Tag: long COVID

Steroids after Severe COVID Reduces One-year Mortality by 51%

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Researchers have shown that severe inflammation during hospitalisation for COVID increases post-recovery mortality risk by 61% – but this risk is reduced again by 51% if anti-inflammatory steroids are prescribed upon discharge. We need to think of COVID as a potentially chronic disease that requires long-term management, argue the authors, whose results are published in Frontiers in Medicine.

Evidence continues to gather that ‘long COVID’, that is, continued negative health impacts months after apparent recovery from severe COVID, is an important risk for some patients. For example, researchers showed last December that hospitalised patients who seemingly recovered from severe COVID run more than double the risk of dying within the next year, compared to those with only mild COVID or who never had COVID.

Now, the same research team shows that among patients hospitalised for COVID who seemingly recovered, severe systemic inflammation during their hospitalisation is a risk factor for death within one year.

“Here we show that the stronger the inflammation during the initial hospitalisation, the greater the probability that the patient will die within 12 months after seemingly ‘recovering’ from COVID.”

Professor Arch G Mainous III

“COVID is known to create inflammation, particularly during the first, acute episode. Our study is the first to examine the relationship between inflammation during hospitalisation for COVID and mortality after the patient has ‘recovered’,” said first author Professor Arch G Mainous III at the University of Florida Gainesville.

“Here we show that the stronger the inflammation during the initial hospitalisation, the greater the probability that the patient will die within 12 months after seemingly ‘recovering’ from COVID.”

Prof Mainous and colleagues analysed electronic health records of 1207 adults hospitalised with COVID in 2020 or 2021 within the University of Florida health system, with at least a one year follow-up after discharge. As a proxy for the severity of systemic inflammation during hospitalisation, they used a common and validated measure: C-reactive protein (CRP), secreted by the liver in response to a signal by active immune cells.

Widespread inflammation in the body

As expected, the blood concentration of CRP during hospitalisation was strongly correlated with the severity of COVID: 59.4mg/L for patients not needing supplemental oxygen, 126.9 mg/L for those who needed extra oxygen without mechanical ventilation, and 201.2 mg/L for the most severe cases, who required ventilation through a ventilator or through ECMO.

After correcting for risk factors, patients with the highest CRP concentration measured their during their hospital stay had a 61% greater risk of all-cause mortality within one year of discharge than patients with the lowest CRP concentration.

Prof Mainous said: “Many infectious diseases are accompanied by an increase in inflammation. Most times the inflammation is focused or specific to where the infection is. COVID is different because it creates inflammation in many places besides the airways, for example in the heart, brain, and kidneys. High degrees of inflammation can lead to tissue damage.”

Importantly, the authors showed that the increased all-cause mortality risk associated with severe inflammation was reduced again by 51% if the patient was prescribed anti-inflammatory steroids after their hospitalisation.

These results mean that the severity of inflammation during hospitalisation for COVID can predict the risk of subsequent serious health problems, including death, from ‘long COVID’. They also imply that current recommendations for best practice may need to be changed, to include more widespread prescription of orally taken steroids to COVID patients upon their discharge.

COVID as a chronic disease?

The authors propose that COVID should be seen as a potentially chronic disease.

“When someone has a cold or even pneumonia, we usually think of the illness being over once the patient recovers. This is different from a chronic disease, like congestive heart failure or diabetes, which continue to affect patients after an acute episode. We may similarly need to start thinking of COVID as having ongoing effects in many parts of the body after patients have recovered from the initial episode,” said Prof Mainous.

“Once we recognise the importance of ‘long Covid’ after seeming ‘recovery’, we need to focus on treatments to prevent later problems, such as strokes, brain dysfunction, and especially premature death.”

Source: Frontiers

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

About 30% of COVID Patients Develop Long COVID

Woman holding her chest
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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

Almost a Third of Older Adults Develop New Condition after COVID

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Almost a third of older adults infected with COVID in 2020 developed at least one new condition requiring medical attention in the months after initial infection, compared to only a fifth who were not infected, according to a study published by The BMJ.

Conditions involved a range of major organs and systems, including the heart, kidneys, lungs and liver as well as mental health complications. Some studies now examine the frequency and severity of sequelae after COVID infection, but few have described the excess risk of new conditions triggered by COVID infection in adults 65 and older.

