The SARS-CoV-2 variants of concern
As the SARS-CoV-2 pandemic unfolds, the new villains
in the drama are 3 viral variants of concern (VOC) which have recently
emerged. The B.1.1.7 was described in the UK. The B.1.351 surfaced in
South Africa and P.1 was born in Brazil. What do we to know about these
viral variants?
All the three variants have the N501Y mutation in the
receptor binding site of the spike protein. The B.1.351 and P.1 also
have two additional mutations which again affect the receptor binding
domain. These mutations have resulted in increased binding to the ACE 2
receptor and subsequently higher infectivity. The British variant is
36-75% more contagious. The South African variant is 50% more
transmissible. Early data from Brazil suggests that the P.1 is 2.5 times
more contagious.
What about disease severity? Initial studies
suggested that the UK variant, B.1.1.7 did not cause more severe
disease. However, more recent data, suggests that the mortality is more
in the new variant. The mortality hazard ratio in the new variant as
compared to the old was 1.64 (95% CI 1.32-2.04). This translates into a
death rate of 4.1/1000 cases for the new variant against 2.5/1000 in the
old variant. In South Africa, the mortality due to the new variants was
20% more than the previously reported death rates. It could also be due
to the rapidly overburdened health care system.
The million dollar question which remains is whether
vaccination or previous infection will protect against the new variants.
Sera from individuals immunized with the Moderna vaccine showed that
they efficiently neutralized the UK variant B.1.1.7. Its efficacy was
slightly reduced for the South African strain but will probably be
effective clinically. However, Moderna has announced that they will
develop a new modified vaccine which will be effective against the new
strains.
Serum from patients vaccinated with the Pfizer-
BionTech vaccine also had a slightly lesser efficacy in neutralizing the
new variants but the vaccine will probably remain clinically effective.
Serum from patients vaccinated with the AstraZeneca vaccine failed to
neutralize the new variants.
Initial data suggests that natural immunity due to
previous infection with the old variant is partially effective in
preventing infection with the new UK strain but hardly effective in
preventing infection with the South African strain. More concrete data
is awaited.
(New SARS-CoV-2 variants- Clinical, public health,
vaccine implications. NEJM 24 March 2021)
mRNA vaccines- transforming medicine
In addition of their sucess against SARS-CoV-2, mRNA
vaccines are also in the race to treat several non-infectious disorders.
It was known for decades that mice injected with mRNA
could produce the proteins that the mRNA coded for. However, the mRNA
itself produced a severe inflammatory response. Secondly, the mRNA would
get degraded very fast in the body, which led to low levels of protein
production.
The major breakthrough came from the work of a pair
of scientists from the University of Pennsylvania - Katalin Kariko and
Drew Weissman. They found that using synthetic nucleosides to produce
the mRNA prevented the inflammatory response and also resulted in more
protein production. The next milestone was the imaginative use of lipid
nanoparticles to coat the mRNA. This prevented the rapid degradation of
mRNA.
When the COVID-19 pandemic swept the world, we needed
a safe vaccine which could be rapidly developed at low cost. mRNA
vaccines ticked all the boxes.
Now, Ugur Sahin, CEO of BionTech and his group have
published another remarkable piece of research. They developed a mRNA
which delivers auto antigens of multiple sclerosis into the lymphoid
dendritic cells. This activates a regulatory T cell which inhibits the
inflammatory response against the targeted autoantigens. In mouse models
of multiple sclerosis, this mRNA vaccine delayed the progression and
reduced the severity of the disease. Most importantly, unlike the
regular therapy of multiple sclerosis it does not induce generalized
immunosuppression.
So besides its potential role in emerging infectious
diseases, mRNA vaccines are purported to be the next blockbuster in the
therapeutic arsenal against chronic diseases like cancers, cystic
fibrosis and heart disease.
(Krienke et al. Science, 8 January 2021)
Nightingale wards
Florence Nightingale pioneered the idea that the
design of hospital wards had a critical impact on the well-being of
patients. The so called Nightingale wards had large windows, which
allowed fresh air and sunlight to flood the rooms. Steven Lockley who
studies circadian rhythm and sleep in Harvard Medical School has
discussed how right Nightingale was when she highlighted the role of
natural light in human health and well-being.
Patients in rooms with good natural light and outdoor
views have been shown to recover faster with fewer painkillers. Heart
rates, blood pressure and mood is better in these patients. Rods and
cones were initially considered to be the only cells involved in visual
inputs. It is now well established that non visual photoreceptors in the
retina modulate our circadian rhythm, mood, alertness and cognitive
functions. A large study from Korea analyzed length of stay of patients
admitted with a bed next to a window versus away from a window. Patients
with beds next to a window had much shorter hospital stays.
The COVID-19 pandemic has further emphasized the need
for sunlight and cross-ventilation. There are many factors we need to
consider while treating patients, and hospital design is often
neglected.
(What Florence Nightingale can teach us about
architecture and health. Scientific American 18 March, 2021)
