Daily Archives: April 6, 2020

SAN RAFAEL, Calif., April 6, 2020 /PRNewswire/ --BioMarin Pharmaceutical Inc.(NASDAQ: BMRN) today announced that based on recent meetings with health authorities in the US and Europe, the Company plans to submit marketing applications to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the third quarter of 2020 for vosoritide.Vosoritide is an investigational, once daily injection analog of C-type Natriuretic Peptide (CNP) for achondroplasia, the most common form of disproportionate short stature in humans.

The marketing applications are based on the outcomes from the randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of vosoritide, announced in Dec 2019, and further supported by the long-term safety and efficacy from the Phase 2 study, ongoing extension studies, and extensive natural history data. If approved, vosoritide would be the first medicine for the treatment of Achondroplasia in the US and Europe.

"We have worked with the regulatory authorities throughout the design and development of our clinical program and look forward to the ongoing interactions in the evaluation of the safety and efficacy of vosoritide in children with achondroplasia," said Hank Fuchs, M.D., President Worldwide Research and Development at BioMarin."We believe that we have a strong data package that combines the gold standard of a randomized, double-blind, placebo-controlled Phase 3 study with the long-term results in the Phase 2 open label study and extensive contemporaneous natural history data to evaluate durability.We are grateful to the children and families who have participated in these studies and are contributing to the greater body of scientific data on a potential treatment for achondroplasia."

"Vosoritide is the first potential pharmacological treatment for the underlying cause of achondroplasia. It could be a medical breakthrough in providing physicians with a new tool to treat individuals with achondroplasia," said John A. Phillips, III, M.D., Vanderbilt University Medical Center (David T Karzon Professor of Pediatrics) and investigator for the vosoritide clinical program. "To have such a possible treatment for achondroplasia on the horizon, where none existed before is significant progress."

"We are making great strides in understanding the biology of skeletal dysplasia and getting closer to a potential treatment," said Klaus Mohnike, Professor of Paediatrics at Magdeburg University Hospital in Germany and investigator for the vosoritide clinical program. "I am looking forward to therapeutic interventions that go beyond treating symptoms and have the potential to make a lasting difference for those affected children."

Vosoritide has received orphan drug designation from the FDA and EMA for the treatment of achondroplasia.The Orphan Drug Designation program is intended to advance the evaluation and development of products that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions.

Description of Phase 3 Study

The global Phase 3 study was a randomized, double-blind, placebo-controlled study of vosoritide in 121 children with achondroplasia aged 5 to 14 for 52 weeks. (The enrollment age criteria were 5 to 18 per the study protocol).Vosoritide is being tested in children whose growth plates are still open. This is approximately 25% of people with achondroplasia. Children in this study have completed a minimum six-month baseline study to determine their baseline growth velocity prior to entering the Phase 3 study.The primary endpoint of the study was the change in growth velocity from baseline over one year in children treated with vosoritide compared to placebo. A wide range of secondary and exploratory endpoints included anthropometric measures such as height Z-score, body and limb proportionality and joint geometry; biochemical, biomarker and radiological assessments of bone growth and health; and evaluations of health-related quality of life (HRQoL), developmental status, and functional independence.These additional endpoints address the overall impact vosoritide has on achondroplasia and continue to be evaluated in an ongoing open-label extension study where all subjects receive active treatment.

Description of Phase 2 Dose Finding Study

The primary objectives of the open-label, sequential cohort, dose-finding study were to evaluate the safety and tolerability of daily subcutaneous vosoritide and to determine the dose to carry forward to Phase 3. Secondary objectives were to evaluate the effects of vosoritide on change from pre-treatment baseline in annualized growth velocity (cm/year), height Z-scores, and body segment proportionality, the vosoritide pharmacokinetic (PK) profile, and biomarkers of vosoritide activity, and endochondral ossification. All children who completed the 24-month dose finding study were then eligible to continue long term follow up in the ongoing extension study which provides long term evidence of efficacy, durability of effect and safety.

About Achondroplasia

Achondroplasia, the most common form of disproportionate short stature in humans, is characterized by slowing of endochondral ossification, which results in disproportionate short stature and disordered architecture in the long bones, spine, face and base of the skull.This condition is caused by a mutation in the fibroblast growth factor receptor 3 gene (FGFR3), a negative regulator of bone growth. Beyond disproportionate short stature, people with achondroplasia can experience serious health complications, including foramen magnum compression, sleep apnea, bowed legs, mid-face hypoplasia, permanent sway of the lower back, spinal stenosis and recurrent ear infections. Some of these complications can result in the need for invasive surgeries such as spinal cord decompression and straightening of bowed legs. In addition, studies show increased mortality at every age.

