Medics affirm political will needed to see through new COVID outbreak

 Crowds holidaying in Nuwara Eliya  seem to be quite unconcerned about spreading COVID virus in the country
Pix by Ranjith Rajapaksha

• Medics opine that since Sri Lanka has chosen the strategy of “Dying with the virus” they opine it remains a better option to continue with AstraZeneca
•  Dr. Wijewickrama affirm that closing borders with the surge of COVID cases has to be a political decision
• We are at a crucial juncture because more young people are being infected and an ‘S drop’ is seen in PCR results and it could be that there is a new variant
• There were concerns about vaccinating pregnant women, but medical professionals advise in favour of getting vaccinated rather than contracting COVID during pregnancy
• Medics underscore that there’s an increase in the number of patients that require an oxygen supply

The epicentre of the COVID-19 pandemic is shifting. From China to Europe and now to neighboring India the virus is showing no mercy to its people. In Sri Lanka, even before the Sinhala and Hindu New Year festivities concluded the country experienced a surge in the number of COVID cases. With more cases being detected people fear whether the country has to experience another lockdown. Medical experts observe that this sudden outbreak was due to relaxed health protocols and warn countries to not put their guard down even if vaccination programmes are implemented. While Sri Lanka awaits its next consignment of vaccines, hopefully in early May, one only has to keep fingers crossed about being COVID negative now that the virus is airborne as mentioned by local medical experts. 

Border controls and proper vaccination strategies paramount 

Speaking to the Daily Mirror Dr. Ravindra Rannan-Eliya, International medical researcher and Director at Institute of Health Policy warned that in order to keep new, more infectious variants out, the first and main response must be to tighten border controls. “I pointed out months ago that Hong Kong and other countries even increased mandatory quarantine to 3 weeks in response to this problem, whilst the government here was relaxing quarantine for tourists. New variants increase the costs to the country during a border leak. The optimal level of border restrictions has to be a balance between risk and the cost of the restrictions. When new variants emerged globally—they are no longer isolated cases—the increased risk required a tightening of border controls.” said Dr. Rannan-Eliya.   

Intensive testing and isolation are the most effective intervention to control spread, and it damages the economy less than any other intervention. Sri Lanka can do isolation well, but until we increase testing and take it seriously that strength is useless”
Dr. Ravindra Rannan-Eliya

He further said that testing must continue and be increased regardless of how the vaccination programme progresses. “Our current vaccination strategy is reliant on AstraZeneca. Even if we vaccinate every adult with this vaccine (which is not going to happen in 2021), it is not good enough to achieve herd immunity if we have variants as infectious as the UK B117 variant. To do that, we need to be using a mix of Pfizer, Moderna and Sputnik. Since the global evidence indicates that more infectious variants are becoming commonplace, we have to plan for them. Intensive testing and isolation are the most effective intervention to control spread, and it damages the economy less than any other intervention. Sri Lanka can do isolation well, but until we increase testing and take it seriously that strength is useless. I have called for testing to be increased to 60,000/day to crush the current outbreak, and when we get to zero for testing to remain at 15-20,000/day indefinitely till the pandemic ends. My view remains unchanged and only confirmed by what we are now hearing,” he added.   

When asked about blood clots, Dr. Rannan-Eliya said that if Sri Lanka had crushed the Brandix outbreak and had zero local transmission, then the risk of death from vaccination would be greater than of dying from the virus. “This is basically why Australia has stopped the use of AstraZeneca. More Australians have died this year from the vaccine than from local transmission of the actual virus. If we had got to zero and we were maintaining tight border controls, my advice would have been to go for Pfizer or Sputnik, and wait it out till we get enough supplies to vaccinate everyone.   

“However, the Government decided not to go for zero and to “live with the virus”, or what I call “dying with the virus”. Under these circumstances, the risk of contracting the virus and dying are much higher for many age-groups than the risk of death from the vaccine. So since we have chosen the “dying with the virus” strategy, I think it still remains a better option to continue with AstraZeneca, since we don’t have any other options. However, I would restrict to 50 years or older as for younger people the vaccine may be more dangerous than the virus. That is now, and this may change if virus spread increases,” he added. 

