Johns Hopkins Medicine researchers are working tirelessly to find ways to better understand, treat and eventually eliminate COVID-19 and the illness that results from infection. New discoveries and observations from Johns Hopkins that we share here, especially those related to clinical therapies, are almost uniformly early in concept. They will require rigorous research, testing and peer review before solid conclusions for clinical care and disease prevention can be made.
In addition, Johns Hopkins researchers are conducting a variety of clinical trials to find new ways to detect, prevent and treat COVID-19. These trials include studies involving Johns Hopkins employees, people who have COVID-19 and analysis of collected data about the illness. Results of these clinical trials will be available when data is analyzed, peer-reviewed and published.
How Coronaviruses Work
Coronaviruses are tiny. They’re so small that scientists need a special microscope to spot them. This video animation is an artist’s rendering of how coronaviruses invade, replicate and assemble a new army of viruses inside a host cell.
To build a better vaccine, stop a virus from replicating or attaching to host cells, help the immune system fight the virus, or any type of remedy to the current pandemic of COVID-19, scientists need to understand how coronaviruses work. These scientists focus on the so-called “basic” or “fundamental” biology of viruses.
For example, coronaviruses are known to invade and replicate within host cells, and newly made viruses escape through the host cell’s outer membrane. But instead of going straight to the cell membrane to get ready to be shipped out of the host cell, coronaviruses stop at a pancake-like structure in the cell called the Golgi complex, a kind of post office that sorts and processes proteins and spits them out of the cell after enclosing the proteins in a compartment called a vesicle.
Johns Hopkins scientists have been working to determine why coronaviruses make this extra stop in their replication and escape process. One reason, they found, is that coronaviruses neutralize the acidity of the Golgi complex, potentially paving a better path to help the viruses, with their spiky halo, escape cells.
Date Posted: August 4, 2020 | Disclaimer
Johns Hopkins researchers have received $35 million in funding from the U.S. Department of Defense to test the effectiveness of a convalescent blood plasma outpatient treatment. The treatment is a transfusion of a blood product from COVID-19 survivors that contains antibodies that may help the patient’s immune system fight the virus.
Two clinical trials totaling 1,100 people will be conducted at over 20 outpatient centers in medical centers across the U.S., including the Navajo Nation, and will help researchers determine whether convalescent blood plasma therapy can effectively be used to treat people in the early stage of COVID-19 illness or prevent the infection in those at high risk of exposure to the virus at their home or jobs.
The prevention trial will include 500 people who have been exposed to COVID-19 in their home or at work as health care providers. A second trial will recruit 600 participants who have early COVID-19 disease, meaning they are within eight days of their first symptoms but are not sick enough to be in a hospital. All participants will be over age 18. The researchers aim to complete recruitment of participants to the trials in early fall 2020.
Convalescent blood plasma therapy involves transfusing a portion of blood called plasma from people who have recovered from the virus. When separated from red and white blood cells and platelets in the blood, plasma is the yellow-tinged liquid that includes proteins called antibodies, which glom on to foreign substances such as viruses and either mark them for destruction by the immune system or disrupt a virus’ ability to multiply and grow.
There is very little clinical data proving the effectiveness of using the therapy in outpatient clinics, according to the researchers. Currently, only hospitalized patients have access to any type of therapy for COVID-19.
Leaders of the trials include Arturo Casadevall, M.D., Ph.D., Bloomberg Distinguished Professor who holds joint appointments in the Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins University School of Medicine, Shmuel Shoham, M.D., associate professor of medicine at the Johns Hopkins University School of Medicine, David Sullivan, M.D., professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, and Daniel Hanley, M.D., director for multisite clinical trials in the Johns Hopkins Institute for Clinical and Translational Research at the Johns Hopkins University School of Medicine.
Date Posted: July 30, 2020 | Disclaimer
Gastroenterologist Brindusa Truta and her colleagues are surveying 3,000 patients with inflammatory bowel disease (IBD), which is often treated with medications that suppress the immune system and reduce inflammation, to determine whether those with IBD are at higher risk of complications from COVID-19 illness.
