Vitamin D Determines Severity in COVID-19: Researchers Urge Government to Change Advice

Researchers from Trinity College Dublin are calling on the government in Ireland to change recommendations for vitamin D supplements.

A new publication from Dr. Eamon Laird and Professor Rose Anne Kenny, School of Medicine, and the Irish Longitudinal Study on Ageing (TILDA), in collaboration with Professor Jon Rhodes at University of Liverpool, highlights the association between vitamin D levels and mortality from COVID-19.

The authors of the article, just published in the Irish Medical Journal, analyzed all European adult population studies, completed since 1999, which measured vitamin D and compared vitamin D and death rates from COVID-19.

Vitamin D is produced in the skin from UVB sunlight exposure and is transported to the liver and then the kidney where it is changed into an active hormone that increases calcium transport from food in the gut and ensures calcium is adequate to keep the skeleton strong and free of osteoporosis.
But vitamin D can also support the immune system through a number of immune pathways involved in fighting SARS-CoV-2. Many recent studies confirm the pivotal role of vitamin D in viral infections.

This study shows that, counter intuitively, countries at lower latitude and typically sunny countries, such as Spain and Northern Italy, had low concentrations of vitamin D and high rates of vitamin D deficiency. These countries also experienced the highest infection and death rates in Europe.

The northern latitude countries of Norway, Finland, and Sweden, have higher vitamin D levels despite less UVB sunlight exposure, because supplementation and fortification of foods is more common. These Nordic countries have lower COVID-19 infection and death rates. The correlation between low vitamin D levels and death from COVID-19 is statistically significant.

The authors propose that, whereas optimizing vitamin D levels will certainly benefit bone and muscle health, the data suggests that it is also likely to reduce serious COVID-19 complications. This may be because vitamin D is important in regulation and suppression of the inflammatory cytokine response, which causes the severe consequences of COVID-19 and ‘acute respiratory distress syndrome’ associated with ventilation and death.

Professor Rose Anne Kenny said:

“In England, Scotland and Wales, public health bodies have revised recommendations since the COVID-19 outbreak. Recommendations now state that all adults should take at least 400 IU vitamin D daily. Whereas there are currently no results from randomized controlled trials to conclusively prove that vitamin D beneficially affects COVID-19 outcomes, there is strong circumstantial evidence of associations between vitamin D and the severity of COVID-19 responses, including death.”

“This study further confirms this association. We call on the Irish government to update guidelines as a matter of urgency and encourage all adults to take supplements during the COVID-19 crisis. Deficiency is frequent in Ireland. Deficiency is most prevalent with age, obesity, in men, in ethnic minorities, in people with diabetes, hypertension and in nursing homes.”

Dr. Eamon Laird added:

“Here we see observational evidence of a link of vitamin D with mortality. Optimizing vitamin D intake to public health guidelines will certainly have benefits for overall health and support immune function. Research like this is still exploratory and we need further trials to have concrete evidence on the level of vitamin D that is needed for optimal immune function. However, studies like this also remind us how low our vitamin D status is in the population (even in sunny countries) and adds further weight to some sort of mandatory vitamin D fortification policy. If the Nordic countries are allowed to do this, there is no reason Ireland, the UK or rest of Europe can’t either.”

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What Is a Coronavirus Antibody Test—and Why Testing Matters

Everybody wants to know when stay-at-home orders will be lifted, but experts agree that’s unlikely to happen until widespread antibody testing has been carried out. While a nasal swab test can detect existing infection, a blood test can determine if a person has been exposed to the new coronavirus. Known as an antibody test or serology test, this may identify those who have recovered from infection and, potentially, have developed some degree of protection from reinfection (by demonstrating an "immune response" to the virus).

Whether you have the virus or not, this development in the fight against COVID-19 affects everybody—wide-scale antibody testing may be key to getting those stay-at-home orders lifted. 

What Is Antibody Testing?

Antibodies are human proteins produced by the body to fight infection. “During an infection, the immune system custom-designs antibodies to recognize a specific part of the virus,” Craig Wilen, MD, an assistant professor in laboratory medicine and immunobiology at Yale University, tells Health.

In the case of the new coronavirus, the most important antibodies target the viral spike protein, which is the protein that binds to the human cell receptor and allows the genetic material of the virus to enter human cells and begin infection. “There are two types of virus-specific antibodies that are relevant for testing,” Dr. Wilen says. “The first is called immunoglobulin M (IgM). This antibody is made earlier in the period of infection and then goes away. The second is called immunoglobulin G (IgG), which is made after IgM, but lasts much longer.”

