Girish Gilly Munavalli

Bio: Girish Gilly Munavalli is an academic researcher. The author has contributed to research in topics: Angiotensin II & Angiotensin-converting enzyme. The author has an hindex of 2, co-authored 2 publications receiving 43 citations.

COVID-19/SARS-CoV-2 virus spike protein-related delayed inflammatory reaction to hyaluronic acid dermal fillers: a challenging clinical conundrum in diagnosis and treatment

Abstract: We present the first reported cases of delayed inflammatory reactions (DIR) to hyaluronic acid (HA) dermal fillers after exposure to the COVID-19 spike protein. DIR to HA is reported to occur in the different scenarios including: secondary to poor injection technique, following dental cleaning procedures, following bacterial/viral illness, and after vaccination. In this report of 4 cases with distinct clinical histories and presentations: one case occured following a community acquired COVID-19 infection, one case occured in a study subject in the mRNA-1273 clinical phase III trial, one case occurred following the first dose of publically available mRNA-1273 vaccine (Moderna, Cambridge MA), and the last case occurred after the second dose of BNT162b2 vaccine (Pfizer, New York, NY). Injectable HA dermal fillers are prevalent in aesthetic medicine for facial rejuvenation. Structural modifications in the crosslinking of HA fillers have enhanced the products’ resistance to enzymatic breakdown and thus increased injected product longevity, however, have also led to a rise in DIR. Previous, DIR to HA dermal fillers can present clinically as edema with symptomatic and inflammatory erythematous papules and nodules. The mechanism of action for the delayed reaction to HA fillers is unknown and is likely to be multifactorial in nature. A potential mechanism of DIR to HA fillers in COVID-19 related cases is binding and blockade of angiotensin 2 converting enzyme receptors (ACE2), which are targeted by the SARS-CoV-2 virus spike protein to gain entry into the cell. Spike protein interaction with dermal ACE2 receptors favors a pro-inflammatory, loco-regional TH1 cascade, promoting a CD8+T cell mediated reaction to incipient granulomas, which previously formed around residual HA particles. Management to suppress the inflammatory response in the native COVID-19 case required high-dose corticosteroids (CS) to suppress inflammatory pathways, with concurrent ACE2 upregulation, along with high-dose intralesional hyaluronidase to dissolve the inciting HA filler. With regards to the two vaccine related cases; in the mRNA-1273 case, a low dose angiotensin converting enzyme inhibitor (ACE-I) was utilized for treatment, to reduce pro-inflammatory Angiotensin II. Whereas, in the BNT162b2 case the filler reaction was suppressed with oral corticosteroids. Regarding final disposition of the cases; the vaccine-related cases returned to baseline appearance within 3 days, whereas the native COVID-19 case continued to have migratory, evanescent, periorbital edema for weeks which ultimately subsided.

Oral angiotensin-converting enzyme inhibitors for treatment of delayed inflammatory reaction to dermal hyaluronic acid fillers following COVID-19 vaccination-a model for inhibition of angiotensin II-induced cutaneous inflammation.

Abstract: 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.

Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of 414 cases.

Abstract: Background Cutaneous reactions after messenger RNA (mRNA)-based COVID-19 vaccines have been reported but are not well characterized. Objective To evaluate the morphology and timing of cutaneous reactions after mRNA COVID-19 vaccines. Methods A provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination. Results From December 2020 to February 2021, we recorded 414 cutaneous reactions to mRNA COVID-19 vaccines from Moderna (83%) and Pfizer (17%). Delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions. Forty-three percent of patients with first-dose reactions experienced second-dose recurrence. Additional less common reactions included pernio/chilblains, cosmetic filler reactions, zoster, herpes simplex flares, and pityriasis rosea-like reactions. Limitations Registry analysis does not measure incidence. Morphologic misclassification is possible. Conclusions We report a spectrum of cutaneous reactions after mRNA COVID-19 vaccines. We observed some dermatologic reactions to Moderna and Pfizer vaccines that mimicked SARS-CoV-2 infection itself, such as pernio/chilblains. Most patients with first-dose reactions did not have a second-dose reaction and serious adverse events did not develop in any of the patients in the registry after the first or second dose. Our data support that cutaneous reactions to COVID-19 vaccination are generally minor and self-limited, and should not discourage vaccination.

Cutaneous reactions after SARS-COV-2 vaccination: A cross-sectional Spanish nationwide study of 405 cases.

Abstract: Background Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized. Objective To describe and classify cutaneous reactions after SARS-CoV-2 vaccination. Methods A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification. Results From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site ('COVID arm', 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment. Conclusions Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.

Cutaneous reactions after SARS-CoV-2 vaccination: a cross-sectional Spanish nationwide study of 405 cases

Abstract: Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized.To describe and classify cutaneous reactions after SARS-CoV-2 vaccination.A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification.From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site ('COVID arm', 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment.Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.

Cutaneous findings following COVID-19 vaccination: Review of world literature and own experience.

Abstract: There is growing evidence that not only the novel coronavirus disease (COVID-19) but also the COVID-19 vaccines can cause a variety of skin reactions. In this review article, we provide a brief overview on cutaneous findings that have been observed since the emerging mass COVID-19 vaccination campaigns all over the world. Unspecific injection site reactions very early occurring after the vaccination are most frequent. Type I hypersensitivity reactions (e.g., urticaria, angioedema, anaphylaxis) likely due to allergy to ingredients may rarely occur but can be severe. Type IV hypersensitivity reactions may be observed, including delayed large local skin lesions ("COVID arm"), inflammatory reactions in dermal filler or previous radiation sites or even old BCG scars, and more commonly moribilliform and erythema multiforme-like rashes. Autoimmune-mediated skin findings after COVID-19 vaccination include leukocytoclastic vasculitis, lupus erythematosus, and immune thrombocytopenia. Functional angiopathies (chilblain-like lesions, erythromelalgia) may also be observed. Pityriasis rosea-like rashes and reactivation of herpes zoster have also been reported after COVID-19 vaccination. In conclusion, there are numerous cutaneous reaction patterns that may occur following COVID-19 vaccination, whereby many of these skin findings are of immunological/autoimmunological nature. Importantly, molecular mimicry exists between SARS-CoV-2 (e.g., the spike-protein sequences used to design the vaccines) and human components and may thus explain some COVID-19 pathologies as well adverse skin reactions to COVID-19 vaccinations.