Hello
DRESS syndrome and Dressler's syndrome - what's in the name?
Hello
DRESS syndrome and Dressler's syndrome - what's in the name?
Hi!
Hypercalcemia and hypervitaminosis-D is seen in patients with sarcoidosis and other granulomatous inflammatory conditions. This is because the granulomatous macrophages have high 1-alpha hydroxylase activity --> high levels of 1,25-OH2 vitamin D (calcitriol), produced in addition to this enzyme's normal activity in the kidneys.
That's all
- Jaskunwar Singh
Hi!
Penicillins such as amoxicillin and ampicillin are currently not recommended in patients with infectious mononucleosis with bacterial secondaries (streptococcal tonsillo-pharyngitis). Why?
The Moderna (mRNA-1273) SARS-CoV-2 vaccine is the second vaccine to receive emergency use authorisation (EUA) by the FDA. Like the Pfizer vaccine, it is also a lipid nanoparticle encapsulated mRNA vaccine, and therefore has the same mechanism of action. Please read about the brief mechanism from the Pfizer vaccine article: https://www.medicowesome.com/2020/12/the-bnt162b2-covid-19-vaccine-pfizer.html I will try to avoid big numbers and statistics in this article.
Both Moderna and Pfizer vaccines start protecting their recipients 10 days after the first dose, with maximum protection two weeks after the second dose. They both have efficacy ranging from 94-95% in protecting against symptomatic Covid-19. However, studies haven't yet evaluated their role in preventing asymptomatic Covid-19, a substantial missing link.
Can Covid-19 vaccines mitigate the pandemic?
People picture vaccines as a way back to normalcy, as before the pandemic; unless these mRNA vaccines' role in controlling asymptomatic SARS-CoV-2 infection is studied, normalcy is out of our reach. The other issues concerning the above question are -
1. Since the phase 3 studies of these vaccines are relatively 'young', we don't have sufficient knowledge about the nature and duration of immunological protection. Animal studies have shown that neutralizing antibodies confer protection and CD4 and CD8 T cells also amplify the immunological response. We don't know how long will the neutralizing antibodies last in our plasma after receiving the vaccine.
2. With both these vaccines, there is an inevitable study flaw. Vaccine recipients faced more systemic adverse events, such as fever, fatigue, headache, myalgia than the placebo group. These symptoms can also occur with Covid-19. Therefore, it is not unlikely that vaccine recipients could have designated their symptoms to the 'shot', and hesitated to refer themselves to be tested for Covid-19.
3. The third issue is quite popular in the daily news. What if the virus mutates and renders itself 'immune' to the vaccine? Some new strains have come up worldwide, and expectedly, the diaspora has started panicking. People need answers quickly while science takes time. So we cannot rule out the possibility that the virus devises a way to escape from the vaccine-induced immunological response.
4. Vaccine-associated enhanced disease (VAED). Earlier preclinical studies with SARS and MERS have demonstrated that low-level neutralizing antibodies in the plasma can trigger a severe form of the disease. Both the Moderna and Pfizer vaccines are 100% effective in protecting against severe Covid-19, notwithstanding this fact, the regulatory authorities should monitor these and other vaccine candidates for this adverse event.
5. Anti-Vaxxers! The anti-vaccine sentiment is appalling, and there have been 'anti-vaccine' protests in many parts of the world, including the US, Germany, Poland, and others. There are numerous fake news and misinformation in social media platforms that misguide people and tarnish their perspective about the vaccines. And this phenomenon has even affected the medical professionals. The healthcare authorities have an onerous task to incite confidence in the general public and safeguard them from misinformation.
Safety
The adverse effect profile of both the vaccines is similar, with the most common being local injection-site reactions. Systemic side effects are more common in the vaccine group and comprise mainly of fatigue and headache. Bell's palsy occurred in three (out of 15,210) vaccine recipients within 28 days of administration. This anecdotal risk would be studied in the planned two-year follow-up.
Being a physician in the Indian subcontinent, there are various reasons to mistrust this vaccine. Both the mRNA vaccines have been studied primarily in the US population (mainly whites), and we don't have any data on its long-term effects. Recently, I have come across various tweets and posts in my social media feed with the headline - " Doctors and nurses are declining the vaccine." I am unaware of these posts' credibility; however, this isn't false in my experience. Well for what it's worth, we haven't seen a whole lot of polio, diphtheria or smallpox recently.
Thanks for reading!
