COVID-19: vaccines and infections

Personalized, precise and predictive vaccinology's holy grail is to anticipate immune response for every individual, depending on their genetic background and all other factors that may impact vaccine immunogenicity, efficacy, and safety.

The high expense of comprehensive genomic and immune-profiling tests, however, prohibits their routine use and this disproportionally affects underserved populations.

A new paper reports preliminary results of an ongoing study of COVID-19 vaccination in geographic neighborhoods and online health support groups. Due to innovative recruitment and monitoring strategies, the study has the largest representation of active "oldest old" - individuals aged 80 or older - than all other trials with diverse age groups. 

Despite widespread belief of a biphasic pattern for the frequency of systemic adverse events post-vaccination (VAEs), the paper reports statistically significant differences in the incidence of VAEs for both younger and 80+ populations when compared to those in the 60-69 and 70-79 age brackets. The subtypes of adverse events in younger and older populations are different. This short paper groups post-vaccination events in three types: "No or minimal VAEs", and short- or long-term reactions that significantly impacted activities of daily living.    

The paper suggests genetic origin for some adverse reactions. Scientists have only just begun to look into genetics of less common VAEs. HLA-A∗03:01 (contributing to low risk of severe COVID-19) was recently found to be associated with increased risk of stronger side effects (including fever and chills) from Pfizer-BioNTech COVID-19 vaccination. In another recent study, HLA-DQB1*06 alleles were found to protect from breakthrough infection during the ancestral SARS-CoV-2 virus and subsequent Alpha-variant waves compared with non-carriers. Hopefully, more studies will follow. 

REFERENCE

Gabashvili IS. The Incidence and Effect of Adverse Events Due to COVID-19 Vaccines on Breakthrough Infections: Decentralized Observational Study With Underrepresented Groups. JMIR Form Res. 2022 Nov 4;6(11):e41914. doi: 10.2196/41914. PMID: 36309347.

Current Impact score of the journal is: 2.38 (Resurchify)

JMIR Formative Research has been accepted for the Web of Science: Emerging Sources Citation Index. The journal will receive a Journal Impact Factor in 2023. 

Resolving the subtypes of COVID-19 in the elderly

SARS-Cov-2 is one of the most complex viruses known to medical science. Patients with COVID-19 present a broad spectrum of clinical manifestations, ranging from asymptomatic infection to lethal outcome. Both the young and the old may have very different clusters of symptoms and responses to medications, including the COVID-19 vaccines.  Each type is associated with how severe of an illness a patient might experience, ranging from asymptomatic to lethal. 

Precision medicine approaches such as whole-exome sequencing can provide insight into the phenotypes, endotypes and underlying mechanisms of the disease. The high cost of cutting-edge approaches, however, keeps these tools out of reach for many research teams. 

In this age of big data and large clinical studies, we should not forget about the value of individual cases. A good case report tells a detailed story. It describes a unique phenotype and offers unique clues to its resolution into an endotype. 

A new systematic review of case reports aims to answer questions about COVID-19 subtypes in octogenarians, nonagenarians, and centenarians and offer possible solutions to organize the knowledge and identify the gaps. 

REFERENCE

Irene S. Gabashvili. The outcomes of COVID-19 vaccination and SARS-CoV-2 infection in octogenarians, nonagenarians, and centenarians. PROSPERO 2022 CRD42022332621 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332621

Irene S. Gabashvili (2022), “COVID-19 vaccine and SARS-CoV-2 in the oldest old: rapid literature review”, Mendeley Data, v1 http://dx.doi.org/10.17632/6sk33d9z7s.1 https://data.mendeley.com/datasets/6sk33d9z7s/1

Irene S. Gabashvili (2022), “The Outcomes of COVID-19 and Vaccination in the Oldest Old: a Longitudinal Observational Study and Literature Review”, April 2022, DOI: 10.13140/RG.2.2.15625.93285

Getting Out of Echo Chambers

Web search is hyper personalized and social media creates echo chambers. 

Nothing new, really. "The Facebook effect" was coined over 10 years ago, and the echo chamber effect of the Internet was known long before that.  Echo chambers existed even in the early blogosphere. But the isolation from a diversity of views and opinions may be reaching the tipping point. 

