RESEARCH BRIEFING – WEEK IN REVIEW
Do patients under 65 years of age have poor outcomes when infected with SARS-Cov-2?
A new paper published in The Lancet from two New York-Presbyterian hospitals affiliated with Columbia University Irving Medical Center in Manhattan monitored patients admitted with laboratory confirmed SARS-CoV-2 from March 2 to April 1, 2020. Patients included critically ill persons with acute respiratory failure (with low blood oxygen levels) and each patient was followed for at least 28 days after the initial evaluation. During the 30-day initial period, 1,150 adults with covid-19 were admitted to these two hospitals, a staggering number. The average age of patients admitted was 62 years, and 22% were deemed to have been in critical condition. At the time of publication, 39% of the patients had died. 79% of the entire cohort required mechanical ventilation, for an average of 18 days, though typical ranges included 9 to 28 days. Over 25% of those patients were under the age of 50 years. Furthermore, 37% remained in the hospital at the time the paper was published; many hospitalized patients soon became sicker, with an average time to in-hospital deterioration of 3 days. This implies that patients "self-diagnosed" the severity of their illness by virtue of having presented to the hospital when they did. Using a statistical model, researchers found that the presence of chronic heart and lung disease and high levels of interleukin-6 and blood d-dimer levels (a marker of abnormal blood clotting) were independent risk factors for dying while hospitalized. Commentary: These data are remarkable both from the perspective of patient outcomes and hospital capacity. The number of patients treated and hospitalized by just two New York City hospitals is highly unusual if not unprecedented in modern history. It is also noteworthy that over one-fourth of all patients who died were under the age of 50 years old. 20 May 2020.
Message in a bottle. Moderna's mRNA vaccine candidate makes a splash
In the past few years, the prospect of a producing vaccines that use messenger RNA instead of proteins derived from infectious pathogens including viruses and bacteria has captivated the biotechnology industry. While potential vaccines for many diseases have been synthesized, none have been approved for use anywhere in the world. Yesterday, Moderna, a company in Massachusetts, announced favorable results from a phase 1 trial testing their first vaccine candidate against SARS-CoV-2. Phase 1 trials are designed to establish doses and safety profiles for drugs and vaccines in development. Generally, phase 1 trials are small and enroll 20 or more test subjects. In addition to reporting on the safety of the vaccine---which so far appears to have caused only minimal side effects---the company announced that the vaccine, known as mRNA-1273, elicited an immune responses in the first eight volunteers who received the vaccine for whom data is currently available. This candidate vaccine is composed of genetic material (mRNA) that codes for a spike protein which extrudes from the surface of SARS-CoV-2 particles. While the theory is well-grounded, reality is what matters. It is therefore encouraging that blood later drawn from test subjects in this phase 1 study exhibited antibody levels that were similar or higher than the levels that have been detected in patients known to have recovered from SARS-CoV-2 infection. The company reports that all participants in the study "seroconverted" with respect to neutralizing antibodies, regardless of the dose given. This suggests that the subjects' immune systems recognized the vaccine appropriately though it does not necessarily mean that these responses rendered the patients immune. But there appears to be good news on that front as well. The first eight patients were also found to have mounted "neutralizing" antibody responses 43 days after the vaccines were given. The blood from these patients were taken to labs and placed on plaques of viral particles. The plaques were observed to have been reduced in size, suggesting that the viral particles were being effectively killed. The levels of neutralizing antibodies were either similar or greater than those observed in blood from recovered covid-19 patients ("convalescent sera"). Based upon these findings, the FDA has permitted a phase 2 trial to begin on an expedited basis, which will further assess the safety of the vaccine using the dose that appears to be most promising. Hundreds of patients are to be enrolled. Generally, potential drugs and vaccines that carry serious but rare side effects are unlikely to be detected in phase 1 trials. The results of phase 2 data (as well as a phase 3 trial which would include thousands of patients and is already being planned for rollout as soon as July) will be watched closely for this reason. If the vaccine works but causes unacceptable rates of serious side effects during phase 2 or phase 3 trials, it would be back to square one. Nevertheless, the stock market rewarded this news in trading yesterday. 19 May 2020.
An update on decreased heart attacks in the US during the pandemic
Recently, Brief19 covered research from the UK that described an possible decrease in the number of ambulance calls for patients with suspected heart attacks and strokes (the decreased number of calls did not reach "statistical significance"). Yesterday, a research letter published in NEJM describes the rate of newly diagnosed heart attacks throughout the entire Kaiser Permanente System in Northern California before and during the covid-19 outbreak. Kaiser Permanente consists of 21 medical centers and 255 clinics and provides comprehensive care for more than 4.4 million persons throughout Northern California. The researchers assessed whether the incidence of weekly heart attacks changed before and after the first reported death from covid-19 in Northern California, which occurred on March 4, 2020. These data were compared to weekly rates of heart attacks from the same period in 2019. These researchers found that the weekly rates of hospitalization for heart attacks decreased by up to 48% after March 4th. When compared to the similar time period in 2019, the numbers after March 4th were also lower. Also reported in the study is that patients diagnosed with heart attacks during the covid-19 period (March 4 - April 14, 2020) were healthier (i.e. had fewer pre-existing chronic medical problems) than heart attack patients who were diagnosed and treated both during the pre-covid-19 period of 2020, as well as in 2019. The authors conclude that overall there were fewer heart attacks diagnosed during the covid-19 pandemic than would be expected, even after considering typical seasonal variations. The large question is whether decreases in usual medical care for life-threatening conditions including major heart attacks have been significant contributors to the increases in the total number of deaths (from all causes combined) that have been observed to have occurred during the US outbreak. The numbers in this study suggest that this is currently unlikely. Abbreviated from Brief19 for 21 May 2020.
