COVID-19 Projects at Columbia
Columbia’s inventors are finding themselves at the center of the fight against COVID-19. Across the university, researchers are exploring how their expertise can best be applied in creating useful diagnostics, therapeutics, prophylactics, and personal protective equipment. Columbia is seeking partners and resources to accelerate the development of these technologies. To learn more or to get in touch with us about any of the technologies listed below, please email [email protected].
Multiplex PCR for differential diagnosis of SARS-CoV-2 and Influenza viruses: Dr. Ian Lipkin, director of the Center for Infection and Immunity at Columbia's Mailman School of Public Health, is developing a simultaneous and differential diagnosis of SARS‐CoV‐2, influenza A and influenza B virus with appropriate reaction control using two assays that could be implemented as multiplex PCR assays. The first utilizes several sets of primers to simultaneously detect SARS-CoV-2, influenza A virus, influenza B virus, and a control gene. The second uses several other sets of primers to target three genes in SARS-CoV-2 and a control. This technology may be useful for the differential diagnosis of infections causing symptoms resembling that of SARS-CoV-2.
Deep Learning for Image-based Diagnosis of COVID-19: Drs. Helen Lu and Shih-Fu Chang of Columbia Engineering are developing a machine-learning-based COVID-19 diagnostic that would require only a microscope and tissue culture followed by software analysis. Currently, the standard method of viral detection for coronavirus is by PCR of patient sputum samples, an approach that can be time-consuming and requires sensitive equipment and expert personnel. Lu and Chang’s method would simplify and expedite diagnosis by using light microscopy images of patient sputum smear, which AI would then scan for differences in cell morphology between healthy and infected states. The AI algorithm developed in this project will be deployed as a stand-alone-application or app, bypassing the need for complex imaging tools, delicate sample preparation, and personnel with extensive lab expertise.
Rapid and Direct Diagnostic Testing of Saliva Samples for SARS-CoV-2: A research team led by Dr. Zev Williams developed a rapid, one-step diagnostic test that detects SARS-CoV-2 in saliva samples. The test is based on loop-mediated isothermal amplification (LAMP) and uses a single tube that contains all of the materials needed to provide reliable results in about 30 minutes. Additional information on the technology can be found in recent news coverage by Columbia University Irving Medical Center as well as in a preprint article: Field-deployable, rapid diagnostic testing of saliva samples for SARS-CoV-2.
Portable qPCR Instrument for Ultrafast Diagnosis of COVID-19: Rover Dx’s mission is to productize its ultrafast, portable qPCR platform for massively distributed infectious disease diagnosis. Spun out of Dr. Sam Sia’s lab at Columbia University, Rover uses microfluidic technology to automate sample prep, and a novel approach to perform PCR 10x faster than current methods. Its sample-to-answer POC instrument will be portable (< 2 pounds), fast (< 8 minutes), and inexpensive (< $2k). Rover’s first product, an ultrafast lab qPCR instrument, has shown 30 thermal cycles in 5 minutes, and is currently being tested on synthetic, then human, COVID-19 samples; results expected April 2020. Rover hopes to advance ultrafast qPCR for COVID-19 system through contract manufacture and FDA EUA before year end 2020 and complete feasibility prototypes of full sample-to-answer ultrafast POC qPCR for COVID-19 system by June 2021.
Point-of-Care COVID-19 Diagnosis: SAFE and Mayo Clinic are developing a Connected Diagnostics and Coordinated Triage Platform that enables remote point of care testing at scale using inexpensive LFIA-based rapid tests. The platform, which also incorporates exclusively licensed software developed by Dr. Sam Sia’s lab at Columbia University, enables individuals to self-administer tests at home and scan the results with their mobile phone, keeping infected populations at home and providing unprecedented real-time surveillance. Positive cases are triaged remotely using crowdsourced telehealth providers mobilized through an Uber-like app. Positive cases trigger delivery of a confirmatory PCR test kit that is sent to lab partners including Quest/LabCorp, with results used to inform a remote treatment plan and reported.
- Lipopeptide fusion inhibitors for prevention and treatment of COVID-19: Drs. Anne Moscona, Matteo Porotto, and Samuel Gellman are developing a set of lipopeptide inhibitors for prevention and treatment of SARS-CoV-2 infection and assays for testing their efficacy. Coronaviruses infect cells by binding to cell surface receptors with the spike glycoprotein, and initiating membrane fusion between the host cell and virus. The engineered lipopeptides bind to transitional stages of the spike protein, subsequently preventing viral fusion and entry. These antivirals, which can be administered intranasally, may be used to treat and prevent the spread of novel coronaviruses, including SARS-CoV-2.This technology has been validated in cell culture, including an ex vivo human airway model, inhibiting SARS-CoV-2 infection of cultured cells and viral spread through airway epithelium.
