Weekly COVID-19 Research Update
April 30, 2020
During the COVID-19 pandemic, it is vital to make objective and informed decisions that affect your family and loved ones. As part of Princeton Longevity Center’s strategic partnership with PinnacleCare, we are excited to bring you their Pandemic Response Research updates as a complimentary resource through the remainder of this crisis. These updates will bring you factual, objective, scientific information to help make safe decisions for you, your family and your community. Updates, while scientifically based, are easy to understand and will include both resources and references for a more clinical insight.
Strokes in Younger Individuals with Mild COVID-19
Doctors in New York City reported last week that they saw a sevenfold increase in the number of strokes over a two-week period in people with COVID-19 (Worcester, 2020). Importantly, all of the cases involved individuals with mild or no symptoms. Those affected were also younger, between the ages of 30 and 40, than those who have previously been reported to have a high risk of severe symptoms from COVID-19. The typical median age for similar types of strokes is 74 years of age (Cha, 2020). Another highly visible news story involved the Broadway star Nick Cordera, aged 42 years, who had to have his leg amputated due to the formation of a blood clot. The scope of the problem is currently unknown, and there are concerns due to the fact that the New York City Fire Department was picking up four times more people who died at home than usual when the number of people infected in the city reached its peak. Few of those who died at home were examined with an autopsy, and it is unknown how many have died from a sudden stroke.
The doctors in New York have submitted a paper to the New England Journal of Medicine that is expected to be published on April 29 with more details of the cases (Worcester, 2020). These reports add to the growing evidence that there are changes in the process of blood clotting from SARS-CoV-2 infection. Blood clots that form when they are not needed, called thrombosis, can block the flow of blood causing a stroke, heart attack, or other life-threatening problems. Doctors have hypothesized that changes in the surface of blood vessels due to an inflammatory response from SARS-CoV-2 infection are driving the thrombosis associated with COVID-19.
Additional reports from hospitals around the world have also highlighted the association between COVID-19 and thrombosis. Johns Hopkins hospital in Baltimore, Maryland and Thomas Jefferson University Hospital in Philadelphia, Pennsylvania have reported an increase in the number of patients in their 30s being treated for COVID19-associated strokes. In the Netherlands, investigators have reported a 31% rate of thrombotic complications in 184 individuals receiving critical care for COVID-19 (McNamara, 2020). Two reports published in the journal Radiology, state that 23% of COVID-19 patients had acute pulmonary embolus at a US center with 30% at a French care center (Wendling, 2020). Autopsies of five people who died from COVID-19 showed “catastrophic microvascular injury” in the lungs due to the formation of blood clots (Magro et al., 2020). In a study of over 200 people in Wuhan, China, 36.4% had neurological manifestations, including cerebrovascular disease, with the incidence higher in those with severe symptoms (Yasgur, 2020). There was also a high degree of activation of blood coagulation pathways in the group with a correlation between higher levels in those who did not survive (Spyropoulos et al., 2020 and Mao et al., 2020).
The Journal of the American College of Cardiology published an overview of the problem that was written by a 36-person international collaboration in two weeks (Wendling, 2020). The report summarizes the available evidence on the pathogenesis, diagnosis, and management of thrombosis in patients with COVID-19. There is a balance needed between medications that prevent the formation of clots and the risk of substantial bleeding events. Physicians at New York–Presbyterian Hospital/Columbia University have observed people with COVID-19 who are being treated with anticoagulant medications with major bleeding events. Prediction of which people would benefit from more intensive anticoagulation has been difficult. The Emory University health system in Atlanta, Georgia has seen as many as 20% to 40% of patients who were on anticoagulation medication that were still developing clots (Cha, 2020).
Chloroquine for COVID-19
The FDA released a warning about the use of chloroquine due to an increased risk of heart dysfunction (FDA, 2020). The safety warning recommends that chloroquine be administered only in a hospital setting or through a clinical trial. There are an increasing number of reports of inappropriate treatment of COVID-19 in non-hospitalized patients or for prevention of SARS- CoV-2 infection. Use of chloroquine is associated with a higher risk of serious heart rhythm problems that can be life-threatening and require monitoring by healthcare professionals during treatment.
The Poison Control Center administration has reported an increase in the number of deaths and serious heart-related adverse events in patients with COVID-19 receiving hydroxychloroquine and chloroquine, either alone or combined with azithromycin.
The FDA recommends use of chloroquine, or the related drug hydroxychloroquine, only when patients can be appropriately monitored in the hospital to prevent cardiac-related events. The types of cardiac problems that have been observed include abnormal heart rhythms and dangerously rapid heart rate (or ventricular tachycardia). People with existing heart or kidney disease are at an even higher risk of cardiac complications.
