LIVE BLOG: R&D response to COVID-19 pandemic (archived)

New research that is due to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in Lisbon, Portugal, 23-26 April, suggests the symptoms connected to long COVID could be different in people infected with different variants.

The study is by Michele Spinicci and colleagues from the University of Florence and Careggi University Hospital in Italy.

Estimates suggest that over half of survivors of SARS-CoV-2 infection experience long COVID. The condition can affect anyone, old and young, otherwise healthy, and those with underlying conditions. It has been seen in people who were hospitalised with COVID-19 and those with mild symptoms.

The researchers carried out a retrospective observational study of 428 patients treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2 and the Alpha variant were circulating in the population.

At least three-quarters of patients reported at least one persistent symptom.

Researchers compared the symptoms reported by patients infected between March and December 2020, when the original SARS-COV-2 was dominant, with those reported by patients infected between January and April 2021, when Alpha was the dominant variant and discovered a substantial change in the pattern of neurological and cognitive/emotional problems.

They found that when the Alpha variant was the dominant strain, the prevalence of muscle aches and pain, insomnia, brain fog and anxiety/depression significantly increased, while anosmia (loss of smell), dysgeusia (difficulty in swallowing), and impaired hearing were less common.

“Many of the symptoms reported in this study have been measured, but this is the first time they have been linked to different COVID-19 variants”, said Spinicci. “The long duration and broad range of symptoms reminds us that the problem is not going away, and we need to do more to support and protect these patients in the long term.”

Despite daily contact with COVID-19 patients early in the pandemic, some health professionals avoided falling ill. Now, a University of Gothenburg study has shown they were protected by immunoglobulin A (IgA) antibodies.

To understand how the immune system builds up its defences against COVID-19, researchers at the university’s Sahlgrenska Academy monitored 156 employees at five primary care health centres, for six months.

None of them had been vaccinated against COVID-19, and most of them met infected patients daily.

“We thought it was important to investigate what happened when completely healthy people encountered the coronavirus, before vaccines became available,” said Christine Wennerås, professor of clinical bacteriology at the Sahlgrenska.

Those staff who did not contract the disease had high levels of IgA in their respiratory tracts. These antibodies, found naturally in the secretions of mucous membranes in the airways and gastrointestinal tract, bind to viruses and neutralise them.

One in ten protected

The study showed that a third of the care workers developed antibodies to COVID-19. These subjects fell into two distinct groups, based on antibody patterns and COVID-19 incidence.

One group, who had IgA antibodies only, never succumbed to COVID-19, while the other group, which had IgG antibodies and T cells against SARS-CoV-2, did contract the infection.

“We all have IgA. It’s found on the mucous membranes, and COVID-19 is an infection that spreads via those membranes,” Wennerås said.

The study aimed to identify health factors that appeared to afford protection against COVID-19. Numerous factors were found by means of questionnaires, blood tests and more.

What all the subjects who neither tested positive, nor fell ill, had in common, were IgA antibodies.

A lot of the COVID-related research has focused on IgG antibodies and T cells, Wennerås noted. “The interesting thing is that when we now examine other people's articles and tables, we find evidence for the conclusion we’ve arrived at about IgA. But it’s not something those studies have highlighted,” said Wennerås.

Measuring blood oxygen levels at home with pulse oximeters is a safe way for people with COVID-19 to spot signs their health is deteriorating and they may need emergency care, according to new research.

It is known that a fall in blood oxygen levels is a critical indicator of severe COVID-19 infection. Now, a study led by Imperial College London’s Institute of Global Health Innovation, has provided the first extensive evidence review of the use of pulse oximeters in home monitoring for people with COVID-19.

It looked at 13 studies involving almost 3,000 participants across five countries, most of which were carried out during the first wave of the pandemic.

The review indicates that with medical guidance, home pulse oximetry can act as a safety net, reducing unnecessary emergency and hospital admissions for patients who can safely stay at home, while spotting early signs of deterioration and escalating care for those who need it.

However, there is a shortage of research on darker skinned patients, for whom oximetry may be less accurate than in white people.

Based on their findings, the researchers put forward recommendations to help standardise the use of oximetry in home COVID-19 monitoring.

This includes the use of a defined cut-off point in blood oxygen levels of 92%, at which professional care should be sought.

Ahmed Alboksmaty, research associate at the Institute of Global Health Innovation said, “Our study shows that people with COVID-19 can safely keep an eye on their blood oxygen levels at home using pulse oximetry. If their oxygen levels drop below a certain point, then this indicates that they need to seek professional medical care.”

Some smartphones and mobile apps also have the capability to measure blood oxygen levels. However, while a number of studies have reported similar accuracy to traditional pulse oximeters, the researchers concluded there is not enough evidence yet to recommend their use for clinical monitoring.

While the Omicron variant appears to be less harmful than previous variants in terms of severity of disease, hospitalisations and deaths, a virology expert told a special COVID-19 meeting of the European Congress of Clinical Microbiology & Infectious Diseases on Wednesday that the evidence so far shows that the period of infectiousness with Omicron is not convincingly shorter than with other variants.

