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
TL;DR: The first reported cases of delayed inflammatory reactions (DIR) to hyaluronic acid (HA) dermal fillers after exposure to the COVID-19 spike protein was reported in this article.
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.
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TL;DR: In this article, a provider-facing registry-based study collected cases of cutaneous manifestations after COVID-19 vaccination and found that delayed large local reactions were most common, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions.
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.
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A. Català, C Muñoz-Santos, Cristina Galván-Casas, M. Roncero Riesco1, D Revilla Nebreda1, A Solá-Truyols, Priscila Giavedoni, Mar Llamas-Velasco, Carlos González-Cruz, Xavier Cubiró, Ricardo Ruiz-Villaverde, S Gómez-Armayones, M P Gil Mateo, D Pesqué, O Marcantonio, Diego Fernandez-Nieto, Jorge Romaní, N Iglesias Pena, L Carnero Gonzalez, J Tercedor-Sanchez, Gregorio Carretero2, T Masat-Ticó, Pedro Rodriguez-Jimenez, Ana Giménez-Arnau, M Utrera-Busquets, E Vargas Laguna, A G Angulo Menéndez, E San Juan Lasser, M Iglesias-Sancho, L Alonso Naranjo, I Hiltun, E Cutillas Marco, I. Polimón Olabarrieta, S. Marinero Escobedo, X García-Navarro, M J Calderón Gutiérrez, G Baeza-Hernández, L Bou Camps, T Toledo-Pastrana, Antonio Guilabert •
TL;DR: 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%) as discussed by the authors.
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.
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TL;DR: 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%) as mentioned in this paper .
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.
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TL;DR: The authors reviewed the dermatologic manifestations of COVID-19 vaccines as reported in clinical trial data and summarized additional observational reports of skin reactions to COVID19 vaccines, concluding that early-onset local injection reactions were the most common cutaneous side effects observed in clinical trials, while delayed injection reactions reported outside of clinical trials.
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References
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Merryn Voysey1, Clemens Sac.1, Shabir A. Madhi, Lily Yin Weckx2, P M Folegatti1, Parvinder K. Aley1, Brian Angus1, Vicky L. Baillie3, Shaun Barnabas4, Q E Bhorat, S Bibi1, Carmen Briner3, P Cicconi1, Andrea M. Collins5, R Colin-Jones1, Clare L. Cutland3, Thomas C. Darton6, Keertan Dheda7, Duncan Cja.8, Emary Krw.1, Katie J. Ewer1, Lee Fairlie3, Saul N. Faust9, Shuo Feng1, Daniela M. Ferreira5, Adam Finn10, Anna Goodman11, Catherine M. Green1, Christopher A Green12, Paul T. Heath13, Christopher Hill3, Helen Hill5, Ian Hirsch14, Hodgson Shc.1, Allen Izu, S Jackson1, D Jenkin1, Joe Ccd.1, S Kerridge1, Anthonet Koen, Gaurav Kwatra3, Rajeka Lazarus15, Alison M. Lawrie1, A Lelliott1, Vincenzo Libri16, Patrick J. Lillie17, R Mallory14, Mendes Ava.18, Eveline Pipolo Milan19, Angela M. Minassian1, Alastair McGregor20, Hazel Morrison1, Y Mujadidi1, Amit J Nana3, P J O’Reilly1, S D Padayachee, A Pittella, E Plested1, Katrina M Pollock, M N Ramasamy1, S Rhead1, Alexandre Vargas Schwarzbold21, Nisha Singh1, Andrew Smith22, R Song23, Matthew D. Snape1, Eduardo Sprinz24, Rebecca K. Sutherland25, R Tarrant1, E. Thomson26, M E Török27, Mark Toshner28, Turner Dpj.29, Johan Vekemans14, Tonya Villafana14, Watson Mee.1, C J Williams30, Alexander D. Douglas1, Hill Avs.1, Teresa Lambe1, Sarah C. Gilbert1, Andrew J. Pollard1 •
University of Oxford1, Federal University of São Paulo2, University of the Witwatersrand3, Stellenbosch University4, Liverpool School of Tropical Medicine5, University of Sheffield6, University of London7, Newcastle upon Tyne Hospitals NHS Foundation Trust8, University Hospital Southampton NHS Foundation Trust9, University Hospitals Bristol NHS Foundation Trust10, Guy's and St Thomas' NHS Foundation Trust11, University Hospitals Birmingham NHS Foundation Trust12, St George's, University of London13, AstraZeneca14, North Bristol NHS Trust15, University College Hospital16, University of Hull17, Escola Bahiana de Medicina e Saúde Pública18, Federal University of Rio Grande do Norte19, Northwest University (China)20, Universidade Federal de Santa Maria21, Glasgow Dental Hospital and School22, Boston Children's Hospital23, Universidade Federal do Rio Grande do Sul24, Western General Hospital25, University of Glasgow26, Cambridge University Hospitals NHS Foundation Trust27, University of Cambridge28, Nottingham University Hospitals NHS Trust29, Aneurin Bevan University Health Board30
TL;DR: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.
