UK Recovery trial showed that baricitinib used for rheumatoid arthritis patients reduced mortality risk in hosptialized Covid-19 patients by 13%. The patients took also other immunomodulators such as dexamethasone. 
• As we move from the pandemic to endemic, we need to protect the immunocompromised and vulnerable population. Such persons when they get infected have high viral load and the virus can evolve in them. They need to be included in clinical trials so that we have better information on how to protect them better.
• Evusheld (combination of tizagevimab and cilgavimab) for preexposure prophylaxis is highly prioritised and very difficult to obtain. We need more such drugs for the at-risk population.
• Telehealth needs to be expanded further to deliver healthcare services to patients without the need to be in the same physical location such as video chat via apps or webcams, phones or video conference software and improve user experience. Patients should be made aware of the process and use it for chronic care management and mental health. We need to continue to encourage the use of wearable technology 
• A survey undertaken by the New York Times found that a significant number of children missed several days of school in the month of January when the schools were open.
• We have to be able to make rapid testing and disease surveillance widely available and accessible.
• Currently in the US there are 45 FDA-approved antigen tests for use in healthcare facilities. Of these 17 have been approved for use at home. The sensitivity of antigen tests is 30-40% lower than that for RT PCR. Sensitivity is increased if the person is symptomatic.
• There is a need to expand genome sequencing. SARS-CoV-2 can adapt and is unpredictable. Variants will continue to emerge. 
• Global surveillance efforts can provide clues to changes and  which ones can be dangerous. We have to develop countermeasures in real-time, prioritise vaccine and treatment.
• We have to continue to fight misinformation. Evaluute the source of information, refer to trusted sources and share on social media only after verifying the source. We have to address the loss of trust in the advice of experts, including doctors and scientists. We have to provide the right science and guidance and be careful about the information we are sharing.
• Cases and deaths will continue to decline through the spring and summer, but we do not know how the immunity from vaccine/booster will wane.
• We need to be able to address the use and effectiveness and availability of Paxlovid and Molnupiravir. WHO updated its treatment guidelines on March3, 2022: “… Molnupiravir should be provided only to non-severe Covid-19 patients who have not received a Covid-19 vaccination, older people, people with immunodeficiencies and people living with chronic diseases.”
• We have to learn how to live with Covid-19 and limit the disease through effective use of vaccines, therapeutics, and other countermeasures. We need to have holistic set of health, economic and social goals to minimise the interruptions in our hospitals and schools and economy and prioritise the vulnerable people. and slow transmission through testing and environmental and workplace modifications.

Participants

Member National Medical Associations

Dr Yeh Woei Chong, Singapore, Chair of Council CMAAO

Dr Kar Koi Chai, Malaysia, Vice Chair Council CMAAO

Dr Alvin Yee-Shing Chan, Hong Kong, Treasurer, CMAAO

Dr Marthanda Pillai, India Member World Medical Council, Advisor CMAAO

Dr Wasiq Qazi, Pakistan, President-elect CMAAO

Dr Heidi Stensmyren, President, World Medical Association

Dr Ravi Naidu, Malaysia

Dr Mvuyisi Mzukwa, South Africa

Dr Akhtar Hussain, South Africa

Dr Qaiser Sajjad, Pakistan 

Dr Md Jamaluddin Chowdhury, Bangladesh 

Dr Muh-Yong Yen, Taiwan

Invitees

Dr Monica Vasudev, USA

Dr Brahm Vasudev, USA

Dr Tai Yuan Chiu, Taiwan

Dr Andrew Lim

Dr Chung mein Peng

Dr Vanessa Phua

Dr Pang Edward

Dr Brian Chang

Dr Carol Lim KC

Dr Manisha Kukreja

Dr Siang Hwa Djeng

Dr Cheng Jew Ping

Dr Grace Lee

Dr Lai Wee Lee

Dr Lim Mui Lee

Dr Patricia La’Brooyi

Dr Wah Seng Chin

Dr EC Ng

Dr Wong Meng Kong

Dr SG Liling

Dr SG Anne

Dr Gideon Ng

Dr Kee Leng Chee

Dr Meenakshi Bamalwa Soni

Dr Joshua Lim

Dr Fouzia Farah

Dr Yvonee See

Dr Zhangjie Zhang

Dr Colin Goldberg

Dr S Sharma, Editor IJCP Group

Moderator

Mr Saurabh Aggarwal