Studies using culturable virus as a marker for infectiousness indicate people with the Omicron variant are infectious from around 2 days before symptoms appear, to 7 days after.

“The decisions being made by different countries around the world to shorten the period of isolation for Omicron infections are partly based on evidence from modelling, but also take account of the fact that Omicron is causing less severe disease, and fewer hospitalisations and deaths,” said Marjolein Irwin-Knoester of the University Medical Centre Groningen, Netherlands. “From the evidence so far, I am not convinced that a person is likely to be infectious for a shorter period of time with Omicron as they would have been with previous variants.”

At a recent time point - and with the situation ever-evolving - required isolation periods varied from four days in Norway and Denmark, to five days in the Netherlands and UK, seven days in Belgium, Spain and vaccinated people in France, to ten days in Germany and unvaccinated people in France.

The legal requirements to isolate have also changed in some jurisdictions. For example, in the UK, there is no longer a legal requirement to self-isolate with COVID-19, it is now just a recommendation.

While there is some evidence that vaccination decreases the time of shedding of infectious virus, the evidence around this subject is conflicting. However, for Omicron, the beneficial effect of vaccination on reducing infectiousness is likely to be lower, most probably due to mismatch between currently designed vaccines and the Omicron variant.

BioAge Labs, a biotech developing drugs that address the molecular causes of ageing, announced its clinical stage oral drug BGE-175, which targets age-related immune deficiencies, protects aged mice from lethal infection with SARS-CoV-2.

In the study, published in Nature, daily doses of BGE-175 prevented death in aged mice infected with a lethal dose of SARS-CoV-2. Ninety percent of mice that received the drug survived, whereas all untreated control mice died.

BGE-175 treatment was initiated two days after infection, when the mice were already ill, mirroring a situation in which a patient receives medication only after developing symptoms.

In both humans and animals, immune function declines with age, increasing the severity of COVID-19 in people over 65. Unlike antivirals for treating COVID-19, BGE-175 corrects these age-related immune deficits rather than targeting the virus.

The drug acts by inhibiting a protein which BioAge has identified as a key target for immune aging. Through this pathway, BGE-175 boosts dendritic cells that help the body identify pathogens and decreases neutrophil infiltration that leads to damaging inflammation, thus combating the decline in immunity that makes older people more vulnerable to infection.

A phase II clinical trial is underway in the US, Brazil, and Argentina to determine whether BGE-175 can prevent respiratory failure and mortality in patients over 50 years of age hospitalised with COVID-19.

A small study has shown that SARS-CoV-2 vaccination in patients who had an inflamed heart muscle (myocarditis) in the past is not associated with a recurrence of the condition or other serious side effects.

“These results provide reassuring data that may encourage patients with a history of myocarditis to get vaccinated against SARS-CoV-2,” said study author Iyad Abou Saleh of Hospices Civils de Lyon, France. “It should be noted that the majority of patients in our study received the [Pfizer/Biontech] vaccine and therefore the findings may not apply to other vaccines.”

Rare cases of myocarditis following SARS-CoV-2 vaccination have been reported in the scientific literature with a prevalence of 2.1 cases for 100,000 people. However, there is a lack of data regarding the risk of myocarditis recurrence after SARS-CoV-2 vaccination in patients with a history of the condition.

“Our experience shows that in some situations patients have avoided vaccination because they, or their GP, were afraid it could cause another bout of myocarditis,” Abou Saleh said.

The researchers included all patients hospitalised in Hospices Civils de Lyon during the last five years (from January 2016 to June 2021) with a diagnosis of acute myocarditis.

A total of 142 patients with a prior history of confirmed acute myocarditis were enrolled in the study. The average age was 31 years and 20.3% were women. Among them, vaccination status was known for 71 patients (50%): 55 patients were vaccinated and 16 were not vaccinated. The main reason given for not getting the vaccine was the fear of myocarditis recurrence (12 patients, 75% of non-vaccinated patients). Vaccination status was unknown for 66 patients and five patients had died before the COVID-19 outbreak.

“We showed that SARS-CoV-2 vaccination in patients with a history of acute myocarditis is not associated with a risk of recurrent myocarditis or other serious side effects,” said Abou Saleh.

A new study has shown that people who have had Covid-19 are at increased risk of developing type 2 diabetes.

This follows on from earlier research showing that the pancreas can be affected by SARS-CoV-2 and that following a COVID-19 infection, reduced numbers of insulin secretory granules in beta cells and impaired glucose-stimulated insulin secretion have been observed.

In addition, after COVID-19, some patients developed insulin resistance and had elevated blood glucose levels, even though they had no previous history of diabetes.

SARS-CoV-2 infection may lead to activation of the immune system that can persist for months, and which impairs insulin effectiveness.

