Post-COVID Syndrome| Long-COVID

Now that we're a year and a half into the COVID19 pandemic we're beginning to have an understanding of the lasting long-term effects the disease has. Prolonged symptoms have colloquially been called long-COVID and those who are experiencing these symptoms are colloquially called "Long haulers." Long COVID may also be referred to as "long term COVID, chronic COVID or Post-COVID syndrome," as no official term has been established yet. 

Although the majority of patients with COVID-19 recover within weeks after being unwell, some people develop Post-COVID symptoms. 

The term 

Post-COVID Syndrome

 is an 

umbrella term used to basically denote any symptoms arising right after the COVID infection.

It's important to remember that research on COVID19 and its prolonged effects on the body have only just begun. And to date we cannot draw any firm conclusions on the long-term effects of the disease. The studies highlighted here represent only initial findings and should be taken with a grain of salt. 

To begin researchers are discovering that long-term complications from COVID19 are fairly common. In October of 2020, the United Kingdom's National Institute for Health Research announced 10 to 20% of people who contracted COVID19 continue to have symptoms or complications of COVID19 one month after diagnosis. 

One study in Italy suggested 87 of patients infected with COVID19 continued to have persistent symptoms 60 days after their initial symptoms began. With the rising number of people experiencing long-term covid19 symptoms, the British National Institute for health and Care Excellence also called NICE, has categorized 3 unique stages of COVID19 recovery: 

1. The Acute COVID19 stage is the period of recovery within 4 weeks after diagnosis.  
2. The Ongoing COVID19 stage lasts 4 to 12 weeks after diagnosis.  
3. The Long COVID19 stage lasts over 12 weeks after diagnosis.

Some of the symptoms include:

• Chest tightness
• Cough
• Shortness of breath
• Fatigue 
• Lack of concentration

Fatigue is the most common symptom that 

appears to continue to persist after covid19 infection. A study in Ireland found over half of all patients continued to have persistent symptoms of fatigue 10 weeks after initial diagnosis regardless of how severe their initial symptoms were.

Cardiopulmonary issues such as shortness of breath cough and chest pain are also common. A study in the United Kingdom found 60% of patients admitted to general medicine floors and 72% of intensive care patients had continuing shortness of breath four to eight weeks after hospital discharge. 

Similarly a Chinese study found over 50 of patients performed worse on spirometry pulmonary function tests 30 days after discharge from the hospital.

Some less common but equally or sometimes more debilitating symptoms are:

• Mobility challenges (muscle & joint pains) 
• Palpitations (fast heart beats) 
• Dizziness 
• tingling/pains in fingers and toes 
• Sensory loss (hearing, vision, smell, taste, numbness)
• Memory loss
• Cognitive impairment
• Hair loss
• Anxiety 
• Depression 
• Headache 
• Skin rashes

Causes of long-term symptoms:

It's not clear if these symptoms are a 

continuation of the initial COVID19 infection or if they are related to an entirely new yet separate Post-COVID19 syndrome. There are however a few hypotheses that have been proposed which could be contributing to the prolongation of COVID19 symptoms. 

1. IMMUNE SYSTEM RESPONSE:

Some people's immune systems may respond to COVID19 more strongly than others weaker immune responses to COVID19 might lead to symptoms lasting several months instead of several weeks. Weak immune response can be caused by advanced age, pre-existing health conditions that impact the immune system such as HIV or possibly immunomodulating drugs such as steroids. 

On the other hand some people's immune response may be too strong. Their immune systems may become too aggressive in trying to fight COVID19 and as a result may cause cellular damage to other organs leading to acute respiratory distress syndrome and systemic inflammatory response syndrome. 

There has been some evidence that severe cases of COVID19 have been in part caused by a sudden and massive release of cytokines called a "cytokine storm" leading to significant tissue inflammation and organ damage.

2. RE-INFECTION: 

Re-infection with COVID19 may also explain persistent symptoms of the disease. Overall, it is unclear why so many people continue to experience COVID19 symptoms beyond the acute phase of the illness and we may not have a clear understanding of this for a few years. 

While the cause of these continuing COVID19 symptoms remains a mystery and there are no COVID19 specific treatment recommendations after acute infection.

