Why does Covid affect people differently?

After living with the virus for almost a year we know that Covid does affect people differently - but the reason why hasn't always been clear. 

At the beginning of the pandemic, health experts warned that those who were older and/or had underlying medical conditions were the ones most vulnerable to the virus. However as the months went by, survivors emerged to suggest that this wasn't the whole story.

Most recently, 113-year old Maria Branyas became the oldest person in Spain to contract Covid and come out the other side, surviving the deadly virus. Yet in March last year, 21-year old Chloe Middleton contracted coronavirus and passed away, after only previously suffering from mild asthma.

The situation only gets more bewildering after you realise that these aren't just one-off cases. Data shows that one in three people are asymptomatic and won't develop any Covid symptoms at all, while 5% of people become critically unwell. Most people are in the middle of this and develop mild coronavirus symptoms that fade after two to six weeks. However, there are also people being diagnosed with long-Covid every day.

Why does Covid affect people differently?

Age and underlying health conditions still have the biggest impact on why Covid-19 affects people differently, according to latest studies on the virus. However, this is mainly to do with how these two factors affect the health of our immune systems.

GP Sonal Shah says, "The answer is not fully known [as to why Covid affects people differently] and there are multiple theories as to why this. It is believed different responses by the immune system when exposed to SARS-CoV-2 virus may have a role, as well as genetics, lifestyle factors. These factors are currently being investigated by scientists all around the world."

While Dr Otto Yang from UCLA told the LA Times that it was impossible to know for sure, but "the big risk factors are diabetes, cardiovascular disease, chronic lung disease and age."

"I think of the immune system like the police and the virus like criminals," Dr Yang said. "If the criminals are easily brought under control, then the police don’t do much collateral damage to the city. But if there is an all-out war with equally matched sides, there is a lot of collateral damage. That’s what we are seeing in the sickest patients."

Age

Research shows that age is a huge factor in why Covid affects people differently. According to research published by Imperial College London, nearly one in five over-80s infected with coronavirus are likely to require hospitalisation, compared with around 1% of people under 30.

For the immune system to effectively combat SARS-CoV-2, the virus that causes Covid-19, it has to perform four essential tasks: recognising the threat, flagging the threat, destroying the threat and then clearing the threat from the body. Older people tend to make fewer cells that can recognise and handle the new infections once they enter the body, partially because ageing damages the cells in our airways, so they can't fight off the infections.

Essentially, each of these four vital processes are proven to become more dysfunctional the older we get and tend to differ a lot from person to person. For this reason, it's also more common for older people to suffer with additional viral illnesses on top of Covid-19 - such as the flu. Although, it's not known at the moment which of these four tasks is most necessary to prevent Covid-19 infection in this age group.

https://www.youtube.com/watch?v=YzpWyXkT6zg&list=PLvrp9iOILTQaJa78zFQ0QgvShQ2HEwHxP&index=45

People over 65 years old are also more likely to have existing health conditions (which themselves increase the risk of dying from coronavirus), including cardiovascular disease, some types of cancer and diabetes. Together with age, these conditions make for a dangerous combination and can drastically change whether someone experiences mild coronavirus symptoms or severe ones.

Underlying health conditions

Since the beginning of the pandemic, the NHS have warned that anyone with an underlying health condition will be more vulnerable to Covid-19. On their website, they list the people most at risk and the main feature of all the conditions is that it affects either the immune system or the respiratory system.

Those who've had an organ transplant, for example, have to remain on immunosuppressant drugs. People with cystic fibrosis have a condition that weakens their respiratory system already, meaning that they would experience Covid-19 significantly more severely than someone with entirely healthy breathing. However, this isn't just the case for severe conditions like these.

https://www.youtube.com/watch?v=SlBpfiPv1S0&list=PLvrp9iOILTQaJa78zFQ0QgvShQ2HEwHxP&index=46

Asthma, bronchitis, heart disease and diabetes are also on the list of conditions that make people more vulnerable to the virus - for exactly the same reasons.

Even pregnant people have been listed as a moderately at risk, which provoked concerns initially around the Covid-19 vaccine and pregnancy.

Pre-existing immunity

Technically, no one who hasn't had Covid-19 before should have immunity to it as it's a new virus. However, at least six studies suggest that 20% to 50% of people who haven't knowingly had the virus before have T-cells, which fight off known infections.

Since this information was revealed, it's been a puzzle for many scientists but there is one theory for why this might be.

“Our hypothesis, of course, was that it’s so called ‘common cold’ coronaviruses, because they’re closely related,” said Daniela Weiskopf, the senior author of a paper in Science that confirmed the hypothesis. “We have really shown that this is a true immune memory and it is derived in part from common cold viruses.”

This means that anyone who's developed T-cells from a cold or flu virus that even slightly resembles Covid could already have some protection from coronavirus. This would be one of the reasons that someone may have significantly less severe symptoms compared to someone else.

T-cells and antibodies are different elements of the body's immune response. Since the beginning of the pandemic, much research has gone into the latter because they're often cheaper and easier to study, according to immunologist Marcus Buggert at the Karolinska Institute. But T-cells offer a more promising picture of the pandemic and future immunity from Covid-19.

While antibodies from coronavirus have been proven to only last a few months, one study from Singapore found that T cells were present in patients 17 years after the infection. The study came from the SARS epidemic in 2002, but is very similar to the one we're experiencing now.

