Nikhil Prasad Fact checked by:Thailand Medical News Team Jul 22, 2026 1 hour, 6 minutes ago
Medical News: Our immune system does not work at the same level throughout the day, and a new study suggests that this daily rhythm may significantly influence how immune cells respond to SARS-CoV-2 spike proteins. Researchers have discovered that the timing of exposure to these viral proteins can alter the behavior of key immune cells by changing their metabolism rather than triggering a classic inflammatory response.
Researchers found that the body's internal clock strongly influences how immune cells metabolically respond to
SARS-CoV-2 spike proteins
The research was conducted by scientists from the Department of Biological Sciences at Rensselaer Polytechnic Institute, Troy, New York, USA, and the Pacific Northwest National Laboratory, Richland, Washington, USA. Their findings shed new light on the complex relationship between the body's biological clock, immune function, and COVID-19.
The Body Clock and Immunity
Nearly every cell in the body follows an internal 24-hour biological clock known as the circadian rhythm. This clock regulates sleep, hormone production, metabolism, and many immune functions. Macrophages, which are among the body's first defenders against invading viruses and bacteria, are also tightly controlled by these daily rhythms.
Macrophages normally patrol tissues, destroy harmful microbes, and help coordinate the body's immune response. However, these activities require enormous amounts of energy, meaning that the cells constantly adjust their metabolism depending on the time of day and the challenges they face.
Previous research had already suggested that vaccination effectiveness can vary depending on the time of administration. However, exactly how the body's internal clock influences immune cell responses to SARS-CoV-2 remained poorly understood.
Scientists Examined Spike Protein Exposure at Different Times
To investigate this question, the researchers exposed both mouse and human macrophages to spike proteins from SARS-CoV-1, the original SARS-CoV-2 virus, and selected SARS-CoV-2 variants at different times across the circadian cycle.
They then performed an extensive multi-omics analysis, examining thousands of proteins, metabolites, and lipids inside the immune cells.
This
Medical News report highlights that the team discovered two distinct biological response states depending entirely on when the macrophages encountered the spike proteins. Rather than producing dramatically different inflammatory reactions, the cells primarily shifted their metabolic activity and mitochondrial function.
Metabolism Changed More Than Inflammation
One of the study's biggest surprises was that classical inflammatory pathways were only modestly affected. Instead, the strongest changes involved the machinery that generates cellular energy.
The researchers found that proteins involved in glycolysis, the tricarboxylic a
cid (TCA) cycle, the pentose phosphate pathway, and oxidative phosphorylation all followed strong circadian patterns. Many important metabolites, including citrate, succinate, malate, and several amino acids associated with inflammation and oxidative stress, also rose and fell naturally throughout the day.
When macrophages encountered spike proteins during certain circadian phases, hundreds of proteins became either more active or less active. The strongest responses occurred during specific biological times, while exposure during other periods produced relatively minor changes.
The study also showed widespread alterations in mitochondrial biology. Mitochondria are often described as the power plants of cells because they generate most of the energy needed for normal function. The researchers observed time-dependent changes in mitochondrial proteins, membrane potential, lipid composition, and overall mitochondrial structure after spike protein exposure. These findings suggest that mitochondrial health plays a central role in determining how immune cells react to viral proteins.
The Internal Clock Remained Stable
Despite these metabolic changes, the researchers found little evidence that spike protein exposure disrupted the macrophages' core circadian clock itself. Important clock proteins remained largely stable, indicating that the biological clock continued functioning normally while directing different metabolic responses depending on the timing of exposure.
The investigators also measured several inflammatory signaling molecules, including IL-6, TNF-alpha, IL-10, and TGF-beta. Although some increases were detected, cytokine production remained relatively modest compared with the strong inflammatory responses triggered by well-known immune stimulators. This further supports the conclusion that metabolism, rather than classical inflammation, was the dominant factor shaping the macrophage response.
Why These Findings Matter
The study suggests that immune cells possess naturally occurring periods of greater metabolic readiness and periods of relative suppression. Since macrophages play a crucial role in viral infections and vaccine responses, these biological timing differences could eventually help explain why immune responses sometimes vary between individuals or even within the same individual at different times of day. Although the research was conducted in laboratory cell models and additional clinical studies will be necessary, the findings provide important evidence that circadian biology deserves greater consideration in future vaccine research, infectious disease studies, and immunometabolic therapies.
The study findings were published in the peer reviewed journal: Microbial Pathogenesis.
https://www.sciencedirect.com/science/article/pii/S0882401026004420
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