In a recent review published in the journal natural medicinethe researchers summarized known findings from the literature on unexplained post-acute infection syndromes (PAIS).
Journal article: Unexplained post-acute infectious syndromes. Image Credit: Donkeyworx / Shutterstock
Overview and Clinical Presentation of PAIS
Unfortunately, chronic sequelae of acute infections often go undiagnosed due to nonspecific symptoms and lack of objective diagnostic features. Such disease characterizes PAIS, in which patients cannot fully recover from acute infections, the cause of which is inexplicable, and the causative pathogen remains unidentifiable by routine diagnostic methods.
Q fever fatigue syndrome is a well-established PAIS that is caused by the Coxiella burnetiidae bacteria and is a very debilitating condition. Another PAIS with an established causative pathogen is post-dengue fatigue syndrome, caused by the mosquito-borne dengue virus.
Other PAIS include post-Ebola syndrome (PES), post-polio syndrome (PPS), and post-chikungunya chronic inflammatory rheumatism (pCHIK-CIR), the causative pathogens of which are Ebola virus, poliovirus, and poliovirus, respectively. chikungunya virus. .
However, several pathogens such as Epstein Barr virus (EBV), West Nile virus, Ross River virus, Coxsackie Ba virus, H1N1/09 influenza virus, Varicella Zoster virus (VZV) have been reported to cause unexplained and unnamed PAIS. Moreover, post-polio syndrome can manifest itself even 15 to 40 years after infection with poliomyelitis.
PAIS by neurotropic organisms such as West Nile virus has been reported to cause persistent changes similar to those seen in post-polio syndrome. Similarly, the symptomatology of Ross River virus-induced PAIS and chikungunya virus infection is known to be similar.
Influenza A virus H1N1/09, VZV and coxsackie B have been associated with an increased risk of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), underlying the development of chronic sequelae during exposure to certain pathogens.
The main symptoms of PIS center on fatigue, exercise intolerance, sensory and neurocognitive impairments, flu-like symptoms, irritability, sleep disturbances, sweating, arthralgia and myalgia, with a wide range of non-specific and varied symptoms.
Neurocognitive symptoms include loss of concentration, brain fog, and memory loss. Symptoms are recurrent or chronic in nature. Other symptoms are disease-specific, such as ocular disorders in Ebola-induced PAIS and anosmia and/or ageusia in long-lasting coronavirus disease (COVID).
Long COVID or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (SASP) is a term that encompasses several chronic effects seen in SARS-CoV-positive patients. 2 after acute infection. PASC has been identified in mild, moderate, and severe COVID 2019 (COVID-19) patients. Symptoms last for several months and cannot be explained by another diagnosis.
Common symptoms of PASC include cough, dyspnea, chest pain, anosmia, cognitive impairment, and fatigue. Symptoms also affect performance of daily activities and may relapse or fluctuate. Long-term COVID patients have varying symptoms that last for different durations.
PASC patients recovering from severe SARS-CoV-2 infections may either have lung damage secondary to acute respiratory distress syndrome (ARDS) or pneumonia, or have persistent symptomatology of post-unit syndrome. intensive care unit (ICU). Most PASC people have been reported to be older men with severe COVID-19.
PASC patients recovering from asymptomatic or mild to moderate COVID-19 may experience fever, arthralgia, myalgia, sensory disturbances, and exercise intolerance, similar to those seen in patients with ME/CFS. Such PASC presentations have mainly been found in females.
Researchers have postulated that SARS-CoV-2 infections can trigger or unmask medical conditions such as diabetes, postural orthostatic tachycardia syndrome (POTS), Guillain-Barré syndrome, and thrombotic disorders.
Pathogenesis of PAIS
All types of pathogenic organisms such as bacteria, fungi, viruses and parasites have been implicated in the pathogenesis of PAIS.
The long-term presence of pathogens (bacteria/viruses/fungi/parasites) presenting as persistent infections or remnants of non-viable persistent pathogens leads to chronic stimulation of the host’s immune system. Subsequently, T-lymphocytes and B-lymphocytes are activated, allowing the interaction of the persistent pathogen with the pathogen-associated molecular patterns (PAMPs) of the host. Subsequently, the pathogenic ribonucleic acid (RNA) binds to the pattern recognition receptors (PRR) of the host cell. Pathogen-PRR binding stimulates innate immunity.
An alternative mode of immune system activation involves the alteration of regulatory T cells (Treg) by the persistent pathogen, following which the autoreactive lymphocytes target host (self) antigens and induce antibodies causing autoimmune damage to the host. systems.
Persistent and chronic infections could also occur due to microbiome dysbiosis or dysregulation of the microbiota-gut-brain axis due to reactivation of latent pathogenic organisms and activation of microglia by afferents of the vagus nerve. Either mechanism could lead to organ damage such as brain atrophy, pulmonary fibrosis, cardiovascular damage, renal dysfunction, vascular damage, and villous atrophy.
In conclusion, PAIS represent an enigmatic spectrum of medical diseases. Further biomedical research is needed to elucidate their underlying molecular mechanisms and develop objective markers for rapid diagnosis and effective treatment.