While there is some variability in timing between people, IgM lasts for weeks to months and is detectable after a week or two, whereas IgG lasts for decades and is detectable days to about one week after IgM. By detecting the different antibodies in a person’s blood, doctors are able to “date” when they had—or still have—the infection.

If My Test Comes Back Positive, Am I Immune?

Unfortunately, scientists don’t yet know whether a positive test means you’re immune or how long such protection may last. “There have been reports of patients getting re-infected with the new coronavirus,” Dr. Wilen says. “It is also known that for many seasonal coronaviruses which cause the common cold, the antibodies go away over time which enables people to get re-infected.” 

The World Health Organization addressed this issue at a news briefing in Geneva on April 13.

"One would expect that a person who generates a full-blown immune response with detectable antibodies should have protection for a period of time," Dr. Mike Ryan, executive director of WHO's emergencies programs, said, per NPR. "We just don't know what that period of time is. We would expect that to be a reasonable period of protection, but it is very difficult to say that with a new virus."

Dr. Wilen suspects that even if the new coronavirus antibodies went away, that past infection would confer a survival advantage to future re-infection. “This is a general principle of the adaptive immune system,” he explains.

Is Testing Available—and What Does It Involve?

The Food and Drug Administration (FDA) recently approved the first test in the US for detecting coronavirus antibodies, and many companies are developing other tests.

Meanwhile, the Centers for Disease Control and Prevention (CDC) has already started carrying out its own antibody testing to help determine how many people have been infected with the virus, including those who never displayed any symptoms, reported Politico. On April 10, the National Institutes of Health announced that it would test 10,000 healthy volunteers from around the country for the presence of antibodies. People can participate in at-home blood sampling using a kit and mail the sample to the NIH lab for analysis.

Typically, the test involves taking blood from the arm or using the finger stick method, in which the finger is pricked with a lancet to obtain a small quantity of capillary blood. “The amount of blood needed depends on the specific test method,” Dr. Wilen says. Either way, it should be quick and simple. 

How Reliable Are Antibody Test Results?
In other parts of the world, some governments have expressed concern that antibody tests are not proving to be as reliable as the swab tests that look for current infection. On April 8, the UK government announced that antibody tests won’t be available until at least May because none of the tests tried so far had been accurate enough.

It’s crucial that the coronavirus antibody testing process isn’t rushed, Gary W. Procop, MD, the chair of American Society for Clinical Pathology’s Commission on Science, Technology and Policy, and vice chair and director of virology at Cleveland Clinic, tells Health. If the tests aren’t sensitive or specific enough, it could result in false positives, which suggest a person has immunity who doesn’t, and false negatives, which fail to detect immunity.

“Both of these are dangerous and hamper the efforts to get Americans safely back to work,” Dr. Procop says. “We need to follow the lead of our colleagues in the UK and not implement tests that have not been thoroughly vetted and may do more harm than good.”

 The information in this story is accurate as of press time. However, as the situation surrounding COVID-19 continues to evolve, it's possible that some data have changed since publication. While Health is trying to keep our stories as up-to-date as possible, we also encourage readers to stay informed on news and recommendations for their own communities by using the CDC, WHO, and their local public health department as resources.

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New robotic device to help patients with spinal cord injury

Researchers from Columbia University in the US have invented a robotic device that can be used to assist and train people with Spinal Cord Injuries (SCIs). The team consisting of an Indian, said the device delivers forces on the torso when the user performs upper body movements beyond the postural stability limits while sitting.The device can help the patient to sit more stably, an advance which may aid the recovery of patients with SCI.

The robotic device— the Trunk-Support Trainer, or TruST—is a motorised-cable driven belt placed on the torso of people with SCI to determine their control limits of posture, and workspace area while sitting.

The study, published on Monday in the journal Spinal Cord Series and Cases, is the first to measure and define the sitting workspace of patients with SCI based on their active trunk control.

"We designed TruST for people with SCIs who are typically wheelchair users," said study co-author Sunil Agrawal from Columbia University.

"We found that TruST not only prevents patients from falling, but also maximizes trunk movements beyond patients' postural control, or balance limits," he added.

Five subjects participated in a pilot study examining TruST with the Postural Star-Sitting Test.

