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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.
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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.
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Background The impact of immunosuppression in solid organ transplant recipients with SARS-CoV-2 infection is unknown. The knowledge about the behavior of different immunosuppression schemes in clinical outcomes is scarce. This study aimed to determine the risk of death in kidney transplant recipients with COVID-19 under two different schemes of immunosuppression. Methods We describe our experience in kidney transplant recipients with SARS-CoV-2 infection in seven transplant centers during the first year of the pandemic before starting the vaccination programs in the city of Bogotá. Demographic characteristics, clinical presentation, immunosuppression schemes at presentation, and global treatment strategies were compared between recovered and dead patients;survival analysis was carried out between calcineurin inhibitors based regimen and free calcineurin inhibitors regimen. Results Among 165 confirmed cases, 28 died (17%);the risk factors for mortality identified in univariate analysis were age older than 60 years (p = .003) diabetes (p = .001), immunosuppression based on calcineurin inhibitors (CNI) (p = .025) and patients receiving steroids (p = .041). In multivariable analysis, hypoxemia (p = .000) and calcineurin inhibitors regimen (p = .002) were predictors of death. Survival analysis showed increased mortality risk in patients receiving CNI based immunosuppression regimen vs. CNI free regimens mortality rates were, respectively, 21.7% and 8.5% (p = .036). Conclusions Our results suggest that the calcineurin inhibitors probably do not provide greater protection compared to calcineurin inhibitor free schemes being necessary to carry out analyzes that allow us to evaluate the outcomes with different immunosuppression schemes in solid organ transplant recipients with SARS-CoV-2 infection.
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BACKGROUND: The impact of immunosuppression in solid organ transplant recipients with SARS-CoV-2 infection is unknown. The knowledge about the behavior of different immunosuppression schemes in clinical outcomes is scarce. This study aimed to determine the risk of death in kidney transplant recipients with COVID-19 under two different schemes of immunosuppression. METHODS: We describe our experience in kidney transplant recipients with SARS-CoV-2 infection in seven transplant centers during the first year of the pandemic before starting the vaccination programs in the city of Bogotá. Demographic characteristics, clinical presentation, immunosuppression schemes at presentation, and global treatment strategies were compared between recovered and dead patients; survival analysis was carried out between calcineurin inhibitors based regimen and free calcineurin inhibitors regimen. RESULTS: Among 165 confirmed cases, 28 died (17%); the risk factors for mortality identified in univariate analysis were age older than 60 years (p=.003) diabetes (p=.001), immunosuppression based on calcineurin inhibitors (CNI) (p=.025) and patients receiving steroids (p=.041). In multivariable analysis, hypoxemia (p=.000) and calcineurin inhibitors regimen (p=.002) were predictors of death. Survival analysis showed increased mortality risk in patients receiving CNI based immunosuppression regimen vs. CNI free regimens mortality rates were, respectively, 21.7% and 8.5% (p=.036). CONCLUSIONS: Our results suggest that the calcineurin inhibitors probably do not provide greater protection compared to calcineurin inhibitor free schemes being necessary to carry out analyzes that allow us to evaluate the outcomes with different immunosuppression schemes in solid organ transplant recipients with SARS-CoV-2 infection.