The effect of needle length and skin to deltoid muscle distance in adults receiving an mRNA COVID-19 vaccine.

BACKGROUND: The mRNA COVID vaccines are only licensed for intramuscular injection but it is unclear whether successful intramuscular administration is required for immunogenicity. METHODS: In this observational study, eligible adults receiving their first ComirnatyTM/BNT162b2 dose had their skin to deltoid muscle distance (SDMD) measured by ultrasound. The relationship between SDMD and height, weight, body mass index, and arm circumference was assessed. Three needle length groups were identified: 'clearly sufficient' (needle exceeding SDMD by >5 mm), 'probably sufficient' (needle exceeding SDMD by ≤ 5 mm), and 'insufficient' (needle length ≤ SDMD). Baseline and follow-up finger prick blood samples were collected and the primary outcome variable was mean spike antibody levels in the three needle length groups. RESULTS: Participants (n = 402) had a mean age of 34.7 years, BMI 29.1 kg/m2, arm circumference 37.5 cm, and SDMD 13.3 mm. The SDMD was >25 mm in 23/402 (5.7%) and >20 mm in 61/402 (15.2%) participants. Both arm circumference (≥40 cm) and BMI (≥33 kg/m2) were able to identify those with a SDMD of >25 mm, the length of a standard injection needle, with a sensitivity of 100% and specificities of 71.2 and 79.9%, respectively. Of 249/402 (62%) participants with paired blood samples, there was no significant difference in spike antibody titres between needle length groups. The mean (SD) spike BAU/mL was 464.5 (677.1) in 'clearly sufficient needle length' (n = 217) compared with 506.4 (265.1) in 'probably sufficient' (n = 21, p = 0.09), and 489.4 (452.3) in 'insufficient needle length' (n = 11, p = 0.65). CONCLUSIONS: A 25 mm needle length is likely to be inadequate to ensure vaccine deposition within the deltoid muscle in a small proportion of adults. Vaccine-induced spike antibody titres were comparable in those vaccinated with a needle of sufficient versus insufficient length suggesting deltoid muscle deposition may not be required for an adequate antibody response to mRNA vaccines.

Perspective: the nose and the stomach play a critical role in the NZACE2-Patari* (modified ACE2) drug treatment project of SARS-CoV-2 infection.

Background: COVID-19 has caused calamitous health, economic and societal consequences globally. Currently, there is no effective treatment for the infection. Areas covered: We have recently described the NZACE2-Patari project, which seeks to administer modified Angiotensin Converting Enzyme 2 (ACE2) molecules early in the infection to intercept and block SARS-CoV-2 binding to the pulmonary epithelium. Expert opinion: Since the nasopharyngeal mucosa is infected in the first asymptomatic phase of the infection, treatment of the nose is likely to be safe and potentially effective. The intercepted virus will be swallowed and destroyed in the stomach. There is however a limited window of opportunity to alter the trajectory of the infection in an individual patient, which requires access to rapid testing for SARS-CoV-2. The proposed strategy is analogous to passive immunization of viral infections such as measles and may be of particular benefit to immunodeficient and unvaccinated individuals.

Perspective: diagnostic laboratories should urgently develop T cell assays for SARS-CoV-2 infection.

Introduction: Diagnostic tests play a critical role in the management of Sars-CoV-2, the virus responsible for COVID-19. There are two groups of tests, which are in widespread use to identify patients who have contracted the virus. The commonly used reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) test becomes negative once viral shedding ceases by approximately 2-3weeks. Antibody tests directed to viral antigens become positive after the second week of infection. IgG antibody responses to the virus are muted in children, pregnant females, and those with mild symptoms. IgA and IgM antibodies rapidly wane, although IgG antibodies directed to the receptor-binding domain (RBD) of the spike (S) glycoprotein are more durable. Current data show variability in the sensitivity of commercial and in-house antibody tests to SARS-CoV-2.Areas covered: The role of T cells in acute illness is uncertain, but long-term protection against the virus may rely on memory T cell responses. Measuring memory T cell responses is important for retrospective confirmation of cases, who may have been infected early in the pandemic before reliable RT-qPCR tests were available and whose SARS-CoV-2 antibodies may have become undetectable. Relevant peer-reviewed published references from PubMed are included up to 15 March 2021.Expert opinion: After surveying the literature, the authors present the case for urgent development of diagnostic T cell assays for SARS-CoV-2 by accredited laboratories.