Weekly COVID-19 Research Update
April 15, 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.
CDC Recommendation Updates
On April 8, the CDC updated its guidelines for essential workers that have been exposed to people infected with SARS-CoV-2 (Waldstein, 2020). Previously after exposure, workers were directed to self-quarantine for 14 days. In the new guidelines, workers who do not feel sick are able to return to work as long as they are able to follow certain precautions, including taking their temperature before leaving for their workplace, wearing a face mask at all times, and practicing social distancing while working (CDC. Implementing Safety Practices, 2020). The CDC also recommends increasing the air exchange where these workers are located and cleaning common surfaces more often. According to Robert Redfield, the director of the CDC, this change was put in place to “get these workers back into the critical work force so that we don’t have worker shortages.”
The CDC also released a report detailing the hospitalization rates for patients admitted with COVID-19 between March 1 and 28 and clinical data on 1,482 patients hospitalized between March 1 and 30, which was the first month of U.S. surveillance (Garg et al., 2020). The rate of hospitalization during this 4-week period was 4.6 people per 100,000 individuals in the population. Most of the people hospitalized were over 50 years of age (74.5%). When the hospitalization rate per 100,000 people in the population was determined based on age, it was found that the rates increased with age, and the rate was 0.3 in persons aged 0 to 4 years, 0.1 in those aged 5 to 17 years, 2.5 in those aged 18 to 49 years, 7.4 in those aged 50 to 64 years, and 13.8 in those older than 65 years. There was also a higher number of men hospitalized than women.
One striking detail about hospitalization rates that was that black Americans were found to require hospitalization more often than other groups. The breakdown of the people hospitalized showed that 45.0% were white, 33.1% were black, 8.1% were Hispanic, 5.5% were Asian, 0.3% were American Indian/Alaskan Native, and 7.9% were of other or unknown race. The percentage of black individuals in the population is estimated to be 18%, suggesting that black populations might be disproportionately affected by COVID-19.
There were 178 individuals whose medical history was available out of the group of 1482. Based on an analysis of this group, 89.3% had one or more underlying medical conditions, and the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). Hypertension seems to be associated with requiring hospitalization, because the prevalence of this condition among U.S. adults is 29% overall, while around 50% of hospitalized patients with COVID-19 are reported to have hypertension.
The CDC also releases weekly estimates of the hospitalization rate and mortality rate (CDC Key Updates, 2020). The hospitalization rate up to the week of March 29 was estimated to be 12.3 per 100,000, with the highest rates in those 65 years and older (38.7 per 100,000) and between the ages of 50 and 64 years (20.7 per 100,000). The mortality rate is determined based on death certificate data. The percentage of deaths attributed to COVID-19 increased from 4.0% the previous week to 6.9% during the week of March 29.
Relaxing Restrictions
With social distancing and more stringent physical distancing measures seemingly beginning to have an effect on the spread of COVID-19, officials have started planning for the eventual relaxation of the restrictions. There are several plans that have been released by public health researchers that outline a safe way to slowly ease restrictions and the consequences of moving too quickly. On April 10, The New York Times described a report from the departments of Homeland Security and Health and Human Services that outlines how removing shelter-in-place type of restrictions after 30 days would lead to a second, very high peak in the number of cases and deaths (New York Times, 2020). In the report dated April 9, government officials outlined that without any response to reduce the spread of COVID-19 there would have been an estimated 300,000 deaths.
Lifting stay-at-home orders after 30 days would still cause an estimated 200,000 deaths even if schools remain closed until summer, 25% of the country continued to work from home, and some social distancing continues.