In this customised postural test, the participants were required to follow a ball with their head and move their trunk as far as possible, without using their hands.

The users repeated the test in eight directions, following which the researchers used the results to compute the sitting workspace of each individual.

TruST was customised for each subject, the researchers said, so that they could apply personalised assistive force fields on the torso while the participants performed the same movements again.

With the new robotic device, the subjects could reach further during the trunk excursions in all eight directions.

According to the study, TruST significantly expanded the sitting workspace around their bodies, on an average of about 25 per cent more.

"The capacity of TruST to deliver continuous force-feedback personalised for the user's postural limits opens new frontiers to implement motor learning-based paradigms to retrain functional sitting in people with SCI. We think TruST is a very promising SCI rehab tool," said study co-author Victor Santamaria, a physical therapist at Columbia University.

Agrawal and his team are now exploring the use of TruST to improve the trunk control of adults and children with SCI.

"The robotic platform will be used to train participants with SCI by challenging them to move their trunk over a larger workspace, with TruST providing assist-as-needed force fields to safely bring the subjects back to their neutral sitting posture. This force field will be adjusted to the needs of the participants over time as they improve their workspace and posture control," Agrawal said. 

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How can one say if a brain is awake?

Scientists commonly use multiple electroencephalograms or EEG tests to determine the brain consciousness level but now a research team, using rats, has been able to demonstrate that the EEG doesn't always track with being awake.

The study team raised questions about what awareness entails.

One of the researcher said, EEG doesn't necessarily co-relate with behaviour. We are raising more questions and asking that people are more cautious when interpreting EEG data.

Under anaesthesia, an EEG reveals a ind of unconsciousness signature: diminished brain connections; sluggish waves which are also correlated with profound sleep, vegetative state, and coma; and less complex or less time-consuming change in brain function.

Researchers wanted to look at the results of these measures when a brain was awakened in anaesthesia based on data from a 2018 study. To do so, they examined a brain are called the medial prefrontal cortex which was shown to play a role in the focus, auto-processing and synchronization of perception.

The team used a drug that imitated neurotransmitter acetylcholine production in that part of the brain to induce some of the rats to walk about despite their continues anesthesiology. The rats were not treated with the same medication on the back of the brain. There was anaesthesia in the brain for both types of rats but only one group was 'awakened.'

Then we took the EEG data and looked at those factors that have been considered correlates of wakefulness. We figures if the animals were waking up, even while still exposed to anaesthesia, then these factors should also come back up. However, despite wakeful behaviour, the EEGs were the same in the moving rats and the non-moving anesthetized rats, said the researcher.
What does this mean for the EEG's ability to reflect consciousness?

The study does support the possibility that certain EEG features might not always accurately capture the level of consciousness in surgical patients, said a senior author.

However, EEG likely does have value in helping us understand if patients are unconscious. For e.g., a suppressed EEG would suggest a very high probability of unconsciousness during general anaesthesia. However, using high anaesthetic doses to suppress the EEG might have other consequences, like low BP, that we want to avoid. So, we will have to continue to be judicious in assessing the many indices available, including pharmacologic dosing guideline, brain activity and cardiovascular activity.

He noted that there is physiological precedent for an EEG mismatching behaviour.

For instance, the brain of someone in REM sleep is almost identical to an awake brain. No monitor is perfect, but the current monitors we use for the brain are good and do their job most of the time. However, our data suggest there are exceptions.

Their research posed interesting questions about the representation in the brain consciousness, said the researcher.

These measures do have value and we have to do more studies. Maybe they are associated with awareness and what we call the content of consciousness. With rats, we don't know we can't ask them !

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Fitness trackers more accurate in predicting patient health outcomes

Researchers found that fitness trackers can better estimate exercise capacity and determine the health status of patients, rather than the cliche 6-minute walk distance test doctors opt for.

Researchers said the test results are another example in how wearable and monitoring devices like Fitbits and Apple watches can be used in patient care to improve outcomes.

For patients, this means we can track their progress more frequently in a manner that's less expensive and more convenient than current standarised testing, said the lead researcher.

The 6 minute walk distance is an important, objective standard used to assess exercise capacity. Patients walk for 6 minutes and then based on how many meters they cover in that time, physicians can predict outcomes and mortality for patients with chronic obstructive pulmonary disease (COPD) and cardiovascular diseases.

Normally, the 6 WMD test is done every few months or once a year. Now, we may be able to measure patients on a regular basis and know if we need to intervene if their estimated 6 WMD by step count changes, said the Dr.