Researchers used US health insurance records to identify 133 366 individuals aged 65 or older in 2020 who were diagnosed with COVID before 1 April 2020. Three (non-COVID) comparison groups were matched: from 2020, 2019, and a group diagnosed with viral lower respiratory tract illness.

The researchers then recorded any persistent or new conditions starting 21 days after a COVID diagnosis (the post-acute period) and calculated the excess risk for conditions triggered by COVID over several months based on age, race, sex, and whether patients were hospitalised with COVID.

The results show that among individuals diagnosed with COVID9 in 2020, 32% sought medical attention in the post-acute period for one or more new or persistent conditions, which was 11% higher than the 2020 comparison group.

Compared with the 2020 comparison group, COVID patients were at increased risk of developing a range of conditions including respiratory failure (an extra 7.55 per 100 people), fatigue (+5.66 per 100), high blood pressure (+4.43 per 100), and mental health diagnoses (+2.5 per 100). Similar findings were found for the 2019 comparison group.

However, compared with the group with viral lower respiratory tract illness, only respiratory failure, dementia, and fatigue showed increased risk differences of 2.39, 0.71, and 0.18 per 100 people with COVID, respectively.

Individuals hospitalised with COVID had a markedly increased risk for nearly all conditions. The risk of several conditions was also increased for men, for those of black race, and for those aged 75 and older.

Limitations include being an observational study – however, the authors warn that the number survivors with sequelae will continue to grow.

“These findings further highlight the wide range of important sequelae after acute infection with the SARS-CoV-2 virus,” they write. “Understanding the magnitude of risk for the most important clinical sequelae might enhance their diagnosis and the management of individuals with sequelae after acute SARS-CoV-2 infection.”

“Also, our results can help providers and other key stakeholders anticipate the scale of future health complications and improve planning for the use of healthcare resources,” they conclude.

Source: The BMJ

COVID is Turning Some Children into ‘Fussy Eaters’

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More and more children could be turning into ‘fussy eaters’ after a bout of COVID, according to smell experts at the University of East Anglia and Fifth Sense, a charity for people affected by smell and taste disorders.

This is because they may be suffering parosmia – a symptom where people experience strange and often unpleasant smell distortions. Once-loved foods like chicken may taste like petrol, for example, making it hard for children to eat those foods and maintain a healthy diet – or even take in enough calories to maintain their weight.

Together, Fifth Sense and leading smell expert Professor Carl Philpott from University of East Anglia, are launching guidance to help parents and healthcare professionals better recognise the disorder.

Prof Carl Philpott said: ”Parosmia is thought to be a product of having less smell receptors working which leads to only being able to pick up some of the components of a smell mixture. It’s a bit like Eric Morecambe famously said to Andre Previn – ‘it’s all the right notes but not necessarily in the right order’.

He said that as COVID swept through classrooms in the UK, there has been a growing awareness that it is affecting children too. “In many cases the condition is putting children off their food, and many may be finding it difficult to eat at all.

“It’s something that until now hasn’t really been recognised by medical professionals, who just think the kids are being difficult eaters without realising the underlying problem. For Prof Philpott, he is seeing teenage patients with parosmia for the first time in his career.

Fifth Sense Chair and founder Duncan Boak said: “We’re hearing anecdotal evidence that children are really struggling with their food after covid.

“If children are suffering smell distortions – and food smells and tastes disgusting – it’s going to be really hard for them to eat the foods they once loved.

“We’ve heard from some parents whose children are suffering nutritional problems and have lost weight, but doctors have put this down to just fussy eating. We’re really keen to share more information on this issue with the healthcare profession so they’re aware that there is a wider problem here.”

Together with Prof Philpott, Fifth Sense have put together guidance for parents and healthcare providers to help recognition and understanding of the problem.

The guidance shows that children should be listened to and believed. Parents can help by keeping a food diary noting those that are safe and those that are triggers.

“Establishing what the triggers are and what tastes ok is really important,” said Prof Philpott.

“There are lots of common triggers – for example cooking meat and onions or garlic and the smell of fresh coffee brewing, but these can vary from child to child.

“Parents and healthcare professionals should encourage children to try different foods with less strong flavours such as pasta, bananas, or mild cheese – to see what they can cope with or enjoy.

