Virus World

Verily is opening its own testing lab. The lab is in-house at the Google sibling company's South San Francisco headquarters. Verily, the life sciences arm of Google's parent company Alphabet, on Tuesday said it has set up its own coronavirus testing lab aimed at getting people faster results. The lab, located on the company's campus in South San Francisco, California, was built to run "several thousand" tests per day, Verily said. The announcement comes as COVID-19 cases have spiked, causing labs to return results at a slower clip. Facilities that used to take two to three days are now taking a week or longer.  

"When the pandemic hit, it became clear that we needed to rapidly establish a lab and to receive California state licensure and CLIA certification, which we have done," said Verily Head of Pathology Deb Hanks, referring to the state's standards for clinical labs. "We've established this lab to provide a focused specialty service with rapid turnaround time."  One way Verily says it's increasing testing capacity is by looking into "pooled" testing, or combining respiratory samples from several people and conducting one lab test on the sample set. The Verily facility will focus primarily on customers of the company's Healthy at Work program, aimed at helping businesses and schools get people back to offices or campus. 

Verily's efforts were the source of drama and confusion earlier during the pandemic, after President Donald Trump announced the federal government was working with Google on a coronavirus testing website. The tool, which was announced unexpectedly by the president, turned out to be a website that allows people to take a screener survey to see if they should go to testing stations for COVID-19. The screening website has drawn privacy scrutiny from lawmakers. In order to take the online screener, the site requires people to sign in using a Google account. Democratic senators have pressed Verily about the issue, but in April, Verily indicated it would keep the requirement for security and authentication reasons.

States should look to New York’s strategies. It’s been six months since the United States reported its first coronavirus case, and getting a test can still take days. National labs are overwhelmed, leaving people to wait as much as two weeks for results. Every day that testing falls short is another day the virus can spread undetected, costing lives and delaying the reopening of our economy, schools and society. As states try to control the virus and as Congress considers the fourth Covid-19 relief bill, New York offers important lessons on how to fix the testing mess. Over the last 10 weeks, New York has used testing to not only flatten the curve, but actually reduce the rate of infection since our phased reopening started. We have kept our testing rates high through partnerships with federal and local governments. In February and early March, New York worked with the Food and Drug Administration to gain the necessary approvals to begin using our own coronavirus test and mobilize a network of hundreds of labs. In April, when our labs were struggling because of shortages of a necessary chemical ingredient, reagents, President Trump and I reached an agreement that helped double New York’s capacity.  Here’s what states should do to build a sustainable testing operation, and how Congress can help.

Mobilize smaller local labs. Almost all states are now using a handful of national testing companies, and they are overwhelmed. New York has managed to avoid the delays because more than 80 percent of our testing does not depend on the national laboratories experiencing long turnaround times for results. In the early days of the pandemic, New York organized hundreds of local labs to conduct as many tests as possible. We moved equipment sitting idle to labs that could run them around the clock. Today, more than 250 labs in the state report results each day — some conducting 10 tests daily, some thousands. All together, New York can now conduct on average 65,000 tests a day...

Streamline the supply chain. In New York and other states, there are high-capacity labs running at partial capacity because they don’t have enough supplies. How can it be, six months after America’s first case was reported, that the United States still doesn’t have an adequate supply chain? What labs need — reagents and plastic pipette tips — are not complicated to manufacture. They can, and should, be made in mass quantity, immediately, and here at home. New York invested $750,000 in Rheonix, an Ithaca-based manufacturer, to build lab instruments and make reagent kits, which are now being used for thousands of tests daily. States should tap their local manufacturing companies to compensate for international shortages, and Congress should allocate funding for businesses that fill these needs...

Invest in innovative solutions. The Food and Drug Administration recently approved pooled testing, where multiple samples are run at once, increasing capacity and saving lab supplies. But for one national lab, the approved pool size is just four samples. In Wuhan, China, up to 10 specimens were pooled, allowing the city to increase its capacity to 1.5 million tests daily, up from 46,000 tests daily.

Fund all necessary testing. Currently, under federal rules, “medically necessary” testing is free for those with Covid-19 symptoms, as well as asymptomatic people who have been exposed to the virus. But states should be able to conduct broad community screening — 40 percent of infected people are asymptomatic — to detect the virus and control its spread. For example, Congress should ensure testing is free for individuals who attend mass gatherings, regularly ride public transportation or interact with members of the public at work. New York is proof that a real testing strategy can control Covid-19. But our future success depends on other states to do the same — a virus anywhere is a virus everywhere.

COVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19.

This preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery.

Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both single and cumulative feature models (ROC AUC=0.72), with additional features providing no significant model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for ~50% of participants and was best predicted by time since illness onset.

Conclusions: As smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (10<OR<4), especially when viral lab tests are impractical or unavailable.

Preprint available at medRxiv (July 26, 2020):

https://doi.org/10.1101/2020.07.22.20157263

Accurate diagnostic strategies to rapidly identify SARS-CoV-2 positive individuals for management of patient care and protection of health care personnel are urgently needed. The predominant diagnostic test is viral RNA detection by RT-PCR from nasopharyngeal swabs specimens, however the results of this test are not promptly obtainable in all patient care locations. Routine laboratory testing, in contrast, is readily available with a turn-around time (TAT) usually within 1-2 hours. 

Here we present a machine learning model incorporating patient demographic features (age, sex, race) with 27 routine laboratory tests to predict an individual's SARS-CoV-2 infection status. Laboratory test results obtained within two days before the release of SARS-CoV-2-RT-PCR result were used to train a gradient boosted decision tree (GBDT) model from 3,346 SARS-CoV-2 RT-PCR tested patients (1,394 positive and 1,952 negative) evaluated at a large metropolitan hospital. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.853 (95% CI: 0.829-0.878). Application of this model to an independent patient dataset from a separate hospital resulted in a comparable AUC (0.838), validating the generalization of its use. Moreover, our model predicted initial SARS-CoV-2 RT-PCR positivity in 66% individuals whose RT-PCR result changed from negative to positive within two days. 

Overall, this model employing routine laboratory test results offers opportunities for early and rapid identification of high-risk SARS-COV-2 infected patients before their RT-PCR results are available. This may facilitate patient care and quarantine, indicate who requires retesting, and direct personal protective equipment use while awaiting definitive RT-PCR results.

Preprint available at medRxiv (June 19, 2020):

https://doi.org/10.1101/2020.06.17.20133892

According to researchers, authorities were able to prevent new infections with tough quarantine measures and strict testing on residents, whether they displayed symptoms or not. Vò, a small town in northern Italy, could offer clues on to how to deal with the coronavirus after health authorities appear to have stopped the spread of COVID-19, preventing any new infections. Italy's first death from COVID-19 was recorded in the northern town of Vò, a 3,300-strong community in the Province of Padua 30 miles (50 kilometers) from Venice. Scientists involved say it was an experimental initiative that enabled them to create a full "epidemiological picture" of COVID-19, Financial Times reports.

Since the start of the outbreak, authorities have been testing and retesting each of the town's inhabitants. The tests were performed on people whether or not they were displaying symptoms of the disease. By some reports, between a half and three-quarters of carriers in Vò, were asymptomatic. Anyone who was found to be infected with the new coronavirus was then put into quarantine—as was everyone they had come into contact with. Testing began in late February when roughly 3 percent of Vò residents were infected with the virus that causes COVID-19. Half were asymptomatic—therefore displayed no symptoms like fever, cough and shortness of breath typical of the disease. A second round of testing days later revealed the infection rate had fallen to 0.3 percent. "On the second testing that was carried out, we recorded a 90 percent drop in the rate of positive cases. And of all the ones who were positive in the second testing, eight people were asymptomatic," said Professor Andrea Crisanti, an infections expert at Imperial College London on sabbatical at the University of Padua in Italy, Sky reports.

The success of the policy suggests aggressive testing combined with thorough quarantine of anyone who may be infected may help curb the outbreak in other places. By testing everyone and not just those who showed symptoms, local authorities were able to quarantine asymptomatic carriers—something that could not be achieved with more typical testing methods used to confirm COVID-19 in people already showing signs of the illness.

Testing for the novel coronavirus in the Seattle area will get a huge boost in the coming weeks as a project funded by Bill Gates and his foundation begins offering home-testing kits that will allow people who fearthey may be infected to swab their noses and send the samples back for analysis.

Results, which should be available in one to two days, will be shared with local health officials who will notify those who test positive. Via online forms, infected people can answer questions about their movements and contacts, making it easier for health officials to locate others who may need to be tested or quarantined, as well as to track the virus’ spread and identify possible hot spots. The goal is to eventually be able to process thousands of tests a day, said Scott Dowell, leader of coronavirus response at the Bill & Melinda Gates Foundation. The project is ramping up as quickly as possible, but it’s not clear exactly when it will launch, he added. Among other things, software needs to be upgraded to handle the expected crush of requests, and a detailed questionnaire finalized for people who request tests. 