A study published last month in PLOS One, analyzed and visualized 60 billion tweets demonstrating how highly the vaccine debate is polarized. 

Users with similar stances interacted preferentially with one another. Interactions between individuals with different views were rare and not productive.  Extending this insight, the authors provide evidence of an epistemic echo chamber effect, where users are exposed to highly dissimilar sources of information, depending on the stance of their contacts. 

But does it make sense to call an article or a blog post provaxx or antivaxx based on pro- or anti-vaccine sentiment?

Why can't we discuss pros and cons of vaccines objectively and admit that medicine should be personalized? Majority of population benefits from vaccines, but there are those that don't. Should not we try to understand why?

The only way to overcome hyperpolarization is to increase our collective cultural intelligence, improve critical thinking skills, counteract destructive polarization, recognize the legitimacy and ongoing necessity of opposing viewpoints.

The new.aurametrix.com site is a collection of scientific papers about the less discussed medical cases. We all know that vaccines work. We dare you to understand why there are cases when they don't. 

REFERENCES

Less Discussed Medical Case Reports

Mønsted B, Lehmann S. Characterizing polarization in online vaccine discourse—A large-scale study. PloS one. 2022 Feb 9;17(2):e0263746.

Ries M. The COVID-19 Infodemic: Mechanism, Impact, and Counter-Measures—A Review of Reviews. Sustainability. 2022 Jan;14(5):2605.

Gorman, J. M., & Scales, D. A. (2022). Leveraging infodemiologists to counteract online misinformation: Experience with COVID-19 vaccines. Harvard Kennedy School (HKS) Misinformation Review. https://doi.org/10.37016/mr-2020-92

Myocarditis and COVID-19: for some people the risk may be higher following vaccination than infection

COVID-19 is a known cause of cardiac complications such as myocarditis and systolic dysfunction. Vaccine associated myocarditis was described following smallpox vaccination, streptococcal pneumonia and influenza vaccine. In some cases, autoimmune/inflammatory syndrome induced by adjuvants used in the vaccine have been also implicated. 

Associations of COVID-19 vaccination and myocarditis have been proposed in multiple publications, but the consensus was that the benefits of vaccine are worth the increased risk even though more personalized approach seems warranted by the evidence.

A new study presents data about the risk of myocarditis increasing with each subsequent dose of mRNA vaccines, especially mRNA-1273. Moreover, in younger males the risk of myocarditis was higher following vaccination than infection. Another study presents a case of fatal breakthrough infection in an older male who experienced myocarditis-like symptoms after his COVID-19 vaccine. Retrospective cohort study of 196,992 adults in Israel did not observe an increased incidence of neither pericarditis nor myocarditis in unvaccinated adult patients recovering from COVID-19 infection. See example case reports. 

REFERENCES

Martina Patone, Winnie Xue Mei, Lahiru Handunnetthi, Sharon Dixon, Francesco Zaccardi, Manu Shankar-Hari, Peter Watkinson, Kamlesh Khunti, Anthony Harnden, Carol AC Coupland, Keith M. Channon, Nicholas L Mills, Aziz Sheikh, Julia Hippisley-Cox Risk of myocarditis following sequential COVID-19 vaccinations by age and sex  medRxiv 2021.12.23.21268276; doi: https://doi.org/10.1101/2021.12.23.21268276

Kim HW, Jenista ER, Wendell DC, Azevedo CF, Campbell MJ, Darty SN, Parker MA, Kim RJ. Patients with acute myocarditis following mRNA COVID-19 vaccination. JAMA cardiology. 2021 Oct 1;6(10):1196-201.

Lazaros G, Anastassopoulou C, Hatziantoniou S, Kalos T, Soulaidopoulos S, Lazarou E, Vlachopoulos C, Vassilopoulos D, Tsakris A, Tsioufis C. A case series of acute pericarditis following COVID-19 vaccination in the context of recent reports from Europe and the United States. Vaccine. 2021 Oct 29;39(45):6585-90.

Hendren NS, Carter S, Grodin JL. Severe COVID-19 vaccine associated myocarditis: Zebra or unicorn?. International journal of cardiology. 2021 Nov 15;343:197-8.

