3- Wednesday Research News – 13th October

1 – Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients

• Maintenance drugs are used to treat chronic conditions.
• Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19.
• This study identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), warfarin, direct factor Xa inhibitors, clopidogrel, famotidine and hydroxychloroquine.
• Among the COVID-19 patients, 209,208 (55.9%) were on at least one study drug.
• The three most common study drugs were ACEI 97,872 (26.1%), ARB 83,329 (22.3%) and clopidogrel 38,203 (10.2%).
• Current users of ACEI, ARB, warfarin, direct factor Xa inhibitor and clopidogrel were associated with reduced risk of getting COVID-19 (3-13%), and reduced risk of dying after a COVID-19 diagnosis (8-19%).
• Famotidine did not show consistent significant effects.
• Hydroxychloroquine did not show significant effects after censoring of recent starters.
• Maintenance use of ACEI, ARB, warfarin, direct factor Xa inhibitor and clopidogrel was associated with reduction in risk of acquiring COVID-19 and dying from it.

Source: MedRxiv

2- Effectiveness of mRNA-1273 against Delta, Mu, and other emerging variants

• Real-world studies have found high vaccine effectiveness (VE) of mRNA-based COVID-19 vaccines, but reduced VE against the Delta variant and waning protection have been reported, with few studies examining mRNA-1273 variant-specific VE.
• They conducted a test-negative case-control study at Kaiser Permanente Southern California.
• Whole genome sequencing was conducted for SARS-CoV-2 positive specimens collected from 3/1/2021 to 7/27/2021.
• Test-positive cases were matched 1:5 to test-negative controls on age, sex, race/ethnicity, and specimen collection date.
• Outcomes included SARS-CoV-2 infection and hospitalization.
• Exposures were 2 doses or 1 dose of mRNA-1273 ≥14 days prior to specimen collection versus no COVID-19 vaccination.
• Two doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants.
• However, VE against Delta moderately declined with increasing time since vaccination.

Source: MedRxiv

3- Endemic Seasonal Coronavirus Neutralisation and COVID-19 severity

• The virus SARS-CoV-2, responsible for the global COVID-19 pandemic, spread rapidly around the world causing high morbidity and mortality because humans have no pre-existing immunity.
• However, there are four known, endemic seasonal coronaviruses in humans (HCoVs) and whether antibodies for these HCoVs play a role in severity of COVID-19 disease has generated a lot of interest.
• Of these seasonal viruses NL63 is of particular interest as it uses the same cell entry receptor as SARS-CoV-2.
• They found that although HCoV neutralisation was very common there was little evidence that these antibodies neutralised SARS-CoV-2.
• Despite no evidence in cross neutralisation, levels of NL63 neutralisating antibodies become elevated after exposure to SARS-CoV-2 through infection or following vaccination.

Source: MedRxiv

4- Immune Memory Response After a Booster Injection of mRNA-1273 for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)

• Rising breakthrough infections of coronavirus-2 (SARS-CoV-2) in previously immunized individuals has raised concerns for a booster to combat suspected waning immunity and new variants.
• Participants immunized 6-8 months earlier with a primary series of two doses of 50 or 100 µg of mRNA-1273 were administered a booster injection of 50 µg of mRNA-1273.
• Neutralizing antibody levels against wild-type virus and the Delta variant at one month after the booster were 1.7-fold and 2.1-fold higher, respectively, than those 28 days post primary series second injection indicating an immune memory response.
• The reactogenicity after the booster dose was similar to that after the second dose in the primary series of two doses of mRNA-1273 (50 or 100 µg) with no serious adverse events reported in the one-month follow-up period.
• These results demonstrate that a booster injection of mRNA-1273 in previously immunized individuals stimulated an immune response greater than the primary vaccination series.

Source: MedRxiv

5- SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines elicit higher levels of antibodies compared to natural SARS-CoV-2 infections in most individuals; however, the specificities of antibodies elicited by vaccination versus infection remain incompletely understood.
• Here, they characterized the magnitude and specificity of SARS-CoV-2 spike-reactive antibodies from 10 acutely infected health care workers and 23 participants who received mRNA-based SARS-CoV-2 vaccines.
• They found that infection and primary mRNA vaccination elicited S1 and S2-reactive antibodies, while secondary vaccination boosted mostly S1 antibodies.
• This data indicate that SARS-CoV-2 mRNA vaccinations elicit fundamentally different antibody responses compared to SARS-CoV-2 infections.

Source: MedRxiv

6- “COVID-19 in twins: What can we learn from them?”

• Investigations on the concordance in monozygotic (MZ) as compared to dizygotic (DZ) twins may reveal if there is a genetic component increasing the susceptibility or resistance against an infectious disease.
• Here, they compared the concordance rates of SARS-CoV-2 infection in MZ versus DZ young twins who shared the same bedrooms and were equally exposed to the virus.
• The concordance rate was higher in the MZ group supporting a complex multifactorial inheritance responsible for SARS-Cov-2 infection.

Source: MedRxiv

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