Category: COVID

South Africa on Cusp of Fifth Wave as Public Apathy Mounts

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South Africa is now on the cusp of a fifth wave, experts warn, as indicators rise and new variants begin to circulate. Social media monitoring indicates a level of public apathy.

After a period of reduced cases, cases rose for three consecutive days, prompting concern. Health Department deputy director-general, Nicholas Crisp, noted possible explanations.

“It may be associated with one of the sub-variants of Omicron, certainly that is what’s dominant at the moment but it also might be just because we are all a bit lax at the moment, we don’t wear our masks so diligently,” he said.

Crisp said that they would be watching the data closely, before pronouncing on whether this was indeed the start of the fifth wave.

“We are not sure if this is the variant that’s going to do whatever is going to happen in the fifth wave, what we are seeing at the moment is what we call a flare-up,” Crisp said.

Wastewater monitoring has seen an uptick in coronavirus levels, according to the NICD’s weekly brief [PDF]. The BA.4 and BA.5 Omicron variants have been observed but it is not clear what impact they will have on the fifth wave. The Delta variant has been sequenced in wastewater, but the significance of this is still unclear.

Gauteng has reported the highest weekly incidence at 27.4 per 100 000 people, followed by Western Cape (23.4 per 100 000), and KwaZulu-Natal (13.4 per 100 000). However, testing rates are down in a number of provinces. The highest incidence is among young teenagers.

As of 25 April, 1954 new cases with a 19.3% positivity rate were recorded by the NICD.

The Health Department’s Vaccine Social Listening progamme has seen a significant drop in engagement across social media, down by 50% on Twitter, 60% on Facebook. Engagements with digital news articles are down 70%. Fears over a fifth wave have been dismissed on social media as “fear mongering” and there is a belief that “covid-19 is over”.

Business Leadership South Africa chief executive Busi Mavuso said the fifth wave will test the government’s new COVID regulations.

Writing in her weekly open letter, Mavuso noted South Africa is currently in the 30 day transition period from the end of the state of disaster on 5 April and the new National Health Act regulations.

She noted some risk, with mistakes from earlier regulations being built upon. However, increased background immunity levels was credited with the reduced impact of the Omicron wave in hospitalisation and deaths. Based on the assumption that the new wave will be less impactful, economically damaging measures can be avoided.

Mavuso added that the previous waves have proven that the country can find the best balance in managing the pandemic and the economy if there is full consultation so that the consequences of regulations can be understood and planned for. “I look forward to engaging our public sector counterparts to find that balance.”

Wits University’s Professor Shabir Madhi said that with a clear increase in cases, the country was on the cusp of a resurgence. The country will however be much better positioned with higher immunity levels and a demonstrated decoupling of infections and disease severity.

Further lockdowns would likely be unnecessary, given how past lockdowns have repeatedly failed.

Long COVID May be Due to Suppressed Immune System

Man wearing mask with headache
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Scientists studying the effect of the monoclonal antibody Leronlimab on long COVID may have found a surprising clue to the baffling syndrome, one that contradicts their initial hypothesis. The cause may be down to an abnormally suppressed immune system, and not a persistently hyperactive one as they initially suspected.

The study was published in Clinical Infectious Diseases.

“While this was a small pilot study, it does suggest that some people with long COVID may actually have under-active immune systems after recovering from COVID, which means that boosting immunity in those individuals could be a treatment,” said senior author Professor Otto Yang.

COVID is known to be caused by hyperactive immune responses against SARS-CoV-2 resulting in damage to lungs and other organs, and sometimes a cytokine storm that overwhelms the individual, which could lead to severe illness and death.

For some who recover from COVID, various symptoms can persist for months, such as fatigue, mental haziness, and shortness of breath. Classified as long COVID, a limited understanding of the causes makes it difficult to develop treatments.

One suggested possibility is that persistence of immune hyperactivity after COVID is a major contributor. The researchers therefore ran a small exploratory trial of Leronlimab, an antibody that attaches to an immune receptor called CCR5 that is involved in inflammation, on 55 people with the syndrome. Leronlimab was originally being developed as an HIV treatment.