 Chinese workers in Sri Lanka get their doses of the Sinopharm vaccine in Colombo (AFP) 

Sri Lanka at a crucial juncture 

In his presentation at an international webinar organised by the Sri Lanka Foundation on Sunday, April 25 Senior Consultant Physician at the Infectious Diseases Hospital (IDH) Dr. Ananda Wijewickrama gave an overview of how Sri Lanka managed COVID during its first and second waves. “But Sri Lanka exceeded 100,000 cases recently as a result of relaxed health protocols during the New Year season. We are at a crucial juncture because more young people are being infected and an ‘S drop’ is seen in PCR results and it could be that there is a new variant. However, we are awaiting further results on this regard.” said Dr. Ananda Wijewickrama.   

Dr. Wijewickrama then explained the delay in getting the second dose of vaccines for Sri Lanka. “The initial plan was to get the second dose at the end of four weeks. But then it was decided that it could be given in 12 weeks. Then with the emergence of cases with blood clots we decided to delay it to 16 weeks. Now the plan is to start from first week of May,” he said.   

But Sri Lanka exceeded 100,000 cases recently as a result of relaxed health protocols during the New Year season.  We are at a crucial juncture because more young people are being infected and an ‘S drop’ is seen in PCR results and it could be that there is a new variant
Dr. Ananda Wijewickrama

Responding to a query on closing borders with the surge of cases in India, Dr. Wijewickrama said that it has to be a political decision even though the answer is obvious from a public health point of view.   

He also said that there’s an increase in the number of patients that require an oxygen supply.   

Ever-changing variants

Shedding light on the variants Clinical and Public Health Virologist at the University of Hong Kong Prof. Malik Pieris reiterated the fact that viruses can replicate inside living cells and copy its genome. “For COVID it’s the RNA genome. There’s a spell-checking and proof reading mechanism in DNA viruses, but this is not so in RNA viruses. This is why they have a high rate of mutations. The initial D614G strain was detected from the Minuwangoda cluster as well. The South African variant B.1.351 had a single mutations. But some strains include E484K and N501Y mutations which arise independently as well.” said Prof. Pieris. 

 
He then highlighted on spike protein mutations and why it is important for these proteins to attach to the ACE2 receptors of cells. “The presence of antibodies block this attachment,” he explained further.   
“Even though there have been many variants in US, the new strain identified from India is known as a ‘double mutant’ even though it has multiple mutations. These mutations have been identified as L452R and E484Q. The latter is going to have an impact on neutralization. But there have been deletions in certain parts of the spike protein as well. However the virus may accumulate in immuno-compromised patients while the virus may try to find an escape from a partially immune population,” he said while adding that the different variants may possibly affect vaccine tests.   

Initial trials and errors 

Professor of Clinical Medicine at the University of Miami – Miller School of Medicine Prof. Dushyantha Jayaweera said, “most patients had extra pulmonary manifestations and the reality was that there was a significant mortality and morbidity rate. When this happened we panicked since we weren’t prepared for isolation. Even though it was a developed economy, we didn’t have swabs to collect samples and send to labs. People were all over the place and drug manufactures were trying to develop and repurpose drugs”.   

Even though there have been many variants in US, the new strain identified from India is known as a ‘double mutant’ even though it has multiple mutations. These mutations have been identified as L452R and E484Q. The latter is going to have an impact on neutralization
Prof. Malik Pieris

