Inclusion Criteria:  Adult, ≥ 18 years of age at the time of consent  For inclusion in the SARS-CoV-2 seronegative population:  No history of laboratory-confirmed SARS-CoV-2 infection (ie, no positive nucleic acid amplification test and no positive antibody test). Seronegative for SARS-CoV-2 at screening (lateral flow test to detect reactivity to the nucleoprotein). Medically stable such that, according to the judgment of the investigator, hospitalization within the study period is not anticipated and the participant appears likely to be able to remain on study through the end of protocol-specified follow-up Able to understand and comply with study requirements/procedures (if applicable, with assistance by caregiver, surrogate, or legally authorized representative) based on the assessment of the investigator Signed informed consent obtained before conducting any study-related procedures  Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.  Previously COVID-19 Vaccinated Participants:  Prior completion of a 2-dose primary homologous vaccination regimen against SARSCoV-2 with either AZD1222 (2 standard doses as authorized vaccine or as investigational product in a clinical trial with a 4 to 12-week dosing interval) or with an mRNA vaccine approved for emergency or conditional use. The second dose in all cases should have been administered at least 3 months prior to first administration of study intervention.  Exclusion Criteria:  History of allergy to any component of AZD1222/AZD2816. History of Guillain-Barré syndrome, any demyelinating disease, or any other neuroimmunologic condition Significant infection or other acute illness, including fever > 100 °F (> 37.8 °C) on the day prior to or day of randomization Any confirmed or suspected immunosuppressive or immunodeficient state, including asplenia or HIV/AIDS. Recurrent severe infections and use of immunosuppressant medication within the past 6 months (≥ 20 mg per day of prednisone or its equivalent, given daily or on alternate days for ≥ 15 days within 30 days prior to administration of study intervention). The following exceptions are permitted: Topical/inhaled steroids or short-term oral steroids (course lasting ≤ 14 days) History of primary malignancy (see protocol) History of thrombocytopenia and/or thrombosis, including participants who have experienced major venous and/or arterial thrombosis in combination with thrombocytopenia following vaccination with any COVID-19 vaccine History of heparin-induced thrombocytopenia, congenital thrombophilia (ie, factor V Leiden, prothrombin G20210A, antithrombin III deficiency, protein C deficiency and protein S deficiency, factor XIII mutation, familial dysfibrinogenemia), auto-immune thrombophilia (antiphospholipid syndrome, anti-cardiolipin antibodies, anti-β2- glycoprotein 1 antibodies), or paroxysmal nocturnal haemoglobinuria. Clinically significant bleeding (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following intramuscular injections or venepuncture Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, or neurological illness, as judged by the Investigator Any other significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study, or impair interpretation of the study data Any autoimmune conditions, except mild psoriasis and vitiligo.