Objective To establish the therapeutic action of a nicotinic cholinergic agonist agent  (CA) composition in the symptoms in a group of human patients infected with SARS-CoV-2 vs. control group. Methods Basic Odds Ratio study (95% confidence interval) in 20 patients for intervention group and 15 patients for the control group. The evaluation in the groups was carried out during 15 days assessing the improvement or worsening of each symptom daily. Results: Cough, (OR = 0.5), Dyspnea (OR = 0.38), Muscle fatigue (OR = 0.69), Ageusia (OR = 0.27), Anosmia (OR = 0.21) General malaise (OR = 0.62), are less than 1 converting the use of the cholinergic agent in a protective and therapeutic factor showing therefore improvement of these symptoms, after its use, compared to the control group. Conclusions: The positive results obtained on the symptoms caused by COVID-19 using cholinergic agonists molecules by delivering a cholinergic agent (CA) composition with special oral and nasal route of administration and specific pharmacological design against COVID-19 in humans infected by SARS-CoV-2 versus the control group, endorse preliminary the nicotinic hypothesis on SARS-CoV-2 and the therapeutic potential of the use of these molecules. Larger multicentrical trials in humans are encouraged.

Objective To establish the therapeutic action of a nicotinic cholinergic agonist agent composition in synergy with other non-cholinergic molecules (CA) in the COVID-19 symptoms in a group of human patients infected with SARS-CoV-2 vs. control group.  Methods Randomized open-label trial pilot study where 80 patients were randomly assigned to receive standard of care (SOC) treatment as outpatient treatment after PCR test; SOC plus CA was administered in the intervention group (40 patients). SOC was administered in the control group (40 patients). Basic Odds Ratio study (95% confidence interval) in 40 patients for intervention group and 40 patients for the control group. The evaluation in the groups was carried out during 15 days assessing the improvement or worsening of each symptom daily. Results: Fever (OR=0.897), Cough (OR = 0.571), Dyspnea (OR = 0.460), Muscle fatigue (OR = 0.250), Cephalea (OR = 0,570), Ageusia (OR = 0.150), Anosmia (OR = 0.650), General malaise (OR = 0.316), Nasal congestion (OR= 0.890), are less than 1 converting the use of the cholinergic agent in a protective and therapeutic factor showing therefore improvement of these symptoms, after its use, compared to the control group. Conclusions: The positive results obtained on the symptoms caused by COVID-19 by delivering mixture of cholinergic agonists molecules and other non-cholinergic supportive molecules (CA) with special oral and nasal route of administration and specific pharmacological design against COVID-19 in humans infected by SARS-CoV-2 versus the control group is a (novel) promising therapeutic approach to fight SARS-COV-2. Larger multicentrical trials in humans are encouraged.

Background:  Since the SARS-CoV-2 pandemic emerged in December 2019, it has triggered 4.4 million deaths and strained health systems across the world. Yet more than a year and a half since the pandemic emerged, therapeutic drugs to treat COVID-19 disease are limited. Objective To investigate the therapeutic potential of a nicotinic Cholinergic Agonists Mixture (CAM), delivered daily as oral drops and as nasal spray, in alleviating ten common COVID-19 related symptoms in 80 symptomatic human adults with confirmed SARS-CoV-2.  Methods This randomized open-label pilot trial recruited 80 symptomatic adults with confirmed SARS-CoV-2 infection after RT-PCR test less than five days. Participants were recruited from databases of several Colombian hospitals and were randomly assigned to the control group, which received the Standard of Care (SOC) treatment (outpatient treatment), or the intervention group, which received SOC combined with the Cholinergic Agent Mixture (CAM SOC). Both groups received their treatment for a total of 14 days. The duration of symptoms was compared across the 14-day period. Results: This study found statistically significant reductions in symptom duration for 5 out of 10 symptoms, including dyspnea (reduction of 4.43 days [95% CI: 2.70 ; 6.15], p <0.0001), cough (reduction of 3.18 days [95% CI: 1.29 ; 5.06],  p=0.0089), cephalea (reduction of 3.13 days [95% CI: 1.53 ; 4.72], p= 0.0019), muscle fatigue (reduction of 4.18 days [95% CI: 2.03 ; 6.32], p=0.0019) and general malaise (reduction of 5.98 days [95% CI: 4.20 ; 7.76],  p <0.0001).The study found no significant reductions in the duration of the following symptoms: fever, ageusia, anosmia, chest tightness, and nasal congestion. Conclusion:  In comparison to the control group, the intervention group witnessed statistically significant and clinically relevant reductions in the duration of 5 out of 10 common COVID-19 disease symptoms within two weeks.  This includes a reduction of approximately 4.4 days in the duration of dyspnea, a symptom that appears to be strongly correlated to severe COVID-19 disease and admission to Intensive Care Units. Further studies are needed to confirm these preliminary findings and to evaluate whether this specific nicotinic cholinergic agonists mixture could have implications for public health.