More than 80% of children with achondroplasia have parents of average stature and have the condition as the result of a spontaneous gene mutation.The worldwide incidence rate of achondroplasia is about one in 25,000 live births.Vosoritide is being tested in children whose growth plates are still "open," typically those under 18 years of age.This is approximately 25% of people with achondroplasia.In the U.S., Europe, Latin America,the Middle East, and most of Asia Pacific, there are currently no licensed medicines for achondroplasia.

About BioMarin

BioMarin is a global biotechnology company that develops and commercializes innovative therapies for patients with serious and life-threatening rare genetic diseases. The company's portfolio consists of six commercialized products and multiple clinical and pre-clinical product candidates. For additional information, please visit http://www.biomarin.com. Information on such website is not incorporated by reference into this press release.

Forward-Looking Statement

This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including, without limitation, statements about: BioMarin's vosoritide development program generally and specifically about the Company's planned submissions for marketing applications in the U.S. to the FDA and in Europe to the EMA, the strength of the data package to be submitted to regulatory authorities, the continued clinical development of vosoritide and the timing and conduct of such clinical program; the possible results of such studies, and the timing of the submissions of marketing applications to health authorities in the U.S. and Europe. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: final analysis of the Phase 3 data, results and timing of current and planned preclinical studies and clinical trials of vosoritide; our ability to successfully manufacture vosoritide; the content and timing of decisions by the U.S. Food and Drug Administration, the European Commission and other regulatory authorities concerning vosoritide; and those other risks and uncertainties detailed from time to time under the caption "Risk Factors" and elsewhere in the BioMarin's Securities and Exchange Commission (SEC) filings, including, without limitation, BioMarin's Quarterly Report on Form 10-K for the year ended December 31, 2019, and future SEC filings and reports by BioMarin. BioMarin undertakes no duty or obligation to update any forward-looking statements contained in this press release as a result of new information, future events or changes in its expectations.

BioMarin is a registered trademark of BioMarin Pharmaceutical Inc.

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BioMarin Pharmaceutical Inc.

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COVID-19 is caused by a coronavirus called SARS-CoV-2. Coronaviruses belong to a group of viruses that infect animals, from peacocks to whales. Theyre named for the bulb-tipped spikes that project from the viruss surface and give the appearance of a corona surrounding it.

A coronavirus infection usually plays out one of two ways: as an infection in the lungs that includes some cases of what people would call the common cold, or as an infection in the gut that causes diarrhea. COVID-19 starts out in the lungs like the common cold coronaviruses, but then causes havoc with the immune system that can lead to long-term lung damage or death.

SARS-CoV-2 is genetically very similar to other human respiratory coronaviruses, including SARS-CoV and MERS-CoV. However, the subtle genetic differences translate to significant differences in how readily a coronavirus infects people and how it makes them sick.

SARS-CoV-2 has all the same genetic equipment as the original SARS-CoV, which caused a global outbreak in 2003, but with around 6,000 mutations sprinkled around in the usual places where coronaviruses change. Think whole milk versus skim milk.

Compared to other human coronaviruses like MERS-CoV, which emerged in the Middle East in 2012, the new virus has customized versions of the same general equipment for invading cells and copying itself. However, SARS-CoV-2 has a totally different set of genes called accessories, which give this new virus a little advantage in specific situations. For example, MERS has a particular protein that shuts down a cells ability to sound the alarm about a viral intruder. SARS-CoV-2 has an unrelated gene with an as-yet unknown function in that position in its genome. Think cow milk versus almond milk.

How the virus infects

Every coronavirus infection starts with a virus particle, a spherical shell that protects a single long string of genetic material and inserts it into a human cell. The genetic material instructs the cell to make around 30 different parts of the virus, allowing the virus to reproduce. The cells that SARS-CoV-2 prefers to infect have a protein called ACE2 on the outside that is important for regulating blood pressure.

