Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and long COVID.

How does the complex, adaptive, and autonomous organization of life emerge from the laws of physics and information? This review argues that the answer lies in a convergent set of universal organizational principles that constitute a physical and informational grammar of the living. Living systems are dissipative structures that achieve organizational closure—materially and energetically open, yet causally closed—thereby attaining genuine autonomy and agency. Their architecture exhibits fractal and modular scaling laws that maximize energy flow, robustness, and evolvability under universal physical constraints. Critically, organisms operate at critical transitions—zones of controlled instability where fluctuations amplify information processing, transforming noise into adaptive signal. This self-organized criticality enables functional degeneracy, relational redundancy, and evolutionary antifragility. Cognition emerges as a distributed process of active inference, operating through a predictive–corrective cycle that integrates perception, action, and learning under the Free Energy Principle. From molecular networks to ecosystems, the same physico-informational grammars unfold recursively, revealing a deep organizational holography: the principles of organization are replicated across scales. Evolution under the Law of Increasing Functional Information is not random drift, but a directional expansion of functional complexity—a thermodynamic gradient towards greater agency. This synthesis challenges biological exceptionalism: the trajectory from thermodynamics to cognition is continuous, physically constrained, and potentially inevitable. Life does not violate physical laws—it fulfills them in regimes of high informational complexity, instantiating fundamental principles in self-organized architectures capable of prediction, memory, and purpose. The objective of this work is to articulate how the synthesis of these principles not only unifies physics and biology, but also illuminates the profound continuity between thermodynamics, chemistry, informational constraints, organization, and the mind.

How does the complex, adaptive, and autonomous organization of life emerge from the laws of physics and information? This review argues that the answer lies in a convergent set of universal organizational principles that constitute a physical and informational grammar of the living. Living sys-tems are dissipative structures that achieve organizational clo-sure—materially and energetically open, yet causally closed—thereby at-taining genuine autonomy and agency. Their architecture exhibits fractal and modular scaling laws that maximize energy flow, robustness, and evolv- ability under universal physical constraints. Critically, organisms operate at critical transitions—zones of controlled instability where fluctuations amplify information processing, transforming noise into adaptive signal. This self-organized criticality enables functional degeneracy, relational redun-dancy, and evolutionary antifragility. Cognition emerges as distributed ac-tive inference—a predictive-corrective cycle that integrates perception, ac-tion, and learning in accordance with the Free Energy Prin- ciple. From molecular networks to ecosystems, the same physico-informational gram- mars unfold recursively, revealing a deep organizational holography: the principles of organization are replicated across scales. Evolution under the Law of Increasing Functional Information is not random drift, but a direc-tional expansion of functional complexity—a thermodynamic gradient to-wards greater agency. This synthesis chal- lenges biological exceptionalism: the trajectory from thermodynamics to cognition is continuous, physically constrained, and potentially inevitable. Life does not violate physical laws—it fulfills them in regimes of high informational complexity, instan- tiating fundamental principles in self-organized architectures capable of prediction, memory, and purpose.

Shannon entropy of single-cell transcript counts reflects composition and sampling. We tested whether interferon-beta (IFN-β) stimulation was associated with donor-consistent diversity changes after employing technical controls. We reanalyzed GSE96583 peripheral blood mononuclear cells from eight donors with lupus, treating donors—not the 8949 target cells obtained from them—as inferential units. Analyses included sampling without replacement at 562 unique molecular identifiers, a 750-molecule sensitivity analysis, Miller–Madow correction, IFN-gene removal, and exact compositional decomposition. Mean paired-donor raw-count plug-in entropy increased by 0.138 bits in CD14+ monocytes and 0.329 bits in FCGR3A+ monocytes and decreased by 0.080 bits in natural killer cells. Directions persisted across prespecified robustness variants. Monocyte increases accompanied higher evenness and lower transcript dominance; natural killer cells showed the opposite pattern, without consistent richness changes. Adding IFN activity to donor-, condition-, and technical-covariate-adjusted models increased R² by at most 0.0108. Entropy contributions strongly overlapped pseudobulk expression changes. In GSE194122, the implemented binary chromatin-accessibility entropy was determined by open-peak count, precluding biological cross-modality coupling claims. These findings support a lineage-divergent association within this single lupus cohort; independent replication is required before broader biological or diagnostic interpretation.

The immune system is a dynamic network that processes information across multiple biological scales, from molecular recognition of antigens to systemic coordination with the neuroimmune axis and microbiota. At the molecular level, pathways such as NF-κB and JAK-STAT regulate gene expression, integrating signals from pathogens and the organism itself while balancing activation through feedback loops. Cellular and tissue-level dynamics are exemplified by germinal centers, where B-cell hypermutation and clonal selection refine the humoral response, and by immunological synapses that regulate T-cell activation and fate. Systemically, the vagus nerve mediates neuroimmune interactions, while the microbiota co-evolves with the immune system, enhancing its plasticity and robustness. These processes embody antifragility, allowing the immune system to strengthen and expand its capabilities with each challenge. By understanding these multiscale processes, novel strategies emerge for precision medicine, including the modulation of the vagus nerve and microbiota, offering personalized approaches to treat infectious, autoimmune, and chronic diseases.