- Antiviral Cocktail for COVID-19: Dr. Stephen Sturley of Columbia’s Department of Biology is leading a multi-departmental team of scientists in the United States, New Zealand, and Japan to develop a prophylactic and treatment for COVID-19. Sturley and Dr. Andrew Munkacsi of Victoria University of Wellington are developing an antiviral cocktail that inhibits the NPC1 pathway, therefore blocking viral replication by preventing enveloped viruses from disassembling in the lysosomes of infected cells. The antiviral cocktail combines an NPC1 inhibitor and inhibitors targeting genes selected from a list of interacting proteins. Sturley and Munkacsi, along with Dr. Szabolcs Marka from Columbia’s Department of Physics and Dr. Zsuzsa Marka from the Columbia Astrophysics Lab, have identified commercially available, FDA-approved drugs that directly engage the NPC1 pathway and are ready to begin testing efficacy against SARS-COV-2. Sturley is also working with Drs. Marka and Marka to develop machine-based monitoring of NPC1 pathway engagement to determine if administered therapeutics are having the intended effect. Read more about this effort here.
- Protease Inhibitors for COVID-19 Treatment: Given that anti-viral protease inhibitors have served as breakthrough treatments for other viral infections such as HIV, and given that the structure of the SARS-CoV-2 3CL protease has been reported, Drs. Brent Stockwell and David Ho propose that structure-guided discovery, optimization, and development of such protease inhibitors is feasible on a rapid timescale to develop a therapeutic option for treating COVID-19 patients. They are investigating optimization of compounds that already potently inhibit SARS1 and/or SARS2 3CL proteases and a screen of > 3 billion compounds for additional binders using a DNA-encoded library. More information is available in this Nature article.
- Monoclonal Antibodies for COVID-19 Treatment: Dr. David Ho will lead an effort aimed at developing monoclonal antibodies, molecules that can bind to the surface of the coronavirus and neutralize the infectivity of the virus. His team will try to isolate antibodies from blood cells of patients who no longer have the virus and have recovered from 2019-nCoV infection. Then they will engineer the virus-neutralizing antibodies further to optimize their potency against 2019-nCoV. The most promising antibodies will be tested against actual coronavirus in the lab as well as in animal models.
- Polymerase Inhibitors for COVID-19 Treatment: A Columbia team led by Drs. Stephen Goff and Yosef Sabo will produce large quantities of polymerase and then screen hundreds of thousands of chemical compounds to identify ones that inhibit the function of the enzyme and thereby block replication of the virus. The most promising ones will again be selected as drug candidates for treatment or prevention of 2019-nCoV.
- Repurposed Antivirals and Polymerase Inhibitors for COVID-19 Treatment: A team led by Dr. Jingyue Ju observed that hepatitis C and coronaviruses use a similar mechanism to replicate their RNA. They believe that a currently FDA-approved antiviral drug, sofosbuvir (for hepatitis C), as well as other approved anti-viral agents, AZT (for HIV/AIDS) and tenofovir alafenamide (for HIV and hepatitis B), may be effective against SARS-CoV-2. They have shown that these drugs inhibit the polymerase enzyme of SARS-CoV-2 and thus block its replication. Dr. Ju and his team will utilize their expertise in synthetic chemistry to generate many more such chemical compounds for testing in collaboration with Drs. Ho, Goff, and Sabo. The best chemical compounds that specifically inhibit the SARS-CoV-2 polymerase will be chosen as drug candidates.
- Protease Inhibitors for COVID-19 Treatment: A team led by Dr. Alex Chavez is using a new highly multiplexed drug screening approach to rapidly screen a large number of compounds that block the protease of SARS-CoV-2. His team, in conjunction with David Ho, will select a handful of positive hits to develop into drug candidates, with the goal of advancing at least one compound into clinical trials.
- Human–virus Interactome Atlas for COVID-19 Drug Discovery: Drs. Barry Honig and Sagi Shapira have created a database of predicted virus-human protein-protein interactions (PPIs). Using in-house algorithms and their supercomputer system, Honig and Shapira will identify interactions between viral and human proteins that accompany infections. These interactions will inform the researchers about possible FDA-approved drugs that may be used for therapeutics for COVID-19.