Physicians from the United States Veterans Health Administration medical centers also recently released a pre-print report on use of hydroxychloroquine alone or in combination with azithromycin (Magagnoli et al., 2020). The report includes a review of the medical records of patients hospitalized with confirmed SARS-CoV-2 infection in all VA Medical Centers until April 11, 2020. There were 368 individuals treated for COVID-19, and 97 received hydroxychloroquine, 113 received hydroxychloroquine and azithromycin, and the remaining 158 were not treated with hydroxychloroquine. The rate of death was lowest, 11.4%, in the group NOT treated with hydroxychloroquine while the rate was 27.8% in those treated with hydroxychloroquine and 22.1% in those treated with hydroxychloroquine and azithromycin.
Based on their results, the authors conclude that there was no evidence that the use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19.
JAMA recently published a randomized and controlled study in Brazil that investigated the outcome of individuals with COVID-19 who were treated with either high or low doses of chloroquine diphosphate (Borba et al., 2020). During the study, 81 adult individuals who were hospitalized with SARS-CoV-2 infection were monitored between March 23 and April 5. In total, 41 received the high-dosage and 40 received the low dose for 13 days. There was a higher rate of lethality during the 13 days of treatment in the high-dose group (39.0%, or 16 out of 41 died) when compared to the low-dose group (15.0%, or 6 of 40 died). The group receiving higher amounts of chloroquine diphosphate also had more people develop an irregular heartbeat, as measured by QTc interval, with 18.9% in the high-dose group and 11.1% in the low-dose group. There was also little improvement in the amount of viral shedding measured by PCR-based testing, and only 22.2% of the entire group had a negative test of respiratory secretions on day four of treatment.
Results from Serosurveys
As mentioned in a previous weekly update, a number of serosurveys are underway or being planned, and the results of the first have been announced. The results of the testing from Stanford, New York, Germany, and the Netherlands suggest that there are a very high number of previously undiagnosed people in the community, and the amount of people with COVID-19 in these studies ranged between 2% and 30% (Vogel, 2020).
These values suggest that the confirmed COVID-19 cases are a much smaller fraction of the true number of people infected and that the vast majority of infections have been mild enough to be undetected.
However, there has been a large amount of criticism over the results from these studies. One problem is that several of the research groups announced their findings in the press rather than in pre-prints or published papers, which allow other scientists to evaluate their research methods and conclusions.
In the Stanford study, a pre-print was released describing the collection of serological data from people in Santa Clara County, California (Bendavid et al., 2020). The same research group also participated in a similar study in Los Angeles County, but the results of that study were only released to the press, without accompanying scientific data and methods (Vogel, 2020). In the Santa Clara County study, 3300 people were recruited through Facebook ads to participate. Of the participants, about 1.5% were found to be positive for antibodies to SARS-CoV-2. There are problems with recruiting participants from Facebook because this method only reaches a particular demographic that normally has few low-income or minority populations. To account for this, Dr. Bendavid and colleagues adjusted the final outcome to better reflect the actual demographics of Santa Clara County. This type of adjustment is not ideal and can introduce errors depending on what assumptions are made in the calculation. After adjustment, the researchers concluded that between 2.49% and 4.16% of the county’s residents had likely been infected.
This figure increases the number of infected individuals to more than 50 times the number that were confirmed through PCR-based testing, which is a staggering difference.
A study based in New York State reported that 14% of those tested were positive for COVID-19 with the rate being as high as 20% in New York City, where the largest outbreak in the United States occurred (Chow, 2020). Similar questions about the results of this study have also been raised.
Critics of the studies also stated that even if the values do prove to be accurate, the number of people infected is still well below that needed to provide herd immunity to COVID-19.Experts report that upwards of 70% to 90% of a population needs immunity to stop community spread of an infection, depending on the how contagious the pathogen is (D’Souza and Dowdy, 2020).
Changes to the Coronavirus Transmission Timeline
New information about the earliest deaths in the United States was recently released that also may change the estimates for transmission within the country (Hohman, 2020). The medical examiner in Santa Clara County in California announced the results of autopsies on three people who died at their houses, which showed that the earliest death resulting from COVID-19 occurred in California on February 6. Previous information indicated that the first COVID-19 death occurred in Seattle, Washington on February 26.
The deaths in California are significant because there is currently no indication that the person who died on February 6 had traveled outside of the country, and therefore would have contracted COVID-19 through spread in the United States.
The discovery shows that there were cases missed due to the restrictions put in place for testing by the CDC. Other reports suggest that there was also spread of COVID-19 in Seattle weeks before official reporting. Genetic testing of the form of SARS-CoV-2 that spread through New York City and surrounding areas indicates that the initiating infections were from Europe rather than China, which could also change the timeline for significant spread occurring in Europe.
This information is important in order to produce accurate models of outbreak that can be used to determine what public health responses are needed.
FDA Approves In-Home PCR-Based Test from LabCorp
The FDA granted emergency approval to the first in-home test, called the Pixel, for the coronavirus, which is a nasal swab kit that will be sold by LabCorp. The company is first making the tests available to healthcare workers and emergency workers who may have been exposed to Covid-19 or be symptomatic. The availability to other consumers was described as “in the coming weeks.” Based on assessments, the home test is as safe and accurate as a sample collection at a doctor’s office or other testing site. After the sample is ready, swabs will be mailed in an insulated envelope to the lab. The test is expected to cost $119 out-of-pocket.