The infection begins when the long spike proteins that protrude from the virus particle latch on to the cells ACE2 protein. From that point, the spike transforms, unfolding and refolding itself using coiled spring-like parts that start out buried at the core of the spike. The reconfigured spike hooks into the cell and crashes the virus particle and cell together. This forms a channel where the string of viral genetic material can snake its way into the unsuspecting cell.

SARS-CoV-2 spreads from person to person by close contact. The Shincheonji Church outbreak in South Korea in February provides a good demonstration of how and how quickly SARS-CoV-2 spreads. It seems one or two people with the virus sat face to face very close to uninfected people for several minutes at a time in a crowded room. Within two weeks, several thousand people in the country were infected, and more than half of the infections at that point were attributable to the church. The outbreak got to a fast start because public health authorities were unaware of the potential outbreak and were not testing widely at that stage. Since then, authorities have worked hard and the number of new cases in South Korea has been falling steadily.

How the virus makes people sick

SARS-CoV-2 grows in type II lung cells, which secrete a soap-like substance that helps air slip deep into the lungs, and in cells lining the throat. As with SARS, most of the damage in COVID-19, the illness caused by the new coronavirus, is caused by the immune system carrying out a scorched earth defense to stop the virus from spreading. Millions of cells from the immune system invade the infected lung tissue and cause massive amounts of damage in the process of cleaning out the virus and any infected cells.

Each COVID-19 lesion ranges from the size of a grape to the size of a grapefruit. The challenge for health care workers treating patients is to support the body and keep the blood oxygenated while the lung is repairing itself.

How SARS-CoV-2 infects, sickens and kills people.

SARS-CoV-2 has a sliding scale of severity. Patients under age 10 seem to clear the virus easily, most people under 40 seem to bounce back quickly, but older people suffer from increasingly severe COVID-19. The ACE2 protein that SARS-CoV-2 uses as a door to enter cells is also important for regulating blood pressure, and it does not do its job when the virus gets there first. This is one reason COVID-19 is more severe in people with high blood pressure.SARS-CoV-2 is more severe than seasonal influenza in part because it has many more ways to stop cells from calling out to the immune system for help. For example, one way that cells try to respond to infection is by making interferon, the alarm signaling protein. SARS-CoV-2 blocks this by a combination of camouflage, snipping off protein markers from the cell that serve as distress beacons and finally shredding any anti-viral instructions that the cell makes before they can be used. As a result, COVID-19 can fester for a month, causing a little damage each day, while most people get over a case of the flu in less than a week.

At present, the transmission rate of SARS-CoV-2 is a little higher than that of the pandemic 2009 H1N1 influenza virus, but SARS-CoV-2 is at least 10 times as deadly. From the data that is available now, COVID-19 seems a lot like severe acute respiratory syndrome (SARS), though its less likely than SARS to be severe.

What isnt known

There are still many mysteries about this virus and coronaviruses in general the nuances of how they cause disease, the way they interact with proteins inside the cell, the structure of the proteins that form new viruses and how some of the basic virus-copying machinery works.

Another unknown is how COVID-19 will respond to changes in the seasons. The flu tends to follow cold weather, both in the northern and southern hemispheres. Some other human coronaviruses spread at a low level year-round, but then seem to peak in the spring. But nobody really knows for sure why these viruses vary with the seasons.

What is amazing so far in this outbreak is all the good science that has come out so quickly. The research community learned about structures of the virus spike protein and the ACE2 protein with part of the spike protein attached just a little over a month after the genetic sequence became available. I spent my first 20 or so years working on coronaviruses without the benefit of either. This bodes well for better understanding, preventing and treating COVID-19.

[Get facts about coronavirus and the latest research. Sign up for our newsletter.]

Benjamin Neuman, Professor of Biology, Texas A&M University-Texarkana

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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What The Coronavirus Does To Your Body That Makes It So Deadly - IFLScience

Hospitals do not have enough PPEs (personal protective equipment gloves, masks, gowns, shoe coverings), nor sufficient access to COVID-19 testing.

When a policy is made to disallow family members from being with loved ones, it is considered inhumane. Yet, hospitals must protect patients from spreading this virus to the medical staff and the public. One contaminating source could be from visiting family members.

Conversely, ill loved ones need a hand to hold and psychological support to alleviate pain and suffering. We know there are aspects of the mind that modern medicine cannot heal.

The initial solution: Utilize cell phone technology to maintain communication if your hospitalized loved one is capable.

The next solution: Find a way quickly to increase hospital PPE supplies and augment COVID-19 testing.