-VM
The BNT162b2 mRNA Covid-19 vaccine, popularly known as the
Pfizer vaccine is the first Covid-19 vaccine to receive authorization for use
in the general public. The first jab was given to a 90-year old lady in the UK on December 8, 2020; a monumental event that brought hope to billions of people all across
the globe. In this article, I will discuss this vaccine’s clinical trial and potential
future implications.
How does it act?
The BNT162B2 is a lipid nanoparticle-formulated,
nucleoside-modified mRNA that encodes the SARS-CoV-2 full-length spike protein,
modified by two proline mutations to lock it in the prefusion conformation. This
means that this is an mRNA that has been modified to resist disintegration by
nucleases and that translates into the SARS-CoV-2 spike protein. However, this
spike protein has also been modified to lock it into its pre-fusion
conformation; so that it doesn’t fuse with the target cell’s plasma membrane and
remain exposed to immunogenic stimulation.
Who is it for?
This primarily depends on the characteristics of the population
included in the vaccine’s clinical trial. This trial randomised 43,458 persons
from six countries: USA, Argentina, Brazil, South Africa, Germany, and Turkey. More
than three-fourth of the study population (76.7%) belonged to the USA. Moving
on to the representation of race or ethnicity in the study population - 82.9% were
white, 27.9% were Hispanic, while African Americans, Asians, and Native
Americans comprised 9.2%, 4.2%, and 0.5% of the study group. Males and females
were almost equally included. The age range is from 16 years to 89 years in the
intervention group. This trial did not evaluate the efficacy of the vaccine in
children, adolescents, and pregnant women.
Is it effective?
Define effective; it depends on the trial’s efficacy end
points. The primary endpoint was the efficacy of the vaccine to prevent Covid-19
infection 7 days after the second dose in participants who had no serologic
(antigen and antibodies) or virologic (RT-PCR) evidence of SARS-CoV-2 infection
up to 7 days after the second dose; the second primary endpoint was to prevent
infection in those with and without evidence of prior infection. Confirmed
Covid-19 was defined as – the presence of at least one symptom (fever, new or
worsened cough, new or worsened dyspnoea, chills, new or worsened muscle pain,
new loss of taste or smell, sore throat, diarrhoea or vomiting combined with a positive
RT-PCR test within 4 days).
Efficacy End Point |
BNT162b2 Group |
Placebo Group |
Vaccine efficacy, % (95% credible interval) |
||
Covid-19 Cases |
N |
Covid-19 Cases |
N |
||
1st Primary |
8 |
18,198 |
162 |
18,325 |
95(90.3-97.6) |
2nd Primary |
9 |
19,965 |
169 |
20,172 |
94.6(89.9-97.3 |
However, the trial results did not show the efficacy in
preventing asymptomatic infection. We don’t know if this vaccine can safeguard
against transmissible asymptomatic infection; therefore, people who have taken
the vaccine should not stop wearing masks for the sake of the people around
them.
Is it safe?
The vaccine group reported more local reactions, such as
pain, redness, and swelling at the injection site than the placebo group. In
general, these were mild-to-moderate in severity and resolved within 1-2 days.
The systemic adverse effects were also reported more in the intervention group,
especially in the younger population (16 to 55 years of age), and more after
the second dose. These included – fever (11%), fatigue (51%), headache (39%),
chills (23%), muscle pain (29%), joint pain (19%), and 38% of the vaccine group
needed to use antipyretic medication. These were generally mild and resolved
within 1-2 days. Two deaths happened in the vaccine group, one from
arteriosclerosis, and one from cardiac arrest. These deaths weren’t related to
the vaccine or Covid-19. The investigators plan to continue the surveillance
for adverse events for further 2 years.
This study has importance beyond the efficacy of the
BNT162b2 vaccine candidate. It demonstrates the utility of RNA-based vaccines, its
speed of development, and its promising efficacy in preventing infectious
diseases. The success of this clinical trial immensely improves our preparedness
for a future pandemic.
Reference:
Polack, FP, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. New England Journal of Medicine. Dec 10, 2020. 10.1056/NEJMoa2034577. C4591001 Clinical Trial group
-Vinayak
The worldwide magnitude of the COVID-19 pandemic is ineffable; it is unsurprisingly compared to the Spanish flu pandemic, which ravaged the world during the First World War (adding fuel to the fire!). One of the pandemic's various positive impacts has been the unprecedented research collaboration and data sharing across the world. Such singular efforts made it possible to cut down the usual time to achieve an approved vaccine from 10+ years to less than a year.