“There is absolutely no data regarding IBD and the virus,” Truta says. “Therefore, we decided to go ahead and interview our patients from time to time about their infection status, their medications and other risk factors.”
It’s not yet clear how being on immunosuppressive medications can alter the variables and risk factors for contracting the pandemic coronavirus compared with typical adults not taking the medications, says Truta. IBD clinic staff at Johns Hopkins will be interviewing patients during telemedicine checkups or through questionnaires about their daily habits and activities, employment status, transportation and living arrangements. If patients have no symptoms of COVID-19 at the time of the interview, clinic staff members follow up with them later. If they do become infected, they’re asked to call the clinic to let them know, and to potentially have their medications adjusted.
“Every step in unlocking the economy is going to come with more interactions among people and more exposure,” she says. “Some of our patients will return to work, so we wanted to deploy our questionnaire at different points of time trying to capture what happens.”
So far, patients have been very willing to share their information. Some who did develop symptoms called the clinic to say what they were doing and how they think they became infected. Based on the evidence gathered so far, says Truta, the virus does not currently appear to impact this population any worse than the general population. Most patients infected and on immunosuppression seem to recover without going to the hospital, with some variations based on age and whether a person has two or more chronic health conditions.
“You would expect that patients who are on medications to lower their immune response, as many of our IBD patients are, would have a higher risk of getting infected [with coronavirus] and a poorer outcome, but based on our data so far, we are not seeing that,” Truta says. “They don’t have better outcomes than the general population, but I think that they are better than we expected.”
Date Posted: July 23, 2020 | Disclaimer
Based on data gathered during the COVID-19 pandemic, researchers at Johns Hopkins Medicine and the Connecticut Children’s Medical Center found that social media, primarily Twitter, is an effective way to keep care teams at pediatric intensive care units (PICUs) around the world connected and informed during a global medical crisis.
Among the massive volume of tweets with a COVID-19 hashtag posted during February to May were ones that included a second hashtag, #PedsICU — a social media designation created long before the pandemic to foster international collaboration, rapidly disseminate information and keep the lines of professional communication flowing among members of the pediatric critical care community.
“We wanted to determine if leveraging social media, specifically Twitter, was a solid strategy for keeping PICUs across the globe connected and informed on the most current information during a pandemic,” says Sapna Kudchadkar, M.D., Ph.D., associate professor of anesthesiology and critical care medicine.
To conduct their study, Kudchadkar and co-investigator Christopher Carroll, M.D., M.S., research director of pediatric critical care at the Connecticut Children’s Medical Center, collected data on all tweets posted worldwide from Feb. 1 to May 2 that contained the hashtag #PedsICU, along with those containing both #PedsICU and a recognizable COVID-19 hashtag, such as #COVID19.
There was a sharp rise in tweets with both hashtags around mid-March, which coincided with the World Health Organization raising COVID-19 to pandemic status. Since then, more than two-thirds of #PedsICU tweets were about the disease. About a third of the tweeters were physicians, but the researchers note there were also tweets from other PICU team members, including nurses, nurse practitioners, respiratory therapists and pharmacists.
The most popular tweets during the study period, the researchers say, were links to medical literature, reviews, educational videos and other open-access resources.
“Our study demonstrates that during a pandemic such as COVID-19, targeted use of #PedsICU combined with a specific disease-related hashtag significantly helps combat misinformation, quickly spreads useful data and news, and optimizes the reach of pediatric critical care stakeholders to others around the world,” says Kudchadkar.
Date Posted: July 20, 2020 | Disclaimer
Tiny, spherical pods float from one cell to another through the crowded space of other cells and fluids such as blood and mucus. These package-like pods are unassuming. They slip past other cells and complex tissues, intent on delivering their contents to the intended recipient.
After pinching off from the cell, these packets carry specific content from the cells they came from, much like a letter in the mail.
These postal pockets that are ferried between cells are known by scientists as extracellular vesicles. Since they carry contents from within a cell, scientists believe these packets can provide clues about pathogens or diseases that may be harboring within cells.