Participants were randomised to receiving either weekly injections of the antibody or a saline placebo for eight weeks, and changes in 24 symptoms associated with long COVID were tracked, including loss of smell and taste, muscle and joint pain, and brain fog.

Originally, the researchers believed that blocking CCR5 would calm an overactive immune system after COVID infection. Indeed, preliminary results from an earlier trial appeared to show an improvement with Leronlimab.

“But we found just the opposite,” Prof Yang said. “Patients who improved were those who started with low CCR5 on their T cells, suggesting their immune system was less active than normal, and levels of CCR5 actually increased in people who improved. This leads to the new hypothesis that long COVID in some persons is related to the immune system being suppressed and not hyperactive, and that while blocking its activity, the antibody can stabilize CCR5 expression on the cell surface leading to upregulation of other immune receptors or functions.”

The findings, the researchers wrote, “suggests a complex role for CCR5 in balancing inflammatory and anti-inflammatory effects, eg through T regulatory cells,” although the results need to be confirmed in a larger, more definitive study.

Source: University of California – Los Angeles Health Sciences

WHO Panel Recommends Paxlovid for at-Risk Mild COVID

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Pfizer’s oral antiviral Paxlovid (nirmatrelvir/ritonavir) is strongly recommended for patients with non-severe COVID with greater hospitalisation risk, such as unvaccinated, older, or immunosuppressed patients, according to a WHO Guideline Development Group writing in The BMJ

The experts explained that Pfizer’s Paxlovid, a comnbination of nirmatrelvir and ritonavir tablets, is likely a better choice for these patients because it may prevent more hospitalisations than the alternatives, is safer than molnupiravir, and is easier to administer than intravenous options such as remdesivir and antibody treatments. 

Use in low-risk patients is not recommended due to trivial benefits. It is also not recommended for patients with severe or critical COVID, as there are currently no trial data on nirmatrelvir/ritonavir for this group.

Their recommendation is based on new data from two randomised controlled trials with 3100 patients.

In these trials, moderate certainty evidence showed that nirmatrelvir/ritonavir reduced hospital admission (84 fewer admissions per 1000 patients), low certainty evidence suggested no important difference in mortality, and high certainty evidence suggested little or no risk of adverse effects leading to drug discontinuation.

Additionally, WHO also makes a conditional (weak) recommendation to use the antiviral drug remdesivir for patients with non-severe COVID at highest risk of hospitalisation.

This is based on new data from five randomised controlled trials involving 2700 patients and replaces a previous recommendation against treatment with remdesivir in all patients with covid-19 regardless of disease severity.

Antiviral drugs should be administered as early as possible, but this may be challenging in low- and middle-income countries, the panel noted, and also that access to these drugs is tied to COVID tests.

The emergence of resistance is also an uncertain risk, they add.

This guidance adds to previous conditional recommendations for the use of molnupiravir for high-risk patients with non-severe COVID and for the use of sotrovimab or casirivimab-imdevimab (monoclonal antibody treatments) in selected patients; and against the use of convalescent plasma, ivermectin and hydroxychloroquine in patients with COVID regardless of disease severity. For patients with severe COVID, WHO strongly recommends corticosteroids, with the addition of IL-6 receptor blockers or baricitinib.

Source: EurekAlert!

About 30% of COVID Patients Develop Long COVID

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A new study published in Journal of General Internal Medicine found that 30% of people treated for COVID developed ‘Long COVID’. Risk of Long COVID was greater in people with a history of hospitalisation, diabetes, and higher BMI; and less in organ transplant recipients and those not on private health insurance. Surprisingly, ethnicity, older age, and socioeconomic status were not linked to the syndrome despite the link to greater risk of severe illness and mortality.

Of the 309 people with long COVID studied, the most persistent symptoms were fatigue and shortness of breath (31% and 15%, respectively) in hospitalised persons, and loss of sense of smell (16%) in outpatients.

The incidence and risk factors of Long COVID, and even how to define the syndrome, have remained unclear throughout the pandemic. The researchers sought evaluate its association with demographics and clinical characteristics in order to devise the most effective treatments.

The study examined 1038 people enrolled in the UCLA COVID Ambulatory Program from April 2020 to February 2021. Of those, 309 developed Long COVID, determined by them reporting persistent symptoms on questionnaires 60 or 90 days after infection or hospitalisation.