He went on to state that, “However we knew it was an RNA virus and subsequently Remdesivir, Favopiravir and Rebavirin were developed. Then there was an expansion of clinical trials from zero to 2800 in 18 months. Clinical trials were done on antiviral drugs to immuno-modulators, neutralizing agents and combinations. But the real tragedy was that most studies weren’t powered enough to obtain correct results. The main issue was funding. There wasn’t enough funding for investigators to increase the sample size. Only 5% of all studies had funding to continue studies and it was a wastage of resources. But we tried to come up with regimens, there were ideas that these may be theoretical possibilities, but they didn’t work from the beginning. This taught us that we couldn’t go by machine learning algorithms. On the other hand good ICU care services saved lives both in Sri Lanka and US”.   
But the administration of drugs had some limitations. “When it comes to corticosteroids they were used for ARDS. Mechanical ventilation had to increase for steroids to work. Therefore Dexamethasone was recommended. On the other hand Remdesivir was a nucleoside analogue and it worked only if people getting oxygen weren’t too sick. Convalescent plasma gave passive immunization with neutralizing antibodies. But here we had to get blood from people with high plasma rate. In fact a 1:320, 1:620 antibody titer was required in the plasma samples. But according to a study done by Amsterdam, it showed that infected patients already had immunizing antibodies in their plasma. US spent around USD 500 million giving convalescent plasma. Finally Remdesivir and Dexamethasone were approved.” said Prof. Jayaweera.   

Speaking about the Johnson and Johnson’s Janssen vaccine, Prof. Jayaweera said that around 8% patients had Cerebal Venous Sinus Thrombosis (CVST). “However it is a rare side effect, but due to this detection the study was paused. We also observed platelet factor 4 induced thrombocytopenia and for that we used non-heparin anticoagulants. But according to the latest update the Janssen vaccine has once again been given the approval so that inoculating patients can be resumed,” said Prof. Jayaweera.   

Multiple funeral pyres of victims of COVID-19 burn at a ground that has been converted into a crematorium for mass cremation in New Delhi, India. (AFP)

Vaccine types and efficacy

Speaking on the types of vaccines, safety and efficacy Consultant and Professor in Clinical Immunology and Allergy at Royal Free Hospital and University College London Centre for Immunodeficiency Prof. Suranjith L. Seneviratne said that coagulation is a big problem and that governments shouldn’t lose sight of it. “Four vaccines failed. Vaccines cannot be developed soon. Clinical trials are done in thousands, but vaccines are given in millions. In UK, around 33 million first doses have been given and many have gotten the second dose as well. In Israel around 119 doses per 100 people had been administered; the highest vaccination rate of any country worldwide. We also need to consider vaccine hesitancy because if people don’t get the vaccine there would be a problem in vaccine roll-out programmes.”   

In Israel around 119 doses per 100 people had been administered; the highest vaccination rate of any country worldwide. We also need to consider vaccine hesitancy because if people don’t get the vaccine there would be a problem in vaccine roll-out programmes
Prof. Suranjith 
L. Seneviratne

RNA viruses mutate rapidly and this is why there are several variants. “When talking about the vaccine landscape, efficacy was with regard to trials, but effectiveness is a real world issue. There are efficacious vaccines developed for emergency use. However there were incidents of blood clots when the AstraZeneca vaccine was given. There were also concerns about vaccinating pregnant women, but it is always advisable to get vaccinated rather than getting COVID during pregnancy.”   

The experts also discussed on the use of aspirin once the first dose of a vaccine is given. However they recommended against it due to lack of sufficient data. “Given the condition of thrombosis with thrombocytopenia, the intake of aspirin could affect the platelet count. In terms of Ivermectin, high doses are required to reach inhibitory levels and even to recommend it there needs to be an adequately powered study,” Prof. Jayaweera further opined.   

Administering the Russian manufactured Sputnik V vaccine in the absence of Phase III clinical trials, similar to the Sinopharm vaccine was also discussed. Adequate data needs to be published on safety and efficacy, prior to administering a vaccine to the masses. There was a problem with data with regard to AstraZeneca and Sinopharm vaccines. However all the experts stressed on the importance of continuing safety protocols even after the first dose is given.   

Most patients had extra pulmonary manifestations and the reality was that there was a significant mortality and morbidity rate. When this happened we panicked since we weren’t prepared for isolation. Even though it was a developed economy, we didn’t have swabs to collect samples and send to labs”- Professor of Clinical Medicine at the University of Miami – Miller School of Medicine
Prof. Dushyantha Jayaweera