For decades, this valuable insight has led researchers to explore the possibilities extracellular vesicles might hold for disease diagnosis, monitoring and even treatment.
Johns Hopkins Medicine researcher Kenneth Witwer, Ph.D., has studied extracellular vesicles for much of his career and is the executive chair of science and meetings for the International Society for Extracellular Vesicles.
Witwer suggests that extracellular vesicles may be able to help researchers studying COVID-19 in three ways:
- Make a stronger vaccine for COVID-19,
- Develop a way to repair lung damage and autoimmune responses to COVID-19 and
- Monitor COVID-19 treatment effectiveness in patients.
Date Posted: July 6, 2020 | Disclaimer
In a new analysis of SARS-CoV-2, the virus that causes COVID-19, test results for nearly 38,000 people have shown a positivity rate among Latinx populations about three times higher than for any other racial and ethnic group. The findings, published June 18 in the Journal of the American Medical Association (JAMA), adds to evidence of much higher COVID-19 infection rates among U.S. minorities, particularly in the Latinx community.
Out of 37,727 adults and children tested between March 11 and May 25 across five Johns Hopkins Health System hospitals, including emergency departments, and 30 outpatient clinics in the Baltimore-Washington area, 6,162 tests came back positive. Of those tests, the positivity rate for Latinx was 42.6%, significantly higher than those who identified as Black (17.6%), other (17.2%) or white (8.8%).
Among those who tested positive, 2,212 were admitted to a Johns Hopkins Health System hospital. The study data show that Latinx patients were less likely to be admitted to the hospital (29.1%), compared with Black (41.7%) and white (40.1%) patients.
Researchers Diego Martinez, Ph.D., assistant professor of emergency medicine, and Kathleen R. Page, M.D., associate professor of medicine and a study member, suggest that crowded living conditions, lack of health insurance, fear of deportation and need to work in conditions more likely to expose them to infection all contributed to the higher rate of positive tests.
Date Posted: July 1, 2020 | Disclaimer
A new study by Johns Hopkins researchers found that it may take between seven and 16 months for surgeons across the U.S. to complete the backlog of elective orthopaedic surgeries that have been suspended during the COVID-19 pandemic. Elective surgeries, not necessarily optional, are ones that can be planned in advance. This accounts for more than a million surgeries in the U.S. for spinal fusion and knee and hip replacements.
The study was published online May 12 in The Journal of Bone and Joint Surgery.
Lead author Amit Jain, M.D., chief of minimally invasive and outpatient spine surgery and associate professor of orthopaedic surgery and neurosurgery at the Johns Hopkins University School of Medicine, says that in fields such as orthopaedic surgery, where procedures are frequently performed in an inpatient setting, the ramp-up may be slower than surgeries typically done in outpatient facilities. “We will keep adding to the backlog as long as we are not operating at 100% capacity,” states Jain.
Jain and his colleagues used the Agency for Healthcare Research and Quality National Inpatient Sample, a national database that contains hospital inpatient data, to model the number of current and forecasted spinal fusion and hip and knee replacement surgeries in the United States. The researchers found that, in an optimistic scenario where most elective surgeries are back to full capacity in June, it would take approximately seven months to get through the backlog. Delays to the ramp-up to full capacity could extend the backlog to 16 months.
To help ease the backlog, Jain proposes several strategies to increase surgical throughput, including more use of telemedicine. At Johns Hopkins, telemedicine use has skyrocketed. He also suggests making more timeslots available in operating rooms for orthopaedic surgeries, increasing care coordination resources and shifting care to ambulatory surgery centers as much as possible.
Along these lines, researchers in the Johns Hopkins dermatology department are working with the Johns Hopkins Carey School of Business to study the impact of deferred procedures on health care operations and finances, the effects on disease and patient-reported outcomes and how to solve the problems that ensue.
Date Posted: June 19, 2020 | Disclaimer
One of the most common ways to diagnose COVID-19 is the reverse transcriptase polymerase chain reaction test (RT-PCR), which uses a sample from a person’s nasal passages to detect particles from the SARS-CoV2 virus, which causes COVID-19.