-> If you observe any of these symptoms, you should observe following points immediately:

• Speak to your doctor immediately 
• Take the prescribed medication
• Rest and hydrate sufficiently
• Practice social distancing
• Hand hygiene 
• Use masks diligently

CAN POST-COVID SYNDROME BE PREVENTED?

The only way to prevent Post-COVID syndrome is to avoid COVID. For this following measures are crucial:

• Maintain social distancing and avoid crowds
• Practice excellent hand hygiene
• Avoid touching your face/ keep your face clean
• Use masks correctly
• Get your COVID vaccination as soon as you are eligible

How were the COVID-19 vaccines developed in such a short period of time?

In the 20th century, most vaccines took well over a decade to research, test, and produce. But the vaccines for COVID-19 cleared the threshold for emergency use in less than 11 months.

The secret behind this speed is a medical technology that’s been developing for decades: the mRNA vaccine.

This new treatment uses our body’s existing cellular machinery to trigger an immune response, protecting us from viruses without ever experiencing an infection. And in the future, this approach might be able to treat new diseases almost as quickly as they emerge.

So how do these revolutionary vaccines work?

The key ingredient is in the name. mRNA, or messenger ribonucleic acid, is a naturally occurring molecule that encodes the instructions for producing proteins. When our cells process mRNA, a part of the cell called the ribosome translates and follows these instructions to build the encoded protein. 

The mRNA in these vaccines works in exactly the same way, but scientists use the molecule to safely introduce our body to a virus.

• First, researchers encode trillions of mRNA molecules with the instructions for a specific viral protein. This part of the virus is harmless by itself, but helpful for training our body’s immune response. 
• Then, they inject those molecules into a nanoparticle roughly 1,000 times smaller than the average cell. This nanoparticle is made of lipids, the same type of fatty material that forms the membrane around our cells. But these lipids have been specially engineered to protect the mRNA on its journey through the body and assist its entry into the cell.
• Lastly, the final ingredients are added: sugars and salt to help keep the nanoparticles intact until they reach their destination. 

Before use, the vaccine is kept at a temperature of -20 to -80 degrees Celsius to ensure none of the components break down. Once injected, the nanoparticles disperse and encounter cells. The lipid coating on each nanoparticle fuses with the lipid membrane of a cell and releases the mRNA to do its work. 

At this point, we should note that while the vaccine is delivering viral genetic material into our cells, it’s impossible for this material to alter our DNA. mRNA is a short-lived molecule that would need additional enzymes and chemical signals to even access our DNA. And none of these DNA altering components are present in mRNA vaccines.

Once inside the cell, the ribosome translates the mRNA’s instructions and begins assembling the viral protein. In COVID-19 vaccines, that protein is one of the spikes typically found on the virus’s surface. Without the rest of the virus this lone spike is not infectious, but it does trigger our immune response. 

Activating the immune system can be taxing on the body, resulting in brief fatigue, fever, and muscle soreness in some people. But this doesn’t mean the recipient is sick— it means the vaccine is working. The body is producing antibodies to fight that viral protein, that will then stick around to defend against future COVID-19 infections. And since this particular protein is likely to be found in most COVID variants, these antibodies should reduce the threat of catching new strains. This approach offers significant advantages over previous vaccines.

Traditional vaccines contain weakened versions of live viruses or amputated sections of a virus, both of which required time intensive research to prepare and unique chemical treatments to safely inject. But mRNA vaccines don’t actually contain any viral particles, so they don’t have to be built from scratch to safely adjust each virus. In fact, every mRNA vaccine could have roughly the same list of ingredients. 

Imagine a reliable, robustly tested vaccine that can treat any disease by swapping out a single component. To treat a new illness, researchers would identify the right viral protein, encode it into mRNA, and then swap that mRNA into the existing vaccine platform. This could make it possible to develop new vaccines in weeks, giving humanity a flexible new tool in the never-ending fight against disease.

Is Sinovac effective enough?| Which COVID vaccines are most effective?

The CoronaVac vaccine against Covid-19, produced by Chinese pharmaceutical firm SinoVac, has been approved for use in 39 countries around the world—with more than 1 billion doses already distributed. Yet, following a series of Covid-19 deaths among Indonesian healthcare workers that were fully vaccinated with SinoVac, Malaysia will stop using the vaccine, and some have called for Thailand to do the same. So the question is: 

Why are countries rejecting SinoVac? 