Potential weaknesses in the study include the subjective nature of how patients rated their symptoms, the limited number of symptoms the researchers evaluated, and limited information about patients’ pre-existing conditions.

“This study illustrates the need to follow diverse patient populations longitudinally to understand the Long COVID disease trajectory and evaluate how individual factors such as pre-existing co-morbidities, sociodemographic factors, vaccination status and virus variant type affect type and persistence of Long COVID symptoms,” said Dr Sun Yoo, health sciences assistant clinical professor at UCLA. “Studying outcomes in a single health system can minimise variation in quality of medical care. Our study also raises questions such as: Why were patients with commercial insurance twice as likely to develop Long COVID than patients insured through Medicaid? Because persistent symptoms can be subjective in nature, we need better tools to accurately diagnose Long COVID and to differentiate it from exacerbations of other emerging or chronic conditions. Finally, we need to ensure equitable access to outpatient Long COVID care.”

Source: University of California – Los Angeles Health Sciences

Vigorous Exercise and Talking Produce Similar Levels of Aerosols

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Vigorous exercise produces a similar level of aerosol particles as speaking, but high-intensity exercise produces more, according to new research published in Communications Medicine. This is the first study to measure exhaled aerosols generated during exercise, to help inform the risk of airborne viral transmission of SARS-CoV-2 for gyms and indoor physical training.

Inhalation of infectious aerosol is considered to be the main route of SARS-CoV-2 transmission. In this study, researchers performed a series of experiments to measure the size and concentration of exhaled particles (up to 20µm diameter) which are generated in our respiratory tracts and breathed out, during vigorous and high-intensity exercise.

Using a cardiopulmonary exercise test, 25 healthy participants (13 male, 12 female) with a range of athletic abilities were recruited to undertake four different activities (breathing at rest, speaking at normal conversational volume, vigorous exercise and high-intensity exercise) on a cycle ergometer. Airflow and particles emitted were measured by particle counter. Experiments were carried out in an orthopaedic operating theatre — an environment with ‘zero aerosol background’, letting the researchers to unambiguously identify the aerosols generated by the participants.

The results showed that the size of airborne particles emitted during vigorous exercise was consistent with those emitted while breathing at rest. However, the rate of aerosol mass exhaled during vigorous exercise was found to be similar to speaking at a conversational volume.

Jonathan Reid, scientific lead on the paper, said: “COVID has profoundly impacted sports and exercise, and this study provides a comprehensive analysis of the mass emission rates of aerosol that can potentially carry infectious virus produced from an individual during exercise. Our research has shown that the likely amount of virus that someone can exhale in small aerosol particles when exercising is comparable to when someone speaks at a conversational volume.  The most effective way to reduce risk is to ensure spaces are appropriately ventilated to reduce the risk of airborne transmission.”

Source: University of Bristol

Kids are a Significant Source of COVID Spread in Households

COVID spreads extensively in households, with children being a significant source of that spread. These are the findings from an antibody surveillance study published in CMAJ Open, which also shows that about 50% of household members were infected from the first-infected individual during the study period.

Although kids were less likely to spread the virus compared to adults, children and adults were equally likely to become infected from the first-infected individual.

The antibody surveillance study included 695 participants from 180 households in the Canadian city of Ottawa in Ontario, between September 2020 and March 2021. Included households had at least one member having had a confirmed COVID infection and at least one child within their household.

“Our study was conducted when we were dealing with a less transmissible virus and pandemic restrictions were strongly in place, and we still had a 50% transmission rate within households. Flash forward to where we are today with an extremely transmissible variant of COVID and the majority of pandemic restrictions lifted; it’s safe to say transmission rates will be higher even though we have a high vaccination rate amongst those who are eligible,” said Dr Maala Bhatt, the study’s lead author. 

“I know many want to ‘live with COVID’ and abandon the layers of protection that were previously mandated, but it’s important to be aware of the high transmissibility of this virus in closed, indoor settings, such as schools,” she cautioned.  “Our most vulnerable and our youngest children who are not yet able to be vaccinated are still at risk for COVID infection.”

