Research Areas

Scientists in the Arditi Lab are testing healthcare workers to determine whether a decades-old vaccine for tuberculosis, Bacillus Calmette-Guérin (BCG) could provide stopgap protection against COVID-19 until more precise vaccines are available. The BCG vaccine won't prevent people from getting infected with the SARS-CoV-2 virus, but may strengthen the immune system to diminish the effect of infection, resulting in fewer COVID-19 hospitalizations and deaths. The idea was born of researchers' observations that the rates of COVID-19 deaths and serious illness are lower in some developing countries where the BCG vaccine is widely used. Moshe Arditi, MD, leads the BCG vaccine trial, which aims to protect healthcare workers. Arditi at Cedars-Sinai teamed up with investigators at Texas A&M University, MD Anderson Cancer Center and Baylor College of Medicine to recruit 1,800 volunteers at those four centers. The BCG vaccination could make a significant difference in the next year or two until a specific and safe vaccine is developed for COVID-19 and made widely available. Repurposing the tuberculosis vaccine, called TICE® BCG, represents a speedy way to address COVID-19 because the drug has already been proven safe and is approved by the U.S. Food and Drug Administration. In addition to preventing tuberculosis, the vaccine is also used to treat bladder cancer.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is a coronavirus closely related to SARS-CoV (SARS) and Middle East Respiratory Syndrome (MERS). COVID-19 can manifest in adults as a severe interstitial pneumonia with hyperinflammation, but severe respiratory manifestations are rare in children. Recently, however, multisystem inflammatory system in children (MIS-C) has been recognized in patients that either tested positive for COVID-19 (by PCR or serology) or had epidemiological links to COVID-19.

After initial reports in the U.K., many cases have now been reported in Europe and New York. MIS-C manifests as persistent fever and hyperinflammation with multi-organ system involvement including cardiac shock, and severe gastrointestinal, renal, hematologic, dermatologic and neurologic symptoms. Although MIS-C was initially described as "Kawasaki disease (KD)-like," it soon became clear that that these diseases are different, and that the symptoms and laboratory findings of MIS-C are highly reminiscent of toxic shock syndrome (TSS), rather than KD. Indeed, several recent studies have concluded that MIS-C is a distinct disease from KD and KD shock. The similarities to TSS and the association of MIS-C with COVID-19 indicate that SARS-CoV-2 may possess superantigenic fragments that induce an inflammatory cascade, which may also contribute to the hyperinflammation and cytokine storm features observed in severe adult COVID-19 cases. We therefore hypothesized that SARS-CoV-2 Spike (S) protein may possess superantigenic fragments that could elicit such reactions upon binding proteins involved in the host cytotoxic adaptive immune response.

Using computational biology and bioinformatics, the Arditi Lab and our colleagues at the University of Pittsburgh have discovered a novel superantigen-like structure in the S1 subunit of the SARS-CoV-2 spike protein, which has the structural characteristics to bind to both T cell receptor and major histocompatibility complex class II (https://www.biorxiv.org/content/10.1101/2020.05.21.109272v1). We also discovered that this SARS-CoV-2-specific superantigen-like structure has a remarkable similarity in both sequence and structure to the Staphylococcal enterotoxin B superantigen toxin. These discoveries may unlock the mechanisms that lead to MIS-C as well as to the cytokine storm seen in adults with severe COVID-19 infection. The Arditi Lab is currently working on proving the biological relevance of this newly discovered viral structure.