To put things into perspective, it took 60 years from the
time of the first polio outbreak to developing its vaccine; in the case of
Ebola, it took 15 years. Vaccine candidates for SARS-CoV-1 and MERS did not receive
the necessary impetus to advance into fruition. However, with SARS-CoV-2, the
situation is very different. Global initiatives such as ACTIV (Accelerating
COVID-19 Therapeutic Interventions and Vaccines), a public-private partnership
comprising of bigwigs like CDC, FDA, EMA (European Medicines Agency), and
numerous leading biopharmaceutical enterprises. Another project on a similar
scale is Operation Warp Speed, which has invited comparison to the infamous
Manhattan Project.
What is an "ideal" COVID-19 vaccine? There are
three criteria from the immunological perspective: 1) It induces a robust humoral
immune response that produces long-lasting neutralizing antibodies against
SARS-CoV-2 antigens, 2) It generates a strong cell-mediated immunity that
includes the production of memory T cells, 3) It should be free of any serious
local or systemic adverse effects. Considering the logistics of vaccinating the entire world, there are three more criteria: 1) It should be easy to administer,
preferably in one or two doses, 2) It should be easy to produce on a
large-scale, 3) Its storage should be uncomplicated, ideally possible at room
temperature.
Let us discuss the vaccines that are currently in
development. We all have heard about a few of them in the news and social media,
namely, Pfizer, Moderna, Covaxin, Astra Zeneca, and so on. There are,
impressively, 125+ SARS-CoV-2 vaccines in development globally. Broadly,
there are six platforms currently being utilized for vaccine development –
3. Protein (Subunit vaccines)
4. Viral vector – replicating/non-replicating
(examples - Oxford/Astra Zeneca, Johnson & Johnson)
5. Live attenuated virus
6. Inactivated virus
Almost all of the above models have targeted the spike glycoprotein,
which is present on the surface of SARS-CoV-2, to interfere with the viral
entry into a cell.
This article is an oversimplified summary of the vaccine development process. I haven't covered the vaccine platforms, molecular targets, and vaccine candidates in detail. With the advent of vaccine administration, whether it's Pfizer's or any other, there will be a massive surge in vaccine-related information. There will be challenges at every step, from distribution to underdeveloped areas of the world to alleviate the concerns of the skeptical anti-vaxxers. Let us hope that these vaccines start the end of the pandemic.
-Vinayak
Some specific antigens when placed in the anterior chamber of the eye result in a suppression of cell mediated immunity, with a normal humoral component.
There is something known as the ' oculo splenic axis' , whereby the antigens travel via the trabecular meshwork and reach the spleen. In the spleen, they secrete MIP 2 which attracts the NK cells. The NK cells in turn secrete IL10 and TGF beta. The T cells in this environment become regulatory cells and suppress the cell mediated immunity. Production of IL2 is suppressed.
The eye is an immuno privileged organ, as it needs to be structurally maintained pristine to preserve it's light carrying capability. ACAID is a mechanism by which Nature attempts to limit unwanted inflammatory responses in the anterior chamber.
It has implications in intraocular tumors, autoimmune, and infectious immune responses.
-Sushrut
PS- The failure of ACAID in the mechanism of lens induced uveitis still remains unexplained!
Hello everyone,
Here's something I learnt today when a case of large pituitary adenoma causing visual field loss was presented today.
But let's talk about my favorite subject first - Immunology!
The intensity of an antigen-antibody interaction depends primarily on the relative proportion of the antigen and the antibody. A relative excess of either will impair adequate immune complex formation. This is called the “high-dose hook effect” or the “prozone phenomenon.”
This is important consideration whe measuring prolactin. Extremely high levels of prolactin can interfere with the assay and produce falsely low readings.
This high-dose hook effect occurs because there is not enough antibody to bind to both ends of all antigenic peptides, in this case, prolactin.
Most prolactin is complexed to a single antibody. Only few remaining prolactin peptides are “sandwiched” and therefore detectable.
This results in a falsely low prolactin value.
Hence, as the antigen concentrations increase, there is a proportional increase in assay titers up to a certain level. Antigen concentrations above this threshold level would “hook” down the assay values resulting in very low measurements.
In order to avoid the high-dose hook effect, the serum prolactin should be estimated in appropriate dilution in all patients with large pituitary tumors.
-IkaN (tired Internal Medicine Resident)
Source:
The 'hook effect' on serum prolactin estimation in a patient with macroprolactinoma. https://www.ncbi.nlm.nih.gov/m/pubmed/11303248/