In the Canadian province of Eastern Ontario, where the study was done, COVID is on the rise once again. Three-quarters of all children admitted to CHEO with COVID have come during the Omicron wave. Since the beginning of January this year a third of the roughly 4900 monthly visits to the Emergency Department were for COVID-related symptoms.

The study hypothesised that children would act as “an even greater source of spread within households with the emergence of more infectious variants.” Children also have “considerable potential to spread” in settings such as school and daycare, where they congregate indoors for long periods, especially now when masking is not required in many jurisdictions.

“While we’re lucky hospitals aren’t currently overloaded, emergency departments are and positivity rates are on the rise, even amongst children,” said Dr Bhatt, paediatric emergency physician and Director of Emergency Medicine Research at CHEO and an Investigator at the CHEO Research Institute.

“We continue to learn more about COVID and its potential long-term health impacts, and we still aren’t clear about how long immunity lasts; these are all things researchers continue to study.”

Source: University of Ottawa

Rare COVID Vaccine Blood Clots May Result from Genetics

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Scientists have discovered that the rare blood clot side-effect associated with some COVID vaccines could be the result of a specific gene variant, which could make a genetic screening test possible.

Vaccine-induced thrombotic thrombocytopenia (VITT), a rare disorder causing thrombosis and thrombocytopenia (low blood platelet counts), was linked to AstraZeneca’s COVID vaccine in early 2021, leading some countries to pause or restrict its use. It is also associated with the Johnson & Johnson vaccine, which also uses a viral vector.

Now, a new study may help to explain what’s causing the rare side effect. The study by Flinders University and SA Pathology is now available on the medRxiv preprint server and is awaiting peer review.

Examining five unrelated individuals who all had the clotting complication after vaccination, the researchers found that all of the patients had unusually structured antibodies against a protein called platelet factor 4 (PF4), which is involved in blood clotting.

In addition, all five shared a specific version of a gene responsible for producing these antibodies.

“We knew previously that PF4 was directly involved in the clotting disorder, and we knew that aberrant antibodies against PF4 are responsible, but what we don’t know is how and why some people develop them,” explained lead author Dr Jing Jing Wang.

The antibodies were all found to be derived from the same amino acid sequence. The researchers then found that all of the patients carried a specific variant of one gene, called IGLV3-21*02, most commonly occurring in people of European descent.

“The other specific amino acid sequences of these antibodies from each patient were derived from separate basic sequences but had all evolved to carry very similar properties, making them very potent attackers of the PF4 protein,” explained research team leader Professor Tom Gordon.

“Together, this suggests that it is the combination of a variant in a gene and the evolution of this antibody towards targeting the PF4 protein in a destructive manner, which is leading to this harmful side-effect.”

Though why the antibody is found in such a tiny number of vaccine recipients remains unknown, the identification of the gene could enable a genetic screening tool to identify patients who are at risk of this severe complication.

“It also provides a unique opportunity for targeted, specific therapy development aimed at neutralising this highly damaging but very specific antibody,” said Dr Wang.

Source: Flinders University

Home Pulse Oximeters in COVID no Better Than Just Asking

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Self-measurement of oxygen levels with pulse oximeters is no better than just regularly asking patients with COVID if they are short of breath, according to new research published in the New England Journal of Medicine. Pulse oximeters have often been applied because of concerns that patients might not notice their blood oxygen levels sliding dangerously. 

However, people in Penn Medicine’s COVID Watch programme, which monitors patients recovering at home via automated text messaging, had the same outcomes whether they used oxygen-measuring devices or not.

“Compared to remotely monitoring shortness of breath with simple automated check-ins, we showed that the addition of pulse oximetry did not save more lives or keep more people out of the hospital,” said the study’s co-lead author, Anna Morgan, MD, medical director of the COVID Watch program and an assistant professor of General Internal Medicine. “And having a pulse oximeter didn’t even make patients feel less anxious.”

The COVID Watch was launched in March 2020 to remotely monitor COVID patients at home, with 28 500 people enrolled to date. Twice a day for two weeks, text messages were automatically sent to these patients asking how they felt and if they were having difficulty breathing. If patients indicated dyspnoea, the programme would alert a nurse to make contact and arrange care.

