Saturday, December 25, 2021

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


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:

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.


Thursday, December 16, 2021

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. 


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.

Friday, November 26, 2021

The Omicron

On 26 November 2021, WHO designated the variant B.1.1.529 a variant of concern, named Omicron. It is associated with substantial ability to evade immunity from prior infection. But many important questions about this variant's severity remain unanswered.
Omicron has more than 30 mutations in the spike protein targeted by COVID-19 vaccines. H655Y (Histidine at position 655 substituted by Tyrosine; first detected in Brazil) was previously shown to confer escape from human monoclonal antibodies. Another mutation borrowed from Gamma variant, N679K, may also increase infectivity.

Cases in US

California man who returned from South Africa mild (was fully vaccinated)

Minnesota man who recently traveled to NYC for a 3-day anime festival - mild (was fully vaccinated)

New York already had cases by that time one of which was a traveler returning from South Africa, 10 cases identified by December 5

Nebraska man who brought it from Nigeria and passed it to 5 other people, only one of whom was vaccinated

Wisconsin man tested positive for Omicron after a recent trip to South Africa 

The 1st Hawaii case is a 65 with no history of travel outside state who already had COVID-19 before. 

A middle-aged woman who recently traveled from South Africa became both New Jersey and Georgia’s first confirmed case after seeking care for moderate symptoms at an emergency room. 

640 deaths since Omicron dominant in South Africa

1st death confirmed in UK on Dec. 13 2021


Juliet R.C. Pulliam, Cari van Schalkwyk, Nevashan Govender, Anne von Gottberg, Cheryl Cohen, Michelle J. Groome, Jonathan Dushoff, Koleka Mlisana, Harry Moultrie Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa  medRxiv 2021.11.11.21266068; doi: 

Rapp M, Shapiro L, Frank J. Contributions of single-particle cryoelectron microscopy toward fighting COVID-19. Trends in biochemical sciences.:S0968-0004.

Liu L., et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature. 2020;584:450–456.

Thursday, August 12, 2021

August 12

When we thought COVID-19 was over, as more individuals were vaccinated against the deadly virus, the fourth wave of the pandemic struck, fueling a rise in breakthrough infections. 

We have documented several cases of fatal breakthrough infections. Publishing it is not easy because of many biases. 

Science has been always linked to the politics of society. Current political polarization hinders not only effective COVID-19 pandemic mitigation measures but also impedes research on side effects of vaccines and fatal breakthrough infections in healthy individuals. Social media fuels the divide encouraging toxic discussion, favoring rude and disrespectful comments. 

Publishing bias is another issue since scientific journals prefer to publish positive results discriminating against negative or null results. 

But we have many documented cases from the COVID-back-to-normal study and information about other COVID victims from genealogy and other sources. Let the truth be told. 


Berkessel J, Ebert T, Gebauer J, Jonsson T, Oishi S. Pandemics Initially Spread Among People of High (not Low) Social Status: Evidence from COVID-19 and the Spanish Flu. PsyArXiv, 12 Jan. 2021. [example of using genealogy sites for medical research]

Gabashvili IS. Community-Based Phenotypic Study of Safety, Tolerability, Reactogenicity and Immunogenicity of Emergency-Use-Authorized Vaccines Against COVID-19 and Viral Shedding Potential of Post-Vaccination Infections: Protocol for an Ambispective study. medRxiv. 2021 Jun 1. medRxiv 2021.06.28.21256779; doi:

Thursday, April 1, 2021

Laughter as Medicine

The pandemics is not over, but should we pause the jokes? Research shows, we shouldn't, as humor makes us feel better.  

Language learning is hard, so we made it soft, said Duolingo in their April 1st announcement of a new product - toilet papers that turns your bathroom into a classroom. “The average human spends 14 minutes every day sitting on a toilet, - explained Duolingo, - Yet, our work shows that it only takes 5 minutes a day to learn a new language. Our learning scientists have systematically engineered a new bottom-up approach to language acquisition.” 

Toilet humor is not my favorite kind of joke … But it’s a solid number two.

In 2020, coronavirus jokes  - including jokes about toilet paper - were spreading almost as fact as the virus itself.  Such a response is not new - as seen from the art associated with the cholera pandemics and other cataclysmic events. Humor, especially the self-enhancing style (vs self-defeating type), was shown to positively correlate with engagement in protective behaviors and negatively correlate with stress and hopelessness. 
Laughter is used therapeutically in health care. According to experts in humor physiology or "gelotology," by aiding ventilation and clearing mucosal plugs, laughter can help those afflicted with chronic obstructive lung disease. It can increase arterial and venous circulation, causing an increased movement of oxygen to tissues. 

Fortunately, not everybody today was as boring as Google. Consumer electronics company Monoprice advertised their new sit-squat desk to "boost productivity by improving comfort and well-being through posture and proper leg day routines”. There were jokes from emergency medicine physicians (on the left), programmers (stack overflow limiting copy-paste of code), furniture and food companies (smoup - new soup and smoothie food), journalists (digging new Suez2 canal), policemen (new drone-mounted dachshund dog squad), and military. You can find a few more on reddit megatrend

Laugh your way to better health.


