Comment

While anticipating the development of a COVID-19-specific vaccine, several randomized controlled trials (RCTs) explored the potential of BCG vaccination to protect against COVID-19, based on trials demonstrating beneficial effects of BCG vaccination on unrelated infections and all-cause mortality in neonates in high-mortality geographical settings. Results are now available from 12 RCTs, which suggest that BCG vaccination is not an effective intervention against COVID-19. That the BCG–COVID-19 trials failed to meet expectation emphasizes the importance of rigorous clinical trials to validate hypotheses, even in urgent situations such as a pandemic.

Considering immune responses through the framework of ‘integrated organ immunity’ could enable the design of a new class of universal vaccines.

In this Comment article, the authors alert us to recent studies of ancient DNA that advance our understanding of the origins of autoimmune disease, providing evidence that our disease risk has been shaped by pathogen-driven evolution.

This Comment article proposes that the transfer of surface molecules between interacting cells by trogocytosis might affect the cellular specificity of monoclonal antibodies, as well as the functionality of receiving cells.

In this Comment article, the authors argue that recent reports showing effects of sodium on cellular immunometabolism support an expansion of the definition of salt sensitivity beyond effects on blood pressure.

Recent evidence of transmission of avian H5N1 viruses among mammals raises concerns about their pandemic potential. We need to increase our awareness and preparedness, and should also be thinking about safe farming practices to prevent the emergence of concerning pathogens in the future.

The successful mRNA vaccines against COVID-19 contain polyethylene glycol (PEG) to stabilize the lipid nanoparticles. Recent data show that PEG-specific antibodies can be induced or boosted by mRNA vaccination. Further research is needed to study the potential links between PEG-specific antibodies, vaccine reactogenicity and enhanced clearance of other PEG-containing medicines.

Laura Santambrogio and Pippa Marrack clarify how the mechanisms of autoreactivity in bona fide autoimmune diseases and in chronic inflammatory and metabolic conditions overlap and how are they distinguished.

Emerging data suggest a lymphoid origin of plasmacytoid dendritic cells (pDCs), which, in most cases, do not share the classical functional properties of myeloid dendritic cells. This Comment proposes that pDCs should be assigned to a subcategory of innate lymphocytes and should be referred to as interferon-producing cells.

Social insects such as ants form a superorganism in which individual colony members cooperate for disease defence, much like the cells of an organism. Studying social insect colonies can help to determine common principles that unite the disease defences of organisms, superorganisms and societies.

Wildfires are increasing globally, with several recent catastrophic wildfires linked to climate change. Here, we consider the negative impact of the toxic contaminants arising from these fires on the immune system, with a focus on how wildfire pollution can exacerbate inflammatory diseases.

Hybrid immunity occurs in those who have been both infected with and vaccinated against SARS-CoV-2. But how well does such hybrid immunity protect against the virus and its emerging variants?

In the time of the COVID-19 pandemic, anti-vaccine activism in the USA accelerated, amplified and formed an alliance with political groups and even extremists. An organized, well-funded and empowered anti-science movement now threatens to spill over and threaten all childhood immunizations in the USA and globally.

Established models of behavioural science can help to explain the suboptimal COVID-19 vaccine uptake even in countries with a plentiful supply, showing that increasing vaccination is not just about increasing knowledge and motivation, but also about increasing the opportunity for vaccination.

Vitamin D has received much interest during the COVID-19 pandemic as a potential prophylactic or therapeutic agent — but do the available data support its use?

The non-pharmaceutical interventions that were introduced to limit the spread of SARS-CoV-2 have also affected the transmission of respiratory syncytial virus, particularly its seasonality, with implications for the deployment of new monoclonal antibodies and vaccines.

In individuals with Down syndrome, immune dysregulation is partially caused by chromosome 21 trisomy. Here, we discuss how these immune differences may result in poorer COVID-19 outcomes, including diminished responses to vaccination and possibly elevated risk for long COVID.

Human immunology may soon benefit from the use of artificial intelligence and blockchain technologies. Here, we discuss how Swarm Learning could foster collaborative worldwide immunology studies that fully respect local data privacy regulations by sharing insights, not data.

Among the multi-organ complications of Long COVID, those associated with cardiometabolic syndrome were some of the most prevalent in recent studies of population-scale data. Given the potential health and economic burdens, there is an urgent need to better define the inflammatory processes involved.

Herd immunity to SARS-CoV-2 has not materialized. In this Comment, David Goldblatt discusses the underlying reasons and their implications.