Once this is done:

Allow at least one garbed family member to be with their loved one;

Educate them on the proper use of PPEs;

Emphasize cleansing techniques like handwashing and keeping the surrounding room sterile;

Get testing for family members as well as staff.

Everyone must be protected and comforted, but lets adapt and find creative solutions to assure continued humanity in hospitals during this crisis.

Gene Uzawa Dorio, M.D., is a geriatric house-call physician who serves as president of the Los Angeles County Commission for Older Adults and Assemblyman to the California Senior Legislature. He has practiced in the Santa Clarita Valley for 32 years.

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Comforting a Loved One | Doctor's Diary with Dr. Gene Dorio - SCVNEWS.com

Dr David Glass - MBChB, FCOG (SA)

Today we celebrate our 100th blog on the subject of lifestyle medicine making wise choices in the area of diet, exercise, rest, sunlight, fresh air, water, relationships and spiritual connection. This is one area of medicine that seems to permeate all others. It is becoming increasingly important as diseases of poor lifestyle choices affect more and more people around the world resulting in rising incidences of heart disease, high blood pressure, diabetes, obesity, auto-immune diseases, cancer and dementia.

ALSO READ : Turning the Tide Lifestyle Medicine and Covid 19

Of course our minds are daily preoccupied with Covid-19, and so should they be. We are facing one of the most devastating challenges to health care and the economy the world has seen this century. Two weeks ago I presented a lifestyle approach to this pandemic, because we know that the virus is particularly aggressive in people who suffer chronic lifestyle diseases.

Today we will get back to our topic for this series breast cancer. Unfortunately Covid-19 doesnt make all the other diseases, to which we are so prone, go away. As mentioned before, this series is based on Dr Kristi Funks book Breasts: The owners manual. This week we will be looking at uncontrollable risk factors.

Next week we will briefly look at some of the interventions on offer in terms of treatment and screening to complete the series on breast cancer.

Stay safe, isolated as much as possible in your home. May you use this time for building family relationships and getting life priorities right. It is good to have some forced time for reflection when we are faced with the prospect of our own mortality or that of our friends and family.

Dave Glass

Dr David Glass MBChB, FCOG (SA)

Dr David Glass graduated from UCT in 1975. He spent the next 12 years working at a mission hospital in Lesotho, where much of his work involved health education and interventions to improve health, aside from the normal busy clinical work of an under-resourced mission hospital.

He returned to UCT in 1990 to specialise in obstetrics/gynaecology and then moved to the South Coast where he had the privilege of, amongst other things, ushering 7000 babies into the world. He no longer delivers babies but is still very clinically active in gynaecology.

An old passion, preventive health care, has now replaced the obstetrics side of his work. He is eager to share insights he has gathered over the years on how to prevent and reverse so many of the modern scourges of lifestyle obesity, diabetes, ischaemic heart disease, high blood pressure, arthritis, common cancers, etc.

He is a family man, with a supportive wife, and two grown children, and four beautiful grandchildren. His hobbies include walking, cycling, vegetable gardening, bird-watching, travelling and writing. He is active in community health outreach and deeply involved in church activities. He enjoys teaching and sharing information.

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The coronavirus disease (Covid-19) first appeared in the Wuhan district of Hubei province of China in early December 2019. The first case was reported by China on January 7, 2020, and this aroused variable interest worldwide, with most countries initially ignoring the novel infection. Fortunately, Indian health authorities sensed the danger, largely because the country has always been alert to new infections. The scientific think-tank at the Indian council of Medical Research (ICMR) became active immediately and the first laboratory confirmed case was identified at ICMRs National Institute of Virology (NIV), Pune, sometime towards the end of January.

A look at the world Covid meter shows that there is striking variation in mortality rates across countries, ranging from 0.2% to 15% depending on age, the smoking habit and pre-existing co-morbidities. It may be too early to tell, but in general, countries in the Northern hemisphere have faced the maximum brunt, and those in the Southern hemisphere (and those located proximate to the Equator) have so far escaped high infection numbers.

Three factors seem to be playing a role in the observed lower numbers in India with almost zero occurrence of severe Covid-19 cases (until now). First, broad-based immunity in the population due to the extensive microbial load. The Indian population has been exposed to a vast variety of pathogens, including bacteria, parasites and viruses leading to the generation of broad specific memory T-cells in the system, ready to attack additional foreign invaders.

