Along with many other Einstein and Montefiore scientists and physicians, infectious disease expert Liise-anne Pirofski, M.D., is working overtime to confront COVID-19, the disease caused by the new coronavirus. She is playing a leading role in two important projects: one evaluating a therapy for both treating and preventing the disease, and the second focused on tracking its effects on patients.
In her first project, Dr. Pirofski is spearheading Einstein and Montefiore's participation in a national, multicenter clinical trial to evaluate passive antibody therapy. The trial involves taking convalescent plasma—extracted from the blood of people who’ve recovered from an infectious disease—and using it to prevent the infection in at-risk people or to treat people who have the disease. Passive antibody therapy is envisioned as a stopgap measure for preventing and treating COVID-19 until new treatments and vaccines are developed.
People need to know that passive antibody therapy is a historically validated approach, used successfully in previous viral epidemics.
Liise-anne Pirofski, M.D.
In the second project, Dr. Pirofski and colleagues are creating a database on COVID-19 patients seen at Montefiore. Finding risk factors associated with the disease will help physicians provide better care for their Bronx patients sickened by the disease.
Dr. Pirofski is professor of medicine and of microbiology & immunology, the chief of the division of infectious diseases in the department of medicine at Einstein and Montefiore, and the Selma and Dr. Jacques Mitrani Chair in Biomedical Research.
Testing an Old Therapy Against the New Coronavirus
How do you confront a viral pandemic when vaccines and drugs are months or years away?
In a March 13 “Viewpoint” article in The Journal of Clinical Investigation, Dr. Pirofski wrote that a treatment called passive antibody therapy could rapidly be developed for use in preventing and treating COVID-19 disease and urged that the therapy be evaluated in a clinical trial, which is expected to begin soon.
The antibody-rich sera used in passive antibody therapy is the only available option for immediately bolstering the immunity of newly infected people or people at risk of infection from SARS-CoV-2, the new coronavirus that causes COVID-19. By contrast, active immunity via vaccination requires an immune response that can take days or even weeks to achieve.
Liise-anne Pirofski, M.D.
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“People need to know that passive antibody therapy is a historically validated approach, used successfully in previous viral epidemics,” said Dr. Pirofski.
Her co-author on the Viewpoint article was Arturo Casadevall, M.D., Ph.D., formerly chair of Einstein’s department of microbiology & immunology and now a Bloomberg Distinguished Professor of molecular microbiology and immunology and infectious diseases at the Johns Hopkins Bloomberg School of Public Health and School of Medicine.
In interviews after their article’s publication, Drs. Pirofski and Casadevall discussed their effort to mount a multicenter clinical trial to evaluate passive antibody therapy for COVID-19. Participating institutions include Montefiore, Einstein, Johns Hopkins, the Mayo Clinic and many others.
Dr. Casadevall said that convalescent plasma could be widely available by early summer if the trial could begin in three to four weeks—which is expected to happen. During the trial, the donors’ plasma (obtained by removing blood cells and platelets from their blood) will be treated to eliminate any pathogens.
We expect that people’s antibody titers will be highest—and therefore most useful for donation—from two to four weeks after they’ve recovered from COVID-19.
Liise-anne Pirofski, M.D.
Dr. Pirofski said that donors will be identified by obtaining blood samples from people who have recovered from COVID-19 and have experienced no symptom of the disease for at least 14 days. Those blood samples will be tested for the presence of antibodies to SARS-CoV-2. In addition, potential donors will undergo nasal-swab testing to ensure that the virus can no longer be detected.
“We expect that people’s antibody titers will be highest—and therefore most useful for donation—from two to four weeks after they’ve recovered from COVID-19,” said Dr. Pirofski.
![Can an old therapy treat COVID-19?]()
Can an old therapy treat COVID-19?
The authors make the following points in their JCI article:
- Passive antibody therapy probably protects against SARS-CoV-2 through viral neutralization, although other immunological mechanisms may also be involved.
- Use of the therapy dates to the 1890s and was the only way to treat certain infectious diseases before the onset of antimicrobial therapy in the 1940s. It has been used to stem outbreaks of polio, measles, mumps, and influenza as well as the 2013 West African Ebola epidemic and two recent coronavirus-caused epidemics: the 2003 severe acute respiratory (SARS) epidemic and the 2012 Middle East respiratory (MERS) epidemic.
- As a general rule, passive antibody therapy is more effective for prevention than for treatment of disease, although it was effective against early pneumococcal pneumonia, i.e., pneumonia caused by bacteria. In the case of COVID-19, prevention could especially benefit people at high risk for disease: those with underlying medical conditions, health care providers (allowing them to avoid quarantine), and anyone exposed to confirmed cases of COVID-19, including family members caring for patients at home. Protection conferred by passive antibody therapy can last from weeks to months, depending on the amount and composition of the antibodies.
- When used as treatment, passive antibody therapy is most effective when given shortly after the onset of symptoms, probably because it “works by neutralizing the initial inoculum [of virus], which is likely to be much smaller than that of established disease.”
- Convalescent plasma reportedly was used as therapy in China during the current outbreak. The authors cite a report in the state-run Xinhua news agency that 91 of 245 patients treated had shown improvement.
- Echoing the axiom that ‘in every crisis there is opportunity,’ the authors note that “as more individuals contract COVID-19 and recover, the number of potential donors will continue to increase.”
We really need data to give us a sense of what our patients are like.
Liise-anne Pirofski, M.D.
Creating a Database to Help Limit Bronx Coronavirus Cases
A Montefiore-Einstein project to compile information on Bronx residents sickened by the novel coronavirus will provide information that could guide treatment and ultimately save lives.
“We really need data to give us a sense of what our patients are like,” said Dr. Pirofski. She is leading the database-creation effort, which received Institutional Review Board approval on March 21 and is expected to begin gathering data this week.
The project will review the charts of patients admitted to Montefiore with a diagnosis of COVID-19 and those who test positive for SARS-CoV-2, the virus that causes the disease. The cohort will be large; New York State has the largest number of cases in the United States and the number of cases at Montefiore is rising by the day.
Staffers conducting the study will record an extensive amount of information on patients, including: their age, sex, where they live, their medical history (including co-morbidities such as asthma, heart and lung disease and hypertension), medications they were taking before becoming ill, their symptoms, laboratory test and radiology results, medications they receive during their care, and their clinical course.
The goal is to identify risk factors associated with the development of COVID-19 in Bronx patients. That will involve seeking correlations between patients’ personal, clinical and laboratory/radiology data, and patients’ outcomes such as recovery, progressive respiratory failure, and death.
The resulting risk profile will help researchers understand why some patients develop severe disease. It may also help clinicians anticipate which patients may do poorly and develop new therapies targeted to patients with defined clinical characteristics. In addition, it will help identify patients willing to participate in studies involving the diagnosis and treatment of COVID-19, including the previously mentioned convalescent plasma studies.
Dr. Pirofski’s co-investigator on the project is Kelsie Cowman, who is also the project coordinator. They and their colleagues in the infectious diseases and allergy divisions at Einstein and Montefiore, along with numerous volunteers, hope to establish the database and analyze the first 100 patients at Montefiore in the coming weeks.
Posted on: Wednesday, March 25, 2020