“Vanilla or flavour-free protein and vitamin milkshakes can help children get the nutrients they need without the taste. And it may sound obvious, but children could use a soft nose clip or hold their nose while eating to help them block out the flavours.”

Smell training’ has emerged as a simple and side-effect free treatment option for various causes of smell loss, and is a final option to consider.

Prof Philpott said: “Smell training involves sniffing at least four different odours – for example eucalyptus, lemon, rose, cinnamon, chocolate, coffee, or lavender – twice a day every day for several months.

“Children should use smells that they are familiar with and are not parosmia triggers. In younger children this might not be helpful, but in teenagers this might be something they can tolerate.”

Source: University of East Anglia

Over 50s Have Greater Risk of Reduced Mobility after COVID

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Adults over 50 with mild or moderate COVID have increased risk of worsening mobility and physical function, even if hospitalisation is not required to treat the virus, new research has found.

The study, published in JAMA Network Open, highlights the burden of COVID among middle-aged and older adults who are not hospitalised, and suggests that even those who experienced even mild COVID have lasting, troublesome symptoms.

Researchers surveyed more than 24 000 people over the age of 50 from across Canada during the initial phase of the lockdown in 2020 to determine the effect of a COVID diagnosis on their mobility. 

The team looked at mobility issues including difficulty getting up from sitting in a chair, ability to walk up and down stairs without assistance and walking two to three neighbourhood blocks, as well as changes in participants’ ability to move around the home, engage in housework and physical activity.

“We found that even those with mild and moderate illness due to COVID experienced adverse changes in mobility and physical function compared to individuals without COVID,” said co-author Professor Susan Kirkland.

“These findings are worth noting because they indicate that the negative effects of COVID are much broader and impact a wider range of older adults than those who are hospitalised for COVID.”

Participants with COVID had nearly double the odds of worsening mobility and physical function, although most had mild or moderate symptoms. Of the 2748 individuals with confirmed, probable or suspected COVID, 94% were not hospitalised.

Individuals with confirmed or probable COVID had double the odds of worsening ability to engage in household activities and participate in physical activity than those without COVID. Similar results were found for those with suspected COVID.

“Our results showed there was a higher risk for mobility problems in people who were older, had lower income, those with three or more chronic conditions, low physical activity and poorer nutrition,” said co-author, assistant professor Marla Beauchamp.

“However, those factors alone did not account for the mobility problems we observed among people with COVID. Rehabilitation strategies need to be developed for adults who avoid hospitalisation due to COVID but still need support to restore their mobility and physical function.”

The researchers concluded that there is a need to further understand the long-term impacts of COVID and consider “the development and implementation of effective intervention and management approaches to address any persistent deficits in mobility and functioning among those living in the community.”

Source: Dalhousie University

Long COVID in More Than Half of Survivors

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More than half of the 236 million people diagnosed with COVID around the world will experience ‘long COVID’ up to six months after recovering, according to Penn State College of Medicine researchers.

During their illnesses, many patients with COVID experience symptoms, such as tiredness, difficulty breathing, chest pain, sore joints and loss of taste or smell.

There have been few studies focussing on patients’ health after recovering from COVID. The researchers examined worldwide studies involving unvaccinated patients who recovered from COVID in order to understand the short and long term impacts of infection. The study found that both adults and children can experience several adverse health issues for six months or longer after recovering from COVID.

The researchers conducted a systematic review of 57 reports that included data from 250 351 unvaccinated adults and children who were diagnosed with COVID from December 2019 through March 2021. Among those studied, 79% were hospitalised, and most patients (79%) lived in high-income countries. Patients’ median age was 54, and 56% were male.

Patients’ health post-COVID was analysed during three intervals at one month (short-term), two to five months (intermediate-term) and six or more months (long-term).

Survivors were found to experience an array of residual health issues associated with COVID,.which generally affected a patient’s general well-being, their mobility or organ systems. Overall, half of survivors experienced long-term COVID manifestations, and these rates remained largely constant from one month through six or more months after their initial illness.