POLICY BRIEFING – WEEK IN REVIEW
New York City's Safety-Net Hospitals Face Financial Collapse
New York City's safety-net hospitals are facing possible closure due to losses related to the coronavirus pandemic and Medicaid cuts by New York State. The city has 29 non-profit safety-net hospitals. They are not part of the city's public hospital system, so they won't be bailed out by City Hall, and they can't tap into generous lines of credit as wealthy Manhattan hospitals can. The Brooklyn Hospital Center, for example---where 79 percent of patients are on Medicaid or combined Medicaid and Medicare or are uninsured---needs $100 million to stay in the black over the next four months. Federal funding formulas have historically dispersed funds inequitably: Of the $12 billion allocated to hospitals in the last federal stimulus bill, the Brooklyn Hospital Center received only $35.2 million. It remains to be seen whether the U.S. Department of Health and Human Services will follow through on a promised "significant infusion of money for high-impact areas." Politico, The New York Times. 18 May 2020.
Loan Relief for Providers
Representative Carolyn B. Maloney last week announced the "Student Loan Forgiveness for Frontline Health Workers Act." The intent is to relieve frontline providers "of the debt they incurred to train for this critical work---in graduate degree programs or other professional certification." The Department of Health and Human Services would be tasked with the creation of a nine-member task force in conjunction with the Departments of Education and Treasury to determine what qualifies as "significant contribution" to coronavirus mitigation, as well as the definitions of healthcare workers, students, laboratory workers, researchers, and a catchall for those involved in the pandemic response. Qualifying federal loans would be forgiven by the Department of Education, and private loans would be assumed by the Department of the Treasury. No refunds would be available for previous loan payments, nor could forgiven loans be claimed in federal tax filings. Applicants would have two years from the creation of the program to apply; loans incurred by workers who died of covid-19 would be eligible for consideration. The House of Representatives. 18 May 2020.
Federal judge weighs in on voting by mail
Last month, after the Supreme Court weighed in, Wisconsin proceeded with in-person voting for its primary elections. The in-person voting has since been linked to an increase in covid-19 infections, the outcome that was feared by advocates for voting by mail. The issue has now appeared in Texas. The Texas Democratic party has filed a lawsuit demanding that mail voting be extended to all Texans to prevent the transmission of the coronavirus. The State has raised concerns about fraud associated with mail voting and wants to limit the extension of absentee ballots only to citizens over age 65. Yesterday, a federal court sided with the Democratic party and held that the risk of illness and death was too great compared to concerns of voter fraud, and that voting by mail should be made available to all voters. Various. 20 May 2020.
Pandemic exacerbates partisan divide
Instead of pulling the country together, the coronavirus pandemic is pulling it apart along familiar partisan lines. One reason: Six of the seven hardest-hit states are led by Democratic governors. Those six states, home to densely packed metropolises and accounting for a third of our country's population, are only represented by 12% of senators. For most senators, therefore, the pandemic is not causing a significant human toll back home, even while it is causing economic devastation. For that majority of senators, the pressure to relieve the economic pain is more intense than the pressure to minimize deaths from the virus. It is not surprising, then, that the Senate is reluctant to pass legislation that would prolong the shutdown and is instead looking to re-open communities as soon as possible. Wall Street Journal. 19 May 2020.
CDC guidance finally issued
This past weekend the Centers for Disease Control and Prevention finally issued recommendations on reopening. Previously, a leaked draft of the recommendations caused public disagreement between the agency and the White House because Trump administration officials felt that some recommendations were overly cautious. The recently published document is far-reaching, and includes a review of the Center's surveillance efforts, recommendations for schools, businesses, and places of worship, among other institutions, on how to safely reopen. Suggestions include that school desks not all face the same direction and that shared objects like reusable menus and shared condiments be removed from restaurants. 20 May 2020. CDC.
Alabama opened on April 30th. Now intense care units are full
After being one of the last states to close in an effort to flatten the covid-19 curve, doing so on April 1st, Alabama's stay-at-home order expired on April 30th. Since then, 5,000 new cases have been recorded, and the number of deaths statewide have nearly doubled. Yesterday, Steven Reed, the mayor of Montgomery (the capital and 2nd largest city in the state) said that intensive care units in the city were running out of beds. The three worst days in terms of new cases and deaths have all occurred since May 5th. Washington Post. 21 May 2020.
Illinois legislators eject colleague for refusing to wear a mask
Many legislative bodies, including Congress, have deferred reconvening in person until the threat of transmitting coronavirus can be abated. But the Illinois General Assembly gathered on Wednesday for the first day of a special pandemic session, meeting in a huge arena to allow for more social distancing. One of the body's first steps was to introduce a new rule requiring all legislators to wear masks. The measure passed with bipartisan support, but one Republican not only voted against the measure, but also refused to comply once the rule was adopted. The representative, Rep. Darren Bailey, who has sued Illinois's Democratic governor, J.B. Pritzker, over his stay-at-home executive order and called unemployment the "second pandemic," said the mask order was "just another Democrat bullying tactic" and that he did not believe it was about protecting people's health. Ultimately his colleagues on both sides of the aisle voted to remove him from the floor. This episode is just one more illustration of an emerging partisan fight over the utility of mask-wearing in public. Washington Post. 22 May 2020.