Genetics

The sheer differences in the way that people's bodies respond to Covid-19 led researchers at UCLA to look into whether people's genetics could play a role.

In particular, the team - led by human genetics professor Daniel Geschwind - are studying the common differences in genes that are shared between people related to each other and rare genetic mutations that have a big effect on health.

"The vast majority of young people can be exposed to the virus and seemingly develop no symptoms, and yet there are a handful of healthy 20- and 30-year-olds ending up in intensive care units on ventilators," said Dr Geschwind, "Likewise, we know age is a major, major factor, but we see some older people who get infected and do quite well."

Dr Manish Butte, professor of pediatric allergy, immunology and rheumatology, said that the team believe this could be because some people have a stronger immune system as a result of their genetics.

"Some viruses, like Ebola and measles, are very cytopathic or cytolytic, meaning they destroy the host's tissues," He said, "SARS-CoV-2 is only mildly cytolytic. When people die of COVID-19, they mostly die because their immune system became hyperactivated."

Not only does this explain why Covid does affect people differently but with this information in hand, they hope to develop a treatment.

"We could look at a patient's genetic data and then warn their physician that they need to watch out for a hyperactive immune response, and maybe administer a treatment to prevent this from happening," Dr Butte said.

Exposure to more viral load

There are some reports that severe cases of Covid-19 are caused by the person being exposed to a higher viral load, i.e. more of the virus particles. The critical cases of illness and death among healthcare workers has been attributed to this, especially earlier in the pandemic when personal protective equipment wasn't being fully utilised in the same way it is now.

Dr Shah says, "Scientists have seen from animal studies, epidemiological data and human challenge trials that the number of infectious viral particles to which people are exposed at the point of infection (the “inoculum”) correlated with severity of ensuing disease. Simply put, those people exposed to a higher viral load of SARS-CoV-2 19 have been shown to have more severe illness."

This contributes to why Covid does affect people differently, as anyone exposed to a smaller viral load could have less severe symtoms. It was certainly a theory that arose towards the beginning of the pandemic, as healthcare workers were caring for those testing positive for Covid-19 without totally effective personal protective equipment.

Gender

Although there's no difference between the rates of men and women contracting Covid-19, evidence suggests that men are more likely to die from contracting the virus than women. In fact, men make up 53% of hospitalisations, 68% of ICU admissions and 57% of deaths globally.

Much like the other reasons why Covid affects people differently, scientists only have minimal answers for this.

Some studies suggest that there are differences in immune responses between sexes, with women developing better antibodies after viral infection or vaccination. This has been largely attributed to sex hormones including oestrogen, progesterone and androgens, as well as genetic differences between the sexes.

The other two are lifestyle habits, so while they have been proven, they won't necessarily be applicable to every situation.

Men are likely to drink alcohol more than women, which weakens any standing immunity to the virus and also increases the chances of developing pneumonia. They're also more likely to smoke, which has been proven to be a very strong risk factor with Covid-19 and another habit that increases susceptibility to respiratory infections and pneumonia.

However, as vulnerability due to gender isn't considered a high risk factor by any major health organisation, there hasn't been significant amounts of research around it. Whether this is a factor contributing to why people experience Covid-19 differently has yet to be decided.

Variants

We already know that new Covid-19 variants are spreading around the world, with the Kent variant now dominant in the UK. New lockdown travel rules have been put in place as well to prevent others, such as the potent South African variant, from spreading too.

While studies into the variants are ongoing, some research suggests that some variants have the potential to be more deadly. Evidence from Public Health England, Imperial College London, the London School of Hygiene and Tropical Medicine and the University of Exeter has been assessed by the New and Emerging Respiratory Virus Threats Advisory Group (Nervtag) around this.

It led to the conclusion that there was a "realistic possibility" for the virus to become more deadly with these mutations, but it was far from certain.

Sir Patrick Vallance, the government's chief scientific adviser, urged caution about making conclusions on this when the news came to light in January. He said, "I want to stress that there's a lot of uncertainty around these numbers and we need more work to get a precise handle on it, but it obviously is a concern that this has an increase in mortality as well as an increase in transmissibility."

https://www.youtube.com/watch?v=4pWSMnpVT0M

Why do some people get long Covid and others don't?

Age, BMI, female sex and experiencing more than five of symptoms during the first week of illness have all been identified as risk factors for long Covid.

A new study from Kings College London discovered these after using data from 4182 people who had logged their symtoms on a tracker. Of these, 13% of people had symptoms lasting for more than 21 days, 5% had symptoms lasting for more than 8 weeks and 2% had symptoms for more than 12 weeks.

Age was one of the most severe risks, with cases of long Covid rising from 10% in 18 to 49 year olds to 22% in those aged over 70, with a clear rise in probability the older someone gets. Although, women aged between 50 and 60 years old were most likely to experience long Covid.

While other health conditions including those affecting the heart and kidneys, obesity and diabetes did play a role in increasing the risk of someone experiencing Covid-19, asthma was the only condition identified as posing a significant risk. This could be linked to the fact that dyspnoea (difficultly breathing) while testing positive with the virus was also shown to be significant predictor of long-term symptoms.

Any of these or a combination of more than one would explain why Covid does affect people differently.