Several trends were observed among survivors, such as:

  • General well-being: More than half of all patients reported weight loss, fatigue, fever or pain.
  • Mobility: Roughly a fifth of survivors had a decrease in mobility.
  • Neurologic concerns: Nearly one quarter of survivors had difficulty concentrating.
  • Mental health disorders: Nearly a third of patients were diagnosed with generalised anxiety disorders.
  • Lung abnormalities: Six in ten survivors had chest imaging abnormality and more than a quarter of patients had difficulty breathing.
  • Cardiovascular issues: Chest pain and palpitations were among the commonly reported conditions.
  • Skin conditions: Nearly a fifth of patients experienced hair loss or rashes.
  • Digestive issues: Stomach pain, lack of appetite, diarrhoea and vomiting were among the commonly reported conditions.

“The burden of poor health in COVID survivors is overwhelming,” said co-lead investigator Dr Paddy Ssentongo, assistant professor at the Penn State Center for Neural Engineering. “Among these are the mental health disorders. One’s battle with COVID doesn’t end with recovery from the acute infection. Vaccination is our best ally to prevent getting sick from COVID and to reduce the chance of long-COVID even in the presence of a breakthrough infection.”

The mechanisms behind long COVID remain little understood. These symptoms could result from immune-system hyperactivation, lingering infection, reinfection or an increased production of tissue-attacking autoantibodies. SARS-CoV-2 can access, enter and live in the nervous system, resulting in commonly occurring nervous system symptoms such as taste or smell disorders, memory impairment and decreased attention and concentration commonly.

Dr Ssentongo noted that the study did not rule out other causes from the symptom besides COVID.

Early intervention will be crucial for improving the quality of life for many COVID survivors, and in the years ahead, health care providers will likely see an influx of patients with psychiatric and cognitive problems, such as depression, anxiety or post-traumatic stress disorder who were otherwise healthy before contracting COVID. Healthcare systems in low- and middle-income countries risked being overwhelmed with 

“Since survivors may not have the energy or resources to go back and forth to their health care providers, one-stop clinics will be critical to effectively and efficiently manage patients with long COVID,” Dr Ssentongo said. “Such clinics could reduce medical costs and optimise access to care, especially in populations with historically larger health care disparities.”

Source: Penn State

Micro Clots Explain Some Long COVID Symptoms

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Researchers at Stellenbosch University had discovered that an overload of inflammatory molecules, literally ‘trapped’ inside insoluble microscopic blood clots, might be behind some Long COVID symptoms.

From almost the beginning of the pandemic, blood clots have been reported in COVID patients in various organs besides the lungs.

Prof Resia Pretorius, a researcher at Stellenbosch University (SU), made this finding when she began examining micro clots and their molecular content in blood samples from individuals with Long COVID. The findings were reported in Cardiovascular Diabetology.

“We found high levels of various inflammatory molecules trapped in micro clots present in the blood of individuals with Long COVID. Some of the trapped molecules contain clotting proteins such as fibrinogen, as well as alpha(2)-antiplasmin,” Prof Pretorius explains.

Alpha(2)-antiplasmin prevents blood clot breakdown, while fibrinogen is the main clotting protein. Normally, the body’s plasmin-antiplasmin system maintains a fine balance between blood clotting and fibrinolysis.

With high levels of alpha(2)-antiplasmin in the blood of COVID patients and individuals suffering from Long COVID, the body’s ability to break down blood clots is inhibited.

Dr Maré Vlok, a senior analyst in the Mass Spectrometry Unit, noticed that the blood plasma samples from individuals with acute COVID and Long COVID continued to deposit insoluble pellets at the bottom of the tubes after dilution (a process called trypsinisation).

He alerted Prof Pretorius to this, which she then investigated further, using fluorescence microscopy and proteomics analysis. This marks the first reported detection micro clots in blood samples from those with Long COVID.
“Of particular interest is the simultaneous presence of persistent anomalous micro clots and a pathological fibrinolytic system,” they wrote. This implies that the plasmin and antiplasmin balance may be central to pathologies in Long COVID, and provides further evidence that COVID, and now Long COVID, have significant cardiovascular and clotting pathologies.

Further research is recommended into a regime of therapies to support clotting and fibrinolytic system function in individuals with lingering Long COVID symptoms.

Working with vascular internist and article co-author, Dr Jaco Laubscher from Mediclinic Stellenbosch, they now plan to perform the same analysis on a larger sample of patients. 

