SARS-CoV-2 emerged in late 2019 in China, causing a global pandemic. Severe COVID-19 is characterized by intensive inflammatory responses, and older age is an important risk factor for unfavorable outcomes.

Summary Background Accumulating evidence suggests a beneficial effective of tumour necrosis factor‐alpha (TNF‐α) inhibitors on the outcomes of COVID‐19 disease, which, however is not validated by all studies. Aims To perform a systematic review and meta‐analysis of existing reports to investigate the impact of anti‐TNF treatments on the clinical outcomes of COVID‐19 patients. Methods A systematic search at PubMed and SCOPUS databases using specific keywords was performed. All reports of COVID‐19 outcomes for patients receiving anti‐TNF therapy by September 2021 were included. Pooled effect measures were calculated using a random‐effects model. The Newcastle Ottawa Scale for observational studies was used to assess bias. Studies that were not eligible for meta‐analysis were described qualitatively. Results In total, 84 studies were included in the systematic review, and 35 were included in the meta‐analysis. Patients receiving anti‐TNF treatment, compared to non‐anti‐TNF, among COVID‐19 cases had a lower probability of hospitalisation (eight studies, 2555 patients, pooled OR = 0.53, 95% CI: 0.42‐0.67, I2 = 0) and severe disease defined as intensive care unit admission or death (two studies, 1823 patients, pooled OR = 0.63, 95% CI: 0.41‐0.96, I2 = 0), after adjustment for validated predictors of adverse disease outcomes. No difference was found for the risk for hospitalisation due to COVID‐19 in populations without COVID‐19 for patients receiving anti‐TNF treatment compared to non‐anti‐TNF (three studies, 5 994 958 participants, pooled risk ratio = 0.97, 95% CI: 0.68‐1.39, I2 = 20) adjusted for age, sex and comorbidities. Conclusions TNF‐α inhibitors are associated with a lower probability of hospitalisation and severe COVID‐19 when compared to any other treatment for an underlying inflammatory disease.

3 9

Human Endogenous Retroviruses (HERVs) are viral sequences integrated into the human genome, resulting from the infection of human germ‐line cells by ancient exogenous retroviruses. Despite losing their replication and retrotransposition abilities, HERVs appear to have been co‐opted in human physiological functions while their aberrant expression is linked to human disease. The role of HERVs in multiple malignancies has been demonstrated, however, the extent to which HERV activation and expression participate in the development of cancer is not yet fully comprehended. In this review article, we discuss the presumed role of HERVs in carcinogenesis and their promising diagnostic and prognostic implications. Additionally, we explore recent data on the HERVs in cancer therapeutics, either through the manipulation of their expression, to induce antitumor innate immunity responses or as cancer immunotherapy targets. Finally, more precise and higher resolution high‐throughput sequencing approaches will further elucidate HERV participation in human physiological and pathological processes.

Being responsible for almost 12% of cancers worldwide, viruses are among the oldest known and most prevalent oncogenic agents. The quality of the evidence for the in vivo tumorigenic potential of microorganisms varies, thus accordingly, viruses were classified in 4 evidence-based categories by the International Agency for Research on Cancer in 2009. Since then, our understanding of the role of viruses in cancer has significantly improved, firstly due to the emergence of high throughput sequencing technologies that allowed the “brute-force” recovery of unknown viral genomes. At the same time, multi-omics approaches unravelled novel virus-host interactions in stem-cell biology. We now know that viral elements, either exogenous or endogenous, have multiple sometimes conflicting roles in human pathophysiology and the development of cancer. Here we integrate emerging evidence on viral causality in human cancer from basic mechanisms to clinical studies. We analyze viral tumorigenesis under the scope of deep-in-time human-virus evolutionary relationships and critically comment on the evidence through the eyes of clinical epidemiology, firstly by reviewing recognized oncoviruses and their mechanisms of inducing tumorigenesis, and then by examining the potential role of integrated viruses in our genome in the process of carcinogenesis.