This blog will help you to go through the scientific literature to give you everything you need to know about SinoVac’s effectiveness. Specifically, It will help you to know what is known about: 

• How effective SinoVac is at preventing infection, hospitalization, and death? 
• How the effectiveness changes against variants, such as gamma or delta? 
• How quickly immunity drops after vaccination?  
• How SinoVac compares to other vaccines? 

And, as a bonus, here you will find a study that actually ranks vaccines for their effectiveness. Before looking at literature let's know: 

What kind of vaccine is SinoVac? Is it like other Covid  vaccines? 

SinoVac’s CoronaVac vaccine is an inactivated virus. This is the most conventional type of vaccine, using the same technology as the polio vaccine in the 1950s. 

Essentially, live SARS-CoV-2 virus was collected from infected patients in China at the beginning of the outbreak. Then, the virus was mass produced in monkey kidney cells, extracted, then treated with chemicals to inactivate it, rendering the virus unable to reproduce. 

This is different from almost all other Covid vaccines, including the mRNA vaccines from Pfizer and Moderna, as well as the viral vector vaccines from Astra Zeneca, Sputnik, and Johnson & Johnson, which all stimulate the in vivo production of viral spike proteins. Only Sinopharm and the Indian Bharat vaccines use the inactivated virus approach that is found in SinoVac.

So, does it work? & How is vaccine effectiveness actually measured?

Vaccine effectiveness cannot be determined from observed trends, like for example, if infections or hospitalizations drop in a city or country once a vaccine is administered in the population. That trend tells us nothing about the vaccine. This is because there is no way to isolate what factor caused that decline to occur—it may have been the vaccine, or it may have been several other factors unrelated to the vaccine. 

Instead, a study design needs to be able to measure both an outcome and a factor in each individual. The outcome is usually infection or hospitalization or death, and the factor would be whether that person has had a vaccine. The most reliable way to do this is with Phase 3 clinical trials—a type of study called a randomized placebo-controlled trial, where participants are randomly assigned into vaccine or placebo groups. 

However, effectiveness can also be determined outside of trials using real-world data through two other study types: retrospective test-negative case-control studies and prospective cohort studies. We’ll be looking at data on SinoVac from all three of these study designs.

So, let’s get into it.

SinoVac had Phase 3 trials registered in Brazil, Chile, Indonesia, and Turkey. However, only data out of Turkey was used in the phase 3 trial publication, which came out in The Lancet on July 8, 2021. 

The analysis included 10,029 participants, with 2/3 assigned to the vaccine and 1/3 assigned to a placebo. The results found that the vaccine was 83.5% effective at preventing symptomatic infection among fully vaccinated people. This number places it in the middle of vaccines for effectiveness based on phase 3 trial data alone. 

So, SinoVac reports a relatively high vaccine effectiveness from this phase 3 trial, but it’s based on a fairly narrow set of data. 

For a clearer answer, we need to look at studies with more data. 

A much better study comes out of Chile. It’s a cohort study, which means it looked at an entire population of people in this case, every adult in the national public health insurance program of Chile, which ultimately included data on 10.2 million people covering 3 months from February 2nd to May 1st, 2021. 

In that time, more than 4 million people received a SinoVac vaccine. And, overall, more than 218,000 people in the cohort got Covid-19, resulting in over 22,000 hospitalizations and 4000 deaths. 

So with this much richer dataset, what did they find? 

Among people fully vaccinated with SinoVac, they estimate the vaccine was: 

• 65.9% effective for preventing Covid-19, 
• 87.5% effective for preventing hospitalization, and 
• 86.3% effective for preventing death from Covid. 

So, with a much larger dataset we see that SinoVac’s actual vaccine effectiveness is probably about 66% for preventing symptomatic illness—a much lower number than the 83% reported from its published phase 3 trial. 

But could any of these difference be due to differences in variants? 

Other vaccines, including AstraZeneca and Pfizer, have reduced effectiveness among the variants alpha, beta, gamma, and delta. However, no such study has directly compared the effectiveness of SinoVac among different variants as of August. 