“The programme made it easy to identify the sickest patients who needed the hospital, and keep the others at home safely,” said David Asch, MD, executive director of the Center for Health Care Innovation and a professor of Medicine, Medical Ethics and Health Policy. “The programme was associated with a 68 percent reduction in mortality, saving a life approximately every three days during peak enrollment early in the pandemic.”

However it was not known if monitoring blood oxygen would help.

“Early in the pandemic, there was a prevalent theory that oxygen levels in the blood dropped before a COVID patient became symptomatic and short of breath,” said study co-lead author Kathleen Lee, MD. “Detecting this earlier with a home pulse oximeter might provide an opportunity to get patients who are on the cusp of deteriorating to the hospital faster and initiate time-sensitive therapies to improve outcomes.”

The use of pulse oximeters was so intuitively appealing that the process got adopted even before this trial, the first randomised trial to test whether it actually worked.

“Several health systems, and even states like Vermont and countries like the United Kingdom, have integrated pulse oximetry into the routine home management of patients with COVID, but there’s been scant evidence to show this strategy makes a difference,” said the research project’s principal investigator M. Kit Delgado, MD.

In this study, more than 2000 patients enrolled in COVID Watch between Nov. 29, 2020, and Feb. 5, 2021, were randomised to receive standard COVID Watch care or the same program with the addition of a pulse oximeter.

However, no statistical difference was seen in the main study measure, the average number of days enrolled patients spent alive and out of the hospital in the 30 days after they were enrolled. For patients with pulse oximeters, the measure was 29.4 days; for those without, it was 29.5, with no difference across racial liines. This was important as black patients are known to have had worse COVID outcomes and concerns had been raised about the accuracy of pulse oximeters in people with darker skin.
The researchers cautioned that the study focused on pulse oximeters in established programme of remote monitoring, and patients don’t have access to a system like COVID Watch or on-call clinicians, self-monitoring with pulse oximeters may still be a reasonable approach until there is evidence to the contrary.

“Overall, these findings suggest that a low-tech approach for remote monitoring systems based on symptoms is just as good as a more expensive one using additional devices. Automated text messaging is a great way for health systems to enable a small team of on-call nurses to manage large populations of patients with COVID,” said co-principal investigator, Krisda Chaiyachati, MD. “There are a lot of other medical conditions where the same kind of approach might really help.”

Source: University of Pennsylvania School of Medicine

Caesarean and Induced Deliveries Fell During Pandemic

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During the first few months of the COVID pandemic, premature births from caesarean and induced deliveries fell by 6.5% – and remained consistently lower throughout, according to research reported in the journal Pediatrics. This is likely a result of fewer prenatal visits due to lockdown and social distancing rules, the researchers suggested, and call into question how many such interventions are necessary.   

The study, the first to examine pandemic-era birth data at scale, raises questions about medical interventions in pregnancy and whether some decisions by doctors may result in unnecessary preterm deliveries, according to Assistant Professor Daniel Dench, the paper’s lead author.

“While much more research needs to be done, including understanding how these changes affected fetal deaths and how doctors triaged patient care by risk category during the pandemic, these are significant findings that should spark discussion in the medical community,” A/Prof Dench said.

In effect, the study begins to answer a question that never could have been resolved in a traditional experiment: What would happen to the rate of premature C-sections and induced deliveries if women didn’t see doctors as often, especially in person, during pregnancy?

Doing such a study would be unethical, but lockdown had a side effect of reducing prenatal care visits by more than a third, according to one analysis. That gave A/Prof Dench and colleagues an opportunity to evaluate the impacts, after all.

The researchers took records of nearly 39 million US births from 2010 to 2020, and compared them to expected premature births (born before 37 weeks) from March to December 2020. 

The researchers found that in March 2020, when lockdowns began in the US, preterm births from C-sections or induced deliveries immediately fell from the forecasted number by 0.4%. From March 2020 to December 2020, the number remained on average 0.35% below the predicted values. That translates to 350 fewer preterm C-sections and induced deliveries per 100 000 live births, or 10 000 fewer overall.

Before the pandemic, the number of preterm C-sections and induced deliveries had been rising. Spontaneous preterm births also fell by a small percentage in the first months of the pandemic, but much less than births involving those two factors. The number of full-term caesarean and induced deliveries increased.