These tests have played a critical role in our nation’s response to the pandemic. But, while they are important, researchers at Johns Hopkins have found that the chance of a false negative result — when the virus is not detected in a person who actually is, or recently has been, infected — is greater than 1 in 5 and, at times, far higher. The researchers caution that the test’s ability to detect the virus may not always yield accurate results, and timing of the test seems to matter greatly in the accuracy.
In the report on the findings published May 13 in the journal Annals of Internal Medicine, the researchers found that the probability of a false negative result decreases from 100% on Day 1, meaning highly likely to be a false negative, to 67% on Day 4, meaning still very likely to have a false negative result. The false negative rate decreased to 20% on Day 8 (three days after a person begins experiencing symptoms). They also found that on the day a person started experiencing actual symptoms of illness, the average false negative rate was 38%. In addition, the false negative rate began to increase again from 21% on Day 9 to 66% on Day 21.
The study, which analyzed seven previously published studies on RT-PCR performance, adds to evidence that caution should be used in the interpretation of negative test results, particularly for individuals likely to have been exposed or who have symptoms consistent with COVID-19.
Date Posted: June 16, 2020 | Disclaimer
The ongoing COVID-19 pandemic has severely impacted the manufacturing and supply chains for many products. But while shortages of toilet paper, disinfectant cleaners and hand sanitizer get most of the news coverage, the diminishing reserve of one item — kidney dialysis fluid, also known as dialysate — presents a grave threat to the lives of people with acute kidney injury (AKI), including the approximately 3% to 9% of COVID-19 patients who develop the disorder.
Without the special type of 24-hour, slowly administered dialysis — called continuous veno-venous hemodialysis, or CVVHD — that is given to AKI patients in an intensive care unit, damaged kidneys cannot remove wastes and excess fluids from the blood as they normally do. Unfortunately, the COVID-19 pandemic has severely tapped dialysate supplies across the nation.
When two New York-based hospitals recently contacted Derek Fine, M.D., clinical director of nephrology at the Johns Hopkins University School of Medicine, to seek spare dialysate to help meet their need for some 3,000 liters per day (for all of their AKI patients in ICUs, both with and without COVID-19), he and Chirag Parikh, M.D., Ph.D., M.B.B.S., director of the medical school’s Division of Nephrology, came up with a better idea to remedy the problem.
Their solution was to replace the dwindling stocks of pre-mixed, commercially produced dialysate required for short-term ICU kidney dialysis machines with a suitable substitute manufactured by conventional hemodialysis devices and designed for long-term treatment.
The latter creates its own dialysate in real time from ultrapure water and concentrated chemical solutions.
Fine, Parikh and colleagues from their division studied the workings of a conventional dialysis machine, learned how it manufactures dialysate and then adjusted the system to override alarms, which if triggered would automatically shut down dialysate production. However, one major obstacle remained: how to get the newly minted dialysate into bags.
No problem, thanks to students from the Johns Hopkins University Department of Biomedical Engineering. In just 12 hours, they designed a connector and used a 3D printer to render the plastic piece.
“When we tried it out, we were successfully able to capture the dialysate, and that was the eureka moment,” Parikh says.
The U.S. Food and Drug Administration has already provided guidelines for the method, calling for all dialysate produced to be tested intermittently for bacteria and used within 12 hours from its origin.
Date Posted: May 29, 2020 | Disclaimer
With a $195,000 grant from the National Science Foundation, Johns Hopkins researchers will use machine learning to study how to predict heart problems, such as heart failure, sustained abnormal heartbeats, heart attacks, cardiogenic shock and death, in people with COVID-19.
Heart problems are a common occurrence in COVID-19 patients, the researchers say, however, there is currently no predictive tool to specifically predict such problems in patients.
"This project will provide clinicians early warning signs and ensure that resources are allocated to patients with the greatest need," says bioengineering expert Natalia Trayanova.
Collecting Data and Testing
In the first phase of the one-year project, researchers will collect data on heart tests, vital signs and imaging data from more than 300 COVID-19 patients. This data will be used to train a computer algorithm.