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Lindsey R. Baden1, Hana M. El Sahly2, Brandon Essink3, Karen L. Kotloff4, Sharon E. Frey5, Rick Novak6, David Diemert7, Stephen A. Spector8, Nadine Rouphael9, C. Buddy Creech, John W McGettigan, Shishir Khetan, Nathan Segall10, Joel Solis, Adam Brosz, Carlos Fierro, Howard J. Schwartz, Kathleen M. Neuzil, Lawrence Corey, Peter B. Gilbert, Holly Janes, Dean Follmann, Mary A. Marovich, John R. Mascola, Laura Polakowski, Julie E. Ledgerwood, Barney S. Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Liang Han, Melanie Ivarsson, Jacqueline Miller, Tal Z Zaks •
Brigham and Women's Hospital1, Baylor College of Medicine2, Emory University3, University of Maryland, Baltimore4, Saint Louis University5, University of Illinois at Chicago6, George Washington University7, University of California, San Diego8, Vanderbilt University9, Fred Hutchinson Cancer Research Center10
TL;DR: The mRNA-1273 vaccine as discussed by the authors is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.
Abstract: Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).
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Lisa A. Jackson1, Evan J. Anderson2, Nadine Rouphael2, Paul C. Roberts3, Mamodikoe Makhene3, Rhea N. Coler4, Michele Paine McCullough2, James D. Chappell5, Mark R. Denison5, Laura J. Stevens5, Andrea J. Pruijssers5, Adrian B. McDermott3, Britta Flach3, Nicole A. Doria-Rose3, Kizzmekia S. Corbett6, Kaitlyn M. Morabito3, Sijy O’Dell3, Stephen D. Schmidt3, Phillip A. Swanson3, Marcelino Padilla3, John R. Mascola3, Kathleen M. Neuzil3, Hamilton Bennett, Wellington Sun, Etza Peters2, Mat Makowski, Jim Albert, Kaitlyn Cross, Wendy Buchanan3, Rhonda Pikaart-Tautges3, Julie E. Ledgerwood3, Barney S. Graham6, John H. Beigel6 •
TL;DR: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified, which support further development of this vaccine.
Abstract: Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vacci...
2,556 citations
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Edward E. Walsh1, Robert W. Frenck2, Ann R. Falsey1, Ann R. Falsey3, Nicholas Kitchin4, Judith Absalon4, Alejandra Gurtman4, Stephen Lockhart4, Kathleen M. Neuzil5, Mark J. Mulligan6, Ruth Bailey4, Kena A. Swanson4, Ping Li4, Kenneth Koury4, Warren Kalina4, David A. Cooper4, Camila R. Fontes-Garfias7, Pei Yong Shi7, Özlem Türeci, Tompkins Kristin Rachael4, Kirsten E. Lyke5, Vanessa Raabe6, Philip R. Dormitzer4, Kathrin U. Jansen4, Ugur Sahin, William C. Gruber4 •
TL;DR: The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation.
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldw...
1,939 citations
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TL;DR: The data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally, and may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity.
Abstract: Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection. We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student’s t test. We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson’s correlation test. ACE2 expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle. ACE2 showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland. ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels, ACE2 expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively. Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.
1,143 citations
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