“Although there’s a lot to be worked out, this has enormous potential to turn the tide of the epidemic,” Dowell said. While Public Health – Seattle & King County has confirmed 71 cases and 15 deaths as of Saturday,  modeling by Trevor Bedford, a computational biologist at Fred Hutchinson Cancer Research Center, estimated on Wednesday that the actual number of cases in the Seattle area was about 600. Unchecked, that could theoretically increase to 12,000 cases – and possibly as many as 30,000 – by the end of March, according to projections from Mike Famulare at the Institute for Disease Modeling in Bellevue. But steps to slow transmission can significantly reduce the number of new infections, underscoring the importance of acting quickly to protect people from the virus. The new effort aims to leverage the formidable resources and expertise of the Gates Foundation, known for fighting disease and epidemics around the globe, to assist local health agencies struggling to keep up with a fast-moving outbreak.....

Even as the United States ramped up coronavirus testing from about 100,000 per week in mid-March to more than 5 million per week in late July, the country fell further behind in stemming the spread of the virus. Now, diagnostics experts, public health officials, and epidemiologists are calling for a radical shift in testing strategy: away from diagnosing people who have symptoms or were exposed and toward screening whole populations using faster, cheaper, sometimes less accurate tests. By making it possible to identify and isolate infected individuals more quickly, proponents say, the shift would slow the virus' spread, key to safely reopening schools, factories, and offices. “America faces an impending disaster,” says Rajiv Shah, president of the Rockefeller Foundation. Testing, he says, needs to focus on “massively increasing availability of fast, inexpensive screening tests to identify asymptomatic Americans who carry the virus. Today, we are conducting too few of these types of tests.” Rebecca Smith, an epidemiologist at the University of Illinois, Urbana-Champaign (UIUC), agrees. To stop outbreaks from overwhelming communities, she says, “we need fast, frequent testing,” which could mean faster versions of existing RNA tests or new kinds of tests aimed at detecting viral proteins. But researchers say the federal government will need to provide major financial backing for the push.

Today, COVID-19 testing relies primarily on the polymerase chain reaction (PCR), a technique to amplify the virus' genetic material, making it easy to detect. If administered properly, such tests are highly accurate, spotting positive cases nearly 100% of the time. That accuracy is vital for decisions about treating individual patients. But PCR tests cost about $100 each, require specialized machinery and reagents, and typically take at least 1 to 2 days to return results. The recent increase in coronavirus cases across the United States has added to the delay, pushing wait times to 2 weeks in some places. While they wait, people who are infected but don't yet know it may continue to interact with others and spread the virus. And if their infective period ends before they get their results, isolating them won't help. “It's like calling the fire department after your house burns to the ground,” says A. David Paltiel, an operations research expert at the Yale School of Public Health. “You can't play catch up with this virus.” A 24 July preprint on medRxiv underscored the downsides of slow tests. Shixiong Hu, a researcher with the Hunan Provincial Center for Disease Control and Prevention, and his colleagues followed 1178 people who tested positive for SARS-CoV-2 from January to April and tested their 15,648 contacts, defined as people who had been within 1 meter of a positive person between 2 days before and 14 days after the person's symptoms began. Based on which contacts were infected and when, the researchers estimated that people were most likely to spread the virus 1.8 days before the onset of symptoms. The finding suggests testing people only when they show symptoms and giving them test results days to weeks later does little to slow viral spread, says Daniel Larremore, an applied mathematician at the University of Colorado, Boulder...

A quick, cheap and painless test that detects SARS-CoV-2 RNA in spit could be used for mass testing. Chantal Vogels at Yale School of Medicine in New Haven, Connecticut, and colleagues developed a simple saliva test — called SalivaDirect — to address the growing demand for extensive testing as lockdowns lift (C. B. F. Vogels et al. Preprint at medRxiv http://doi.org/d5s3; 2020).

Compared with the gold-standard nose and throat swab, the saliva test is less invasive, does not need to be conducted by a trained professional and avoids the use of scarce chemicals that are needed to store and extract viral RNA. In validation experiments, SalivaDirect detected 32 out of 34 samples that tested positive in nose and throat swabs, and 30 out of 33 negative samples. The researchers estimate a cost-per-spit of US$1.29–$4.37, and have requested that the United States Food and Drug Administration authorize the test for emergency use.

