Medic Debate

Antibody-based drugs and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being expedited through preclinical and clinical development. Data from the study of SARS-CoV and other respiratory viruses suggest that anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through antibody-dependent enhancement (ADE). Previous respiratory syncytial virus and dengue virus vaccine studies revealed human clinical safety risks related to ADE, resulting in failed vaccine trials. Here, we describe key ADE mechanisms and discuss mitigation strategies for SARS-CoV-2 vaccines and therapies in development. We also outline recently published data to evaluate the risks and opportunities for antibody-based protection against SARS-CoV-2

The Centers for Disease Control and Prevention (CDC) announced Thursday it will convene an emergency meeting of its advisers on June 18 to discuss higher-than-expected reports of heart inflammation following doses of Pfizer and Moderna COVID vaccines, CBS News reported.

According to the CDC, a total of 475 cases of myocarditis or pericarditis were recorded in patients 30 and younger. The CDC identified 226 reports that might meet the agency’s “working case definition” of myocarditis and pericarditis following the shots, the agency disclosed Thursday during an FDA hearing.

Researchers in the United States have developed a new method for controlling the brain circuits associated with complex animal behaviours, using genetic engineering to create a magnetised protein that activates specific groups of nerve cells from a distance.

Understanding how the brain generates behaviour is one of the ultimate goals of neuroscience – and one of its most difficult questions. In recent years, researchers have developed a number of methods that enable them to remotely control specified groups of neurons and to probe the workings of neuronal circuits.

The most powerful of these is a method called optogenetics, which enables researchers to switch populations of related neurons on or off on a millisecond-by-millisecond timescale with pulses of laser light. Another recently developed method, called chemogenetics, uses engineered proteins that are activated by designer drugs and can be targeted to specific cell types.

Approximately 96 COVID-19 vaccines are at various stages of clinical development.1 At present, we have the interim results of four studies published in scientific journals (on the Pfizer–BioNTech BNT162b2 mRNA vaccine,2 the Moderna–US National Institutes of Health [NIH] mRNA-1273 vaccine,3 the AstraZeneca–Oxford ChAdOx1 nCov-19 vaccine,4 and the Gamaleya GamCovidVac [Sputnik V] vaccine)5 and three studies through the US Food and Drug Administration (FDA) briefing documents (on the Pfizer–BioNTech,6 Moderna–NIH,7 and Johnson & Johnson [J&J] Ad26.COV2.S vaccines).8 Furthermore, excerpts of these results have been widely communicated and debated through press releases and media, sometimes in misleading ways.9 Although attention has focused on vaccine efficacy and comparing the reduction of the number of symptomatic cases, fully understanding the efficacy and effectiveness of vaccines is less straightforward than it might seem. Depending on how the effect size is expressed, a quite different picture might emerge (figure ; appendix).

ARR is also used to derive an estimate of vaccine effectiveness, which is the number needed to vaccinate (NNV) to prevent one more case of COVID-19 as 1/ARR. NNVs bring a different perspective: 76 for the Moderna–NIH, 78 for the AstraZeneca–Oxford, 80 for the Gamaleya, 84 for the J&J, and 117 for the Pfizer–BioNTech vaccines. The explanation lies in the combination of vaccine efficacy and different background risks of COVID-19 across studies: 0·9% for the Pfizer–BioNTech, 1% for the Gamaleya, 1·4% for the Moderna–NIH, 1·8% for the J&J, and 1·9% for the AstraZeneca–Oxford vaccines.

"Ring vaccination calls for the rapid mobilization of mobile teams to carry out the epidemiological investigation and to administer an emergency dose of vaccine to all primary contacts of a confirmed case, as well as to all secondary contacts of these contacts. primary, regardless of the vaccination status of these people.

As part of a ring vaccination strategy, a strict and monitored quarantine should be imposed on people identified as primary or secondary contacts, and who refuse vaccination."

COVID-19-attributed case and death rates for the U.S.A. were analyzed through May 2020 in three ways – for all 50 states, the country’s largest counties, and the largest counties in California – and found to be statistically significantly higher for states and counties with compared to those without 5G millimeter wave (mmW) technology. 5G mmW index was a statistically significant factor for the higher case and rates in all three analyses, while population density, air quality and latitude were significant for only one or two of the analyses. For state averages, cases per million were 79% higher (p = 0.012), deaths per million were 94% higher (p = 0.049), cases per test were 68% higher (p = 0.003) and deaths per test were 81% higher (p = 0.025) for states with vs. without mmW. For county averages, cases per million were 87% higher (p = 0.005) and deaths per million were 165% higher (p = 0.012) for counties with vs. without mmW. While higher population density contributed to the higher mean case and death rates in the mmW states and counties, exposure to mmW had about the same impact as higher density of mmW states on mean case and death rates and about three times as much impact as higher density for mmW counties on mean case and death rates. Based on multiple linear regression, if there was no mmW exposure, case and death rates would be 18-30% lower for 5G mmW states and 39-57% lower for 5G mmW counties. This assessment clearly shows exposure to 5G mmW technology is statistically significantly associated with higher COVID-19 case and death rates in the U.S.A. The mechanism–should this be a causal relationship–may relate to changes in blood chemistry, oxidative stress, an impaired immune response, an altered cardiovascular and/or neurological response.

The mRNA-based BNT162b2 vaccine from Pfizer/BioNTech was the first registered COVID-19 vaccine and has been shown to be up to 95% effective in preventing SARS-CoV-2 infections. Little is known about the broad effects of the new class of mRNA vaccines, especially whether they have combined effects on innate and adaptive immune responses. Here we confirmed that BNT162b2 vaccination of healthy individuals induced effective humoral and cellular immunity against several SARS-CoV-2 variants. Interestingly, however, the BNT162b2 vaccine also modulated the production of inflammatory cytokines by innate immune cells upon stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli. The response of innate immune cells to TLR4 and TLR7/8 ligands was lower after BNT162b2 vaccination, while fungi-induced cytokine responses were stronger. In conclusion, the mRNA BNT162b2 vaccine induces complex functional reprogramming of innate immune responses, which should be considered in the development and use of this new class of vaccines.