The spike in the number of cases and deaths was projected to occur about 150 days after lifting the stay-at-home restrictions. Several countries in Asia and Europe have begun lifting restrictions due to a reduction in the number of new cases of COVID-19 reported each day, and public health officials are watching carefully to see if a second spike in new cases emerges (New York Times, 2020). In Italy, some businesses are being allowed to reopen with the rest of the country on lockdown until May 3. In Spain, construction workers are being allowed to return to work, but there are questions about whether there has been a sustained reduction in the number of new cases in Spain because of a small spike over the weekend of April 11. China has been restarting factories and lifting travel restrictions in Wuhan, but there has been a recent uptick in the number of new cases stemming from citizens returning from Russia, where the infection rate is climbing rapidly.
In an interview with international media, a doctor from Wuhan’s Jinyintan Hospital raised a concern that a small number of people have remained hospitalized for an extended time after contracting COVID-19 (Page, 2020). There are patients that have been hospitalized for more than 60 days, which reduces the capacity to deal with future outbreaks. Hospitals in the United States are starting to see shortages of antibiotics, antivirals and sedatives required for patients on ventilators, and other drugs produced in countries where the pandemic has halted or curbed manufacturing (Rowland and Slater, 2020). There are also shortages of albuterol inhalers to treat asthma in hospitals and retail pharmacies because physicians have had to stop using nebulizer treatments due to concerns over aerosol formation. In the case of the sedatives, a lack of the required drugs would keep doctors from being able to safely intubate patients even if ventilators are available. The FDA has a limited ability to monitor the global supply chains for drugs and the ingredients imported by the United States to produce the medicines needed at higher demand from the increase in COVID-19 cases. Because of a lack of a system to monitor supplies, the sudden jump in demand resulted in only a few days warning for manufacturers. The University of Minnesota has analyzed the supply chain and has identified 156 drugs that could go into shortage in the next 90 days, but they have not released the list as it is considered preliminary and could lead to further panic buying.
Sufficient amounts of personal protective equipment will also be required for use in a potential second outbreak of COVID-19. The Center for Health Security at the Johns Hopkins Bloomberg School of Public Health released an estimate of the needed personal protective equipment for a 100 day long outbreak in the United States with an assumption of strict adherence to social distancing efforts in place as of April 8 (Toner, 2020). They included equipment needed for hospital inpatients (intensive care and non-intensive care), emergency departments, emergency medical services, outpatient visits, and nursing homes.
They added that if there is also widespread use of medical-grade masks by the public, an additional 150 million or more per day (or 4.575 billion per month) would be needed until a vaccine is available.
Serological Testing
Serological testing is an evaluation of antibodies in the blood to determine if an individual has been exposed to SARS-CoV-2. When they are properly calibrated they can also report on whether an individual is expected to be immune to future infection. A number of tests have been developed, but there is still ongoing research to determine their accuracy. The first role of serological tests is expected to be measuring transmission in the population rather than determining immunity (Abbott and Roland, 2020).
The FDA granted emergency use authorization to a serology test made by Cellex Inc. on April
- At least 70 other companies and laboratories have told the agency they are offering serological testing, though the FDA has not reviewed those tests. Several localities have started broad serological testing measures in the United States to estimate the spread of the virus.
Potential Treatments for COVID-19
A number of trials for different drugs are ongoing. The trial investigating remdesivir that began at the University of Nebraska in February has indicated that the first results will be ready within weeks as of April 9 (Kolata, 2020). About 400 patients are now enrolled at multiple sites, which allows for a preliminary analysis to determine if the results are promising and should continue.
Chloroquine
The pivotal study from researchers in France that focused interest on chloroquine has received a large amount of criticism from researchers around the world (Retraction Watch, 2020). There have been questions about the report’s ethical underpinnings, messy variables that may affect the outcome, missing patients, rushed and conflicted peer review, and confusing data. Based on the subsequent reviews, the International Journal of Antimicrobial Agents, the journal that published the report, has since released a statement from the International Society of Antimicrobial Chemotherapy, which is responsible for publication of the journal. The statement asserts that the article “does not meet the expected standard, especially relating to the lack of better explanations of the inclusion criteria and the triage of patients to ensure patient safety.” While the response suggests that the validity of the study is in question, the typical process of retracting the article from the journal has not occurred. Additionally the International Society of Antimicrobial Chemotherapy has not announced that it is taking any additional action, which has left researchers in the field confused on the reaction.
