Persistent Immune Chaos Lingers One Year After COVID-19 Infection and Fuels Long COVID and Lung Damage
Nikhil Prasad Fact checked by:Thailand Medical News Team Apr 19, 2025 12 hours, 16 minutes ago
Medical News: A new study conducted by researchers from multiple prominent Spanish medical institutions has uncovered a disturbing reality—one year after recovering from COVID-19, many individuals are still battling hidden immune system abnormalities and organ damage, even if they seem outwardly well. The investigation sheds light on why some people develop long COVID symptoms while others suffer lung complications, known as pulmonary sequelae (PS).
Persistent Immune Chaos Lingers One Year After COVID-19 Infection and Fuels Long
COVID and Lung Damage
The research was conducted by teams from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER), Respiratory Institute at Hospital Clinic Barcelona, Immunology and Autoimmune Disease Departments at Hospital Clinic, and the Immunology Unit of the University of Barcelona.
This
Medical News report reveals that the underlying immune responses in long COVID (LC) and pulmonary sequelae are not the same. Although both groups show signs of chronic inflammation and disrupted immune activity, the biological mechanisms behind each condition differ significantly. The researchers studied 113 unvaccinated adults who had been hospitalized for COVID-19 in 2020, examining blood samples and lung function over the course of a year.
Different Symptoms Different Mechanisms
Participants were divided into three groups: those who fully recovered (Rec), those with long COVID symptoms but normal lung function (LC), and those with lung impairment (PS). Patients with PS had reduced diffusion capacity in the lungs (DLCO < 80%) and many still experienced fatigue and chest discomfort. LC patients, in contrast, had persistent symptoms like brain fog, joint pain, or fatigue without any obvious lung damage.
One striking finding was that patients in both PS and LC groups showed elevated levels of immune proteins linked to inflammation and antimicrobial defense, suggesting that the immune system remained activated a year later. However, the nature of this activity varied. For example, individuals with PS had higher levels of C3, a protein involved in immune system activation and associated with lung damage. They also had a significantly higher rate of anti-nuclear autoantibodies—immune proteins that mistakenly attack the body’s own cells.
Meanwhile, those with long COVID showed increased markers of organ damage, particularly proteins linked to cardiac stress and inflammation. This hints at ongoing harm to the heart and other tissues, long after the virus was cleared from the body. Several of these proteins have been previously associated with viral replication and immune dysregulation.
Key Biomarkers Reveal Hidden Damage
One of the most important findings was the identification of key immune proteins—CCL3, CCL19, CCL20, and IFN-γ—that were strongly elevated in PS patien
ts. CCL20 and IFN-γ were already elevated at 6 months post-infection and remained high at 12 months. CCL3 and CCL19 increased significantly between months 6 and 12, signaling ongoing immune activity and possibly worsening lung damage. These markers were also negatively correlated with DLCO values, indicating that higher levels were linked to poorer lung function.
The study also measured GDF15 and WFDC2, two proteins associated with chronic lung disease. Both were elevated in PS patients and correlated with lung damage, adding another layer of evidence that these patients were experiencing ongoing injury even a year after infection.
In contrast, LC patients displayed elevated levels of proteins such as FKBP1B, PRKAB1, FOXO1, and others involved in viral replication, inflammation, and autoimmune disease. Interestingly, some markers like Troponin I (TNNI3) and calcitonin (CALCA), which are typically linked to acute COVID severity, were found to be reduced in the LC group, suggesting a shift in the type of damage occurring over time.
Immune Profiles Suggest Persistent Viral Reservoirs
Both LC and PS patients showed protein patterns that point to a persistent immune response, potentially driven by hidden viral reservoirs in the body. In PS, the immune response was skewed toward lung-related inflammation and immune cell recruitment. In LC, the immune system appeared to be responding to ongoing tissue stress and damage, especially in the heart and other organs.
This differentiation is critical. It suggests that although long COVID and post-COVID lung complications share a root in persistent immune disruption, they evolve differently and may require tailored treatments.
What This Means for the Future
The study highlights the urgent need for long-term monitoring of COVID-19 survivors—even those who appeared to recover well initially. Many may harbor unseen immune or organ abnormalities that could worsen over time. The researchers emphasize the value of using specific biomarkers to track disease progression and help guide personalized treatments in the future.
The research also raises questions about whether these ongoing immune responses are due to how the virus behaved in each person, or whether some individuals have an immune system that simply cannot "shut off" properly. More studies are needed to understand these mechanisms and to determine if vaccination or antiviral treatments after infection can help prevent these long-term effects.
Conclusions
Twelve months after an acute COVID-19 infection, patients with pulmonary sequelae or long COVID continue to suffer from distinct yet equally troubling immune disturbances. Pulmonary sequelae are characterized by biomarkers like CCL3, CCL19, and elevated complement C3, which are tied to declining lung function and suggest persistent inflammation and potential fibrosis. Meanwhile, those with long COVID exhibit abnormal levels of cardiac and tissue stress markers, including FKBP1B and FOXO1, as well as others involved in viral replication and autoimmunity, indicating systemic organ involvement. These findings suggest a continued, unresolved antiviral response in both groups, though driven by differing underlying biology. The need for individualized diagnostics and therapeutic strategies has never been clearer, as the long shadow of COVID-19 continues to affect millions worldwide.
The study findings were published in the peer reviewed journal: Respiratory Research
https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-025-03200-1
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