What we can do, however, is look at genomic sequencing data to see what variants were spreading throughout each study. For example, the phase 3 study in Turkey covered the period from September 2020 to March 2021.

Looking at genomic sequencing data out of Turkey, we see that D614G was circulating. This form of the virus predates Alpha, Beta, and all other variants and is close to the original wild-type virus out of Wuhan. 

On the other hand, the cohort study from Chile took place from February to May 2021. There, Lambda and Gamma were widely circulating. Using this information, we can see that variants may partly explain differences in the effectiveness estimates seen between Turkey and Chile. And, one more study out of Brazil shows how SinoVac did against Gamma.

In the study, which looked at the elderly in Sao Paolo, effectiveness of SinoVac against Gamma was: 

• 46.8% for infection, 
• 55.5% for hospitalization, and 
• 61.2% against death.

What we see is that SinoVac’s effectiveness against all outcomes drops with older age and with more virus mutations. 

But what about Delta? 

Researchers in Thailand collected blood samples from healthcare workers who had been fully vaccinated with SinoVac and then tested to see if antibodies in that blood could neutralize the virus, looking at the original viral strain, known as wild-type, and also with the variants alpha, beta, and delta. What they found was that antibodies from people vaccinated with SinoVac were very good at neutralizing wild-type SARS-CoV-2—able to do it about 98% of the time. 

This makes sense, since SinoVac is just an inactivated form of the wild-type virus. However, against alpha and beta, that neutralization rate dropped to 75 and 70%. Against, Delta, SinoVac antibodies could only neutralize the virus 48% of the time. So, SinoVac’s effectiveness is reduced against the current variants. 

But what about waning immunity in our bodies over time?

We know already that immunity requires time to develop. Even after receiving a full vaccine dose, the full immune response generally develops about two weeks later. 

But, what about after that? Once immunity does develop, how long does it last?

Researchers in both Brazil and China have shown that SinoVac’s antibody levels drop quickly. In Brazil, researchers looked at 133 healthcare workers that received two full doses of SinoVac and collected blood samples from them starting on the day of the first dose, then again at days 10, 20, 40, 60, and 110 days after the first dose. Then they measured levels of antibodies against SARS-CoV-2 proteins. After the first dose, virtually no antibodies developed. Then, about two weeks after the second dose, so 40 days after the first dose, antibodies peaked. Then, they steadily dropped. Antibody levels dropped in half about every 1 to 2 months. Even data from SinoVac itself confirms this drop. They found that after 6 months only 18% of people had neutralizing antibody levels considered sufficient for protection.

Now, the immune system has other tools beyond neutralizing antibodies, so this doesn’t mean a person’s immune system is completely helpless 6 months after vaccination with SinoVac. But, a major study in the journal ''Nature'' shows that neutralizing antibody levels are highly predictive of immune protection. 

So with that in mind, let’s rank the vaccines. Looking strictly at phase 3 trial data, SinoVac might appear to be somewhere in the middle of the pack among Covid vaccines. 

So who’s number one? 

According to the study, Moderna is the most effective Covid vaccine. Next is Novavax. Third is Pfizer. And fourth is Sputnik. Then, we start to drop down to the next tier of vaccines. At 5 we have Astra Zeneca. Behind that is Johnson & Johnson. And, coming in last is SinoVac.

So, what does all this mean? 

Because SinoVac has the lowest levels of neutralizing antibodies among widely used Covid vaccines, it is not an effective tool for creating herd immunity or preventing the spread of the coronavirus. That said, a SinoVac vaccine is still better than no vaccine when it comes to reducing risk of death and severe disease—at least for a short window of time. 

However, compared to other Covid vaccines, SinoVac and its cousin Sinopharm, are less effective at preventing death, especially against current variants like Delta. Thus, the logical policy would be to seek better alternatives—just like Malaysia has already done. 

However, experience thus far has shown that decisions to approve vaccines seem to be motivated more by geopolitical and financial interests, rather than on scientific data. Therefore, it’s up to citizens to keep pressure on their government officials to ensure transparency in vaccine agreements. One tool is the UNICEF vaccine market dashboard, which can be used to track vaccine agreements across the world.