For example, the three main killers of Tuberculosis, HIV and Malaria have plagued India, Africa and several countries in the Southern hemisphere much more than the European and North American nations. In the context of CoV-2 coronavirus, the beneficial role of chloroquine and hydroxychloroquine has been much talked about and debated, while there has already been an extensive usage of this drug at the community level in India this too may ultimately prove beneficial.

Also read: In fight against coronavirus, India has age on its side. Numbers show

Second, epigenetic factors that include environment and food habits may also play a beneficial role for countries such as India; much literature is already available in Ayurveda and other Indian systems of medicine on the definitive beneficial effects of Indian spices in augmenting immunity.

Third, and most important, is the possible role of immune response genes in the Indian population. These genes are collectively referred to as comprising the human leucocyte antigen system or simply, the HLA genes. Their main biological function is to present invading foreign antigens to the immune systems, since T-cells, which act as the bodys soldiers come into play only when pathogens are presented to them in a more formal manner in association with HLA genes. In other words, the pathogen must first attach to compounds created by HLA genes before T-Cells attack it. If no such compounds are produced by the body, then the T-Cells are ineffective. As a consequence of the microbial load, the Indian population possesses a high genetic diversity of HLA, much more extensive than Caucasian populations. Indeed, studies by the author at the All India Institute of Medical Sciences, New Delhi, over several decades revealed the presence of several novel HLA genes and their alleles in the Indian population, most of which do not occur in other ethnic groups. Such genetic diversity of HLA could affect viral fitness.

The question then is:Why should genetic variation in HLA genes play a role in the Covid-19 progression? One hint comes from earlier studies in related viral diseases: Certain genetic variants of the HLA system provide protection against such viruses, while others increase genetic susceptibility to them. Another source of indirect evidence comes from recent clinical Covid-19 studies which showed that rapid T-cell response appears to be crucial for recovery from Covid-19, and reduced functional diversity of T cells in peripheral blood could predict progression of Covid-19.

The big question is:Does this give Indians a better chance at fighting the virus effectively? From the epidemiological data so far, it seems so (although much more extensive research is required). However, it is important for us to keep viral loads in check and below the threshold levels. In this context, the complete lockdown announced by the government is highly timely and most desirable. It is imperative that the virus replication cycle gets disrupted as early as possible before it gains numbers that may become difficult for us to counter.

To this end, the images of crowds gathering in several places whether for panic buying or interstate movements are disturbing. They could jeopardise all efforts and mitigate whatever natural advantages we enjoy.

The State must act fast to enforce the lockdown, even forcibly if necessary. India may be the outlier in fighting the coronavirus infection and succeed in keeping the overall numbers lower than the rest of the world with minimal deaths.

Narinder Kumar Mehra is the ICMR National chair and former Dean of the All India Institute of Medical Sciences, New Delhi

The views expressed are personal

By special arrangement with

Also read: Indias fight against Covid-19 needs wartime industrial production, not more red tape

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As the COVID-19 pandemic spreads across the world, patients, technicians and scientists depend on state-of-the-art molecular-analysis instruments as they fight against SARS-CoV-2, the virus causing this disease. Optics and photonics technologies embedded in these instrumentssuch as high-quantum-efficiency multispectral cameras, visible-light laser diodes and LEDs, infrared bolometer arrays, narrowband optical filters and wideband multispectral optical spectrometersplay an essential part in the story.

Whether in the hospital or in the lab, optics technologies make possible rapid preliminary screening of potentially infected individuals, more accurate molecular diagnosis, reliable monitoring of disease progression and even, potentially, disinfection of contaminated surfaces. Our community developed these enabling technologies over the past several decades for applications ranging from telecommunications to machine and night vision. Now, theyre playing a life-saving role in the battle against SARS-CoV-2.

Early detection of infected patientsone of the primary challenges of the COVID-19 pandemicis complicated by the wide variability in the diseases symptoms. Monitoring for an increase in body temperature is the most commonly used preliminary screen. Under normal circumstances, direct body-cavity temperature measurements are the most accurate way to monitor a fever; however, given the pathogenicity of SARS-CoV-2, remote, non-contact options that employ infrared imaging cameras to simultaneously image and measure groups of individuals provide a significant safety advantage.