To date, however, it was unclear whether these metabolic changes are transient or whether COVID-19 increases the risk of diabetes. To investigate this question, researchers from the German Diabetes Centre, the German Centre for Diabetes Research and the health data company IQVIA conducted a retrospective cohort study.

The study included 1,171 physician practices across Germany and ran from March 2020 to January 2021, covering 8.8 million patients. Follow-up continued until July 2021.

As a control group, the researchers selected people with acute upper respiratory tract infections (AURI), which are also frequently caused by viruses. The two cohorts were matched for sex, age, health insurance, month of COVID-19 or AURI diagnosis, and comorbidities (obesity, hypertension, high cholesterol, heart attack, stroke).

During the study period, 35,865 people were diagnosed with COVID-19 and the analysis showed they were more likely to go on to develop type 2 diabetes than people with AURI.

The incidence of diabetes with COVID-19 infection was 15.8 compared to 12.3 per 1,000 people per year with AURI, meaning that the relative risk of developing type 2 diabetes was 28% higher in the COVID-19 group than in the AURI group.
 

Seven in ten long COVID patients experience concentration and memory problems several months after the initial onset of their disease, with many performing worse than their peers on cognitive tests, according to new research from Cambridge University.

Half of the patients in the study reported difficulties in getting medical professionals to take their symptoms seriously, perhaps because cognitive symptoms do not get the same attention as lung problems or fatigue.

The findings are among the first results of an online study called ‘COVID and Cognition’ monitoring the symptoms of 181 long COVID patients over 18 months. The majority suffered COVID-19 at least six months before the study began. Very few people had been ill enough with COVID-19 to be hospitalised. A further 185 people who have not had COVID-19 are involved in the study as controls.

Of the 181 long COVID patients, 78% reported difficulty concentrating, 69% reported brain fog, 68% reported forgetfulness, and 60% reported problems finding the right word in speech.  These self-reported symptoms were reflected in significantly lower ability to remember words and pictures in cognitive tests.

Participants carried out multiple tasks to assess their decision-making and memory. These included remembering words in a list, and remembering which two images appeared together. The results revealed a consistent pattern of ongoing memory problems in those who had suffered COVID-19 infection. Problems were more pronounced in people whose overall ongoing symptoms were more severe.

People who experienced fatigue and neurological symptoms, like dizziness and headache, during their initial illness were more likely to have cognitive symptoms later on. They also found that those who were still experiencing neurological symptoms were particularly impaired on cognitive tests.

 “This is important evidence that when people say they’re having cognitive difficulties post-COVID, these are not necessarily the result of anxiety or depression. The effects are measurable; something concerning is happening,” said Muzaffer Kaser, a researcher in the Department of Psychiatry at Cambridge University and a consultant psychiatrist, who was involved in the research.

People with impaired immunity are at high risk of severe complications from COVID-19, but there is also uncertainty about the safety and effectiveness COVID-19 vaccines.

A new study in carried out in Italy has found the two mRNA-based vaccines are well tolerated by these high-risk patients. The trial found that the vaccines were safe and did not cause unexpected adverse events in a group of patients with various cancers, neurological, and rheumatological conditions that are associated with immunosuppression.

The original clinical trials for COVID-19 vaccines were conducted in healthy volunteers. While this is standard practice, it means that high-risk immunocompromised patients, such as those taking immunosuppressant drugs for neurological conditions, were not included in the trials.

The study enrolled 566 high-risk patients in the trial, and administered two doses of either the Pfizer-BioNTech or Moderna mRNA vaccine. The patients reported any adverse events in a questionnaire. 

The most common reported side-effects were also commonly reported by people with a fully functioning immune system who have received the vaccine. The study also found no evidence that the underlying disease of the patients was affected, and vaccination did not interfere with the patient’s ability to undergo standard treatment for their conditions.

The Omicron variant of SARS-CoV-2 can partially evade vaccine immunity, but a new study of 38 vaccinated individuals has shown that three leading vaccines still elicit antibodies that can bind to the virus.

The discovery suggests that vaccines can still protect against Omicron through immune mechanisms besides neutralising antibodies, potentially explaining the relative mildness of Omicron infections in vaccinated individuals.

Omicron rapidly became the dominant SARS-CoV-2 variant due to its very high transmissibility and its ability to infect people who have received vaccines. Although the virus can evade the neutralising antibodies elicited by vaccines, vaccinated individuals have a far lower chance of hospitalisation or death.

In addition, death rates haven’t climbed at the same rate as case counts during the rapid spread of Omicron worldwide, suggesting that vaccines may be providing protection through various immune mechanisms.

The researchers examined the binding activity of antibodies in plasma samples from 11 individuals who received the Moderna vaccine, 14 individuals who received the Pfizer vaccine, and 13 individuals who received the Chinese Sinovac vaccine.

Although many vaccine-induced antibodies failed to bind to the Omicron variant’s receptor binding domain, they still showed some ability to bind to the viral spike protein. Furthermore, non-neutralising antibodies that help activate the innate immune system could still bind to the spike protein across all 3 vaccines.