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Cutaneous manifestations of SARS-CoV-2 and COVID-19 vaccines

 COVID-19 is associated with a wide range of skin signs. 

The following six main clinical patterns have been proposed for such manifestations most recently: (i) urticarial rash, (ii) confluent erythematous/maculopapular/morbilliform rash, (iii) papulovesicular exanthem, (iv) chilblain-like acral pattern, (v) livedo reticularis/racemosa-like pattern, and (vi) purpuric "vasculitic" pattern. Livedo or necrosis - blotchy red or blue appearance with a net-like pattern - was associated with increased disease severity while measles-like (morbilliform) rash was generally seen in patients with moderate to severe infection (like in the patient shown on the left who died) and pseudo-chilblains, a late sign of COVID-19, was associated with decreased severity and more likely to happen for younger patients. The median duration of chiblain-like acral pattern, however, was significantly longer that all other patterns. One study of 200 patients found the following frequencies of these signs: 10.2% for Urticarial rash; 25.7% for confluent erythematous/maculo-papular/morbilliform rash; 15.5% for papulovesicular exanthem, 24.6% for a chilblain-like acral pattern; 2.1% for a livedo reticularis/racemosa-like pattern; and 6.9% for a purpuric vasculitic pattern. 15% of skin patterns were not clearly classified while 6.5% had more than one pattern present.

The prevalence of cutaneous involvement was 7.8% in a binational Chinese-Italian cohort of 678 hospitalized adults with laboratory-confirmed disease. Dermatologic reactions after COVID-19 vaccines have been also reported and can mimic SARS-CoV-2 infection itself (eg, pernio/chilblains). The prevalence was the highest after the 2nd dose of mRNA-1273 (over 12% in Moderna), although only 1-2% experienced it with ChAdOx1 nCov-19 vaccine (AstraZeneca).

Delayed large local reactions were most common among vaccinees, followed by local injection site reactions, urticarial eruptions, and morbilliform eruptions. In a study of 414 people, forty-three percent of patients with first-dose reactions experienced second-dose recurrence. Additional less-common reactions included pernio/chilblains, dyshidrotic eczema, psoriasiform dermatitis, cosmetic filler reactions, zoster, herpes simplex flares, and pityriasis rosea-like reactions. 

Some of more serious reactions could be exacerbation of Erythema multiforme. It mostly happens in mild form of a sudden rash that goes away in a few weeks but could progress to larger raised patches that look like a target or "bulls-eye" and may have a blister or crust. Relapses of autoimmune bullous disease have been also reported as well as new onset Lichen planus, immune complex vasculitis or flares of subacute cutaneous lupus erythematosus, psoriasis and atopic dermatitis. 

Morphologic misclassification is, however, possible. 

REFERENCES

Tan SW, Tam YC, Oh CC. Skin manifestations of COVID-19: A worldwide review. JAAD international. 2021 Mar 1;2:119-33.

Slimani Y, Abbassi R, El Fatoiki FZ, Barrou L, Chiheb S. Systemic lupus erythematosus and varicella‐like rash following COVID‐19 in a previously healthy patient. Journal of Medical Virology. 2021 Feb;93(2):1184-7.

Genovese G, Moltrasio C, Berti E, Marzano AV. Skin manifestations associated with COVID-19: current knowledge and future perspectives. Dermatology. 2021 Jan 1:1-2. 

Marzano AV, Genovese G, Moltrasio C, Gaspari V, Vezzoli P, Maione V, Misciali C, Sena P, Patrizi A, Offidani A, Quaglino P. The clinical spectrum of COVID-19–associated cutaneous manifestations: An Italian multicenter study of 200 adult patients. Journal of the American Academy of Dermatology. 2021 May 1;84(5):1356-63. 

Bogdanov G, Bogdanov I, Kazandjieva J, Tsankov N. Cutaneous adverse effects of the available COVID-19 vaccines. Clinics in Dermatology. 2021 Apr 27.

Rice SM, Ferree SD, Mesinkovska NA, Kourosh AS. The art of prevention: COVID-19 vaccine preparedness for the dermatologist. International journal of women's dermatology. 2021 Jan 12.