Many clinicians now rely on infrared-based thermometers for measuring forehead temperature. These imaging and spot-measurement thermometric devices provide medical personnel with a safer and useful non-contact patient screen. These thermometers are based on single detectors or arrays of MEMS-based microbolometers or semiconductor diode detectorsthermal sensors that are sensitive in the far-infrared spectral region (8 to 14 m) and detect changes in the blackbody radiation intensities in persons with above-normal body temperatures.

Cepheid doctors office RT-PCR instrument. [Image: Courtesy of Cepheid]

In TaqMan real-time polymerase chain reaction, a nucleic-acid probe molecule, tagged with a fluorescent molecule and an accompanying quencher, attaches to the stretch of DNA or RNA being copied. With each round of amplification, the fluorescent molecule is released into the buffer solution and separated from the quencher, allowing the amplification of the targeted genetic sequencesuch as one from SARS-CoV-2to be detected via fluorescence in real time. [Image: Wikimedia Commons]

If a patient presents with a fever or other symptoms typical of viral infection (sore throat, dry cough, muscle aches and fatigue), the next step is a molecular diagnostic test. This screen, based on a technique called real-time reverse transcription polymerase chain reaction (RT-PCR), uses sensitive spectroscopic methods to detect extremely small quantities of viral genetic material from a patients nasal or throat swab. And once again, optical technology is an essential component for disease detection.

The diagnostic procedure requires significant sample processing, beginning with a specimen collected from a patient. Real-time RT-PCR works by copying specific nucleic acid sequences within that sample, using probesnucleic-acid primersthat selectively bind very specifically to the RNA sequences present in the SARS-CoV-2 virus. The probes are tagged with molecules of fluorescent dye.

Enzymes are then used to copy the nucleic-acid sequences bound to the probes. The sample is thermally cycled roughly 40 times between37 C and 95 C. If the target nucleic-acid sequences are present, they are amplified twofold with each cycle.

It is optical technology that puts the real time in RT-PCR. As the amplification enzymes create the duplicate copies, the fluorescent molecules are released into the buffer solution. The overall fluorescence is measured in real time after each cycle, increasing as the number of amplicons increases for positive samples. By measuring the intensity buildup during the thermal cycling, the virus is detected and the amount of virus present (the viral load) can be estimated.

Real-time RT-PCR instruments employ narrowband visible laser diodes or LEDs as excitation sources and semiconductor diodes or photomultipliers with narrow band-pass optical filters for detection. These instruments are fully automated and can typically process 96 or 384 samples in parallel in less than an hour.

Real-time RT-PCR is one of the most sensitive and specific molecular-analysis techniques available today. This assay is crucial for tracking and controlling the spread of COVID-19. However, the overall sensitivity of the method may be limited by the efficiency of the sample collection and preparation process. The amount of virus present in the sampled tissue, which varies between individuals and as the disease progresses in each patient, may also be a limiting factor.

The false-negative rate of this approach is currently estimated at roughly 30%. Repeated testing can reduce this admittedly significant percentage, which is why many hospitals require two or three sequential negative real-time RT-PCR tests after a patient has recovered before that patient is classified as non-infectious.

In addition to molecular diagnostics, imaging of the lungs of COVID-19 patients has also proved very sensitive for detecting SARS-CoV-2 infection using high-resolution computed tomography (CT) scans. Clinicians look for signs of lung damage as evidenced by ground-glass patterns in the lung tissue or fluid accumulation as signatures of pneumonia. Clinics in China have reported that this approach can detect a significant number of infected individuals that have negative RT-PCR readingsonly, however, later in disease progression, once lung damage manifests.

If a patient is diagnosed with COVID-19, disease progression and respiratory function are determined using an oxygen-saturation meter, which measures the percentage of oxygenated hemoglobin in blood. As the disease progresses, breathing can become difficult, causing a reduction in oxygenated hemoglobinif levels dip below certain thresholds, then supplementary oxygen or a ventilator may be warranted.

Oxygen-saturation devices use LEDs emitting at two different wavelengths, typically around 665 nm and 894 nm. The oxygen-saturation percentage is measured from the ratio of the absorption at these two wavelengths. These battery-powered devices fit comfortably on a finger or toe, providing real-time measurement of oxygen-saturation levels.