Peptides to Regulate Cytokine Storm Associated with COVID-19: Dr. Lloyd Greene has developed cell-penetrating peptides CEBPB and CEBPD that may be used to quell excessive cytokine production (cytokine storm) associated with SARS-CoV-2. Due to their cell-penetrating properties, these peptides can cross various tissue barriers to reach poorly accessible cells not reachable by other agents. By targeting transcription factors, CEBPB and CEBPD may simultaneously target multiple components of the uncontrolled cytokine response, as opposed to existing treatments aimed at single components such as the IL6 receptor. In contrast to cytokine receptor blockers or antibodies, which can elevate circulating cytokine levels via feedback loops, these peptides act at the level of transcription to directly lower cytokine synthesis. Finally, because CEBPB and CEBPD each target multiple transcription factors, they have the potential to block harmful inflammation by interfering with multiple transcriptional pathways and thus treat medical conditions that are causally associated with harmful inflammation.
A Therapeutic for COVID-19 Pulmonary Edema: Dr. Carol Troy has identified mechanisms critical for the formation of cerebral and retinal edema that are operative in COVID-19 induced pulmonary edema, a major cause of death from SARS-CoV-2. Vascular dysfunction is prevalent in COVID-19. Early data indicates that lung pathology shows a range of damage from minimal pathologic findings to blood clots, congestion, edema, and infarction, which is very similar to the pathology Troy has seen in the brain and retina. Troy’s initial studies will analyze the presence of apoptotic markers and cytokines in lung tissue sections from COVID-19 patients and controls. In parallel, Troy’s team will set up an in vitro system to study the effects of the SARS-CoV-2 Spike protein and a pseudovirus that contains the SARS-CoV-2 Spike protein on primary human pulmonary endothelial cells, analyzing apoptotic markers, cytokine, and RNA expression. These will then lead to the development of a pre-clinical model in which Troy’s team can test the efficacy of their lead compound.
A Compound for the Treatment of Patient-ventilator Asynchrony During Mechanical Ventilation: Dr. Paul Garcia has identified a compound with the potential to treat patient-ventilator asynchrony during mechanical ventilation. As the COVID-19 pandemic continues, increasing numbers of critically ill patients develop acute respiratory distress syndrome (ARDS), requiring treatment in the intensive care unit and mechanical ventilation. A common challenge of mechanical ventilator use, especially in the most severely hypoxic patients, is patient-ventilator asynchrony, in which the patient’s breath patterns become out of sync with the ventilator. Sedatives, analgesics, and neuromuscular blockers are often administered to increase comfort and synchrony. However, with increased neuromuscular blockade, there are higher incidences of prolonged ICU stays and muscle weakness. The compound identified by Garcia is currently being used on COVID-19 patients to determine efficacy in promoting ventilator synchrony and its resulting ability to shorten ICU stays and decrease days spent on a mechanical ventilator.
Mapping and Analysis
- Effects of SARS-CoV-2 on alveolar epithelial cells and macrophages: Dr. Jahar Battacharya, in collaboration with Drs. Ira Tabas and Christine Garcia, is interested in understanding the basic mechanisms that SARS-CoV-2 uses to infect critical cells in the pulmonary alveoli and cause acute respiratory distress syndrome. They plan to infect mice with a pseudovirus or the spike protein to evaluate the immunologic response, as well as the mechanistic processes that occur, such as the binding of ACE2 to enter the lung and disruption of macrophage and type 2 cell communication.
- Viral modeling using hPSC-derived lung organoids: Dr. Hans Snoeck, in collaboration with Drs. Megan Sykes and Adolfo Garcia-Sastre, is generating human lung organoids from embryonic stem cells or iPSCs as a resource to model COVID-19. Snoeck is using two methods: lung bud organoids that are grown on kidneys in culture and growing the organoids in Matrigel. While there are limitations, he is collaborating with Dr. Michael Shen to model the effects of TMPRSS2 and with investigators at Mount Sinai to infect the organoids with live virus. He is also collaborating with Dr. Anne Moscona.
- Identifying biomarkers of COVID-19: Dr. Raul Rabadan is investigating individuals’ predispositions to COVID-19, with the hope of identifying biomarkers of COVID-19 severity that can lend to immediate management of patients at risk, including cancer patients. Rabadan and his group are already leveraging their cancer genomics expertise and algorithms to analyze the UK Biobank data (comprising 500,000 individuals, with genetic and clinical data) and patient data from Columbia University Irving Medical Center and NewYork-Presbyterian Hospital, as well as transcriptomic data from lung aspirates and patient electronic health records. This effort will help researchers better understand the SARS-CoV-2 mechanism of action.