Then, the researchers will test the algorithm with data from COVID-19 patients with heart injury. The hope is to create a predictive risk score that can determine, up to 24 hours ahead of time, which patients are at risk of developing heart problems.
"As a clinician, major knowledge gaps exist in the ideal approach for new heart problems that are common and may be life-threatening. These patients have varying clinical presentations and a very unpredictable hospital course,” says cardiologist Allison G. Hays.
Making the Tool Widely Available
This project will shed more light on how COVID-19-related heart injury could result in heart dysfunction and sudden cardiac death, which is critical in the fight against COVID-19. The project will also help clinicians determine which biomarkers are most predictive of the potential for harm to the patient.
Once the research team creates and tests their algorithm, they will make it widely available to any interested health care institution to implement.
Date Posted: May 26, 2020 | Disclaimer
As the COVID-19 pandemic was initially spreading, data from China and Italy suggested that only about 15% of people under the age of 50 were being hospitalized. However, when the disease reached the United States, physicians anecdotally noted what seemed like an uptick in the number of younger patients with COVID-19 serious enough to require intensive care.
Risk Factors for Severe COVID-19 Illness
Although preexisting conditions such as heart disease, diabetes or high blood pressure have been linked to greater susceptibility to the virus, obesity wasn’t on the radar as a risk factor early in the coronavirus outbreak. That’s because only about 6% of Chinese people and 20% of Italians are obese. The United States, on the other hand, has a 40% rate of obesity in adults, making researchers wonder if this might factor into the younger population’s showing up with severe disease.
Obesity and COVID-19
In a correspondence published on April 30, 2020, in The Lancet, Johns Hopkins researchers examined the link between age and obesity of American patients with COVID-19 hospitalized in intensive care units (ICUs).
- Seventy-five percent of the patients had a body mass index (BMI) of 26 or greater, indicating the person as overweight.
- 25% had a BMI higher than 35, designating the person as morbidly obese.
In general, they found that those patients in the ICU that were younger had higher BMIs, suggesting that younger Americans with obesity are likely at greater risk from COVID-19. The researchers say that young people should pay attention to physical distancing and stay vigilant about when to seek medical treatment in the early stages of their disease to help reduce the risks.
Date Posted: May 22, 2020 | Disclaimer
During the COVID-19 pandemic, most medical researchers have focused their studies on better understanding the direct effects of the disease in order to develop treatments and hopefully in the near future, a cure. However, two Johns Hopkins pediatric neurovirologists, Emily Severance, Ph.D., and Robert Yolken, M.D., are planning a study that will look for evidence of a possible secondary, long-term impact of COVID-19: greater susceptibility to serious psychiatric illnesses such as schizophrenia.
Researchers have long suspected that prenatal (before birth) and perinatal (during and immediately after childbirth) exposure to respiratory viruses — including coronaviruses such as the one behind the current outbreak — may increase a person’s chances of later developing a psychiatric disorder. In a 2011 study, Severance and Yolken showed that more than 90% of adults diagnosed with psychoses had high levels of antibodies to one or more of four coronaviruses common at that time.
Severance and Yolken now plan to look for a similar immunological link between psychiatric disorders and SARS-CoV-2, the virus that causes COVID-19.
Date Posted: May 14, 2020 | Disclaimer
As COVID-19 spreads around the globe, the disease has a severe impact on the lungs and may, unexpectedly, affect other parts of the body as well. One area of particular concern among researchers is the virus’s potential impact on the brain.
Among the first symptoms of COVID-19 is the loss of smell and taste, and there are reports of people in recovery struggling with cognitive impairment or stroke. According to researchers, these symptoms could be caused by neurons degenerating or damage to blood vessels that feed the brain.
“We need to get an understanding of how brain cells are affected by COVID-19, which cells are affected and how we can slow the damage,” says Valina Dawson, Ph.D., director of the neuroregeneration and stem cell programs at Johns Hopkins’ Institute for Cell Engineering.
