The lymphatic system: a pathway for meta-inflammation in permafrost immunity.

The lymphatic system is the anatomical substratum of immunity. Lymphatics collect tissue exudates, which contain cell debris, peptides, micronutrients and pathogens, as well as immune naive and memory effector cells from the body tissues and organs into the lymph. Lined by endothelial cells cemented together by tight junctions to ensure their impermeability, lymphatics contain valves that prevent the backward flow of the lymph as it moves forward toward the right and left venous angles, the anatomical site of confluence with the venous blood. Meta-inflammation increases the permeability of lymphatics, rendering the elderly more susceptible to novel and ancient airborne viruses released by melting glaciers and permafrost. Simple public health protocols (e.g., mask-wearing, quarantine) are essential to minimize colliding epidemics/pandemics, and favor permafrost immunity.

Colliding Pandemics and CoViD-19.

Cases of the respiratory syncytial virus (RSV), monkeypox virus (MPXV), and avian influenza A Virus (IAV) have increased during our current prolonged Corona Virus Disease 2019 (CoViD-19) pandemic. The rise of these viral infectious diseases may be associated or even inter-dependent with acute, latent or recurrent infection with Systemic Acute Respiratory Syndrome Corona virus-2 (SARS-CoV2). The nonsensical neologism 'tripledemic' was tentatively introduced to describe the confluent nature of these trends (epidemic comes from two Greek words: epi=on, about, demos=people; pandemic is also derived from Ancient Greek: pan=all, demos=people; but 'tripledemic' would derive from Latin triplus=three, Greek demos=people, and would at best signify 'three countries, three peoples', but certainly not the current threat of confluence of three, or perhaps more pandemics). Emerging evidence suggests that monkey pox and CoViD-19, among several other viral diseases, produce significant observable manifestations in the oral cavity. From a clinical standpoint, dentists and dental personnel may be among the first health professionals to encounter and diagnose clinical signs of converging infections. From the immune surveillance viewpoint, viral recombination and viral interference among these infectious diseases must be examined to determine the potential threat of these colliding pandemics.

Virus interference in CoViD-19.

Virus interference is one of the oldest concepts in immunology. Recent findings indicate that it may depend on the host's anti-viral cellular immune surveillance processes, as well as on sequence-specific gene silencing mechanism guided by double-stranded RNA. Other biological events, unrelated to some degree at least from immune-dependent IFN or RNA-dependent viral interference may be at play as well. We discuss these biological mechanisms in the context of of the Systemic Acute Respiratory Syndrome Corona virus2 (SARS-CoV2) virus responsible for Corona Virus Disease 2019 (CoViD-19).

Post acute CoViD-19 syndrome (PACS) - Long CoViD.

Patients sero-positive for the Systemic Acute Respiratory Syndrome Corona virus2 (SARS-CoV2) virus develop the Corona Virus Disease 2019 (CoViD-19). CoViD-19 may be asymptomatic in some individuals, proffer mild symptoms in other patients, and can be a serious and even lethal disease in a sub-group of the population. The variables that determine the severity of CoViD-19 have not been fully characterized. What is clear is that the patients who survive CoViD-19 return to a state of sero-negativity for SARS-CoV2 generally within 3-5 weeks. However, several cases of repeated infection have been reported, and a large proportion of CoViD-19-recovered patients manifest multi-system and multi-organ symptomatic pathologies several weeks-to-months after resuming sero-negativity for SARS-CoV2. This new pathological condition, originally termed Long Covid, is now recognized as the Post Acute CoViD-19 Syndrome (PACS). The original principal clusters of signs and symptoms of PACS: likelihood of relapse and reinfection, physical fatigue and cognitive slowdown, may actually be broadened to include immune deregulation, cardiovascular disease and coagulation abnormalities. The development and evaluation of new and improved clinical interventions for PACS are critical and timely.