Covid19 research updates

DNAIQ is committed to using its resources in support of increased understanding of SARS-CoV-2 host genetic susceptibility, immunity and Covid19 treatment. A curated list of recent research highlights and links follows.

Please note that some articles are sourced from preprint servers and have yet to be peer-reviewed.

Above: electron microscope image of a single coronavirus becoming attached to the surface of a human cell. Note the ‘spike’ glycoproteins on its surface which the virus uses to infect human cells.

The virus uses these glycoproteins to anchor to angiotensin-converting enzyme 2 (ACE2) receptors on human cells.

If the transmembrane protease encoded by TMPRS22 is also on the human cell near the site of attachment, the viral membrane and host cell membrane fuse and the virus injects its RNA into the host cell.

AI-driven tools that mine coronavirus literature

Google Research Explorer

Covid Scholar

Covid Primer

SciSight

KnetMiner

characteristics of currently available vaccines

NB all vaccines aim to introduce the SARS CoV2 spike protein to the adaptive immune system

	Pfizer-BioNTech	Moderna	Johnson & Johnson	Oxford-AstraZeneca	Novavax
age group	12+	18+	18+	18+	12-84
mechanism of SARS CoV-2 virus spike protein exposure	polyethylene glycol lipid nanoparticle mRNA	polyethylene glycol lipid nanoparticle mRNA	primate adenovirus vector	primate adenovirus vector	spike protein nanoparticle
dosage	2 doses, 21 days apart; fully effective two weeks after second shot	2 doses, 28 days apart, fully effective two weeks after the second dose.	1 dose. Fully effective two weeks after vaccination.	2 doses, four to 12 weeks apart	2 doses, three weeks apart
effectiveness	84% after 6 months	90%	72%	85%	91%
rare but high risks	can trigger anaphylaxis (due to polyethylene glycol), treatable with epinephrine	can trigger anaphylaxis (due to polyethylene glycol), treatable with epinephrine	can trigger fatal blood clotting (due to adenovirus carrier)	can trigger fatal blood clotting (due to adenovirus carrier)	no high risk effects reported
genomic integration of SARS-CoV-2 RNA or Adenoviral genes	speculative SARS-CoV-2 RNA [33958444]	speculative SARS-CoV-2 RNA [33958444]	speculative SARS-CoV-2 RNA [33958444] and Adenoviral [33722288]	speculative SARS-CoV-2 RNA [33958444] and Adenoviral [33722288]	not possible
storage (C)	-70	-70	-20	-20	2-8
comments	rapid design, cheap manufacture	rapid design, cheap manufacture	may have existing immunity to adenovirus rendering ineffective	may have existing immunity to adenovirus rendering ineffective	safest, may be used in vulnerable people
Availability in AU	good	good	–	good (also locally produced at Melbourne CSL)	pending TGA

vaccine development

An mRNA Vaccine against SARS-CoV-2 — Preliminary Report
Clinical Trials Link
mRNA vaccines introduce an mRNA molecule that encodes an aspect of the virus that becomes expressed from cells as an antigenic determinant – in this case the spike protein of SARS-Cov-2. So far this vaccine has demonstrated the production of higher titres of neutralising antibodies compared to patients recovered from COVID19, however there were significant (but non-lethal) side effects in over 50% of participants.

Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial

immunity

Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection
Antibody levels in confirmed COVID-19 patients decline dramatically within two months. In some cases antibody levels following recovery are undetectable.

Human leukocyte antigen susceptibility map for SARS-CoV-2

Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals
SARS-Cov-2 reactive T cells detected in 40-60% of unexposed individuals due to exposure from common cold coronaviruses

Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans

serology test performance

Evaluation of nine commercial SARS-CoV-2 immunoassays

Test performance evaluation of SARS-CoV-2 serological assays

Post-market validation of three serological assays for COVID-19 (Australia)

use of dried blood spots in serology

Enzyme immunoassay for SARS-CoV-2 antibodies in dried blood spot samples: A minimally-invasive approach to facilitate community- and population-based screening

infection sites

SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes

Salivary Glands: Potential Reservoirs for COVID-19 Asymptomatic Infection
Salivary glands express high levels of ACE2 receptor and virus is detected in saliva before it is detectable in throat and lungs

infection duration

Clearance and persistence of SARS‐CoV‐2 RNA in patients with COVID‐19
Evidence of patients with mild symptoms continuing to test positive via PCR for 40 days or more; based on antibody presence, suggests a weaker immune response results in attenuated disease severity

platelets

Platelet‐to‐lymphocyte ratio is associated with prognosis in patients with coronavirus disease‐19
Elevated platelet counts associated with greater disease severity

Platelet Gene Expression and Function in COVID-19 Patients
Platelets do not express the ACE2 receptor but SARS-CoV-2 mRNA is present in platelets of infected patients (suggesting an additional yet unidentified viral receptor); platelets become hyperactive and may contribute to COVID-19 pathology such as the presence of micro clots

treatment

Evidence Based Management Guideline for the COVID-19 Pandemic – Review article

Pharmacologic Treatments – Review Apr 2020

Acute Treatment Guidelines

Preliminary Convalescent Plasma Results

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial

Association of Treatment Dose Anticoagulation with In-Hospital Survival Among Hospitalized Patients with COVID-19

prophylaxis & treatment hypotheses

Existing bitter medicines for fighting 2019-nCoV-associated infectious diseases

Therapeutic Potential for Tetracyclines in the Treatment of COVID-19

Targeting SARS-CoV-2: A Systematic Drug Repurposing Approach to Identify Promising Inhibitors Against 3C-like Proteinase and 2′-O-RiboseMethyltransferase

Risk Factors:

Neanderthal genes

The major genetic risk factor for severe COVID-19 is inherited from Neandertals
the genetic region showing the strongest signal for risk of severe COVID-19 is a 50 kb segment of the genome that is inherited from Neaderthals; for 23andme/Ancestry users the SNP that tags this site is rs10490770 (G)

male sex

Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin–angiotensin–aldosterone inhibitors

low testosterone in males

Testosterone, a key hormone in the context of COVID-19 pandemic

The majority of male patients with COVID-19 present low testosterone levels on admission to Intensive Care in Hamburg, Germany: a retrospective cohort study.

air pollution

Assessing nitrogen dioxide (NO2) levels as a contributing factor to coronavirus (COVID-19) fatality

SARS-Cov-2 RNA Found on Particulate Matter of Bergamo in Northern Italy: First Preliminary Evidence

inflammatory response

Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients

Association of inflammatory markers with the severity of COVID-19

Interleukin-6 in COVID-19: A Systematic Review and Meta-Analysis