Project Team

Timothy Henrich, MD, MMSc, Professor of Medicine at the University of California, San Francisco in the Division of Experimental Medicine

Zian H. Tseng, MD, MAS, Professor of Medicine in the Division of Cardiology and a cardiac electrophysiologist with expertise in risk stratification and pathogenesis of patients prone to sudden death and ventricular arrhythmias.

Ellen Moffatt, MD, County of San Francisco Assistant Medical Examiner and an Associated Professor at UCSF

Michael Peluso MD, Assistant Professor of Medicine in the Division of HIV, Infectious Diseases and Global Health

Project summary:

The project is expanding the one-of-a-kind POstmortemSystematic InvesTigation of Sudden Cardiac Death (POST SCD) autopsy study to examine key questions regarding SARS-CoV-2 persistence including mechanisms of tissue damage that may impact Long COVID. These questions include:

  • What is the tissue distribution and burden of SARS-CoV-2 RNA or proteins in the tissues of sudden death victims with active infection at the time of death as well as in various stages of recovery, including those with and without recorded Long COVID?
  • What is the cross-sectional prevalence of persistent tissue SARS-CoV-2 infection in an entire community among persons dying suddenly of causes apparently unrelated to COVID-19?
  • What are the transcriptional and proteomic host responses in various tissue regions and cell types in acute and convalescent COVID-19 and how do these responses correlate with potential SARS-CoV-2 persistence?
  • Are there differences in tissue SARS-CoV-2 persistence and host responses in acute and convalescent COVID-19 in pre- and post-Omicron variant infection waves, and what is the effect of vaccination on these processes?

To answer these questions, the team has added deep profiling for the SARS-CoV-2 virus to their existing longitudinal POstmortemSystematic InvesTigation of Sudden Cardiac Death (POST SCD) Study: a tissue autopsy study of consecutive victims of out-of-hospital sudden death in San Francisco County to bank samples and autopsy data. To date, the Study has collected extensive cryopreserved, nucleic acid stabilized and formalin-fixed paraffin embedded tissue samples, including multiple brain regions, lung, pancreas, lymph nodes, liver, spleen, gut, heart, pulmonary vasculature, or bone marrow from thousands of sudden cardiac death (SCD) victims prior to the pandemic and during the pandemic.

The Study also includes complete access to decedents’ medical records to determine whether victims had active COVID-19 at the time of sudden death, or a history of recovered COVID-19 and any symptoms following initial SARS-CoV-2 infection. An estimated >80% of San Francisco residents have been infected over the past three years, thus analysis of SCD victims during this time will provide a cross-sectional survey of the prevalence of active and prior SARS-CoV-2 infection in an entire community and provide critical information as to viral persistence and Long COVID pathology among people dying suddenly of causes apparently unrelated to COVID-19 countywide. Samples will be analyzed via methods including cutting-edge tissue-based transcriptomic/proteomic profiling, and ultra-high multiplexed immuno-histochemical imaging to clearly define persistence of SARS-CoV-2 in various tissues, and how COVID-19 impacts long-term host cell gene and protein expression and subsequent tissue inflammation and damage.

Project background:

The COVID-19 pandemic has unleashed an unprecedented increase in mortality and morbidity including a rise in cardiovascular disease and fatal heart conditions. In addition to death from SARS-CoV-2, persistence of virus has been demonstrated across the body and brain. Multiple studies suggest that this persistence contributes to the Long COVID disease process. However, persistence in asymptomatic individuals has also been documented. The extent to which SARS-CoV-2 persistence occurs in both Long COVID and asymptomatic persons and drives pathological tissue injury requires urgent further investigation. To fill this gap, the team is leveraging the POST SCD study in collaboration with the San Francisco Medical Examiner’s Office to perform a comprehensive autopsy study investigation on SCD victims prior to and during the COVID-19 pandemic countywide. Unlike prior autopsy studies which involved small convenience cohorts or victims of severe COVID-19, the availability of samples for the study include an entire cross-section of SCD victims prior to and following the COVID-19 pandemic, providing an unprecedented opportunity to study viral persistence and tissue pathology among persons dying suddenly of causes apparently unrelated to COVID-19, with active or convalescent infection –  a key innovation.