Cell Types Affected by Coronavirus
Dawson plans to study cells in the nervous system that may be susceptible to damage from the virus. A Johns Hopkins team will start with the basic question of which cell types are affected by the coronavirus, looking at neurons as well as supportive cells in the brain, called glia and microglia, and the brain’s blood cells. Then, the team aims to use human stem cells to create “minibrains” in the laboratory that replicate how COVID-19 infections may affect the human brain.
“If we know how the disease progresses and in which brain cells, we can help inform future treatments,” says Dawson.
Studying Long-term Outlook for COVID-19 Patients
A second facet of the study will look at the long-term outlook for COVID-19 patients. Dawson aims to collaborate with pathology experts to examine the brains of people who died from COVID-19 illness. They will examine proteins in the brain, such as Tau and alpha synuclein, that are susceptible to misfolding. This trait causes them to aggregate in the brain, leading to damage to the surrounding tissues. These are the same proteins Dawson believes are responsible for the progression of neurodegenerative disease including Parkinson’s disease, Alzheimer’s disease and amytrophic lateral sclerosis (ALS).
Dawson suspects that the stress of a coronavirus infection on a person’s brain could drive these proteins to accumulate more quickly.
“We want to know if we could potentially face a tsunami of increased neurodegenerative disease onset among COVID-19 survivors,” says Dawson.
Read more about Valina Dawson’s work on Parkinson’s Disease in the Institute for Cell Engineering.
Date Posted: May 12, 2020 | Disclaimer
The COVID-19 tracker app is part of a research trial
Identifying the next COVID-19 outbreak may seem impossible to predict, but a new app that collects body temperature recordings may give researchers advance warning of an impending hotspot of illness.
The app, available through Google Play and the Apple App Store, asks users to record their body temperature and respond to questions about key COVID-19 symptoms. The data, which is not connected to a person’s name to protect privacy, is linked to a randomly generated ID and stored on a secure server. Temperature and symptom data are mapped geographically to provide a display of anomalies occurring across the country.
“This type of data tracking could be really useful to enable targeted large-scale testing efforts,” says Robert Stevens, M.D., associate professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine. “It could allow us to identify beforehand areas that are at increased or decreased risk and inform decisions regarding mitigation and lifting physical distancing restrictions.”
Stevens worked with Frank Curriero at Johns Hopkins University’s Bloomberg School of Public Health and Ralph Etienne-Cummings at the Whiting School for Engineering to develop the app, which they dubbed ‘COVID Control – A Johns Hopkins University Study.
The team will analyze the data collected to identify unexplained increases in body temperatures and generate real-time risk estimates of potential COVID-19 outbreaks. This predictive tool will allow healthcare systems and government agencies to better deploy resources to mitigate the effects of the disease.
Read a recent article about the app in the HUB.
Date Posted: May 11, 2020 | Disclaimer
It’s one of the tiniest machines on the planet — about a hundred times smaller than the average cell. It’s so small that no scientist can spot it through a typical light microscope. Only with an electron microscope can we see its spiky surface. It’s not alive, and it’s not what most of us would think of as “dead.” This teensy machine seems to survive in a kind of purgatory state, yet it has traveled across continents and oceans from host to host, and brought hundreds of nations to a standstill.
Despite its diminutive size, the novel coronavirus, dubbed SARS-CoV-2, has seemingly taken the world by surprise with its virulence. However, it’s not a surprise to cell biologist Carolyn Machamer, who has studied viruses for the past 45 years. Understanding the complex interaction between viruses and the cells they infect can help scientists develop better ways to prevent and treat the illnesses they cause.
Date Posted: May 6, 2020 | Disclaimer
A clinical guidebook is now available to help hospitals and medical centers rapidly increase their ability to deliver so-called convalescent plasma therapy, which leverages immune system components found in the plasma portion of blood from people who have recovered from COVID-19.
Right now there are no therapies or effective vaccines for treating COVID-19. The U.S. Food and Drug Administration has paved the way for researchers at Johns Hopkins to proceed with clinical trials to test convalescent plasma therapy in people who are at high risk for severe COVID-19 and have been exposed to people who have tested positive for the virus that causes it.
Date Posted: May 6, 2020 | Disclaimer