Department of Justice Disrupts Hundreds of Online COVID-19 Scams
On April 22, 2020, the Department of Justice announced they had reviewed more than 3,400 complaints related to COVID-19 scams (DOJ, 2020). The scammers advertised fake vaccines and cures, operated fraudulent charity drives, delivered malware, or hosted various other types of scams. Some use known organizations such as the American Red Cross and look-alike IRS stimulus payment domains to steal money or information from consumers. The FBI, Secret Service, U.S. Postal Service, and the FDA are coordinating their efforts against these types of scams. They state:
If you think you are a victim of a fraud or attempted fraud involving COVID-19, call the National Center for Disaster Fraud Hotline at 1-866-720-5721 or email at firstname.lastname@example.org. If it is a cyber scam, submit your complaint through https://www.ic3.gov.
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Borba MGS, Val FFA, Sampaio VS, et al. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial. JAMA Netw Open. 2020;3(4.23):e208857. Published 2020 Apr 24. doi:10.1001/jamanetworkopen.2020.8857
Cha AE. A mysterious blood-clotting complication is killing coronavirus patients. The Washington Post. Published April 22, 2020. Accessed on April 27, 2020 at https://www.washingtonpost.com/health/2020/04/22/coronavirus-blood-clots/
Cha AE. Young and middle-aged people, barely sick with COVID-19, are dying of strokes. The Washington Post. Published April 25, 2020. Accessed on April 27, 2020 at https://www.washingtonpost.com/health/2020/04/24/strokes-coronavirus-young-patients/
Chow D. What we can (and can’t) take away from New York’s antibody testing results. NBC News. Published April 23, 2020. Accessed April 27, 2020 at https://www.nbcnews.com/science/science-news/what-we-can-can-t-take-away-new-york-s- n1191106
Department of Justice. Department of Justice Announces Disruption of Hundreds of Online COVID-19 Related Scams. Published April 22, 2020. Accessed on April 27, 2020 at https://www.justice.gov/opa/pr/department-justice-announces-disruption-hundreds-online-covid- 19-related-scams
D’Sousa G, Dowdy D. What is Herd Immunity and How Can We Achieve It With COVID-19? COVID-19 School of Public Health Expert Insights. Published April 10, 2020. Accessed on April 23, 2020 at https://www.jhsph.edu/covid-19/articles/achieving-herd-immunity-with-covid19.html
FDA. Hydroxychloroquine or Chloroquine for COVID-19: Drug Safety Communication – FDA Cautions Against Use Outside of the Hospital Setting or a Clinical Trial Due to Risk of Heart Rhythm Problems. Published April 24, 2020. Accessed on April 27, 2020 at https://www.fda.gov/safety/medical-product-safety-information/hydroxychloroquine-or- chloroquine-covid-19-drug-safety-communication-fda-cautions-against-use
Magagnoli J et al. Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19. medRxiv. Published April 23, 2020. Accessed April 23, 2020 at https://doi.org/10.1101/2020.04.16.20065920
Magro C, Mulvey JJ, Berlin D, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases [published online ahead of print, 2020 Apr 15]. Transl Res. 2020;S1931-5244(20)30070-0. doi:10.1016/j.trsl.2020.04.007
Mao L, Jin H, Wang M, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China [published online ahead of print, 2020 Apr 10]. JAMA Neurol. 2020;e201127. doi:10.1001/jamaneurol.2020.1127
McNamara D. COVID-19 Linked to Large Vessel Stroke in Young Adults. Medscape News. Published April 24, 2020. Accessed on April 27, 2020 at https://www.medscape.com/viewarticle/929345
Spyropoulos AC, Ageno W, Barnathan ES. Hospital-based use of thromboprophylaxis in patients with COVID-19 [published online ahead of print, 2020 Apr 21]. Lancet. 2020;S0140- 6736(20)30926-0. doi:10.1016/S0140-6736(20)30926-0
Thomas K. F.D.A. Approves First In-Home Test for Coronavirus. The New York Times. Published April 21, 2020. Accessed on April 21, 2020 at https://www.nytimes.com/2020/04/21/health/fda-in-home-test-coronavirus.html
Wendling P. Finding the Right Balance in COVID-19 Thromboprophylaxis. Medscape News. Published April 24, 2020. Accessed on April 27, 2020 at https://www.medscape.com/viewarticle/929368
Worcester S. COVID-19 Daily: Stroke in Young Adults, Abbott Test Safety Issues. Medscape News. Published April 25, 2020. Accessed April 27, 2020 at https://www.medscape.com/viewarticle/929394
Yasgur, BS. COVID-19: First Data Confirm Neurologic Symptoms Common. Medscape News. Published April 16, 2020. Accessed April 27, 2020 at https://www.medscape.com/viewarticle/928848