A 7-year-old girl with diagnosed lateral mandibular deviation and other related temporomandibular joint disorders was referred for an anteroposterior x-ray examination to study a possible cervical spinal misalignment prior to the application of the Atlasprofilax method. The purpose of this radiographic examination was to assess probable improvement in her cervical spinal alignment after the application of the Atlasprofilax Method that already showed benefits in temporomandibular joint disorders and fibromyalgia in previous studies. Determination and probable improvement of Atlas and Axis tilt, lateral atlantodental asymmetry and cervical spinous processes misalignment were taken as endpoints. An x-ray examination was performed before the application of this method confirming Atlas and Axis tilt, lateral atlantodental asymmetry and cervical spinous processes misalignment from C2 to T1. The result in a posterior x-ray examination following the same radiological guidelines for anteroposterior open mouth examination determined a clear improvement in the Atlas and Axis tilt as well in the lateral atlantoodontoid interval alongside with correction of the previously misaligned vertebrae of the cervical spine. Such radiological improvements on the described structures poses the question on the benefits and clinical relevance of using specific targeted vibropressure used by the Atlasprofilax method on some key spots related to fascia and skeletal muscles. Thus, through a complex combination of mechanisms that involve mechanotransduction and cell metabolism, this clinical and non-invasive intervention could ameliorate preliminarily several ailments related to fascia and muscle skeletal disorders associated commonly with pain such temporomandibular disorders among others. Finally, it is relevant to the authors to raise awareness that it may be a gap between defining hard structures such as spine and joints asymmetries that cause pathological conditions and that can be observed by means of imaging such CT, MRI or x-ray examinations and the probable etiological underlying relationship coming from the understudied principles of fascial tensegrity. This etiology may include clinical or subclinical metabolic abnormalities in muscles, specially in the neck muscles but more specifically in the suboccipital muscles and its surrounding or inner soft tissues such as the myodural bridge.

We present the case of 4 subjects exhibiting asymmetry of the lateral atlantodental interval (within the accepted standard ranges of normal asymmetry) on open mouth x-ray examination. The asymmetry was clearly ameliorated after the Atlasprofilax procedure. Improvements in atlas tilt and axis spinous process deviation also were demonstrated. We discuss the preliminary validity of the Atlasprofilax non-invasive approach for treating such conditions and whether the debate on commonly accepted asymmetry in the lateral atlantodental interval should remain open and be further investigated. We further ask if such a lateral atlantodental interval asymmetry could probably be a pre-manifestation or subclinical pathomechanic condition that could underly some clinical conditions. Asymmetry in lateral atlantodental interval or odontoid-lateral mass interspaces through x-ray examination often has been found in healthy and unhealthy subjects and is associated with atlantoaxial rotatory subluxation. Its clinical relevance remains a controversial subject. Some authors affirm that this asymmetry is a normal variant. Other authors point out that such asymmetry could be considered a manifestation of pathological rotatory conditions of atlas and axis consistent with atlantoaxial rotatory subluxation and possibly lead to musculoskeletal disorders and related chronic pain ailments. X-rays provide information only on bony structures and do not visualize soft tissue structures such as suboccipital muscles and fascia. Therefore, open mouth x-rays alone may not be sufficient to determine a radiological pathological condition specially one that is not yet presenting clinical symptoms because soft tissue alterations in this region are not visualized on x-ray. Several x-ray protocols and studies have been performed on this craniocervical segment with different results and interpretations. In this case series, we examine changes in the asymmetry of the lateral atlantodental interval, atlas vertebra tilt and axis spinous process deviation before and after application of the Atlasprofilax method in four patients. This method focuses on mechanotransduction through vibropressure on soft structures of the craniocervical joint, targeting deep cervical fascia, suboccipital muscles and cartilage. The aim is to restore normal structural and metabolic patterns in the extracellular matrix. This also would imply changes in chondrocytes, telocytes, and fibroblasts through a piezoresistive effect. This effect could lead to amelioration of connective tissue alterations in the craniocervical junction involving collagen synthesis, hyaluronic acid and abnormal patterns in fibroblasts and in the microvacuolar fascia. These changes ultimately could result in an improvement in the lateral atlantodental interval and craniocervical joint position.