In the study, researchers conducted a 12-week, blinded, randomised, cross-over trial with 52 patients, a group that included adults with a history of respiratory problems during periods of elevated air pollution. Wrist step counters tracked patient steps for those 12 weeks, and patients also filled out respiratory symptoms questionnaires.

Researchers found they could effectively estimate a patient's 6WMD results by using step counters, instead of having patients come in a clinical setting to do the 6WMD test.

Instead of having one measurements every few months, you could have weekly measurements, and have information at disease progression at more frequent intervals. This is a significant improvement and enhanced convenience for our patients, said the Dr.

The implications? Using wrist step counters will allow physicians to track how their patients are doing, the progression of the disease and whether a patient requires immediate intervention.

Being able to distill step counts into this clinically important metric is a first step in being able to think about how to use step counters in order to better manage health and detect deterioration earlier, added the Dr.

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MRI guided prostate biopsy best way of active surveillance for prostate cancer

Prostate cancer is a common type of male cancer which is highly treatable in the early stages. All over the world tens of thousands of men are diagnosed with low-risk prostate cancer. All such patients are asked just to monitor their slow-growing tumours as they need no active treatment.

Magnetic resonance imaging-guided prostate biopsy best way of active surveillance for prostate cancer, find researcher. MRI imaging, let doctors see the majority of prostate tumours and take a biopsy from the exact location of cancer within the prostate.

Doctors relied  on ultrasound to guide a biopsy needle into the prostate in the past. However,  ultrasound doesn't allow the visualisation of prostate tumours, so a biopsy may have missed a tumour. Over the past decade, it's become possible to instead perform a MRI guided biopsy.

Prostate cancer is typically detected with a blood test measuring levels of prostate-specific antigen (PSA). However, elevated PSA levels detect not only aggressive prostate tumours, but also very slow-growing cancers that are unlikely to become life-threatening. Men with higher than usual PSA levels are referred to get a biopsy, in which cells are collected from the prostate reveal more details about a tumour.

We've found that when you use an MRI-guided biopsy to confirm what appears to be a low-risk prostate cancer, you can then tell the patient with pretty good accuracy what the future is going to entail and what his risks are of having a cancer that will require treatment in the future, said the senior author of the study.

If you know exactly where to put the biopsy needle, you've a much better chance of getting answers about a tumour, said a researcher. Earlier this year, his group reported that combining MRI-guided biopsies with a more traditional approach of sampling throughout the prostate detects more cancers than either approach alone. However, he said questions have lingered about the clinical benefit of MRI imaging guided biopsies and exactly when they should be used in the monitoring process.

From 2009-2018, 606 men with prostate cancers of apparent low risk were enrolled in the active surveillance program. For the new study, researchers analysed data on 332 of those men, all of whom received an initial MRI-guided biopsy and at least one follow-up biopsy an average of 3.9 years later.

The researchers found that when a man's prostate tumour had a Gleason Score of 7 at the time of an MRI-guided biopsy, there was a three-and-a-half times greater risk that the man would develop higher-risk cancer compared to men who had a negative biopsy. ( The Gleason Score is a grading system used to determine the aggressiveness of prostate cancer). A score of 6 is generally considered low-risk cancer recommended for active surveillance, while a score of 7 or more may require radiation or surgery.

Moreover, combining an MRI-guided biopsy with the more standard approach of taking a systematic sampling of biopsies from around the prostate boosted the likelihood that a positive initial biopsy result was truly positive.

In the study, the risk of later developing high-grade prostate cancer was less than 8% for men whose biopsies were negative, 11% if the biopsy revealed a Gleason Score of 6, and 23% with a score of 7.

While MRI-guided biopsy is being used, it is still not being very widely used and our results have the potential to establish a new standard for using it in active surveillance, said the researcher.

MRI-guided biopsy can be used to determine which men should receive more frequent follow-up biopsies or even active intervention before a higher-grade tumour develops, he said.

The study also integrated the use of tracked biopsies- in which technology lets physician take a follow-up biopsy from the same location as a previous biopsy to determine how cancer is changing. The team found that the tracked biopsy detected more upward changes in the grading of cancer-- from a low-grade to high-grade tumour-- than non-tracked biopsies. However, more work is needed to study the value of tracked biopsies.

All these new technologies are advancing the field and serving patients better, he said.

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