Comment on Kopanska et al. Disorders of the Cholinergic System in COVID-19 Era-A Review of the Latest Research. Int. J. Mol. Sci. 2022, 23, 672.

We read the recent review article by Marta Kopanska et al. [...].

SARS-CoV-2 infection after vaccination in Italian health care workers: a case report

Following the approval of COVID-19 vaccination program by EMA and national authorities, an immunization campaign started in Italy with BNT162b2mRNA vaccine, initially focused on healthcare workers. The active immunization was monitored by systemic antibody titration and continuous surveillance was guaranteed by antigenic/molecular tests on swabs. Cases of infection have been recently observed in vaccinated healthcare workers. Herein we describe an outbreak of infection occurring in five physicians out of 656 healthcare workers belonging to a private hospital, referring mild symptoms of COVID-19. Healthcare workers underwent complete vaccination and screening for antibody titration. Five out of 656 healthcare workers were tested positive for SARS-CoV-2 in nasopharyngeal swabs and referred mild COVID-19 symptoms. Molecular analyses were carried out to identify possible variants of Spike protein. Their genotyping performed on RNA extracts highlighted the presence of del69/70, N501Y, A570D, and 1841A > G (D614G) sequence variants, all indicative of VOC 202012/01-lineage B.1.1.7, suggesting a common source of infection. These cases might represent a serious emergency because outbreaks can compromise frail patients with important concomitant diseases.

Could Small Neurotoxins-Peptides be Expressed during SARS-CoV-2 Infection?

SARS-CoV-2 pathogenesis has been recently extended to human central nervous system (CNS), in addition to nasopharyngeal truck, eye, lung and gut. The recent literature highlights that some SARS-CoV-2 spike glycoprotein regions homologous to neurotoxin-like peptides might bind to human nicotinic Acetyl-Choline Receptors (nAChRs). Spike-nAChR interaction can probably cause dysregulation of CNS and cholinergic anti-inflammatory pathways and uncontrolled immune-response, both associated to a severe COVID-19 pathophysiology. Herein, we hypothesize that inside the Open Reading Frame (ORF) region of spike glycoprotein, the RNA polymerase can translate small neurotoxic peptides by means of a "jumping mechanism" already demonstrated in other coronaviruses. These small peptides can bind the snAChRs instead of Spike glycoproteins. A striking homology occurred between these small peptides observed by sequence retrieval and proteins alignment. Acting as nAChRs antagonists, these small peptides (conotoxins) could be the explanation for the extrapulmonary clinical manifestations (neurological, hemorrhagic and thrombotic expressions, the prolonged apnea, the cardiocirculatory collapse, the heart arrhythmias, the ventricular tachycardia, the body temperature alteration, the electrolyte K+ imbalance and finally the significant reduction of butyryl cholinesterase (BuChE) plasma levels, as observed in COVID-19 patients. Several factors might induce the expression of these small peptides, including microbiota. The main hypothesis regarding the presence of these small peptides opens a new scenario on the etiology of COVID-19 clinical symptoms observed so far, including the neurological manifestations.

Angiotensin System Polymorphisms' in SARS-CoV-2 Positive Patients: Assessment Between Symptomatic and Asymptomatic Patients: A Pilot Study.

INTRODUCTION: The renin-angiotensin-aldosterone system (RAAS), a metabolic cascade regulating pressure and circulating blood volume, has been considered the main system involved in the pathogenesis of severe lung injury and organs decline in COVID-19 patients. The angiotensin I-converting enzyme (ACE1), angiotensin-converting enzyme 2 (ACE2), angiotensinogen (AGT) and receptors angiotensin II receptor type 1 (AGTR1) are key factors for SARS-CoV-2 entering in the cells, sodium and water retention with an increase blood pressure, promotion of fibrotic and inflammatory phenomena resulting in a cytokine storm. METHODS: In this pilot study, the frequencies of six polymorphisms in the ACE1, ACE2, AGT and AGTR1 genes were analysed in symptomatic patients affected by COVID-19 and compared with the results obtained from asymptomatic subjects. RESULTS: Thus, we have identified that rs2074192 (ACE2), rs1799752 (ACE1) and rs699 (AGT) SNPs could potentially be a valuable tool for predicting the clinical outcome of SARS-CoV-2 infected patients. A genetic predisposition may be prospected for severe internal organ damages and poor prognosis in patients with COVID-19 disease, as observed in symptomatic vs asymptomatic. CONCLUSION: This study provides evidence that analysis of RAAS polymorphisms could be considered the key point in understanding and predicting the SARS-CoV-2 course infection.

SARS-CoV-2 Detection in Fecal Sample from a Patient with Typical Findings of COVID-19 Pneumonia on CT but Negative to Multiple SARS-CoV-2 RT-PCR Tests on Oropharyngeal and Nasopharyngeal Swab Samples.

Reverse transcriptase polymerase chain reaction (RT-PCR) negative results in the upper respiratory tract represent a major concern for the clinical management of coronavirus disease 2019 (COVID-19) patients. Herein, we report the case of a 43-years-old man with a strong clinical suspicion of COVID-19, who resulted in being negative to multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR tests performed on different oropharyngeal and nasopharyngeal swabs, despite serology having confirmed the presence of SARS-CoV-2 IgM. The patient underwent a chest computed tomography (CT) that showed typical imaging findings of COVID-19 pneumonia. The presence of viral SARS-CoV-2 was confirmed only by performing a SARS-CoV-2 RT-PCR test on stool. Performing of SARS-CoV-2 RT-PCR test on fecal samples can be a rapid and useful approach to confirm COVID-19 diagnosis in cases where there is an apparent discrepancy between COVID-19 clinical symptoms coupled with chest CT and SARS-CoV-2 RT-PCR tests' results on samples from the upper respiratory tract.