- Biorepositories for use in COVID-19 research: Drs. Muredach Reilly, Wendy Chung, Kevin Roth, and David Goldstein, along with Drs. George Hripcsak, Krzysztof Kiryluk, Soumitra Sengupta, Steve Spitalnik, and Eldad Hod, have launched the COVID-19 Biobank (COB). In partnership with NewYork-Presbyterian Hospital, the new biobank at Columbia University Irving Medical Center will be crucial in collecting, processing, storing, and disseminating biological specimens, biomarkers, and clinical and related data for researchers at Columbia and beyond. Columbia’s Department of Pathology and Cell Biology has established a COVID-19 clinical pathological lab and intends to facilitate access to residual clinical samples. The primary focus will be to enroll COVID-19 positive patients but will also aim to enroll all patients who have been tested for the novel coronavirus at CUIMC and NewYork-Presbyterian to cast a wide net of samples. To request or contribute samples, click here.
- Estimating undocumented cases of COVID-19: Dr. Jeffrey Shaman and his team used observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with SARS-CoV2, including the fraction of undocumented infections and their contagiousness. They estimate 86% of all infections were undocumented prior to travel restrictions on Jan. 23, 2020, and that undocumented infections were the infection source for 79% of documented cases. Estimation of the prevalence and contagiousness of undocumented SARS-CoV2 infections is critical for understanding the overall prevalence and pandemic potential of this disease. Read Shaman’s article here.
Personal Protective Equipment (PPE) and Disinfectants
Face Shields: A team of Columbia engineers led by Drs. Jeff Kysar, Yevgeniy Yesilevskiy, Anil Lalwani, Keith Yeager, and Elizabeth Hillman rapidly designed face shields for healthcare workers. Some of the designs have already been ordered by hospitals. View photos and videos of the designs here.
Isolation Unit for Intubation and Respiratory Procedures: Dr. Darcy S. Peterka and Tanya Tabachnik of Columbia’s Zuckerman Institute are developing an isolation unit for intubation and respiratory procedures taking place during the COVID-19 pandemic. The device is a portable transparent glove box and barrier that sits over a patient's head and neck while allowing easy procedural access during aerosolizing procedures like intubation and extubation, protecting the healthcare provider from droplets and direct streams of contaminated air. The device is configured with a miniature filtered blower system that creates a negative pressure environment, filtering out contaminated air before release, further protecting healthcare providers in the room, and reducing cross contamination. The device allows for tubing, pressure monitoring, and easy access, and is designed to fit on a traditional OR bed.
Bag-in-Bottle-Valve-Mask Ventilator: Dr. Joseph Lidestri is developing a pneumatically driven Bag-in-Bottle to automatically actuate a commercial off-the-shelf (COTS) Bag-Valve-Mask (BVM) resuscitator. A BVM is a manual resuscitator commonly used to provide positive pressure ventilation to patients who are not breathing adequately. This innovation would provide breathing assistance to COVID-19 patients suffering from severe acute respiratory syndrome by automatically actuating BVMs in the event of a ventilator shortage.
- Disinfecting Foam: Dr. Ponisseril Somasundaran is developing an optimized and robust antimicrobial foam that can be safely delivered as a disinfectant with numerous applications. Typical disinfectants do not always have uniform dispersion when applied, may dissipate too quickly, and be hazardous to personnel that are applying it, resulting in an increased risk of chronic lung disease. Dr. Somasundaran is tackling these issues with the creation of a “green” disinfecting foam that is safer to use and more efficacious as an antimicrobial agent. This and other disinfecting foams are being optimized for uniform coverage and deposition, penetration, and consistency for the desired length of time. Multiple synthetic and natural surfactants and polymers are being tested, as well as a number of reagents produced by microbes that have antiviral properties. These foams are currently being in applied in several applications including West Nile Virus.
- UV Sterilization System: USHIO, a Tokyo-based developer of light instruments, licensed ultraviolet light technology from Columbia in 2015 and is working to launch a product by the end of the year. The UV technology was developed by Dr. David Brenner, Director of the Center for Radiological Research at CUIMC, and acts as a sterilization system that selectively kills bacteria and viruses without damaging human cells and tissues, permitting prolonged human exposure. In health care facilities and beyond, this tool could be used to disinfect both air and surfaces that may expose patients and others to COVID-19.
- Sanitation Verification System: Drs. Szabolcs Márka and Zsuzsa Márka are developing a sanitation verification system that allows a person to see where on skin or surfaces was sanitized, the duration of sanitization per surface area, last time of sanitization, and what sanitization chemical was used. This would allow authorities or employers to verify that sanitization policies were properly followed in hospitals, restaurants, and public transportation stations during infectious disease outbreaks like COVID-19.
- Open Respiratory Profile Monitoring: Dr. Gerard Ateshian, in collaboration with multiple faculty in Engineering, Medicine, and Anesthesiology, developed the open Respiratory Profile Monitoring (openRPM) system to provide real-time proximal monitoring of ventilated COVID-19 patients. The standalone openRPM flow meter design is available here.