Inclusion Criteria:  Male and female participants ≥18 years of age with 1 or more co-morbidities. For the co-morbidities chronic kidney disease, chronic obstructive pulmonary disease (COPD), chronic cardiovascular disease and diabetes mellitus, the first 25 participants per co-morbidity should include only mild to moderate cases. Thereafter, more severe conditions may be recruited following Internal Safety Review Committee (iSRC) and Data Safety Monitoring Board (DSMB) Chair approval. Participant has no overt clinical signs or symptoms of COVID-19. Participant has to sign the informed consent form (ICF) before any trial procedures. Participants with a life expectancy of at least 1 year as per the Investigator's assessment. Expected to be compliant with protocol procedures and available for clinical follow-up through the last planned visit. Physical examination without acute clinically significant findings according to the Investigator's assessment.  Female participants: At the time of enrollment, negative human chorionic gonadotropin (hCG) pregnancy test (serum) for women presumed to be of childbearing potential on the day of enrollment. On Day 1 (pre vaccination): negative urine pregnancy test (hCG) (only required if serum pregnancy test was performed more than 3 days before).  Note: Women that are postmenopausal (defined as amenorrhea for ≥ 12 consecutive months prior to screening without an alternative medical cause) or permanently sterilized will be considered as not having reproductive potential.  Female participants of childbearing potential must use highly effective methods of birth control from 2 weeks before the first administration of the trial vaccine until 3 months following the last administration .  Exclusion Criteria:  A previous clinical and laboratory-confirmed diagnosis of COVID-19 within the last six months prior to screening. Use of any investigational or non-registered product (vaccine or drug) other than the trial vaccine within 28 days preceding the administration of the trial vaccine, or planned use during the trial period. Receipt of any other vaccines within 28 days prior to enrollment in this trial or planned receipt of any vaccine within 28 days of trial vaccine administration. Planned vaccination with an inactivated influenza vaccine is permitted. Receipt of any investigational, authorized or licensed SARS-CoV-2, other coronavirus vaccine or any other lipid nanoparticles (LNP)-containing messenger ribonucleic acid vaccine prior to the administration of the trial vaccine. For authorized or licensed SARS-CoV-2: planned administration during the trial up to 6 weeks after the foreseen date of second dose administration of CVnCoV.  Any treatment with immunosuppressants or other immune-modifying drugs (including, but not limited to, corticosteroids, biologicals, and methotrexate) for >14 days in total within 6 months prior to the administration of the trial vaccine or planned use during the trial. For corticosteroid use, this means prednisone or equivalent, 0.5 mg/kg/day for 14 days or more. The use of inhaled, topical, or localized injections of corticosteroids (e.g., for joint pain/inflammation) is permitted.  Note: This exclusion does not apply to the renal transplant cases and is at the Investigator's discretion for participants with other co-morbidities (e.g., COPD).  Participants with chronic human immunodeficiency virus (HIV) infection with controlled Hepatitis B infection with therapy or aviremic Hepatitis C may be eligible for the trial, based on the Investigator's judgment. History of immune-mediated or autoimmune disease. History of anaphylaxis or allergy to any component of CVnCoV or aminoglycoside antibiotics. History of or current alcohol and/or drug abuse. History of confirmed severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) disease. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of any dose of the trial vaccine.  Presence or evidence of significant uncontrolled acute or chronic medical or psychiatric illness, excluding the co-morbidities specified in the protocol. Significant medical or psychiatric illnesses include but are not limited to:  Uncontrolled respiratory disease. Uncontrolled neurological disorders or Guillain-Barré syndrome or history of seizure, except for febrile seizures during childhood. Current or past malignancy, unless completely resolved without sequelae for >5 years Foreseeable non-compliance with protocol, as judged by the Investigator. For female participants: pregnancy or lactation. Participants with impaired coagulation or any bleeding disorder in whom an IM injection or a blood draw is contraindicated. This includes participants on treatment with anticoagulants (e.g., vitamin K antagonists, novel oral anticoagulants, and heparin). Use of platelet aggregation inhibitors is not exclusionary. However, use of anticoagulants is accepted in certain co-morbidities according to the clinical Investigator's judgment and if the international normalized ratio (INR) remains ≤3. Participants employed by the Sponsor, Investigator, or trial site, or relatives of research staff working on this trial.