Olah AR, Hempelmann CF. Humor in the age of coronavirus: a recapitulation and a call to action. HUMOR. 2021 Mar 17.

Olah AR, Ford TE. Humor styles predict emotional and behavioral responses to COVID-19. HUMOR. 2021 Mar 22.

Sebba-Elran T. A pandemic of jokes? The Israeli Covid meme and the construction of a collective response to risk. HUMOR. 2021 Mar 22.

Chiodo CP, Broughton KK, Michalski MP. Caution: wit and humor during the COVID-19 pandemic.

Chłopicki W, Brzozowska D. Sophisticated humor against Covid: the Polish case. HUMOR. 2021 Mar 22.

Kao A. April Fool's Day and the Medicinal Value of Humor. AMA Journal of Ethics. 2000 Apr 1;2(4):34.

Sebba-Elran T. A pandemic of jokes? The Israeli Covid meme and the construction of a collective response to risk. HUMOR. 2021 Mar 22.

Sunday, March 28, 2021

AI for Eyes

Ophthalmology is dominated by imaging. Volumetric, three dimensional (3D) ophthalmic imaging using optical coherence tomography (OCT) has revolutionized assessment of the eye and artificial intelligence (AI) improved clinical decision-making.  Current commercial OCT instruments, especially spectral domain (SD) OCT, are widely used in diagnosis and management of patients with retinal diseases.  Yet, standard 2D cross-sectional images of the retina, that remain the most commonly used OCT images and can be even taken by patients themselves, using smartphone apps, can also provide valuable information utilizing AI models. 

Fundus photography - serial photographs of the interior of the eye (opposite the lens)
taken through the pupil by low-power microscope can help to examine optic disc, retina, and lens. With the drastic improvement in smartphone optics, smartphone fundoscopy has been used with increasing frequency since 2010. Machine learning, particularly deep learning, could analyze millions of such images, to identify and quantify pathological features in almost every ophthalmic disease. Even more, it can detect other health conditions such as hypertension, stroke risk, heart disease, and diabetes. 

Using deep learning models, systolic blood pressure could be detected as hypertensive with 60% accuracy (Dai t al., 2020) or within 11 mmHg, major cardiac adverse events with accuracy 70% (Poplin et al., 2018) and glaucoma predicted with 96% accuracy (Gheisari et al, 2021). 

The ImageNet dataset - a very large collection of human annotated photographs (over 14 mln)  - is a good starting point for obtaining a model that performs well in recognizing retinal images. A well-known class of deep neural networks - such as a successful CNN trained on ImageNet can be applied to a retinal dataset, and another classifier learns to work with CNN-encoded features - the method known as transfer learning.  Deep learning can be also combined with traditional machine learning methods and fine-tuning approaches. However, many retinal health variables, such as intraocular pressure, cannot be yet adequately predicted from clinical parameters or retinal photographs even using state-of-art molecular learning or deep learning techniques (Ishii et al., 2021). Only one out of three AI-based algorithms designed to detect diabetic retinopathy was able to outperform human screeners. Possibly, we just need more data. But we might be also needing new models.  

Three principal applications of AI for image analysis are classification, segmentation and prediction.  Automated image segmentation and classification can be done without AI methods, just by  applying a set of mathematical functions on the content of an image and classic ML approaches like SVM or random forest. Deep learning approaches could enhance these tasks. One of newer deep learning techniques, generative adversarial network (GAN), can greatly improve resolution of images (super resolution (SR) estimation from a low-resolution counterpart) and image segmentation. GANs can be also used to synthesize images with various eye pathologies, increasing accuracy of classification tasks. 

Thanks to the advances in AI and smart portable or home devices, the future of medicine, including teleophthalmology, is truly exciting. 


Schmidt-Erfurth U, Sadeghipour A, Gerendas BS, Waldstein SM, Bogunović H. Artificial intelligence in retina. Progress in retinal and eye research. 2018 Nov 1;67:1-29.  

Gheisari S, Shariflou S, Phu J, Kennedy PJ, Agar A, Kalloniatis M, Golzan SM. A combined convolutional and recurrent neural network for enhanced glaucoma detection. Scientific reports. 2021 Jan 21;11(1):1-1.

Poplin R, Varadarajan AV, Blumer K, Liu Y, McConnell MV, Corrado GS, Peng L, Webster DR. Prediction of cardiovascular risk factors from retinal fundus photographs via deep learning. Nature Biomedical Engineering. 2018 Mar;2(3):158-64.

Dai G, He W, Xu L, Pazo EE, Lin T, Liu S, Zhang C. Exploring the effect of hypertension on retinal microvasculature using deep learning on East Asian population. PloS one. 2020 Mar 5;15(3):e0230111.

Ishii K, Asaoka R, Omoto T, Mitaki S, Fujino Y, Murata H, Onoda K, Nagai A, Yamaguchi S, Obana A, Tanito M. Predicting intraocular pressure using systemic variables or fundus photography with deep learning in a health examination cohort. Scientific Reports. 2021 Feb 11;11(1):1-0.
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