Source: Stellenbosch University

After Anti-vaxx Protest, Western Cape Government Speaks Out

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After a group of anti-vaxxer demonstrators gathered outside Groote Schuur Hospital (GSH), Western Cape Health authorities have slammed anti-vaxxers for inflaming vaccine hesitancy. Even so, there was a record vaccination turnout on Friday when inoculations were offered to over 18s.

“I just don’t understand why people don’t believe us when we say that the vaccines are safe,” Western Cape Health Department’s Dr Saadiq Kariem said, warning of the damage that misinformation can do.

“There’s no 3G in the vaccine. There’s certainly no conspiracy theory. All we’re trying to do is help by making sure that the population is as protected as possible against coronavirus,” Dr Kariem said, adding that it was even more dangerous when medical professionals were against the shots.

“It just baffles my mind how other medical professionals can, in fact, be anti-vaccination because people will believe professionals, you know, and take their word as they’ve studied this field,” he added. Some of the protesters were carrying signs in support of controversial anti-vaxxer doctors.

IOL reports that one man who was employed by the hospital and chose not to be named, stood alone in the street and faced down the protesters with a sign saying “Covidiots”. He said the pandemic had been happening for 18 months, and that the ignorance of the crowd was disgraceful.

Just before the protests got underway, the University of Cape Town had released a statement in support of GSH. “The Faculty stands in solidarity with the staff (including cleaners, security, admin staff, drivers etc) of GSH. We stand in support of their work and the herculean efforts they have taken across the era of this pandemic under extremely challenging circumstances and often at personal risk. We salute the work of our partners in delivering the best possible care in responding to the world’s greatest human tragedy.”

Source: Eyewitness News

Why COVID is So Hard to Treat

The SARS-CoV-2 coronavirus. Photo by CDC on Unsplash

A comprehensive review of what is so far known about the coronavirus its functions suggests the virus has a unique infectious profile, explaining why COVID is so difficult to treat and often leaves survivors with debilitating ‘long COVID’ symptoms.

In a review recently published in The Lancet Respiratory Medicine, the authors review what is currently known about COVID, and find that it works differently to most pathogens.   

Evidence increasingly points to the virus infecting both the upper and lower respiratory tracts. In contrast, ‘low pathogenic’ human coronavirus sub-species typically settle in the upper respiratory tract, causing cold-like symptoms, while ‘high pathogenic’ viruses, such as those that cause SARS and ARDS, typically settle in the lower respiratory tract.

Additionally, COVID has evolved a uniquely challenging set of characteristics as evidenced by more frequent multi-organ impacts, blood clots, and an unusual immune-inflammatory response not commonly associated with other similar viruses.

While animal and experimental models imply an overly aggressive immune-inflammation response is a key driver, it seems things work differently in humans: Although inflammation is a factor, it is a unique dysregulation of the immune response that causes our bodies to mismanage the way they fight the virus.

This could explain the ‘long COVID’ phenomenon that some people experience after infection, struggling with significant health issues months after infection. Long COVID is characterised by symptoms of fatigue, headache, difficulty breathing and loss of sense of smell. It is more likely with increasing age, body mass index and female sex

“The emergence of severe acute respiratory syndrome coronavirus two (SARS-CoV-2), which causes COVID-19, has resulted in a health crisis not witnessed since the 1918 Spanish flu pandemic. Tragically, millions around the world have died already,” said co-author Ignacio Martin-Loeches, Clinical Professor in Trinity College Dublin’s School of Medicine, and Consultant in Intensive Care Medicine at St James’s Hospital.

“Despite international focus on the virus, we are only just beginning to understand its intricacies. Based on growing evidence we propose that COVID-19 should be perceived as a new entity with a previously unknown infectious profile. It has its own characteristics and distinct pathophysiology and we need to be aware of this when treating people.

“That doesn’t mean we should abandon existing best-practice treatments that are based on our knowledge of other human coronaviruses, but an unbiased, gradual assembly of the key COVID-19 puzzle pieces for different patient cohorts—based on sex, age, ethnicity, pre-existing comorbidities—is what is needed to modify the existing treatment guidelines, subsequently providing the most adequate care to COVID-19 patients.”

Source: Medical Xpress

Journal information: Marcin F Osuchowski et al, The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity, The Lancet Respiratory Medicine (2021). DOI: 10.1016/S2213-2600(21)00218-6