The Link between a Common Variant in HLA Genes and Asymptomatic SARS-CoV-2 Infection

So far most global efforts have focused on severe illness in COVID-19, for example:

• The Link between TLR7 Variants and Critical COVID-19

However, examining asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance. 

Asymptomatic COVID-19

At least 20% of people who become infected with the SARS-CoV-2 coronavirus never feel sick.^[4-7] Now scientists have identified a genetic mutation (i.e.,  HLA-B*15:01) that is linked to a higher likelihood of avoiding symptoms during infection.^[1]

Here variation in the human leukocyte antigen (HLA) loci may underly processes mediating asymptomatic infection was postulated.

Initially, scientists suspected that this genetic association is due to pre-existing T cell immunity.  After further study, now they show that:

The structural similarity of the peptides underpins T cell cross-reactivity of high-affinity public T cell receptors, providing the molecular basis for HLA-B*15:01-mediated pre-existing immunity.

 

What is HLA genes?

Among the many genes involved in human immune responses, Human leukocyte antigens (HLA) variants have among the strongest associations with viral infections.^[2]

HLA are genes in major histocompatibility complexes (MHC) that help code for proteins that differentiate between self and non-self.

They play a significant role in disease and immune defense. They are beneficial to the immune system but can also have detrimental effects.

T Cell Cross-Reactivity

Cross-reactivity is the ability of an antigen to bind with an antibody that was raised to a different antigen. It may arise by one of two mechanisms: shared epitopes on multivalent antigens, or conformational similarity of epitopes.

In the study, scientists sought to determine whether the T cell cross-reactivity observed previously in patients with infection could be observed in unexposed individuals.  Here are their observation:^[1]

T cells from a subset of healthy donors carrying HLA-B*15:01 who were never exposed to SARS-CoV-2 were reactive to the SARS-CoV-2 peptide NQK-Q8, and most of the reactive cells displayed a memory phenotype. The sequence identity between SARS-CoV-2 and seasonal coronaviruses peptides, except for a single amino acid substitution, could explain the T cell cross-reactivity.

Seasonal Coronaviruses

Based on a Croatia study on the role of seasonal coronaviruses, rhinoviruses, adenoviruses and bocaviruses in the etiology of respiratory infections, it states that:

An overall global prevalence in respiratory tract infections was found to be between 0.5 and 18.4% for seasonal coronaviruses, between 13 and 59% for rhinoviruses, between 1 and 36% for human adenoviruses, and between 1 and 56.8% for human bocaviruses. 

Pre-Existing Immunity to SARS-CoV-2

In the study of [1],  scientists concluded that pre-existing immunity to SARS-CoV-2 is found to reflect T cell memory to circulating 'common cold' coronaviruses:  Here are their findings and conclusions:

T cells from pre-pandemic samples from individuals carrying HLA-B*15:01 were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF. The majority of the reactive T cells displayed a memory phenotype, were highly polyfunctional and were cross-reactive to a peptide derived from seasonal coronaviruses.

Finally, they have surmised that the structural similarity of the peptides underpins T cell cross-reactivity of high-affinity public T cell receptors, providing the molecular basis for HLA-B*15:01-mediated pre-existing immunity.

References

1. A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection
2. Biochemistry, HLA Antigens
3. Seasonal Coronaviruses and Other Neglected Respiratory Viruses: A Global Perspective and a Local Snapshot
4. Meyerowitz, E. A., Richterman, A., Bogoch, I. I., Low, N. & Cevik, M. Towards an accurate and systematic characterisation of persistently asymptomatic infection with SARS-CoV-2. Lancet Infect. Dis. 21, e163–e169 (2020).
5. Oran, D. P. & Topol, E. J. Prevalence of asymptomatic SARS-CoV-2 infection. Ann. Intern. Med. 173, M20-3012 (2020).
6. Buitrago-Garcia, D. et al. Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: a living systematic review and meta-analysis. PLoS Med. 17, e1003346 (2020).
7. Ra, S. H. et al. Upper respiratory viral load in asymptomatic individuals and mildly symptomatic patients with SARS-CoV-2 infection. Thorax 76, 61–63 (2021). 

Orchid Care for Beginners

Unveiling Life: A Petal-Painted Symphony of Renewal (12/19/2023)

(Updated on 12/19/2023)

This document details the full orchid life cycle, encompassing hibernation and the opening of a bud signifying a new cycle.

Figure 1.  Orchid varieties

Orchids are plants that belong to the family Orchidaceae, a diverse and widespread group of flowering plants with blooms that are often colorful and fragrant.^[1]

The orchid flower is typically has an outer whorl of three sepals, an inner loop of three petals, a single large column in the center, and an enlarged bottom petal called a lip or labellum (see Figure 2). The overall flower shape is characteristically bilaterally symmetrical (the left and right halves of the blossom are mirror images), a necessity for reliable pollination by bees.

Figure 2.  Basic structure of orchid^[1]

Orchid Care

There are more than 20,000 species of orchids, and contrary to popular belief, they are extremely easy to look after, yet many homeowners flounder by overwatering or putting orchids in the wrong place.

Lighting

Orchids do not like direct sun. They require low light levels, but they do need sunlight. It is possible for them to survive in offices but they may struggle. Avoid placing your orchid on windowsills because of the direct light.

Temperature

It is best to keep your orchid between 60 F and 80 F.

Fertilizer

It is not necessary to add fertilizer to your water or feed your orchid. At the greenhouse, the growers sometimes give low amounts of fertilizer and your orchid has plenty of energy to continue its bloom cycle.

For our orchid in 5 inch pot, we water them weekly using the cup shown

Watering

Orchids do not require water often and do not need a lot.^[2]

When giving water using the measuring cup (see Figure 1), be aware about the size of orchid you bought. Mini orchids in 2.5 inch pot need 1.5oz of water weekly. Orchids in 5 inch pots instead need 3oz of water per week.

Trimming Stems at the End of Bloom Life

At the end of your orchid's bloom cycle, the blooms will begin to wilt and fall off. This should start with the oldest (lower) flowers first. Based on grandmom's advice, this is the time for you to cut them down at the stem base.^[2]

To prepare your orchid for the flower break you should remove wilted flowers and keep the stems as long as they are still green. The plant will send all energy from the stems back into the roots. Only when the stems are getting brown you should cut them down at the stem base.

The following caring tips were given by a grandmom as you can see in the below pictures.  Note that she never repot her orchids.  If you plan to repot, be very careful not to damage the roots.

This orchid plant has been grown for around 7 years with each cut represents one year 

Yesterday (07/17/2023) grandmom had cut off two stems from the below orchid plant

To prepare this orchid for the flower break, trimming was done

A velvety green bonnet swells with anticipation, cradling a hidden surprise (12/10/2023)

Like a tiny sunrise, a vibrant bloom explodes from the bud, painting the air with its radiance (12/19/2023)

References

1. Anatomy of an Orchid
2. Orchid Care