A study in Brazil investigating the effect of chloroquine in people with COVID-19 was halted due to a high number of cardiac complications (Thomas and Sheikh, 2020). The study included 81 participants who were hospitalized due to COVID-19. The doses used in the study were 450 milligrams of chloroquine twice daily for five days or 600 milligrams for 10 days. All the participants were also treated with azithromycin, which has been shown to have heart-related complications in the past. Within three days of starting treatment, there was evidence of heart arrhythmia in patients taking the higher dose, and after six days, eleven of the patients had died. At that time the high-dose section of the study was halted. Based on the information a researcher from Toronto who was not involved in the study stated that the results suggest that “chloroquine causes a dose-dependent increase in an abnormality in the ECG that could predispose people to sudden cardiac death.” ECG (also called EKG) is a way to measure the electrical activity in the heart.
Information from China reported on April 9 in The Wall Street Journal suggests that there was not a large effect on the outcome of COVID-19 from use of chloroquine (Page, 2020). Several doctors involved in treatment of the outbreak in Wuhan gave interviews recounting their experiences to international journalists. The head of Wuhan’s Jinyintan Hospital stated that the effectiveness of chloroquine was inconclusive. He mentioned that people were taking the drug on their own, and some got better, but there was also a group of people who still had positive evidence of infection after taking the drug for seven to ten days. He mentioned that physicians at his hospital had not observed any difference in the outcome based on the treatment they received.
Vaccine Trial
The WHO announced that it has organized a large, international trial that will be performed at multiple different sites to speed investigations on potential COVID-19 vaccines (WHO, 2020). The trial, which is called the SOLIDARITY vaccine trial, is a randomized and controlled trial that will allow for evaluation of multiple promising candidates at the same time. The structure of the trial is reported to allow for the determination of benefits and risks of new vaccines within three to six months of being made available to the trial investigators. This quick turnaround is expected to be possible due to expected high rates of enrollment in the trials and an adaptive design. Using a trial that includes all of the candidate vaccines allows for a direct comparison of the vaccine outcomes and use of a single placebo group for comparison.
Typical Hospital Admissions
While hard-hit areas around the world are struggling with meeting the demand for severe cases of COVID-19, doctors are also concerned by the lack of patients being seen for typical health issues (Krumholz, 2020). In a Commentary in The New York Times, Harlan Krumholz a cardiologist from the Yale New Haven Hospital voices his concern for those experiencing medical problems other than COVID-19, specifically those with heart attack or stroke. In an informal poll in an online community of cardiologists, over half have observed a 40% to 60% reduction in admissions for heart attacks, and around 20% of those responding have seen a larger than 60% reduction. Other doctors have also reported decreases in the number of cases of appendicitis and gall bladder disease. This phenomenon has also been evident in Italy and Hong Kong. In Hong Kong, doctors reported an increase in the number of people coming to the hospital late in the course of a heart attack when treatments are less effective.
Doctors fear that people are avoiding getting medical care for fear of being infected at the point of care. A small decrease in the number of emergencies would be expected with the changes that people have made to their daily lives that may also remove some of the triggers for stroke or heart attack. However, other factors currently present should elevate the number of cases observed, including respiratory infections, stress, depression, anxiety, and frustration.
Dr. Krumholz concludes that doctors and administrators have equipped the hospitals to safely care for non-COVID-19 cases. He stresses
“Don’t delay needed treatment. If fear of the pandemic leads people to delay or avoid care, then the death rate will extend far beyond those directly infected by the virus. Time to treatment dictates the outcomes for people with heart attacks and strokes. These deaths may not be labeled Covid-19 deaths, but surely, they are collateral damage.”