Preprint of study available at medRxiv (August 4, 2020):

https://doi.org/10.1101/2020.08.03.20167791

Early and accurate detection is critical for preventing the spread of COVID-19 and providing appropriate care for patients. Nasopharyngeal (NP) swabs, which require inserting a long shaft into the nasal cavity to collect a sample from the back of the nose and throat, are currently the gold standard for collecting a specimen for diagnosis. But the procedure is technically challenging, often uncomfortable for patients and requires personal protective equipment that may be in short supply. Other approaches to collecting specimens—including from an oropharyngeal swab and sputum—have been tested in small studies, but there is uncertainty about which method is best for detecting the virus. In a new study published in EBioMedicine, investigators from Brigham and Women's Hospital conducted a systematic review and meta-analysis, analyzing data from more than 3,000 specimens to compare the three approaches. The team found that sputum testing detected the RNA of the virus that causes COVID-19 at significantly higher rates while oropharyngeal swab testing had lower rates. Regardless of the collection method, the earlier samples were collected after symptoms began, the higher the detection rate.

"The accurate diagnosis of COVID-19 has implications for health care, return-to-work, infection control and public health," said corresponding author Jonathan Li, MD, a faculty member in the Division of Infectious Diseases at the Brigham. "Our gold standard in and out of the hospital is the nasopharyngeal swab, but there's a lot of confusion about which sampling modality is best and most sensitive. Our study shows that sputum testing resulted in significantly higher rates of SARS-CoV-2 detection and supports the use of this type of testing as a valuable method for the diagnosis and monitoring of COVID-19 patients." Li and his colleagues scoured the literature—both preprints and published papers—for studies that assessed at least two respiratory sampling sites using an NP swab, oropharyngeal swab or sputum. From more than 1,000 studies, they identified 11 that met their criteria. These studies included results from a total of 3,442 respiratory tract specimens. The team examined how often each collection method produced a positive result. For NP swabs, the rate was 54 percent; for oropharyngeal swabs, 43 percent; for sputum, 71 percent. The rate of viral detection was significantly higher in sputum than either oropharyngeal swabs or NP swabs. Detection rates were highest within one week of symptom onset for all three tests.

Study Published in EbioMedicine (July 18, 2020):

https://doi.org/10.1016/j.ebiom.2020.102903

Millions of people in Wuhan will be tested for the novel coronavirus within the coming days, after a new cluster of cases emerged despite a strict 76-day lockdown that was intended to eliminate the virus. Over the weekend, six new cases were reported in the city, the first in 35 consecutive days. None of the new cases were imported from overseas, sparking concern that the infection could still be spreading in the city where the virus is thought to have first emerged. In response to the outbreak, authorities in Wuhan will conduct city-wide nucleic acid testing over a period of 10 days, according to an emergency notice issued by local authorities and circulated by state run media outlet The Paper.

Nucleic acid tests work by detecting the virus' genetic code, and can be more effective at detecting the infection, particularly in the early stages, than tests which examine a body's immune response, though the latter are easier to conduct. The ambitious screening drive, described in the report as a "ten-day battle," could see up to 11 million people tested -- more than the entire population of Greece. Wuhan was the first city in the world to enter into lockdown and great effort has been expended in an attempt to eliminate the virus.

South Koreans are tested for COVID-19 in “drive-thru” spots. Patients go through a pre-screening booth where their symptoms are recorded and body temperature taken, then a nasal swab is taken. Results are received by text in 24h. If you have COVID-19 symptoms, the test is covered by the Government and you pay only 20% of the cost, about US$ 30. If you have no symptoms and you still wish to get tested, then you pay the entire amount, about US$ 150.

All South Koreans enjoy a universal “Medicare-type” insurance system provided by their government. Citizens pay a monthly tax in their paycheck. The cost varies depending on the income of the person. Cost is heavily biased, so wealthier individuals pay significantly more. A significant fraction of the population pays nothing at all. On average, South Koreans pay about US$ 100 per month (yes ! no typo, one hundred dollars).

The Government-based care usually covers most needs at 80%, and some at 100%. Citizens have the freedom to choose the hospitals and health facilities they visit. South Koreans can also access to corporate-based medical insurance if they wish. The South Korean government, as the major provider of health care, plays a major role in taken care of the prevention, surveillance and administration of therapies to its population. The differences with the US system are clear. Few people in South Korea complain about their health care system, which runs in the top 10% of the world’s health systems.

Next time you have to vote, think about the next pandemic, the choices you’ll have, and what your candidate plans to do with the dysfunctional insurance-bases health care system we have in the U.S.