In collaboration with the Bill and Melinda Gates Foundation we launched an RFA in April 2020 to address following critical questions:

1. What is driving lung organ damage in SARS-CoV-2 infection, and can this be targeted for therapeutics/ host directed therapy? How does the host response develop over time, and what drives subsequent progression to systemic inflammation and multi-organ failure in a subset of patients as opposed to resolution? 
2. Vaccine candidates in the pipeline aim to drive high (and ideally durable) neutralizing antibody titers. How can we understand which adjuvants are best for this? 
3. What role do T cells play in effective viral/disease control in naïve humans? What about re-infection? 
4. The potential for antibody-enhanced disease and vaccine-enhanced disease weighs heavily on those trying to develop vaccines and biologics. What are the other immunological features that are important to have or avoid? Will we know disease-enhancement when we see it? Do we know how to avoid it? 
5. What have we learned from autoimmunity and allergy that could be put to good use here? 
6. If antibody titer and viral neutralization aren’t a sufficient correlate of protection, what else is important to measure in early vaccine studies? 
7. What is driving the age difference in morbidity/mortality if it isn’t the underlying conditions? 
8. Why do some individuals remain asymptomatic? 

Following projects were selected for funding starting May 1, 2020:

• Development and validation of molecular viability assays for SARS-CoV-2
  Jason Andrews, MD; Yvonne Maldonado, MD

• Evaluating the potency and durability of slow-delivery SARS-CoV-2 subunit vaccines and testing of cGAMP as an innate immune adjuvant
  Eric Appel, PhD; Lingyin Li, PhD
  
  
• Systems analysis to characterize effective vs. ineffective COVID-19 immune profiles and establishing the role of granulocytes in progression of COVID-19
  Catherine Blish, MD, PhD; Angela Rogers, MD; Holden Maecker, PhD
  
  
• SARS-CoV-2 tissue tropism and its role in progression to multi-organ failure
  Scott Boyd, MD, PhD; Sandra Abel Nielsen, PhD
  
  
• Identifying robust T cell determinants for SARS-CoV-2 responses
  Mark M. Davis, PhD; Kari Nadeau, MD, PhD; Tho Duc Pham, MD; Vamsee Mallajosyula, PhD
  
  
• Single cell profiling of SARS-CoV-2 infection of human lung cells
  Mark Krasnow, MD, PhD; Catherine Blish, MD, PhD, Stephen Quake, PhD
  
  
• Human lung organoid models of SARS-CoV-2 infection
  Calvin Kuo, MD, PhD; Manuel Amieva, MD, PhD; and Catherine Blish, MD, PhD
  
  
• The Spatial Immune Landscape of Respiratory Coronavirus Infections
  Garry Nolan, PhD ; David McIlwain, PhD; Sizun Jiang, PhD
  
  
• SARS-CoV-2 vaccine designed to enhance immunogenicity of the receptor binding domain
  Taia Wang, MD, PhD
  
  
• Differential Immune Responses in Pediatric versus Adult Patients with COVID-19
  Katja Gabriele Weinacht, MD, PhD; Lael Yonker (MGH, Harvard Medical School)
  
  
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