96 sample well plate ELISA instrument. [Image: 2020 Berthold Technologies. Used under permission. http://www.berthold.com]

Schematic of ELISA, which measures the presence of specific antibodies in a COVID-19 patients sample. The technique relies on a colorimetric change in the sample generated by an enzyme attached to antibodies specific to SARS-CoV-2 virus. [Image: Cavitri/Wikimedia Commons, CC-BY 3.0]

Optical instruments are also used to test whether a person has been exposed to SARS-CoV-2 virus and has developed an immune response. These instrumentswhich can be automated to analyze hundreds to thousands of samples per dayuse a technique called an Enzyme-Linked Immunosorbent Assay (ELISA) to measure the presence of antibodies specific to the SARS-CoV-2 virus in a patients blood-serum sample.

In a typical assay, an antigen found on the virus surface is immobilized on the bottom of a sample well, which is optically transparent. Antibodies in the serum sample are attached to an enzyme (typically horseradish peroxidase) and allowed to incubate on the surface containing the immobilized antigen. Any antibodies specific for the SARS-CoV-2 antigen bind to the target and become immobilized on the surface of the optical window. The unbound, nonspecific antibodies are washed off.

A solution containing the enzymes substrate with a colorimetric indicator is then added to the sample well, and the enzyme linked to the antibody reacts with the substrate, producing a color change in the sample. The enzyme reacts with multiple substrate molecules, thereby amplifying the signal. SARS-CoV-2 antibodies in the blood serum can then be detected and quantified, via multispectral imaging of the sample substrates fluorescence or absorption indicator.

This approach is used to measure the extent of the virus spread within a community, even after the pandemic has passed; to measure the duration of an individuals immune response; and to investigate the efficacy of antiviral drug candidates and potential vaccines. Currently, medical workers who have recovered from COVID-19 and have a protective immune response to the virus are being identified using an ELISA. Once immunity is confirmed, these personnel safely resume working with infected patientsa common approach in pandemic medicine.

Optical devices also form the core technology for the most common high-throughput gene-sequencing instruments. These typically use high-quantum-efficiency, very-high-resolution multispectral cameras to map the sequences of hundreds of millions of target DNA molecules simultaneously and can sequence the complete genome of the SARS-CoV-2 virus in just a few hours. Virus genetic sequences can vary with location, since the SARS-CoV-2 virus occasionally mutates during its replication phase. Infections in separate geographic regions can be compared, and the origins of infections traced, by comparing the specific mutations in samples taken from patients in different locations.

High-throughput sequencing of the virus genome also can determine the proteins in the virus and identify suitable targets for synthetic vaccines that will safely stimulate immune response. This technology has greatly improved over the past 20 years, largely due to the human genome project, and will be an essential tool for developing effective vaccines and antiviral drugs to combat the COVID-19 pandemic.

Prototype of an LED sterilization system being tested by Bolb Inc. [Image: Bolb Inc.]

Beyond the molecular-biology lab, optics is emerging as a weapon on another vital front: the sterilization of surfaces. Most viruses and bacteria are very sensitive to ultraviolet light, particularly in the UV-C spectral region (200280 nm), which causes mutations in the RNA that is essential for viral replication. Recently, great progress has been made in the development of UV LEDs that emit in this region. LED arrays emitting hundreds of milliwatts have been developed with lifetimes of over 1000 hours and electrical efficiencies around 10%.

Arrays of these diodes can generate significant UV power levels to potentially decontaminate certain surfaces more efficiently than chemical reagents. Recent lab results indicate that exposure times of about 1 minute were sufficient to kill bacteria and viruses with a 1-W-average-power device located about 1 meter above a contaminated surface. Further testing on the efficacy of UV LEDs for decontaminating surfaces infected with SARS-CoV-2 virus is in progress.

As global health faces this novel and deadly threat, laboratories around the world are using technologies developed by the optics and photonics community to help stem the spread and save lives. In the near future, as social distancing begins to slow the spread of COVID-19 disease, medical focus will shift to the early detection and isolation of COVID-19 recurrence in hot spots, which will present new challenges for diagnostic and decontamination technologies. These challenges represent new opportunities for optics and photonics technologieswith their advantages of low cost, high speed, sensitivity and specificityto make major contributions to global health. OPN

Note: This article will also be published in the May 2020 issue of Optics & Photonics News.

2009 OSA President Thomas M. Baer (tmbaer@stanford.edu) is with Stanford University, USA. Christina E. Baer is with the University of Massachusetts Medical School, USA.

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Optics, Photonics and COVID-19 - Optics & Photonics News