“If you look at 1000 births in a single hospital, or even at 30 000 births across a hospital system, you wouldn’t be able to see the drop as clearly,” said A/Prof Dench. “The drop we detected is a huge change, but you might miss it in a small sample.”  

The researchers also corrected for seasonality, for example, preterm births are higher on average in February than in March, which helped them get a clearer picture of the data.

The research comes with caveats. Up to half of all preterm C-sections and induced deliveries are due to a ruptured membrane, which is a spontaneous cause. But in the data Dench and his team used, it’s impossible to distinguish these C-sections from the ones caused by doctors’ interventions. So, Dench and co-authors are seeking more detailed data to get a clearer picture of preterm deliveries.

Still, these findings are significant because the causes for preterm births are not always known.

“However, we know for certain that doctors’ interventions cause preterm delivery, and for good reason most of the time,” A/Prof Dench said. “So, when I saw the change in preterm births, I thought, if anything changed preterm delivery, it probably had to be some change in how doctors were treating patients.”

The researchers’ findings raise a critical question: Was the pre-pandemic level of doctor intervention necessary?

“It’s really about, how does this affect foetal health?” said A/Prof Dench. “Did doctors miss some false positives – did they just not deliver the babies that would have survived anyway? Or did they miss some babies that would die in the womb without intervention?”  

A/Prof Dench plans to use foetal death records from March 2020 to December 2020 to answer this question. If he finds no change in foetal deaths at the same time as the drop in preterm births, that could point to “false positives” in doctor intervention that can be avoided in the future. Learning which pregnancies required care during the pandemic and which ones didn’t could help doctors avoid unnecessary interventions in the future.  

“This is just the start of what I think will be an important line of research,” A/Prof Dench said.

Source: Georgia Institute of Technology

Increased Risk of DVT, Pulmonary Embolism, and Bleeding after COVID

3D illustration of a thrombus. Credit: Mecder, CC BY-SA 4.0, via Wikimedia Commons

There is an increased risk of developing deep vein thrombosis (DVT) for six months after a COVID, a study published in the BMJ suggests, as well as increased risk of pulmonary embolism and bleeding for shorter periods. The risk was particularly evelated for those with severe COVID as well as those infected during the first wave.

This highlights the importance of COVID vaccination, the researchers said. While there has been concern over the risk of blood clots after vaccination, the risk is far smaller, according to a large study last year.

It had previously been observed that people who had COVID had an increased risk of blood clots, and the researchers wanted to find out when that risk returns to normal levels.

The researchers tracked the health of just over one million people in Sweden who tested positive for COVID between February 2020 and May 2021 in Sweden, comparing them against four million people age- and sex-matched non-infected individuals.

Adjusting for confounding factors such as comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event, the researchers found an increased risk of:

  • first DVT, for up to three months
  • first pulmonary embolism, for up to six months
  • first bleeding event, such as a stroke, for up to two months

Comparing blood clot risk after COVID to the normal level of risk, the results showed that:

  • four in every 10 000 COVID patients developed DVT compared with one in every 10 000 non-infected individuals
  • about 17 in every 10,000 COVID patients had a blood clot in the lung compared with fewer than one in every 10,000  non-infected individuals

The authors wrote that the increased risk of blood clots was higher in the first wave than later waves, probably because treatments improved during the pandemic and older patients were starting to be vaccinated by the second wave.

Pulmonary embolism risk in people with severe COVID was 290 times greater than normal, and seven times higher than normal after mild COVID. However, there was no increase in bleeding risk in mild cases.

“For unvaccinated individuals, that’s a really good reason to get a vaccine – the risk is so much higher than the risk from vaccines,” said principal study investigator Anne-Marie Fors Connolly, from Umea University in Sweden.
While COVID’s causing the blood clots cannot be proven in this study, the researchers have a number of theories on the mechanism. It could be the direct effect of the virus on the layer of cells which line blood vessels, an exaggerated inflammatory response to the virus, or the body making blood clots at inappropriate times.

Though vaccines are very effective against severe COVID, but less so against infection, especially with the Omicron variant. This means repeat symptomatic infections are commonplace.

Source: BBC News