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ACE-I: angiotensin-converting enzyme inhibitor ACE2: angiotensin-converting enzyme receptor AngII: angiotensin II DIR: delayed inflammatory reaction mRNA: messenger RNA RAS: renin-angiotensin system INTRODUCTION We present 4 cases of delayed inflammatory reaction (DIR) to facial dermal hyaluronic acid filler rapidly following vaccination for COVID-19. All DIRs occurred after a hyaluronic acid filler had been placed more than 1 year before vaccination. All patients responded rapidly to therapy with a low dose of oral lisinopril, an angiotensin-converting enzyme inhibitor (ACE-I), which decreases the cutaneous filler-related inflammatory reaction and edema by a novel proposed mechanism.