virus: A virus that is closely related enough—probably more than 99 percent—to SARS-CoV-2 to have been its direct ancestor or plausible immediate origin of the outbreak. The closest known relative to SARS-CoV-2 is only around 96 percent similar; to put this into context, humans and chimps are around 99 percent similar, demonstrating the signficant differences even at this similarity. RaTG13: A coronavirus with the closest known whole genome to SARS-CoV-2, although it is widely believed to not be a direct ancestor of SARS-CoV-2. Resevoir species/host: An organism that harbors a pathogen, which is endemic within the population. RNA (ribonucleic acid): A molecule essential for gene coding, decoding, regulation, and expression. Certain viruses use RNA as a genetic blueprint. Transmissibility: The measure of new infections initiated by an existing infection. Virus: A replicating piece of genetic material—DNA or RNA—and associated proteins that use the cellular machinery of a living cell to reproduce. Wet market: A market where fresh food and live and dead animals, including wildlife, are sold. Zoonosis: An infection or a disease that is transmissible from animals to humans under natural conditions. A zoonotic pathogen may be viral, bacterial, or parasitic, and can sometimes be transmitted through insects, such as mosquitoes. Zoonotic spillover: An initial infection or disease that is caused by contact between an animal and human under natural conditions. [ 13 ] IC analysts have examined a number of open-source articles from a variety of sources that have raised theories about SARS-CoV-2 and COVID-19’s origin. The IC assesses that these theories generally do not provide diagnostic information on COVID-19 origins, and in some cases, are not supported by the information available to us. However, several have drawn on insightful methods or identified potential leads. Theory of Abnormal Activity at the WIV in Fall 2019 The IC assesses that an assessment about abnormal activity at the WIV in fall 2019 lacks support and does not offer diagnostic insight. The Multi-Agency Collaboration Environment (MACE) published a report assessing that the pandemic began in October 2019 because of a release at the WIV. · Although the methodology is insightful, the IC has concerns with the small data set and analytic rigor used to derive the group’s findings, and our review of information directly contradicts some of its findings. Theory That SARS-CoV-2 Was a Biological Weapon The IC assesses that public claims from a Hong Kong virologist that Beijing created SARS-CoV-2 as a biological weapon are inconsistent with available technical information on coronaviruses. We assess that the articles contain several technical inaccuracies and omit key data points. · Since September 2020, a virologist who worked in a WHO-affiliated laboratory in Hong Kong has publicly stated that Beijing created SARS-CoV-2 from bat coronaviruses and that China’s researchers intentionally released it. The scientific community did not peer review these articles and some publicly rejected the articles’ claims as scientifically unsound. Theory That SARS-CoV-2 Was Genetically Engineered The IC assesses that public claims that some distinguishing features in SARS-CoV-2 are the result of genetic engineering are not diagnostic of genetic engineering. The IC has been evaluating how SARS-CoV-2 could have developed these features and notes that the furin cleavage site (FCS)—a region in the spike protein that enables infection and has been the topic of open-source debate—can also be consistent with a natural origin of the virus. We do not fully understand the diversity of natural coronaviruses or how often they recombine, suggesting that there are plausible natural means by which these features in SARS-CoV-2 could have emerged beyond what we currently understand. · For example, the author of an article in April notes the SARS-CoV-2’s FCS is unique among known betacoronaviruses. The author argues that such features are rare and so well-adapted for human infection that they are more likely emerged from laboratory work than from natural selection. · Although an IC review of scientific literature has indicated that no known betacoronaviruses in the same subgenus have this FCS in the same region of the spike protein as SARS-CoV-2, similar FCSs are present in the same region of the spike protein as other naturally occurring coronaviruses, according to scientific articles. We also do not find credible a now-withdrawn preprint article from two Indian educational institutes posted in January 2020 that asserted SARS-CoV-2 was genetically engineered using sequences from the human immunodeficiency virus. We assess it is unlikely that scientists would have chosen to intentionally engineer the specific sequences that were the focus of the scientific article. Annex B: IC Examination of Open-Source Theories [ 14 ] Theory That SARS-CoV-2 Originated Outside China We are aware of scientific studies claiming to have found SARS-CoV-2 viral fragments or antibodies in samples taken before November 2019 outside China. However, technical flaws in some of these studies, uncertainties in the methodologies, and in some cases, the lack of a credible review process make us skeptical of their utility in determining the pandemic’s origin. · We assess that the first